Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study is to evaluate what factors influence the risk of occurrence of motor fluctuations in patients with Parkinson's disease (PD) with particular reference to the role of early or delayed introduction of levodopa therapy during the course of the disease. One hundred twenty-five consecutive newly diagnosed patients with PD started levodopa treatment at the time diagnosis and were followed for 2 to 10 years. During follow-up, 60 patients had wearing-off or early morning akinesia. We estimated the cumulative time-dependent risk of motor fluctuation occurrence through a multivariable analysis. The risk was lower for patients with tremor-predominant PD, for those with shorter disease duration prior to levodopa, and for those who were relatively older at levodopa initiation. Our results suggest that, as far as motor fluctuations are concerned, disease prognosis is not influenced by early levodopa treatment. These observation support the introduction of levodopa as soon as there is a subjective need for the patients to maintain their level of social and work performance.
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PMID:The occurrence of motor fluctuations in parkinsonian patients treated long term with levodopa: role of early treatment and disease progression. 200 5

A dementing syndrome has been identified in a group of psychiatric cases aged 71-90 years, presenting initially with a subacute/acute confusional state, often fluctuating and associated with visual hallucinations and behavioural disturbances. Clinically, these cases did not meet criteria for a diagnosis of Alzheimer's disease, and many were assigned to the multiinfarct dementia group, although no significant ischaemic lesions were evident at autopsy. Mild extrapyramidal features were apparent in a number of cases but the characteristic clinical triad of Parkinson's disease, i.e., tremor, rigidity, and akinesia, was absent. Detailed neuropathological examination revealed Lewy body formation and selective neuronal loss in brain stem and other subcortical nuclei, accompanied by Lewy body formation in neo- and limbic cortex, at densities well below those previously reported in diffuse Lewy body disease. A variable degree of senile degenerative change was present; numerous senile plaques and minimal neurofibrillary tangles in most cases. Neither the clinical nor the neuropathological features of this group are typical of Parkinson's or Alzheimer's disease, but suggest a distinct neurodegenerative disorder, part of the Lewy body disease spectrum, in which mental symptoms predominate over motor disabilities and lead to eventual psychogeriatric hospital admission. In a sequential series of autopsies conducted on clinically assessed demented patients, neuropathological analysis has indicated that such cases may comprise up to 20% of a hospitalized population of demented old people over the age of 70 years, an observation clearly relevant to the diagnosis and management of dementia in the elderly.
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PMID:Senile dementia of Lewy body type. A clinically and neuropathologically distinct form of Lewy body dementia in the elderly. 215 23

Parkinson's disease (PD) is a common neurodegenerative disease of old age characterized by triad of akinesia, rigidity and tremor, reduction of dopamine (DA) content in the nigrostriatum, and severe degeneration of neuron in the substantia nigra. The significant changes after the use of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to rhesus monkeys and C57 black mice are (a) serotonin-like reactions and Parkinsonian symptoms in monkeys and "stickclimbing" disturbance in mice; (b) marked DA reduction in substantia nigra (72.5%), putamen (93.3%), caudate nucleus (91.2%) of monkeys and striatum (94%) of mice; (c) reduction of Met-enkephalin (75%) and Leu-enkephalin (66%) in mouse striatum; and (d) severe degeneration of neurons in the substantia nigra of monkeys and mice. The results suggest that MPTP-treated monkey and C57 black mouse provides useful Parkinsonian animal models and produces behavioral, biochemical and histopathological changes similar to those of human PD.
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PMID:[Experimental research on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian animal models in the rhesus monkey and C57 black mouse]. 216 92

The interim results obtained up to the end of the 3rd year of the multicenter nationwide cooperative study on the long-term effects of bromocriptine in parkinsonian patients are reported. Bromocriptine monotherapy could be continued in approximately 33% of the patients at the mean maintenance dose of 11.4 mg/day. The combined use of bromocriptine (11.1 mg/day) in parkinsonian patients already treated with levodopa had a favorable influence on the long-term side effects of levodopa such as the on-off phenomenon and dyskinesia. The beneficial effects of bromocriptine, levodopa and an early combination on parkinsonian symptoms such as rigidity and tremor remained at the end of the 3rd year. However, the effects of each mode of therapy on another parkinsonian symptom, akinesia, ceased by the end of the 3rd year.
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PMID:Third interim report of the nationwide collaborative study on the long-term effects of bromocriptine in the treatment of parkinsonian patients. 217 38

Movement disorders are subdivided based on a variety of criteria. One useful and popular approach to movement disorders, based on clinical phenomenology, categorizes these disorders into two groups, those displaying a poverty of movement (akinesia) and those displaying excessive movement (hyperkinesia). This article discusses diagnosis and treatment of the latter. By necessity, certain hyperkinesias such as hyperexplexia, akathisia, and restless leg syndrome are omitted or only briefly discussed. The major hyperkinesias, dystonia, tremor, tics, chorea (including tardive dyskinesia and ballism), and myoclonus are reviewed and a guide to practical management emphasizing symptomatic treatment is presented.
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PMID:Treatment of hyperkinetic movement disorders. 218 Dec 68

When used to treat patients with Parkinson's disease pergolide acts at dopamine receptors in the corpus striatum to improve locomotor activity, reducing the tremor, gait disturbances, bradykinesia or akinesia and rigidity experienced by such patients. Treatment with pergolide often allows substantial reductions in concomitant levodopa dosage, and occasionally levodopa can be completely replaced by pergolide therapy in short term use. Pergolide has a long duration of action, thus reducing the wearing-off and end-of-dose phenomena frequently seen with long term levodopa therapy, suppressing fluctuations in levodopa response, and increasing total 'on' time. Despite a lack of well controlled studies comparing this drug with other dopamine agonist agents, pergolide appears to result in adverse effects and anti-Parkinson responses similar to those of bromocriptine and lisuride. Thus, pergolide would appear to be at least as useful as other dopamine agonists such as bromocriptine or lisuride for the management of patients with Parkinson's disease when administered in combination with levodopa. Future research should be directed towards establishing which patients are most likely to benefit from pergolide therapy, and clarifying the relative efficacy and safety of the anti-Parkinsonian drugs available to the clinician. If pergolide does provide clinical benefit when substituted for levodopa-adjunct drugs that are producing less than optimal control, this will be an advantage in a disease area which at present has few therapeutic options.
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PMID:Pergolide. A review of its pharmacological properties and therapeutic potential in Parkinson's disease. 218 10

Intracerebral injections of the broad spectrum excitatory amino acid antagonist kynurenic acid (50 ug) alleviated the symptoms of akinesia, tremor and rigidity in a severely parkinsonian monkey. Unilateral injection of kynurenic acid within the medial pallidal segment produced rotational behaviour away from the side of the injection, and the limbs on the contralateral side showed relief of the MPTP-induced parkinsonian symptoms. The subsequent bilateral injection of the excitatory amino acid antagonist allowed the monkey to move freely, unhindered by tremor or rigidity. In addition unilateral injections of the NMDA antagonist MK-801 (5, 25 and 50 ug) within the medial pallidum also produced dose-related rotational behaviour, with alleviation of parkinsonian symptoms in the contralateral limbs. Systemic administration of MK-801 (1 ng/kg - 1 ug/kg i.m.) was without effect.
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PMID:Injection of excitatory amino acid antagonists into the medial pallidal segment of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated primate reverses motor symptoms of parkinsonism. 225 May 73

After preliminary observations on 5 psychotic and 7 nonpsychotic parkinsonian patients had shown unexpected impressive beneficial effects of the atypical neuroleptic clozapine on tremor, an open clinical study including 12 patients was started. Under a dosage-range approximately 25-50 mg/day significant reduction of tremor intensity and tremor related functional disability (CURS, Sweet's scale) was achieved. Akinesia was not deteriorated, initial fatigue disappeared spontaneously. Pharmacological mode of action of clozapine's antitremor effect remains unclear. Its broad receptor binding spectrum with strong antiserotonergic properties might here play a major role.
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PMID:Treatment of parkinsonian tremor with clozapine. 225 63

Akinesia refers to failure of willed movement to occur, and bradykinesia refers to slowness of movement that is ongoing. One mechanism of bradykinesia is failure to energize muscles up to the level necessary to complete a movement in a standard amount of time. Akinesia may occur for two possible reasons. One is that the movement is so slow (and so small) that it cannot be seen. A second is that the time needed to initiate the movement becomes excessively long; this can be studied by evaluation of reaction time. One simple factor in prolongation of reaction time is present in patients with rest tremor, who appear to have to wait for a beat of tremor in the agonist muscle of the willed movement in order to initiate the movement. Reaction time studies in patients with Parkinson's disease demonstrate that simple reaction time is delayed, while choice reaction time is normal. Additionally, there does not appear to be any slowness of thinking or difficulty with storage of a motor program. Hence, the difficulty with reaction time in these patients appears to be the time that it takes to execute a motor program. Studies with magnetic stimulation of the motor cortex during the reaction time period seem to support this hypothesis. Slowness of activation of the motor cortex to trigger a movement may well be analogous in mechanism to the slowness of bradykinesia.
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PMID:Clinical neurophysiology of akinesia. 226 21

The GABA/benzodiazepine receptor complex in the basal ganglia of primates treated with the neurotoxin n-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been studied by semi-quantitative autoradiography with [3H]flunitrazepam ([3H]FNZ). Systemic treatment with MPTP produced a stable and lasting parkinsonian condition, with pronounced bradykinesia, akinesia and tremor. In the lateral segment of the globus pallidus (GPL) there was a significant reduction of [3H]FNZ binding compared with non-treated animals. There were no significant changes in the [3H]FNZ binding in the caudate nucleus, putamen and medial globus pallidus (GPM). This suggests that MPTP-treatment increases GABA release within the GPL exclusively. In view of the available evidence suggesting increased striatal output, and reduced unit activity within the GPL of the MPTP-treated primate, it seems likely that the striatal GABAergic output to the GPL is overactive in this model of Parkinson's disease. Furthermore, as there is no evidence for a change in GABA function within the GPM using this measure, the striatal neurones which innervate the GPM may be differentially affected by loss of dopamine innervation. In line with structural evidence and extrastriatal dopamine receptor distribution this suggests that the two striatopallidal systems are functionally heterogeneous. A hemi-parkinsonian primate model has also been used in this study. This model was produced by injection of MPTP directly into one carotid artery. The substantia nigra pars compacta (SNc) was destroyed on the injected side alone, and consequently the appearance of parkinsonian symptoms was confined to the contralateral side. [3H]FNZ binding in the GPL appears to be bilaterally reduced in this model, suggesting an interaction between the treated and non-treated side of the brain. In addition there is increased binding in the putamen and GPM with respect to the non-treated side of the brain. The increased [3H]FNZ binding in the GPM of the unilateral model may be due to the greater disruption of the nigropallidal and/or nigrostiatal dopamine neurones relative to the systemic model. The former would have the effect of uncoupling D1 dopamine receptors located on the terminals of striatal efferents from nigropallidal dopamine input, and as D1 dopamine receptors are implicated in the presynaptic control of GABA release from the terminals of striatal efferents, this would consequently reduce the level of GABA release in the GPM. The latter possibility would suggest that striatopallidal neurones projecting to GPM are more resistant to the effects of dopaminergic denervation than those projecting to GPL.
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PMID:The role of striatopallidal neurones utilizing gamma-aminobutyric acid in the pathophysiology of MPTP-induced parkinsonism in the primate: evidence from [3H]flunitrazepam autoradiography. 228 39


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