Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0233565 (bradykinesia)
 2,352 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The selective dopaminergic antagonist ligands [3H]SCH 23390 and [3H]sulpiride were used to reveal autoradiographically dopamine D1 and D2 receptors, respectively, in brain sections from monkeys which had received unilateral intracarotid infusions of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), causing loss of dopamine-containing neurones of the substantia nigra pars compacta. The monkeys developed hemi-parkinsonian symptoms (tremor, bradykinesia) in limbs contralateral to the side of the toxin infusion. Administration of apomorphine (0.05-0.25 mg/kg) caused contralateral rotational behaviour, and reversal of the parkinsonian symptoms. Loss of forebrain dopaminergic terminals was assessed autoradiographically using [3H]mazindol to label dopamine uptake sites. A reduction in these sites of 97% (mean brain value) in the caudate nucleus, and 91% in the putamen, as compared with binding values from untreated control monkeys, was accompanied by a significant increase in the binding of [3H]sulpiride (D2) in these structures. In contrast, in the same animals there was no similar increase in [3H]SCH 23390 binding to D1 receptors in the denervated areas. These results suggest that in the parkinsonian brain, where the dopaminergic innervation of the caudate nucleus and putamen has been lost, D2 receptors may be more susceptible than D1 receptors to changes, revealed here as an increase in [3H]sulpiride binding sites.
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PMID:Autoradiographic studies in animal models of hemi-parkinsonism reveal dopamine D2 but not D1 receptor supersensitivity. II. Unilateral intra-carotid infusion of MPTP in the monkey (Macaca fascicularis). 219 72

Thirty-eight patients with biochemically proven Wilson's disease underwent magnetic resonance-imaging (MRI) of the brain as well as neurological examinations. The patients were scanned using spin-echo (SE) sequences; the neurologist was looking for typical symptoms: dysarthria, tremor, ataxia, rigidity/bradykinesia and chorea/dystonia. Pathological MR findings believed secondary to this uncommon inherited disorder of copper metabolism were found in twenty-two subjects. Focal abnormalities were seen in the lenticular, thalamic and caudate nuclei as well as in brain stem and white matter; these lesions were best demonstrated on T2-weighted sequences as hyperintense areas. In eight patients we found diffuse brain atrophy with consecutive widening of the ventricular system. Five subjects showed mild, nineteen severe neurologic deficits. Generally there was no correlation between MR findings and clinical neurological symptoms; the impairment of cell-metabolism causing functional alterations of the brain precedes morphological changes. During treatment with the copper chelator D-penicillamine there seemed to be a phased course of disease. Shortening of T1-relaxation due to paramagnetic influence of copper was not seen; a possible explanation could be intracellular deposition--a proton-electron-dipolar-dipolar-interaction would therefore be impossible.
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PMID:Cranial MRI in Wilson's disease. 221 6

The DATATOP database, which includes clinical information on 800 patients with early untreated Parkinson's disease (PD), is well suited to explore clinical heterogeneity in PD. Patients with early-onset PD (less than or equal to 40 years, N = 33) reached the same level of disability as the late-onset PD (greater than or equal to 70 years, N = 85) group at a significantly slower rate (2.9 vs. 1.7 years). Early-onset PD patients functioned cognitively better than late-onset PD patients. Bradykinesia, and postural instability and gait difficulty (PIGD), were more common at onset in patients with a rapid rate of disease progression ("malignant PD"; duration of symptoms less than 1 year and Hoehn/Yahr stage of 2.5, N = 11) as compared with those with a relatively slow rate of progression ("benign PD"; duration of symptoms greater than 4 years, N = 65). Comparisons of tremor-dominant PD (mean tremor score/mean PIGD score less than or equal to 1.5, N = 441) with the PIGD-dominant type (mean tremor score/mean PIGD score greater than or equal to 1.0, N = 233) provided support for the existence of clinical subtypes. The PIGD group reported significantly greater subjective intellectual, motor, and occupational impairment than the tremor group. Stage II patients had higher depression scores than stage I patients. Among the patients participating in the DATATOP, older age at onset with bradykinesia, or with the PIGD form of PD, is associated with more functional disability than when the symptoms are dominated by tremor or begin at a younger age.
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PMID:Variable expression of Parkinson's disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group. 221 43

We evaluated 11 patients with hemiparkinson-hemiatrophy syndrome, 6 with body and contralateral cerebral hemispheric hemiatrophy, 4 with only body hemiatrophy, and 1 with just brain hemiatrophy. The mean age of symptom onset was 38.1 years (range, 18 to 54) with 5.2 +/- 3.1 (mean +/- SD) years of illness until the last follow-up visit. The presenting symptom was unilateral tremor in 6 patients, hand dystonia in 2, bradykinesia in 2, and abnormal gait in 1 patient. Three patients had a good response to levodopa, 4 had moderate response, and 2 patients had a poor response. During a mean follow-up period of 1.7 years (range, 4 months to 5 years), the Hoehn and Yahr score changed in only 3 patients: 2 gained 1.5 points and 1 gained 3 points over 2.5 years. We discuss the association between hemiparkinsonism-body hemiatrophy and contralateral hemispheric hemiatrophy, and raise the possibility of early childhood brain insult with delayed-onset parkinsonism.
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PMID:Hemiparkinsonism-hemiatrophy syndrome: clinical and neuroradiologic features. 223 29

Extrapyramidal signs, particularly rigidity and tremor, have been reported in a proportion of patients with dementia of the Alzheimer type. To test the hypothesis that these extrapyramidal signs are similar clinically and neurochemically to the extrapyramidal signs of Parkinson's disease, a group of 20 patients satisfying clinical criteria for probable Alzheimer's disease were studied and assessed clinically for the presence of rigidity, tremor, and bradykinesia. In those patients with extrapyramidal signs, qualitative differences were observed between the signs in these patients and in subjects with Parkinson's disease. Fifteen of 20 patients underwent fluoro-18-dopa scans, which showed no significant difference in fluoro-18-dopa uptake into the caudate and putamen between normal subjects and the rigid and nonrigid patients with Alzheimer's disease, in contrast to the marked reduction in fluoro-18-dopa uptake into the putamen that is observed in Parkinson's disease. This provides clinical and in vivo neurochemical support for the hypothesis that extranigral factors may be involved in the pathogenesis of rigidity in Alzheimer's disease.
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PMID:Clinical and positron emission tomographic studies in the 'extrapyramidal syndrome' of dementia of the Alzheimer type. 225 49

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

Two sibling cases of cerebrotendinous xanthomatosis with parkinsonism were reported. One was a woman of 39 years old, and another was her sister of 36 years old. In both cases, febrile convulsion appeared on 1.5 year old, and mental deterioration, ataxic -spastic gait, cataract and swelling of Achilles tendons developed in order since entrance into elementary school. Five years ago, while they were in hospital at the first time, they were diagnosed as cerebrotendinous xanthomatosis by mental disturbance, cerebellar ataxia, pyramidal tract sign, histologically xanthomatous granuloma of Achilles tendons and hypercholestanolemia and family history of autosomal recessive trait. After the second admission, parkinsonism was noticed in addition to those findings above. Parkinsonism consisted of the following: Resting tremor of parkinsonian type, mild muscle rigidity of forearm and intrinsic-plus hand were observed in the elder sister, and generalized severe rigidity and bradykinesia in the younger sister. In both cases, brain CT showed the pontocerebellar atrophy, and the bilateral low density area in corona radiata, posterior portion of internal capsule, cerebral peduncle, tegmentum of midbrain and deep matter of cerebellum. Brain MRI also showed abnormal intensity in the same regions as on the brain CT. Administration of anti-parkinsonian drugs was challenged for the parkinsonism. Oral L-dopa test (500 mg) moderately improved parkinsonism in both cases. Therapy of diphenylpyraline hydrochloride (10 mg/day) entirely inhibited parkinsonian tremor and mild rigidity in the elder sister but was less effective for severe rigidity in the younger sister than administration of L-dopa.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Parkinsonism associated with cerebrotendinous xanthomatosis]. 226 9

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

Quantitative 2-[14C]deoxyglucose autoradiography was used to map the pattern of alterations in local cerebral glucose utilization associated with unilateral lesions of the substantia nigra pars compacta produced by the infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into one internal carotid artery of rhesus monkeys. These monkeys become hemiparkinsonian, displaying rigidity, bradykinesia, and tremor of the limbs contralateral to the side of MPTP infusion; during spontaneous activity they turn toward the side of the lesion. Eighty-two brain areas were examined, and statistically significant metabolic changes were confined mainly to basal ganglia structures ipsilateral to the side of the lesion. Glucose utilization was reduced in the substantia nigra pars compacta and ventral tegmental area, i.e., in the areas of cell loss. Increases in glucose utilization in regions normally innervated by the lesioned area were observed in the post-commissural portions of the putamen and dorsolateral caudate. Other structures showing statistically significant metabolic changes were the external segment of the globus pallidus (+40%), subthalamic nucleus (-17%), and pedunculopontine nucleus (+15%). There were also smaller changes in portions of the thalamus (ventral anterior nucleus, parafascicular nucleus) and premotor cortex. All significant metabolic changes were confined to the side of the substantia nigra lesion and were essentially restricted to regions involved in the production of movement or maintenance of posture.
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PMID:Local cerebral glucose utilization in monkeys with hemiparkinsonism induced by intracarotid infusion of the neurotoxin MPTP. 231 6


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