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)

Twelve Parkinson disease (PD) patients were submitted to a single night of total sleep deprivation (SD). Disease duration had a median of 5.1 years and all were using either anticholinergic or L-Dopa or the combination of both drugs. After SD there was an improvement of rigidity, bradykinesia, gait and posture disturbances and functional disability that remained significant for 2 weeks. No effect was observed on tremor. Concerning depressive symptoms, a significant difference was noted, that remained for one week. These results suggest that SD may be an useful procedure to improve PD symptomatology. It is discussed a possible change of dopaminergic receptors, induced by SD, to explain the improvement.
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PMID:Total sleep deprivation and Parkinson disease. 343 4

Systemic administration of the neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to macaque monkeys induced a profound parkinsonian state marked by hypokinesia/bradykinesia, rigidity and tremor. Postmortem studies revealed severe pathological changes in the substantia nigra, pars compacta and in the ventral tegmental area. The levels of dopamine and its major metabolites were reduced by about 90% in the neostriatum, including the nucleus accumbens, when compared to controls. In one animal, the locus coeruleus showed severe pathological changes in association with a reduction in forebrain noradrenaline. 2-deoxyglucose uptake studies suggested that in experimental parkinsonism there if a profound change in the activity of the striatopallidal pathway, but not necessarily in the striatonigral pathway.
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PMID:N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in the monkey: neurochemical pathology and regional brain metabolism. 346 25

It has been shown that the autosomal recessive mutation, gray tremor (gt) was associated in the homozygous state (gt/gt) with a rapidly fatal spongiform encephalopathy. Heterozygotes (+/gt) developed mild asymptomatic spongiform brain lesions as did recipient inbred mice inoculated with gt/gt brain homogenates, some of whom also showed behavioral abnormalities [Sidman, R. L., Kinney, H. C. & Sweet, H. O. (1985) Proc. Natl. Acad. Sci. USA 82, 253-257]. In these studies, inbred NFS/N mice inoculated intracerebrally at birth or as adults with gt/gt or first passage gt brain homogenates developed a progressive disease characterized by tremor, ataxia, and spasticity. The symptoms were milder and more slowly progressive than in the gt/gt homozygote, in the paralytic syndrome that followed neonatal inoculation of NFS/N mice with a wild murine leukemia virus (Cas-Br-M MuLV), or in the rapidly progressive ataxia and terminal bradykinesia that followed scrapie inoculation of NFS/N mice. The noninflammatory spongiform encephalopathy in affected NFS/N mice resembled that observed in gt/gt homozygotes, +/gt heterozygotes, and asymptomatic recipient inbred mice inoculated with gt/gt brain homogenates. Neither infectious MuLV nor MuLV proteins were detected in gt/gt brain homogenates or in affected recipient mouse brains. Scrapie-associated fibrils, readily identifiable in subcellular fractions of brains from scrapie-inoculated NFS/N mice, were not detected in similar brain fractions from NFS/N mice inoculated with gt brain homogenates. These results confirm and extend the suggestion that gt spongiform encephalopathy has both heritable and transmissible properties. Moreover, the transmissible agent of gt disease differs from both Cas-Br-M MuLV and scrapie in its disease-inducing properties in NFS/N mice. The capacity of NFS/N mice to express transmitted gt encephalopathy as clinical disease, to rapidly express Cas-Br-M MuLV spongiform encephalomyelopathy, and to develop mouse-adapted scrapie after a very short incubation time suggest a distinct sensitivity of NFS/N mice to transmissible spongiform encephalopathy.
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PMID:Transmission in NFS/N mice of the heritable spongiform encephalopathy associated with the gray tremor mutation. 347 86

The study concerns symptoms and behavioral characteristics induced by MPTP in a 20-year-old Macaca cynomolgus fascicularis, their evolution over 7 months, and the animal's response to 1-dopa treatment. The symptoms which the animal developed include those that have been described earlier in Macaca mulatta and Saimiri sciureus, i.e., rigidity, action tremor, postural tremor, postural flexion, hypokinesia, and bradykinesia. In addition, however, the animal developed a 3.8 Hz resting tremor which in humans is pathognomonic of Parkinson's disease, as well as cogwheeling, the glabellar tap sign, drooling, impaired ability to relax, and many other symptoms. Also unlike previously described MPTP monkeys, the animal's symptoms neither improved spontaneously, nor did they remain stable shortly after MPTP injection. Instead, symptoms steadily progressed to reach a severe status 2 months after MPTP, and further progression was apparent after another 5 months. Therapeutic responses to 1-dopa required accumulation of or kindling by the 100 mg unit doses that were spaced 4 hr apart, were often organized in time as ON episodes that alternated with OFF episodes, and were associated with dyskinesias and bizarre behavior. Of particular interest is that the animal showed kinesia paradoxa which, in humans, constitutes a feature that is unique to Parkinson's disease among the extrapyramidal disorders. In addition to available evidence, the present findings validate the syndrome induced by MPTP in monkey as an animal analogue of Parkinson's disease. Taxonomic category, age, and the occurrence of shock in response to MPTP are discussed as variables that may possibly co-determine the pathology which MPTP may induce in monkey.
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PMID:Symptoms and behavioral features induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in an old Java monkey [Macaca cynomolgus fascicularis (Raffles)]. 348 98

Twenty-one de novo parkinsonian patients in stage I to III of the Hoehn and Yahr scale completed a 6-month, double-blind, placebo-controlled study. Low-dose bromocriptine (15 mg daily) was effective. Rigidity improved more than tremor or bradykinesia. Sustained satisfactory benefit was seen only in patients with mild Parkinson's disease.
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PMID:Low-dose bromocriptine therapy in Parkinson's disease: double-blind, placebo-controlled study. 351 5

The etiology, pathophysiology, diagnosis and clinical presentation, and clinical management of Parkinson's disease are reviewed. The cause of Parkinson's disease, a progressive, degenerative neurologic motor disorder, is unknown. Both endogenous and environmental factors appear to play a role. The clinical features of parkinsonism result from a depletion in dopaminergic transmission in the corpus striatum; the dopamine deficiency is caused by a loss of melanin-containing nerve cells within the substantia nigra and locus ceruleus. In the remaining neurons, hyalin-like masses called Lewy bodies increase in number, but the importance of this is unclear. The diagnosis of Parkinson's disease is based on the clinical presentation of the patient, which initially includes sensory complaints of aching pains, paresthesias, numbness, and coldness. As the disease progresses, the four classic symptoms become prominent: tremor, rigidity, bradykinesia, and postural difficulties. Drug therapy is the cornerstone of clinical management of Parkinson's disease, but no treatment has been found that will retard or reverse the disease. Therapy is usually initiated with anticholinergic agents such as biperiden hydrochloride or trihexyphenidyl hydrochloride with or without amantadine. The mainstay of therapy is levodopa, which is used in combination with dopa decarboxylase inhibitors to decrease the peripheral conversion of levodopa to dopamine. Bromocriptine is a dopamine agonist useful in treating Parkinson's disease. Therapy, which must continue for life, eventually becomes less effective or completely ineffective in all patients. Drug therapy has improved greatly the functional ability of patients with Parkinson's disease, but new agents that can extend the length of effective treatment or reverse the disease are needed.
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PMID:Current concepts in clinical therapeutics: Parkinson's disease. 353 Jun 16

This paper presents a review of the literature on the therapeutic action and the side effects of the two main dopaminergic agents: L-DOPA/decarboxylase inhibitor (L-DOPA/DI) and bromocriptine (Parlodel used either as monotherapy or in combination in patients with Parkinson's disease. The combination of L-DOPA/DI and bromocriptine gives the best therapeutic efficacy (49% improvement) in the total score (bradykinesia, rigidity and tremor). However, treatment by monotherapy or combination gives the same pattern of activity: greatest improvement in tremor, followed by rigidity and bradykinesia. Improvement observed in the short term is not sustained over longer periods of time for monotherapy with either drug. The short-term side effects are similar for each treatment, whereas long-term complications (dyskinesia, end-of-dose deterioration and on-off phenomenon) appear only when levodopa is used, alone (high incidence) or in combination with bromocriptine (low incidence). The overall optimum treatment is obtained with a combination of L-DOPA/DI and bromocriptine.
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PMID:Optimum symptomatic control of Parkinson's disease with dopaminergic therapy. 367 21

Low-dose bromocriptine therapy (average dose 14.5 mg/day at 2 years) produced significant improvement in 25 of 39 parkinsonian patients. Bradykinesia was less in de novo subjects; tremor and rigidity improved most in the levodopa subjects. Five of six patients improved after a low-dose bromocriptine drug "holiday." After the addition of bromocriptine any reductions in levodopa dosage were small, with repeated cuts made gradually over months preventing the deterioration commonly seen with larger sudden reductions in levodopa dosage. Five patients withdrew because of intolerable adverse effects, two because of worsening response. Adverse effects were mild and generally dose dependent, and in some patients they disappeared without reduction in continuing bromocriptine therapy. Eighty percent of those who tolerated bromocriptine maintained response over 2 years. Bromocriptine did not induce dyskinesia, the wearing-off response, or the on-off phenomenon in de novo subjects and was used as a first choice drug in these parkinsonian patients. Best results were obtained from a combination of bromocriptine and levodopa.
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PMID:Bromocriptine: long-term low-dose therapy in Parkinson's disease. 370 99

Metoclopramide hydrochloride is an antiemetic and gastric motility stimulant with a wide variety of extrapyramidal side effects, including parkinsonism. We describe two patients with end-stage renal disease secondary to diabetes mellitus treated with hemodialysis who developed extrapyramidal symptoms during treatment with metoclopramide. One patient with preexisting, well-controlled Parkinson's disease developed increasing rigidity and bradykinesia that became completely refractory to treatment with L-dopa and bromocriptine while taking metoclopramide for diabetic gastroparesis. A second patient with no history of Parkinson's disease developed a resting tremor and facial dyskinesia during treatment with metoclopramide. In both cases, discontinuation of metoclopramide therapy led to prompt improvement of symptoms.
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PMID:Metoclopramide-induced parkinsonism in hemodialysis patients. Report of two cases. 376 55

Thirty-one patients with Wilson's disease were evaluated with detailed neurologic and medical examinations. Mean age (+/- SD) at onset was 21 +/- 5 years and at examination was 28 +/- 6 years. Of the 90% of patients who were first treated with penicillamine, 31% deteriorated initially despite therapy, and half never recovered to pretherapy baseline. At the time of our evaluations, the most common neurologic findings were dysarthria (97%), dystonia (65%), dysdiadochokinesia (58%), rigidity (52%), gait and postural abnormalities (42%), and tremor (32%). Chorea and dementia were rare. Twenty-two patients underwent magnetic resonance imaging. All but one of the 19 symptomatic patients had abnormal scans. The three asymptomatic patients had normal scans. Most lesions were seen in the caudate, putamen, subcortical white matter, midbrain, and pons. Generalized brain atrophy was also common. Lesions were less common in the thalamus, cerebellar vermis, midbrain tegmentum, globus pallidus, red nucleus, and dentate nucleus. Dystonia and bradykinesia correlated with putamen lesions, and dysarthria correlated with both putamen and caudate lesions.
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PMID:Clinical assessment of 31 patients with Wilson's disease. Correlations with structural changes on magnetic resonance imaging. 382 91


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