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)

Occurrence of extrapyramidal signs was investigated in a follow-up study of 32 patients with probable Alzheimer's disease (AD). Bradykinesia and rigidity were observed in 39% and 11% of the neuroleptic-free patients at entry and in 72% and 61% at year 3, respectively. Tremor was not a predominant feature nor did its occurrence increase over time. Use of neuroleptics contributed to extrapyramidal signs; 75-100% of the neuroleptic-treated patients showed bradykinesia, rigidity or orofacial dyskinesia. The homovanillic acid (HVA) concentrations of the cerebrospinal fluid at entry were comparable to those of age-matched controls. Nor did HVA levels correlate with rigidity or bradykinesia in these early AD cases. Presence of bradykinesia or rigidity at the initial evaluation predicted more severe dementia and a poor prognosis over the period of 3 years, although interaction of initial clinical severity of dementia was significant. Of 15 patients with these signs 3 (20%) died and 8 (53%) needed institutional care, while of 17 patients without these signs only 1 (6%) died and 2 (12%) were institutionalized by year 3 (p less than 0.01).
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PMID:Extrapyramidal signs in Alzheimer's disease: a 3-year follow-up study. 134 10

Current concepts suggest that parkinsonian bradykinesia is a consequence of an imbalance between striatopallidal and striatonigral output pathways. Dopamine appears to oppositely effect these neurons due to the selective localization of the D1 receptor on striatonigral neurons and the D2 receptor on striatopallidal neurons. Studies measuring changes in gene regulation suggest how selective D1 and D2 dopamine agonist treatments may be used to restore the normal balance between the striatal output pathways.
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PMID:Molecular neuroanatomic mechanisms of Parkinson's disease: a proposed therapeutic approach. 135 51

Behavioural and neurochemical effects of acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment in mice have been studied in order to determine the change in the neurotransmitter profile of the following areas of the brain: substantia nigra (SN), nucleus caudatus putamen (NCP), limbic system (LS; tuberculum olfactorium and nucleus accumbens), medulla oblongata (MO) and cerebellum (CER). Subcutaneous administration of MPTP (40 mg/kg) caused behavioural syndromes including restlessness, straub tail, hindlimb abduction, tremor, jumping, bradykinesia and akinesia in Balb/c mice. There existed a well-defined biphasic profile of motor activity comprising of an initial excitatory phase followed by an inhibitory phase lasting about two and a half and five hours, respectively. A significant rise in 5-hydroxytryptamine (5-HT) content together with a decreased 5-HT utilization as evidenced by lower 5-hydroxyindole acetic acid (5-HIAA) to 5-HT ratio in the above brain areas demarcated the excitatory phase, whereas the inhibitory phase was distinguished by a significant decrease in dopamine (DA) content along with an increased turnover of the amine as shown by a higher homovanillic acid (HVA) to DA ratio in the functionally important nuclei of the extrapyramidal system like SN, NCP and LS. Methysergide, a nonspecific 5-HT receptor blocker, but not ketanserin, a specific 5-HT2 antagonist, prevented the occurrence of the initial excitatory phase without affecting the depressive phase. Administration of apomorphine, a dopamine agonist, 30 minutes prior to MPTP was ineffective, whereas its application 90 minutes after MPTP prevented the occurrence of bradykinesia and akinesia. Interestingly, treatment with haloperidol, the dopamine (D1/D2) antagonist, before and after MPTP administration caused an early onset and prolongation of the inhibitory phase without affecting the initial hyperexcitement. The results provide direct evidence for the involvement of serotoninergic and dopaminergic mechanisms in the genesis of the early and late syndromes of acute MPTP poisoning respectively.
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PMID:Dissociation of serotoninergic and dopaminergic components in acute effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice. 135 Apr 96

The effects of the selective dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) on the kinematics of two-dimensional arm movements in the primate were studied. Two rhesus monkeys were trained to move a manipulandum at various distances and directions in horizontal space from a centrally located target box. Several kinematic parameters including reaction time, and time and amplitude of peak tangential velocity were analysed. Following an extensive control evaluation period, the animals were unilaterally injected with MPTP into the internal carotid artery. The animals were restudied for up to 289 days following induction of hemiparkinsonism. Larger-amplitude movements (greater than 3.5 cm) were more severely affected than smaller amplitude movements. Both animals exhibited marked changes in the arm movements including increased time-to-peak velocity and decreased peak velocity. The degree of the kinematic changes was spatially dependent, with the decrease in velocity as well as the time-to-peak velocity being more pronounced for the larger, outward movements. Reaction time increased but showed no spatial dependency. Kinematic deficits persisted over the entire time-period studied. Also, the kinematic changes were reduced by levo-3,4 dihydroxyphenylalanine in a dose-dependent manner. Tyrosine hydroxylase immunohistochemistry documented extensive cell loss in the substantia nigra. These results show that both the timing as well as the amplitude of the velocity profiles are disrupted by MPTP consistent with the known akinesia and bradykinesia of parkinsonism. Although abnormalities were present for all directions and distances, a spatial dependency to the deficits was detected. The observation of more pronounced changes for larger, outward movements suggests a role for the basal ganglia in production of larger-amplitude movements directed away from the body.
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PMID:Effects of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP)-induced hemiparkinsonism on the kinematics of a two-dimensional,multijoint arm movement in the rhesus monkey. 135 Dec 72

Because of the number of different types of anti-Parkinsonian medications, a number of options in the treatment of PD are now available. Each patient's medication regimen should be individualized. Many of the medication choices are made based on the stage of the disease. For patients who have newly diagnosed PD, and who are on no medications, treatment with deprenyl should be strongly considered. While some controversy remains concerning its possible slowing of the rate of disease progression, there is no evidence to suggest that its use is detrimental. It is generally well tolerated in patients with early disease. These factors must be weighed against the cost of the medication, and the fact that little if any therapeutic effect is seen in most patients who are not being treated with LD. A useful analogy when considering this issue is the prophylactic use of aspirin for cerebrovascular or cardiovascular disease. Newly diagnosed patients requiring treatment, who have tremor as their only symptom or their most prominent symptom, may be given an anticholinergic medication. Patients who have significant bradykinesia, rigidity or gait disturbance can be given amantadine. A combination of these two medications may be useful, and a combination of deprenyl with an anticholinergic drug or amantadine may provide excellent relief of early symptoms. At some point, most patients' symptoms progress such that treatment with LD is considered. Given its possible, but unproven, acceleration of the rate of disease progression, this decision should be weighed carefully. In a relatively young patient who may be treated for many years, a dopamine receptor agonist can be initiated without LD therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Recent progress in the treatment of Parkinson's disease. 135

We report on a 44-year-old woman with a right frontal meningioma, who presented with resting tremor, rigidity and bradykinesia in the left limbs. There were no other neurologic manifestations. A computed tomography scan demonstrated a huge high-density mass in the right frontal lobe and marked surrounding edema causing compression of the basal ganglia. Cerebral angiography showed a typical sunburst tumor stain and three feeding vessels from the bilateral middle meningeal arteries and the right callosomarginal artery. The pathologic diagnosis was transitional type meningioma. Before surgery, treatment with levodopa and bromocriptine was significantly effective in controlling hemiparkinsonism, which completely disappeared after surgical removal of the tumor. This outcome supports the notion that local compression due to edema may cause a functional disorder in the basal ganglia producing reversible contralateral parkinsonism.
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PMID:Hemiparkinsonism in a patient with frontal meningioma. 136 48

Four patients with severe form of Parkinson's disease received transplantation of fetal dopaminergic cells into the caput of the caudate nucleus. The operation was done by an original method using a device designed specially for this purpose. In all cases the duration of the disease was 10 to 15 years, and the predominating signs were tremor, bradykinesia, and markedly pronounced side effects of the treatment (on-off syndrome and involuntary movements). One patients died 5 weeks after the operation. Autopsy demonstrated good survival of the transplanted cells with good integration with the brain of the recipient and traces of positive immunocytochemical reaction for tyrosine hydroxylase. In the other patients a significant clinical improvement was noted after the operation, with reduced intensity of parkinsonian symptomatology, shortening of the duration of the off phase, improved motor ability and reduced intensity of the involuntary movements. The longest follow-up was 24 months.
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PMID:[Transplantation of fetal dopaminergic cells in Parkinson disease]. 140 86

The purpose of this study was to analyze the kinematic properties of upper limb trajectories in Parkinson's disease (PD) patients and to investigate the role of visual feedback from the moving limb. Beyond the characteristic bradykinesia, PD patients differed from controls by generating hand trajectories with asymmetrical velocity profiles that lacked smoothness and were composed of a short initial accelerative phase, followed by a prolonged interval composed of alternating decelerative and accelerative phases. In both groups, the reaction times for movements directed away from the body were longer than for movements directed toward the body; this effect was accentuated in PD. In both groups, initial peak accelerations were significantly larger for distally as compared to proximally directed movements. In the absence of visual feedback from the limb a deterioration in the accuracy of reaching the target was observed in both control and PD patients only for distally directed movements. However, this deterioration and the effect of target location on final accuracy was substantially larger in PD. Taken together, our study suggests that in PD visual information is continuously relied upon for ongoing movement correction, therefore accentuating the bradykinesia. The deficit in final accuracy in the absence of visual feedback reflects the important role played by the basal ganglia in sensorimotor integration.
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PMID:Kinematic analysis of upper limb trajectories in Parkinson's disease. 142 28

To determine how the response to levodopa is altered by long-term therapy, we examined the dose response to 2-hour infusions of levodopa in three groups of parkinsonian patients: those who were previously untreated, those who exhibited stable responses, and those who exhibited fluctuating responses to levodopa therapy, using tapping speed as an index of bradykinesia. The baseline tapping speed was greater in the patients with stable responses than in the untreated patients, probably representing a "long-duration response" to levodopa therapy. A "short-duration response," indicated by an increase in tapping speed lasting hours, was observed in most patients in all groups. The onset of the short-duration effect was more rapid and the incremental increase in tapping speed was twice as large in the patients with fluctuating responses compared with the untreated patients and patients with stable responses. The duration of the short-duration effect was greatest in the untreated group but did not differ between the groups with stable and fluctuating responses. Dyskinesia was not observed in any of the de novo patients but was observed in three of 12 patients with stable responses and eight of nine patients with fluctuating responses to levodopa therapy. Dyskinesia appeared before or with the antiparkinsonian effects in patients with stable responses, giving no indication of a higher threshold for dyskinesia in these patients compared with those with fluctuating responses. The plasma half-life clearance, volume of distribution, and maximum plasma concentrations of levodopa did not differ among groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of long-term therapy on the pharmacodynamics of levodopa. Relation to on-off phenomenon. 144 77

Vascular pseudoparkinsonism may be confused with idiopathic Parkinson's disease. Patients may be unnecessarily treated with anti-parkinsonian drugs while their underlying vascular disease is ignored. We investigated 250 parkinsonian patients seen in our Movement Disorders Clinic for a possible vascular etiology. After excluding those with a known secondary cause such as drug-induced parkinsonism, progressive supranuclear palsy, multiple system atrophy and hyperparathyroidism, brain computed tomography and/or magnetic resonance imaging were performed on those who showed poor or no response to levodopa. In those with an ischemic lesion demonstrated on neuroimaging, anti-parkinsonian drugs were stopped and the patients were reassessed. Eleven patients (4.4%) had ischemic brain lesions accounting for their parkinsonism. All were initially diagnosed as Parkinson's disease because of the prominence of bradykinesia and rigidity. Gait disturbance was also common, but resting tremor was distinctly absent. Three anatomical patterns with different prognosis were identified. Three patients with basal ganglia lacunar infarct recovered spontaneously, three with frontal lobe infarcts remained static and five with periventricular and deep subcortical white matter lesions had progressive deterioration. Autopsy in one patient confirmed bilateral frontal lobe watershed infarcts and the absence of brain stem Lewy bodies. Parkinsonian patients with poor or no response to levodopa therapy should be investigated for a vascular etiology.
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PMID:Vascular pseudoparkinsonism. 148 45


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