Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Freezing episodes and related phenomena (as a general term, motor blocks [MBs]) are poorly understood, particularly disabling, and a therapeutically frustrating problem in Parkinson's disease (PD). Epidemiologic and clinical characteristics of MBs, as well as risk factors to develop MBs, have never been fully addressed. Herein, we report our database survey on 990 PD patients, of whom 318 (32%) had MBs. The majority of MBs were linked to gait. Start hesitation occurred in 86%, blocking on turning in 45%, and blocking in narrow spaces in 25% of patients. Initial parkinsonian symptoms in the upper body and tremor as the initial motor symptom were less likely to be associated with the presence of MBs (odds ratios [OR] 0.6 and 0.7, respectively), while initial symptoms affecting gait or trunk had higher association with MBs (OR = 1.58). Longer disease duration, higher Hoehn and Yahr stage, and longer duration of levodopa treatment are all significantly associated with the presence of MBs. We observed significant association between the existence of MBs and levodopa-induced dyskinesias to suggest similar pathophysiology. We propose that MBs in PD are abnormal retrieval or execution of complex motor tasks that can occur as a result of disease progression or as short- or long-term side effects of levodopa treatment.
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PMID:Motor blocks in Parkinson's disease. 173 61

The French selegiline multicenter trial was conducted in 1990 to test the possibility to improve disability of de novo parkinsonian patients (P.P.) during the first three months of treatment with selegiline (S) (10 mg/day) monotherapy. 93 P.P. were included in this double-blind, randomized, placebo controlled, clinical trial, in which 13 centers participated. Both parallel groups were followed up from inclusion (D0) to D30, D60 and D90. Drug efficacy was judged with Hoehn and Yahr (HY), Hamilton Depression Rating Scale (HDRS), Unified Parkinson's Disease Rating Scale (UPDRS), Schwab and England scores, decision to introduce levodopa and selfassessment. Biological and clinical parameters (cardio- vascular, weight, side-effects reports) were assessed for tolerability. 84 P.P. (38 P, 46 S) were evaluable for efficacy at D90. When considering the main parameters, S appears superior to placebo: HY scores (p less than 0.001), global UPDRS scores (p less than 0.001) and UPDRS subscores: mental (p less than 0.001), daily living activities (p less than 0.01), motor activities (p less than 0.01). Depressive scores (HDRS) are significantly improved only at D90 (p = 0.005). Levodopa therapy was introduced in 45% of the cases in S groups versus 18.4% in P group. Global impression of efficacy was largely in favor of S; failure was noted in half of the cases in P group and only in 1/5th of the cases in S group. Side-effects were rare and minor. S 10 mg/day monotherapy is statistically superior to placebo in improving de novo P.P. during the first three months treatment. Motor symptoms rapidly improve; mood is only modified after 3 months. S appears to be well tolerated. S may be considered as a good candidate for the initial treatment of P.P.
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PMID:Selegiline in de novo parkinsonian patients: the French selegiline multicenter trial (FSMT). 180 41

Parkinson's disease patients are frequently impaired in a variety of neuropsychological tasks involving memory, perceptual motor performance and cognitive flexibility. Although various theories have been forwarded to explain specific impairments, few attempts have been made to account for all the deficits within a single theoretical framework. Furthermore, the frequent occurrence of dementia, the adverse side effects of medication and the motor symptoms of the disease tend to interfere with neuropsychological performance. This has hindered the clear delineation of the neuropsychological profile of Parkinsonian patients. The present paper examines the evidence for intellectual deficits in non-demented Parkinson's disease patients. A number of problems inherent in cognitive research on Parkinson's disease are discussed. The contribution of dementia, motor symptom severity and medication in the expression of these intellectual impairments is examined. It is suggested that many of the neuropsychological deficits described in Parkinson's disease may result from a common underlying deficit in some aspect of information processing. Although it is not possible to pinpoint the precise mechanism(s) involved on the basis of the available evidence, several possibilities are suggested by cognitive and electrophysiological data.
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PMID:Parkinson's disease: a conceptualization of neuropsychological deficits within an information-processing framework. 269 79

MPTP induces parkinsonism in monkeys by destruction of the substantia nigra, pars compacta. It can also damage ventral tegmental dopamine neurones and the noradrenergic locus coeruleus, both of which may be affected in Parkinson's disease. Motor symptoms in MPTP-treated monkeys respond readily to levodopa or dopamine agonist therapy. Administration of levodopa over 4-8 weeks leads to the emergence of "peak-dose" dyskinesia. Such abnormal movements are not seen following challenge doses of levodopa in animals not on long-term therapy. Radioligand studies reveal a 40-180% increase in D2 receptor binding in the striatum of parkinsonian monkeys. 2-deoxyglucose studies of regional brain metabolism indicate that MPTP-induced parkinsonism is characterised by abnormally increased activity of medial pallidal neurones which project to the thalamus and pedunculopontine nucleus and reduced activity of subthalamic nucleus neurones.
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PMID:MPTP-induced parkinsonism in the monkey: neurochemical pathology, complications of treatment and pathophysiological mechanisms. 311 80

Lesions of the subthalamic nucleus (STN) have been found to reduce the severe akinetic motor symptom produced in animal models of Parkinson's disease, such as in monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or in monoamine-depleted rats. However, little is known about the effect of STN exclusion on subtle motor deficits induced by moderate dopaminergic lesions in complex motor tasks. The present study was thus performed on rats trained in a reaction time (RT) task known to be extremely sensitive to variations of dopamine transmission in the striatum. Animals were trained to release a lever after the onset of a visual stimulus within a time limit to obtain a food reward. Discrete dopamine depletion produced by infusing the neurotoxin 6-hydroxydopamine (6-OHDA) bilaterally into the dorsal part of the striatum, produced motor initiation deficits which were revealed by an increase in the number of delayed responses (lever release after the time limit) and a lengthening of RTs. In contrast, bilateral excitotoxic lesion of the STN with ibotenic acid induced severe behavioral deficits which were opposite to those produced by the dopaminergic lesion, as shown by an increase in the number of premature responses (lever release before the onset of the visual stimulus) and a decrease of RTs. Surprisingly, the performance of the animals bearing a double lesion (striatal dopaminergic lesion followed 14 d later by STN ibotenic lesion) was still impaired 40 d after the ibotenic lesion. As expected, the 6-OHDA-induced motor initiation deficits were reversed by a subsequent STN lesion. However, the dramatic increase of premature responses contributing to major behavioral deficits induced by the STN lesion remained unchanged. Thus, the bilateral lesion of the STN was found to alleviate the motor deficits in this model of parkinsonism, but essentially produced over time, long lasting deficits that might be related to dyskinesia or cognitive impairment. The present results strongly support the recent concept of a predominant control of the STN on basal ganglia output structures.
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PMID:In a rat model of parkinsonism, lesions of the subthalamic nucleus reverse increases of reaction time but induce a dramatic premature responding deficit. 747 15

Olfactory dysfunction occurs in most patients with idiopathic Parkinson's disease (PD). In this study, we sought to determine whether such dysfunction is also present in progressive supranuclear palsy (PSP), a condition which shares a number of motor symptoms with PD and is commonly misdiagnosed as PD. We administered the University of Pennsylvania Smell Identification Test, a standardized test of odor identification ability, to 21 PSP patients; 17 also received a forced-choice odor detection threshold test. We compared the olfactory test scores to those obtained from PD patients and normal controls matched to the PSP patients on the basis of age, sex, and smoking habits. Overall, the olfactory function of the PSP patients was markedly superior to that of the PD patients and did not differ significantly from that of the normal controls. There was no association in either the PSP or PD patient groups between (1) the olfactory test scores and (2) measures of motor symptom severity, disease stage, and medication usage. These findings demonstrate that patients with PSP and PD differ markedly in their ability to smell and suggest that olfactory testing may be useful in their differential diagnosis.
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PMID:Olfactory testing differentiates between progressive supranuclear palsy and idiopathic Parkinson's disease. 849 53

Signs of attentional dysfunction mimicking spatial neglect have been described both in humans with lateralised Parkinson's Disease (PD) and in animals with MPTP-related hemiparkinsonism. Such deficits have been attributed to dopamine loss in basal ganglia and cortical targets. However, in previous studies the existence of neglect was assumed from behavioural tests which needed a motor output, thus entailing interpretation ambiguities due to effects of directional hypokinesia. We recorded brain event-related potentials (ERPs) evoked by the presentation of target somatic stimuli to the affected and non-affected sides in 44 patients with unilateral or asymmetrical PD. The N2 and P3 ERP components were specifically analysed, since (a) they are triggered selectively by task-relevant, attended sensory stimuli; (b) their latency reflects stimulus evaluation time, independently from the execution of a motor response, and (c) they have proved to be abnormal in hemineglect syndromes due to focal brain lesions. Irrespective of the side (left or right) of motor symptom predominance there were no significant ERP differences to stimulation of the affected and non-affected limbs, nor was there any correlation between ERP latencies and the degree of dopamine-related motor impairment. The P3 latency was abnormally delayed in 23% of the patients, but there was no trend for abnormalities to concentrate on the affected side. This study does not confirm the existence of a significant attentional impairment toward the affected limb in lateralised PD, and suggests that previous clinical evidence of "neglect' behaviour in PD might be linked to directional hypokinesia, thus reflecting intentional, rather than attentional lateralised deficits.
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PMID:Brain responses to detection of right or left somatic targets are symmetrical in unilateral Parkinson's disease: a case against the concept of "parkinsonian neglect'. 895 46

To verify possible dysfunction of sympathetic skin activity in Parkinson's disease (PD), we studied the electrically evoked sympathetic skin responses (SSR) bilaterally at hands and feet in a group of 50 PD patients and in normal subjects. SSR was present in all patients. Nevertheless, significant differences in the latency and amplitude values were noted. In the group of patients prolongation of latency as well as the reduction of SSR amplitude correlates with age. The longer the disease the more SSR abnormalities could be found. Gender, type of clinical manifestation of PD or medication had no statistically significant effects. However, motor symptom asymmetries evaluated separately for each body side correlated well with interside asymmetries of SSR.
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PMID:Autonomic dysfunction in Parkinson's disease assessed by sympathetic skin response: a prospective clinical and neurophysiological trial on 50 patients. 918 5

This study was designed to investigate the influence of white matter hyperintensities (WMH) on clinical features of Parkinson's disease (PD) patients. The study subjects were 44 patients with PD who took a brain MRI. The severity of Parkinsonian symptoms was assessed in both 'on' and 'off' states, using the UPDRS-motor score. Thirteen patients (30%) showed WMH. The patients with WMH were significantly older than those without WMH (67 +/- 5.7 vs 60 +/- 6.4 years). In both 'off' and 'on' states, the gait scores were significantly higher in patients with WMH than in those without WMH (1.6 +/- 0.18 vs 1.1 +/- 0.12, P < 0.05), but other motor symptom (tremor, bradykinesia, rigidity) scores between the two patient groups were not statistically different. After taking a single dose of oral levodopa/benserazide (200mg/50mg), the patients with WMH showed significantly less improvement in bradykinesia score than those without WMH (25 +/- 4.1% vs 40 +/- 4.0%, P < 0.05), but the improvements in other symptoms were comparable between the two groups. These results suggest that WMH on MRI may influence Parkinsonian motor symptoms, particularly gait symptom and levodopa-responsiveness to bradykinesia symptom.
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PMID:The influence of white matter hyperintensities on the clinical features of Parkinson's disease. 952 85

The distinction between procedural and declarative memory is widely accepted in the memory literature. Converging evidence makes a strong case that the medial aspects of the temporal lobes and the diencephalon subserve the declarative memory system. However, the neuroanatomy of procedural memory is much less clear. In animal studies, damage to the basal ganglia has been found to affect procedural memory, but studies of patients suffering from degenerative diseases of the basal ganglia (e.g., Parkinson's and Huntington's disease) are less conclusive. Two groups of Parkinson's disease subtypes, with tremor (PDt) and bradykinesia (PDb) as the predominant motor symptom, were compared to controls on declarative and procedural memory tasks. The two patient groups did not differ from each other on the declarative tasks. However, in the procedural learning tasks, the PDb but not the PDt group, was significantly impaired compared to the control group. The results are discussed in terms of the differential involvement of discrete neuroanatomic loops connecting the basal ganglia and the prefrontal cortex.
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PMID:Declarative and procedural learning in Parkinson's disease patients having tremor or bradykinesia as the predominant symptom. 980 94


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