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)

This article is a review of autonomic dysfunction in idiopathic Parkinson's disease (iPD), as well as the clinical features of a specific form of PD, i.e. autonomic failure (AF) with PD, and is based mainly on the results obtained from our recent studies. Since James Parkinson's original discription, the definition of autonomic dysfunctions in iPD and their clinical characteristics have undergone changes. Autonomic dysfunction is considered to be uncommon and rarely severe on one hand, while not infrequent but not as severe as in Shy-Drager syndrome on the other hand. AF with PD is characterized by severe orthostatic hypotension, postprandial hypotension, supersensitivity to noradrenaline, low or absent uptake of m-[123I]iodobenzylguanidine scintigraphy of the limbs, and preserved arginine vasopressin response to head-up tilt, suggesting a postganglionic sympathetic lesion resembling pure AF (PAF). On the other hand, reduced cortical glucose metabolism in positron emission tomography study may indicate that AF with PD has diffuse nervous system lesions resembling diffuse Lewy body disease.
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PMID:Autonomic dysfunction in Parkinson's disease. 938 97

We used PET with the tracers [18F]fluorodeoxyglucose (FDG), [18F]fluorodopa (FDOPA) and [11C]raclopride (RACLO) to study striatal glucose and dopa metabolism, and dopamine D2 receptor binding, respectively, in nine patients with multiple system atrophy. Ten patients with classical Parkinson's disease were investigated with the same three PET tracers' and three separate groups, each of 10 healthy subjects, served as control populations. We found that striatal FDOPA values separated all healthy subjects from patients with parkinsonism but they were not useful in distinguishing multiple system atrophy from Parkinson's disease. Conversely, striatal RACLO as well as FDG values discriminated all multiple system atrophy from Parkinson's disease patients as well as from healthy control subjects. Metabolic and receptor binding decrements in the putamen of multiple system atrophy patients were significantly correlated. Stepwise regression analysis revealed that a linear combination of putamen RACLO and FDOPA values accurately predicted clinical measures of disease severity in the multiple system atrophy group. Our findings suggest that striatal FDG and particularly RACLO are sensitive and effective measures of striatal function and may help characterizing patients with multiple system atrophy. In contrast, FDOPA measurements are accurate in detecting abnormalities of the nigrostriatal dopaminergic system but may not distinguish among different forms of parkinsonism.
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PMID:Complementary PET studies of striatal neuronal function in the differential diagnosis between multiple system atrophy and Parkinson's disease. 944 74

We have used [18F]fluorodeoxyglucose (FDG) with PET to identify regional metabolic covariance patterns associated with Parkinson's disease and normal ageing. In this study we utilized these patterns as metabolic markers to assess the relative roles of these processes in the progression of parkinsonism. We studied 37 Parkinson's disease patients and 20 normal volunteer subjects with FDG/PET to calculate regional metabolic rates for glucose. We applied the Parkinson's disease and normal ageing regional covariance patterns separately to these data to compute the expression of both these markers in each subject on an individual case basis. The measured expression of the normal ageing pattern provided an estimate of subject age, based entirely upon the FDG/PET data. The normalized difference between this metabolic estimate and chronological age (delta) was then computed, where delta = (metabolic age - real age)/(real age). We found that delta values were negative and significantly reduced in the Parkinson's disease cohort compared with normal subjects (P < 0.005) indicating a consistent underestimation of chronological age by FDG/PET in parkinsonism. In the Parkinson's disease group, delta correlated negatively with disease duration (r = -0.38, P < 0.04); extrapolation of this linear relationship to delta = 0 yielded an estimate of the mean preclinical period of 4.5 years. These findings suggest that the Parkinson's disease process is likely to be associated with a progressive disruption of the normal age-metabolism relationship, rather than with an exaggeration of the normal ageing process. Our metabolic data also suggest that the preclinical period in Parkinson's disease is of relatively short duration.
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PMID:Divergent expression of regional metabolic topographies in Parkinson's disease and normal ageing. 944 75

In a previous report, Alzheimer's disease risk factors, including alcohol abuse, depression, Down's syndrome, cerebral glucose metabolism defect, head trauma, old age, Parkinson's disease, sleep disturbance, and underactivity, were shown to have an association with reduced cerebral blood flow. In this report an attempt is made to strengthen a hypothesis that reduced cerebral blood flow may be a required cofactor in the cause of Alzheimer's disease with examples of additional putative risks, including aluminum, ApoE 4 alleles, estrogen deficiency, family history of dementia, low education-attainment, olfactory deficit, and underactivity coupled with gender, considered to have a relationship or potential relationship with reduced cerebral blood flow. Factors, believed to ameliorate Alzheimer's disease, associated with improved or stabilized cerebral blood flow are tabulated. A tentative cerebral blood flow nomogram is shown as a potential model to possibly help predict Alzheimer's disease susceptibility.
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PMID:Alzheimer's disease risk factors as related to cerebral blood flow: additional evidence. 948 78

Positron emission tomography (PET) scanning provides a sensitive means of detecting and characterizing regional changes in brain metabolism and receptor binding in movement disorders. PET allows the quantitative examination of regional cerebral blood flow, regional glucose and oxygen metabolism, and brain pharmacology. In this article, the particular use of PET to determine the effects of therapeutic stereotactic surgery, including transplantation, on brain function in Parkinson's disease and in tremor patients is highlighted.
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PMID:Positron emission tomography studies in movement disorders. 949 90

The clinical differentiation between typical idiopathic Parkinson's disease (IPD) and atypical parkinsonian disorders (APD) is complicated by the presence of signs and symptoms common to both forms of parkinsonism. Metabolic brain imaging with [18F]fluorodeoxyglucose (FDG) and positron emission tomography (PET) may be a useful adjunct in differentiating APD from IPD. To explore this possibility, we studied 48 parkinsonian patients suspected as having possible APD because of a deteriorating response to dopaminergic treatment, the development of autonomic dysfunction, or both. A group of 56 patients with likely IPD served as control subjects. We used quantitative FDG/PET to measure regional rates of cerebral glucose use in IPD and APD patients. We used discriminant analysis to categorize IPD and APD patients based on their regional metabolic data. We found that a linear combination of caudate, lentiform, and thalamic values accurately discriminated APD from IPD patients (p < 0.0001). Significant metabolic abnormalities were present in the striatum and the thalamus of 36 of 48 (75%) APD patients. Our findings show that measurements of regional glucose metabolism can be used to discriminate patients with suspected APD from their counterparts with classic IPD. FDG/PET may be a useful adjunct to the clinical examination in the differential diagnosis of parkinsonism.
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PMID:Differential diagnosis of parkinsonism with [18F]fluorodeoxyglucose and PET. 953 40

We investigated, by positron emission tomography (PET) with [18F]fluoro-2-deoxy-d-glucose (FDG) (FDG-PET), brain glucose metabolism in 19 patients with parkinsonian features. We compared local pattern of FDG uptake and asymmetry indexes in patients with therapeutic response to levodopa (L-dopa) (group 1, presumed Parkinson's disease, n = 9) and patients without L-dopa therapeutic response (group 2, presumed striatonigral degeneration, n = 10). Limb dystonia was present in 11% of patients in group 1 and in 40% of patients in group 2. Asymmetry in basal ganglia metabolism was distributed differently in the two groups (analysis of variance, p < 0.04). In superior and inferior putamen, superior and middle caudate, ventral striatum, and inferior thalamus, relative reduction in metabolism on the side contralateral to predominant parkinsonian signs was associated with L-dopa unresponsiveness. On the contrary, in middle caudate, ventral striatum, and inferior thalamus, a relative increase in metabolism on the side contralateral to the predominant side, parkinsonian signs were found in L-dopa-responsive patients. Our FDG-PET study using simple statistical procedures demonstrates inverse asymmetry of basal ganglia glucose metabolism in parkinsonian patients grouped on the sole basis of L-dopa responsiveness.
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PMID:Asymmetry of basal ganglia glucose metabolism and dopa responsiveness in parkinsonism. 953 41

The trapping of decarboxylation products of radiolabelled dopa analogs in living human brain occurs as a function of the activity of dopa decarboxylase. This enzyme is now understood to regulate, with tyrosine hydroxylase, cerebral dopamine synthesis. Influx into brain of dopa decarboxylase substrates such as 6-[18F]fluorodopa and beta-[11C]dopa measured by positron emission tomography can be analyzed by solution of linear differential equations, assuming irreversible trapping of the decarboxylated products in brain. The isolation of specific physiological steps in the pathway for catecholamine synthesis requires compartmental modelling of the observed dynamic time-activity curves in plasma and in brain. The several approaches to the compartmental modelling of the kinetics of labelled substrates of dopa decarboxylase are now systematically and critically reviewed. Labelled catechols are extensively metabolized by hepatic catechol-O-methyltransferase yielding brain-penetrating metabolites. The assumption of a fixed blood-brain permeability ratio for O-methyl-6-[18F]fluorodopa or O-methyl-beta-[11C]dopa to the parent compounds eliminates several parameters from compartmental models. However, catechol-O-methyltransferase activity within brain remains a possible factor in underestimation of cerebral dopa decarboxylase activity. The O-methylation of labelled catechols is blocked with specific enzyme inhibitors, but dopa decarboxylase substrates derived from m-tyrosine may supplant the catechol tracers. The elimination from brain of decarboxylated tracer metabolites can be neglected without great prejudice to the estimation of dopa decarboxylase activity when tracer circulation is less than 60 minutes. However, elimination of dopamine metabolites from brain occurs at a rate close to that observed previously for metabolites of glucose labelled in the 6-position. This phenomenon can cause systematic underestimation of the rate of dopa decarboxylation in brain. The spillover of radioactivity due to the limited spatial resolution of tomographs also results in underestimation of dopa decarboxylase activity, but correction for partial volume effects is now possible. Estimates of dopa decarboxylase activity in human brain are increased several-fold by this correction. Abnormally low influx of dopa decarboxylase tracers in the basal ganglia is characteristic of Parkinson's disease and other movement disorders. Consistent with postmortem results, the impaired retention of labelled dopa is more pronounced in the putamen than in the caudate nucleus of patients with Parkinson's disease; this heterogeneity persists after correction for spillover. Current in vivo assays of dopa decarboxylase activity fail to discriminate clinically distinct stages in the progression of Parkinson's disease and are, by themselves, insufficient for differential diagnosis of Parkinson's disease and other subcortical movement disorders. However, potential new avenues for therapeutics can be tested by quantifying the rate of metabolism of exogenous dopa in living human brain.
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PMID:Compartmental analysis of dopa decarboxylation in living brain from dynamic positron emission tomograms. 955 74

Stereotactic posteroventral pallidotomy was carried out in 13 cases with rigid-akinesia-type Parkinson's disease with the aid of depth microrecording. The outcome of the pallidotomy was classified into four groups: excellent (6 cases), good (3 cases), moderate (3 cases) and fair (1 case). Electrophysiological study during the operation showed continuous high-frequency and high-amplitude spike discharges in the globus pallidus (GPi) in the excellent-response group. Before the operation, a PET study had revealed low regional cerebral glucose metabolism in the prefrontal area in all the patients. Unilateral sequential opposite finger movement induced less increase of regional cerebral blood flow both in the supplementary and primary motor area in the less effective-response groups. The indications of pallidotomy for the treatment of rigid-akinesia-type Parkinson's disease are discussed.
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PMID:Study on the function of the basal ganglia and frontal cortex using depth microrecording and PET scan in relation to the outcome of pallidotomy for the treatment of rigid-akinesia-type Parkinson's disease. 971 39

Inactivation of the subthalamic nucleus (STN) has attracted interest as a therapeutic tool in Parkinson's disease. The functional consequences of the inactivation, however, are uncertain. In this study definition of the pattern of changes of cerebral functional activity associated with lesion of the STN and dopaminergic stimulation, by using the [14C]deoxyglucose method, was sought. Six or 7 days following unilateral lesion of the STN, the animals were divided into two groups: One group (n = 10) was administered apomorphine (1 mg/kg) subcutaneously; the second group (n = 10) received saline. The [14C]deoxyglucose procedure was initiated 10 minutes following the drug or saline injection. The results show that systemic administration of apomorphine to rats with unilateral lesion of the STN causes ipsiversive rotational behavior and asymmetries of glucose utilization of defined brain areas, including the substantia nigra reticulata, globus pallidus, and entopeduncular nucleus. These nuclei are the main targets of the subthalamic excitatory projections. Lesion of the nucleus per se (without challenge with apomorphine) has no significant consequences on glucose utilization. The findings indicate that the STN is involved in the activation of the basal ganglia output nuclei induced by systemic dopaminergic stimulation.
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PMID:Modifications of local cerebral metabolic rates for glucose and motor behavior in rats with unilateral lesion of the subthalamic nucleus. 1002 70


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