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)

Differentiation between Parkinson's disease (PD) and other neurodegenerative disorders with parkinsonian features, such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), is difficult on clinical grounds. We studied the pattern of dopaminergic degeneration in 18 patients with probable MSA, 8 patients with PSP, 4 patients with CBD, 48 patients with PD and a similar degree of disability, and 14 control subjects performing single photon emission computed tomography (SPECT) 20 hours after injection of [123I]beta-CIT. Overall striatal binding was significantly reduced in MSA (-51% of normal mean), PSP (-60%), CBD (-35%), and PD (-58%), without overlap with control values. Asymmetry of striatal beta-CIT binding was significantly increased in patients with CBD and PD, as compared with control subjects. Although asymmetry seemed to be less pronounced in MSA and PSP than in PD, this was not statistically significant. Putamen-caudate nucleus ratios in patients with PD, MSA, and PSP, but not with CBD, were significantly reduced, as compared with control subjects. In conclusion, [123I]beta-CIT SPECT reliably enables the visualization of the presynaptic dopaminergic lesion in patients with MSA, PSP, and CBD. In most patients, however, it does not seem to be possible to differentiate these disorders from PD with this method.
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PMID:[123I]beta-CIT SPECT in multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration. 1110

Parkinson's disease (PD) is characterized neuropathologically by degeneration of the nigrostriatal dopaminergic pathway. With natural aging there is loss of dopaminergic cells in the substantia nigra and, consequently, loss of dopamine transporters in the striatum. It has been suggested that PD is caused by an accelerated rate of cell death. Conceptually, symptoms in idiopathic PD become apparent after a critical level of cell loss, the "symptom threshold." It has been suggested that this symptom threshold is independent of age. In this study, [123I]FP-CIT SPECT was used to assess the effect of aging on the density of striatal dopamine transporters in vivo in controls (n = 36) and early, drug-naive, patients with PD (n = 32). We found a significant age-associated decline of [123I]FP-CIT binding to striatal dopamine transporters in controls, but not in parkinsonian patients. This finding might give further support for the existence of an age-independent threshold in PD. In a subgroup of patients with hemi-PD, we found a significant loss of dopamine transporters bilaterally in the caudate nucleus and putamen. This loss was more pronounced in the putamen than in the caudate nucleus and the contralateral binding was significantly lower than the ipsilateral binding. By using age-corrected data, we estimated that in our particular patient group motor signs started when the loss of [123I]FP-CIT binding ratios in the putamen was 46-64%.
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PMID:Imaging of dopamine transporters with [123I]FP-CIT SPECT does not suggest a significant effect of age on the symptomatic threshold of disease in Parkinson's disease. 1118 Apr 97

This paper gives an overview of the clinical importance of SPECT and PET imaging of the dopaminergic system in the differential diagnosis and for the determination of the progression rate of Parkinson's disease (PD). D2 receptor imaging can help to differentiate multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) from PD. In patients treated with neuroleptics it is possible to determine the rate of striatal D2 receptor blockade using this technique. This occupancy rate parallels the occurrence of parkinsonian side effects. Its measurement helps in the selection of newer atypical neuroleptics, which can be used to treat drug-induced psychosis in PD because they do not aggravate parkinsonian symptoms. Imaging of dopaminergic neurons with [123I]beta-CIT SPECT or [18F]DOPA PET is a way to visualize and quantify the nigrostriatal dopaminergic lesion in PD. Findings correlate with clinical rating scales and demonstrate the feasibility of detecting the preclinical lesion in patients with hemiparkinson or familial PD. [123I]beta-CIT SPECT can easily distinguish patients with essential tremor and patients with "lower body parkinsonism" due to a subcortical vascular encephalopathy. MSA and PSP cannot be separated from PD with this method alone. Longitudinal studies with [123I]beta-CIT SPECT and [18F]DOPA PET can quantify the progression rate in PD. SPECT results from our own group show a low rate of progression in patients with a long duration of disease and a more marked progression rate in patients with shorter disease duration. In the former group regions in the striatum with higher beta-CIT binding at the time of the first SPECT scan decline faster than regions with lower binding. These findings suggest a curvilinear course of progression which starts at different time points in different striatal regions and which levels off after several years of disease duration. These findings are in line with data from PET studies and underline the importance of an early start of neuroprotective strategies. Preliminary data from PET and SPECT studies in early PD suggest that dopamine agonists might have a slight neuroprotective effect and might slow down the rate of progression of the disease.
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PMID:SPECT and PET imaging of the dopaminergic system in Parkinson's disease. 1119 11

A patient suffering from liver cirrhosis presented with a bradykinetic-rigid syndrome suspected as Parkinson's disease. A detailed work-up of the case revealed hepatic encephalopathy as the cause of the neurological symptomatology. An alteration of striatal dopamine D2 receptor binding and dopamine re-uptake sites was demonstrated by 123I-iodobenzamide (IBZM) and 123I-beta-CIT single photon emission computed tomography (SPECT), respectively. It is suggested that the alteration of the dopamine re-uptake in cirrhotics may be the cause of an increased catabolism of dopamine in HE.
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PMID:Altered striatal dopamine D2 receptor density and dopamine transport in a patient with hepatic encephalopathy. 1120 86

Striatal dopamine transporters (DATs) and serotonin transporters (SERTs) were evaluated in untreated patients with Parkinson's disease (PD) and controls using single-photon emission computed tomography (SPECT) with 2beta-carboxymethoxy-3beta-(4-iodophenyl)tropane ([123I]beta-CIT). The striatal DAT specific to non-displaceable uptake ratios of 29, and the SERT uptake measurements of 27, PD patients were compared with those of 21 and 16 controls, respectively. The results were correlated with Unified Parkinson's Disease Rating Scale (UPDRS) scores, the Hoehn & Yahr stage, age, duration of the disease, and the major PD signs. The specific DAT binding in the caudate, the putamen and the caudate/putamen ratio were measured. In all of the PD patients the striatal uptake values were bilaterally reduced, being 36.9% (P < 0.001) lower than those of the controls. In the hemiparkinsonian patients the reduction was greater on the side contralateral to the initial symptoms (33.3% vs. 27.8%) and the uptake ratios indicated a more pronounced deficit in the putamen (39.1%) than in the caudate (27.9%). The DAT uptake correlated with the UPDRS total score and activities of daily living (ADL) and motor subscores, the Hoehn & Yahr stage, and rigidity score. PD patients had significantly higher caudate to putamen ratios than the controls. In the PD patients the SERT values were lower in the thalamic and frontal regions. The SERT uptake ratio of the frontal area correlated with the UPDRS subscore I. [123I]beta-CIT SPECT provides a useful method for confirming the clinical diagnosis of PD with correlation to disease severity. Additionally, this technique allows the simultaneous measurement of SERT uptake and shows that PD patients, interestingly, seem to have decreased SERT availability in the thalamic and frontal areas.
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PMID:[123I]beta-CIT SPECT demonstrates decreased brain dopamine and serotonin transporter levels in untreated parkinsonian patients. 1121 71

Single photon emission computed tomography (SPECT) imaging of dopamine transporters by using the cocaine derivative [123I]-(1R)-2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane ([123I]-beta-CIT) has been shown to be useful in patients with Parkinsonism. The aim of this study was to compare beta-CIT imaging with single-headed (SHS) and three-headed gamma camera systems (THS). In 17 patients with Parkinsonism, SPECT imaging with an SHS and a THS was performed 24 h after injection of 180 MBq of [123I]-beta-CIT. The SPECT studies were evaluated by visual assessment of the caudate nucleus (CN) and the putamen (PT) and the calculation of the striatal/cerebellar (S/C) ratios (with additional comparison to clinical symptoms measured by the Unified Parkinson's Disease Rating Scale (UPDRS)). The S/C ratios measured by the SHS and THS showed highly significant correlation (two-tailed P < 0.01) with Spearman correlation coefficients (SCCs) of 0.864 for the right side, 0.676 for the left side, and 0.761 for both sides. By the SHS, a sufficient visual differentiation between the CN and the PT could not be achieved. A significantly better distinction could be achieved by using the THS (Wilcoxon P<0.05). The S/C ratios of the THS only showed a significant (P < 0.05) SCC of -0.514 comparing to the UPDRS. Pathological alterations in the beta-CIT uptake pattern could be identified by using the SHS, but a significantly better differentiation of CN and the PT was possible by using the THS. The significant correlation of the S/C ratios measured by THS only emphasizes the value of THS in beta-CIT imaging.
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PMID:SPECT imaging with [123I]-beta-CIT in Parkinsonism: comparison of SPECT images obtained by a single-headed and a three-headed gamma camera. 1125

[123I]FP-CIT (N-omega-fluoropropyl-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane) has been developed successfully as a radioligand for single-photon emission tomography (SPET) imaging of dopamine transporters, which are situated in the membrane of dopaminergic neurons. Imaging of these transporters has shown promise as a clinical tool to detect degeneration of the dopaminergic nigrostriatal pathway. Several "presynaptic parkinsonian" syndromes, such as Parkinson's disease or multiple system atrophy, are characterised by degeneration of the nigrostriatal pathway. [123I]FP-CIT SPET imaging studies have shown the ability to detect loss of striatal dopamine transporters in such syndromes. However, in clinical practice it is sometimes difficult, but important, to discriminate patients with "presynaptic parkinsonism" from those with other forms of parkinsonism not characterised by loss of presynaptic dopaminergic cells (e.g. psychogenic parkinsonism or drug-induced postsynaptic parkinsonism). In these inconclusive cases, it may be of value to confirm or exclude the existence of degeneration of nigrostriatal dopaminergic cells by using imaging techniques such as [123I]FP-CIT SPET. Using [123I]FP-CIT SPET, we have imaged the striatal dopamine transporters in a group of patients with inconclusive forms of parkinsonism, and, moreover, have been able to perform clinical follow-up of these patients 2-4 years after imaging. In 33 inconclusive cases, ratios of specific to non-specific binding were calculated for the caudate nucleus and putamen following [123I]FP-CIT SPET imaging and compared with ratios obtained in healthy controls. In nine of the patients, degeneration of the nigrostriatal pathway was found scintigraphically and in all these cases, presynaptic parkinsonism was confirmed by clinical follow-up. In the other 24 subjects no degeneration was found scintigraphically. Forms of parkinsonism other than the presynaptic were confirmed at follow-up in 19 cases, and in three cases no conclusive diagnosis was established, but presynaptic parkinsonism was excluded clinically. A clinical diagnosis of presynaptic parkinsonism was established in two cases: one case of multiple system atrophy (in this patient loss of dopamine D2 receptors was found with [123I]iodobenzamide SPET performed 2 weeks after [123I]FP-CIT imaging) and one case of Parkinson's disease. Our data suggest that the positive predictive value of [123I]FP-CIT imaging is very high, and although the negative predictive value is lower, dopamine transporter imaging offers the prospect of a quick, objective method to confirm or exclude presynaptic parkinsonism in inconclusive cases.
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PMID:The clinical benefit of imaging striatal dopamine transporters with [123I]FP-CIT SPET in differentiating patients with presynaptic parkinsonism from those with other forms of parkinsonism. 1131 92

Dopamine receptor agonists are playing an increasingly important role in the treatment of not only patients with advanced Parkinson's disease and those with levodopa-induced motor fluctuations, but also in the early treatment of the disease. This shift has been largely due to the demonstrated levodopa-sparing effect of dopamine agonists and their putative neuroprotective effect, with evidence for the latter being based largely on experimental in vitro and in vivo studies. In this article we review the evidence for neuroprotection by the dopamine agonists pramipexole, ropinirole, pergolide, bromocriptine and apomorphine in cell cultures and animal models of injury to the substantia nigra. Most of the studies suggest that dopamine agonists may have neuroprotective effects via direct scavenging of free radicals or increasing the activities of radical-scavenging enzymes, and enhancing neurotrophic activity. However, the finding that pramipexole can normalise mitochondrial membrane potential and inhibit activity of caspase-3 in cytoplasmic hybrid cells derived from mitochondrial DNA of patients with nonfamilial Alzheimer's disease suggests an even broader implication for the neuroprotective role of dopamine agonists. Although the clinical evidence for neuroprotection by dopamine agonists is still limited, the preliminary results from several ongoing clinical trials are promising. Several longitudinal studies are currently in progress designed to demonstrate a delay or slowing of progression of Parkinson's disease using various surrogate markers of neuronal degeneration such as 18F-levodopa positron emission tomography and 123I beta-CIT (carbomethoxy-beta-4-iodophenyl-nortropane) single positron emission computed tomography. The results of these experimental and clinical studies will improve our understanding of the action of dopamine agonists and provide critical information needed for planning future therapeutic strategies for Parkinson's disease and related neurodegenerative disorders.
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PMID:Are dopamine receptor agonists neuroprotective in Parkinson's disease? 1141 13

We studied a correlation of urinary dysfunction with nigrostriatal dopaminergic deficit in Parkinson's disease (PD) by single-photon emission computed tomography (SPECT) imaging of dopamine transporter with [123I]-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane (beta-CIT). Eleven patients were enrolled in the study, including four men and seven women, with a mean age of 64 years. Seven patients had urinary symptoms 1-5 years after the onset of motor disorder, which included nighttime frequency in six, urinary retardation in four, daytime frequency in one and urge urinary incontinence in one. Using a SPECT camera, the ratio specific to nondisplaceable [123I]-beta-CIT uptake, designated as "striatal V3" was obtained in the caudate, anterior and posterior putamen 24 h after the tracer injection. The striatal V3 was compared in patients with and without urinary dysfunction, and between men and women, using unpaired Student's t-test. Correlation of motor dysfunction and duration of illness with urinary dysfunction, was also analyzed. In the patients, there was a reduction of [123I]-beta-CIT binding in the striatum on both sides, particularly in the putamen contralateral to the affected body side. The striatal V3 of the caudate (p<0.01, Rt; p<0.05, Lt), anterior putamen (p<0.05, Rt) and posterior putamen (p<0.05, Rt) in patients with urinary dysfunction was significantly reduced than those without urinary dysfunction. No sex difference was seen in reduction of [123I]-beta-CIT binding. Urinary dysfunction in PD was more common in patients with higher Unified Parkinson's Disease Rating Scale (UPDRS) score, higher Hoehn-Yahr grade, but not in those with longer duration of disease, although there was no statistical significance. It is likely that our results reflect the association of urinary dysfunction and degeneration of the nigrostriatal dopaminergic cells in PD.
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PMID:SPECT imaging of the dopamine transporter with [(123)I]-beta-CIT reveals marked decline of nigrostriatal dopaminergic function in Parkinson's disease with urinary dysfunction. 1144 Jul 45

Parkinson's disease affects various neurotransmitter systems. Using SPECT, the authors measured [(123)I]beta-CIT binding ratios of the caudate, putamen, medial thalamus, and dorsal midbrain over cerebellum in 16 patients with Parkinson's disease, and examined correlations with clinical ratings. Whereas striatal binding ratios (reflecting regional dopamine transporter densities) were associated with motor symptoms, dorsal midbrain binding ratios (reflecting regional serotonin transporter densities) were significantly correlated with the mentation, behavior, and mood subscale of the Unified Parkinson's Disease Rating Scale. These findings indicate that degeneration of the nigrostriatal dopaminergic neurons and a dysfunctional serotonergic raphe system contribute differentially to motor deficits and neuropsychiatric symptoms in Parkinson's disease.
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PMID:In vivo evidence for differential association of striatal dopamine and midbrain serotonin systems with neuropsychiatric symptoms in Parkinson's disease. 1144 29


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