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)

Cognitive deficits affecting executive (frontal) functions have been widely described in Parkinson's disease (PD). However, dopa therapies are generally ineffective at reversing these deficits, except for tasks involving a sharing of attention such as working memory or simultaneous processing tasks. The aim of this study was to assess the relation between the nigrostriatal dopaminergic denervation in PD, as measured by SPECT with (123)Iodine-beta-CIT and the cognitive deficits, as measured by a simultaneous processing task, which had already been shown to be sensitive to dopa treatment. Ten patients with PD and ten control subjects were selected and matched for age, sex, and education. All subjects were assessed using computed visuo-auditory tasks which allow for the measurement of three cognitive processing conditions: 1) a Selective Processing Time; 2) a Competitive Processing Time; and 3) a Simultaneous Processing Time. Patients with PD were assessed both with (ON) and without (OFF) their usual dopaminergic treatment. The simultaneous processing condition but not the selective or the competitive conditions took significantly more time for patients with PD OFF than for either the control subjects or the patients with PD ON. In addition, when patients with PD were OFF, the simultaneous processing condition was correlated with the (123)Iodine-beta-CIT binding, but not when they were ON. These results suggest that nigrostriatal DA denervation may be involved in the specific impairment that patients with PD experience with simultaneous cognitive processing.
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PMID:Cognitive deficits and striatal dopaminergic denervation in Parkinson's disease: a single photon emission computed tomography study using 123iodine-beta-CIT in patients on and off levodopa. 1215 9

The effect of MK-801, a noncompetitive NMDA receptor antagonist, on both in vivo and in vitro binding of [(125)I]beta-CIT (RTI-55) was investigated in a rat model of Parkinson's disease. The binding experiments were performed 2 weeks after unilateral intranigral microinjection of 6-hydroxydopamine (6-OHDA). In the in vitro binding study, no alterations in [(125)I]beta-CIT binding in rat brain sections were observed after addition of MK-801, 0.03 microM or 3 microM, to the incubation medium. However, in vivo [(125)I]beta-CIT binding to the dopamine transporter in both nonlesioned and 6-OHDA-lesioned striatum was significantly increased by pretreatment with MK-801. In vivo [(125)I]beta-CIT binding to the serotonin (5HT) transporter in nonlesioned cerebral cortex, hypothalamus, and thalamus was also significantly increased by MK-801. However, the degree of change in the specific binding of [(125)I]beta-CIT induced by MK-801 was smaller in the lesioned cerebral cortex. Kinetic analysis, by a simplified three-compartment model with the cerebellum as the reference region, revealed that these alterations in the in vivo [(125)I]beta-CIT binding induced by MK-801 were mainly due to changes in the rate constants of in vivo binding, the input rate constant, k(3), and the output rate constant, k(4). These results indicate that the glutamatergic system significantly affects the function of dopamine transporters in the degenerated dopaminergic neurons in Parkinson's disease.
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PMID:Effect of glutamatergic systems on in vivo binding of [(125)I]beta-CIT in the brain of a rat model of Parkinson's disease. 1221 Oct 97

We present a patient with posttraumatic tremor who did not show any [(123)I]FP-CIT uptake in the contralateral putamen and caudate. The absence of hypokinesia and rigidity is surprising in the presence of a striatal dopaminergic denervation that is even more severe than in Parkinson's disease. An explanation, therefore, could be that the lesion in the subthalamic nucleus in our patient prevented the onset of a Parkinson syndrome.
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PMID:Posttraumatic tremor without parkinsonism in a patient with complete contralateral loss of the nigrostriatal pathway. 1236 May 65

Movement disorders, including Parkinson's disease and parkinsonian syndromes, e.g. progressive supranuclear palsy, multiple system atrophy, and Lewy body dementia, may be difficult to differentiate among each other at an early stage, since they may share similar clinical features and response to dopaminergic drugs. As new tracers for imaging the dopamine transporters become available, the use of positron emission tomography (PET) for the differential diagnosis of movement disorders is gaining clinical relevance. Visual interpretation is generally used for PET image analysis. However, the use of some form of less subjective analysis is desirable in order to detect subtle changes that may be difficult to identify by visual interpretation and to achieve an operator independent analysis. To this end this study was aimed at assessing the feasibility of using statistical parametric mapping (SPM) for the clinical evaluation of single PET scans performed with 2-beta-carbomethoxy-3-beta-(4-fluorophenyl)-tropane ( C-beta-CIT-FE). Eleven healthy volunteers and five patients with movement disorders (Parkinson's disease, essential tremor, PSP and Lewy body dementia) were included in this study. Each subject underwent a PET study after i.v. injection of C-beta-CIT-FE. The PET images of C-beta-CIT-FE distribution acquired between 60 and 90 min were spatially fitted into the Talairach and Tournoux space. A template of normal C-beta-CIT-FE distribution was derived from studies in the 11 normal control subjects. Different patterns of reduction of the uptake of the tracer were detected in the basal ganglia of the five patients, in relation to each pathological condition. The patterns of distribution were all consistent with the severity and type of disease. The results of this study demonstrate the feasibility of differentiating among different states of dopaminergic impairment, due to Parkinson's disease and parkinsonian syndromes, by using PET scans with C-beta-CIT-FE and by using the SPM procedure for analysis of the data.
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PMID:The feasibility of statistical parametric mapping for the analysis of positron emission tomography studies using 11C-2-beta-carbomethoxy-3-beta-(4-fluorophenyl)-tropane in patients with movement disorders. 1241 32

The diagnosis of Parkinson's disease is based on clinical features with pathological verification. However, autopsy has been found to confirm a specialist diagnosis in only about 75% of cases. Especially early in the course of the disease, the clinical diagnosis can be difficult. Imaging of presynaptic dopamine transporters (DAT receptors) has provided a possible diagnostic probe in the evaluation of Parkinson's disease. The cocaine analogue [(123)I]-2-beta-carboxymethoxy-3-beta(4-iodophenyl)tropane ([(123)I]-beta-CIT) is one of several radioligands that have been developed for single-photon emission tomography (SPET). The purpose of this study was to evaluate the impact of [(123)I]-beta-CIT SPET on the diagnosis and clinical management of patients with a primary, tentative diagnosis of parkinsonism. We undertook a retrospective evaluation of the clinical records of 90 consecutive patients referred to [(123)I]-beta-CIT SPET from the neurological department, Bispebjerg Hospital. In 58 subjects the scans revealed altered tracer uptake consistent with Parkinson's disease, progressive supranuclear palsy and multiple system atrophy. A significant change in the management or treatment because of the scan was found in 25 patients (28%). The sensitivity of the examination was 97% and the specificity 83%. In conclusion, a significant clinical impact of DAT receptor SPET imaging was found. DAT receptor imaging is a useful diagnostic probe in patients with a possible diagnosis of parkinsonism.
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PMID:Clinical impact of diagnostic SPET investigations with a dopamine re-uptake ligand. 1245 97

During the past decade, in vivo imaging of the nigrostriatal dopaminergic system has been developed as a research tool to monitor progressive dopaminergic neuron loss in Parkinson's disease (PD) and to assess the effect of medication on imaging outcomes. Recently two similar studies compared the effect of initial treatment with a dopamine agonist (pramipexole (CALM-PD CIT) or ropinirole (REAL-PET)) or levodopa on the progression of PD as measured by [123I]beta-CIT or [18F]Dopa imaging. These two clinical imaging studies targeting dopamine function with different imaging ligands and technology both demonstrate slowing in the rate of loss of [123I]beta-CIT or [18F]Dopa uptake in early PD patients treated with dopamine agonists compared with levodopa. The relative reduction in the per cent loss from baseline of [123I]beta-CIT uptake in the pramipexole versus the levodopa group was 47% at 22 months, 44% at 34 months and 37% at 46 months after initiating treatment. The relative reduction of 18F-dopa uptake in the ropinirole group versus the levodopa group was 35% at 24 months. These results should be very cautiously interpreted with regard to the effect of dopamine agonists or levodopa on clinical disease progression. These data highlight the need to compare imaging outcomes of dopamine neuronal loss with multiple meaningful clinical endpoints of disease progression in placebo controlled, larger and long-term studies.
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PMID:Do dopamine agonists or levodopa modify Parkinson's disease progression? 1246 17

Nonimmunosuppressant immunophilin ligands have been shown to have neurotrophic properties in rodent models of Parkinson's disease (PD), although little is known about the effects of these ligands in primates. The immunophilin ligand, GPI-1046, promotes the regeneration of dopamine (DA) cells in association with functional recovery in rodent models. We explored the regenerative effects of GPI-1046 in an MPTP primate model of PD. We used single photon emission computed tomography (SPECT) and the DA transporter tracer (DAT), [(123)I]beta-CIT, to evaluate DAT density and clinical recovery before and after treatment with GPI-1046 or vehicle. Subsequent histological studies were also performed. No effects of GPI-1046 were found on any of these measures. These findings show that GPI-1046 does not have regenerative effects in MPTP-treated primates and suggest that there may be species differences with respect to the trophic effects of GPI-1046 on nigrostriatal DA neurons.
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PMID:The immunophilin ligand GPI-1046 does not have neuroregenerative effects in MPTP-treated monkeys. 1250 82

Neuroprotection may be defined as measures to protect neurons from degenerative processes by use of medication, to stop or prolong cell death and to positively interfere with the underlying cell death mechanism(s) in Parkinson's disease. So far, the question whether neuroprotection exists in parkinsonian treatment was difficult to answer because we had no objective method to check for dopaminergic cell death. Imaging techniques such as beta-CIT-SPECT or F-Dopa-PET are the best methods to approach this goal. This paper critically reviews the two most recently published studies on the possible neuroprotective effect of the dopamine agonists pramipexole and ropinirole. For the first time, these two drugs have shown a significantly smaller decrease in dopamine cell function when compared to levodopa. Nonetheless, there may still be some hesitation to accept the good correlation between imaging techniques and dopamine cell function. For obvious reasons, neither study included a placebo arm, since ethical reasons forbid a period of 2 to 4 years without treatment. Thus, the question, whether these two dopamine agonists are really neuroprotective or whether levodopa increases cell death in Parkinson's disease has to stay open. A rather remarkable finding was that, in both studies, motor function was slightly better in the levodopa arm, which raises the question whether imaging techniques really reflect improvement in cell function in those patients treated with dopamine agonists. We certainly have to continue our search for even better tools to evaluate neuroprotection.
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PMID:Neuroprotection in idiopathic Parkinson's disease. 1252 67

We used single photon emission computed tomography (SPECT) to study striatal [(123)I]beta-CIT binding and polysomnography to study periodic leg movements during sleep (PLMS) in eleven patients with idiopathic Parkinson's disease (PD). The reduced striatal [(123)I]beta-CIT binding was significantly correlated with the number of PLMS. We propose that striatal dopaminergic nerve cell loss is involved in the increased number of PLMS in PD patients.
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PMID:Periodic leg movements in patients with Parkinson's disease are associated with reduced striatal dopamine transporter binding. 1252 97

In the past 10 years, significant progress on the development of new brain-imaging agents for single-photon emission computed tomography has been made. Most of the new radiopharmaceuticals are designed to bind specific neurotransmitter receptor or transporter sites in the central nervous system. Most of the site-specific brain radiopharmaceuticals are labeled with (123)I. Results from imaging of benzodiazepine (gamma-aminobutyric acid) receptors by [(123)I]iomazenil are useful in identifying epileptic seizure foci and changes of this receptor in psychiatric disorders. Imaging of dopamine D2/D3 receptors ([(123)I]iodobenzamide and [(123)I]epidepride) and transporters [(123)I]CIT (2-beta-carboxymethoxy-3-beta(4-iodophenyl)tropane) and [(123)I]FP-beta-CIT (N-propyl-2-beta-carboxymethoxy-3-beta(4-iodophenyl)-nortropane has proven to be a simple but powerful tool for differential diagnosis of Parkinson's and other neurodegenerative diseases. A (99m)Tc-labeled agent, [(99m)Tc]TRODAT (technetium, 2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo [3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino] ethanethiolato(3-)]oxo-[1R-(exo-exo)]-), for imaging dopamine transporters in the brain has been successfully applied in the diagnosis of Parkinson's disease. Despite the fact that (123)I radiopharmaceuticals have been widely used in Japan and in Europe, clinical application of (123)I-labeled brain radiopharmaceuticals in the United States is limited because of the difficulties in supplying such agents. Development of (99m)Tc agents will likely extend the application of site-specific brain radiopharmaceuticals for routine applications in aiding the diagnosis and monitoring treatments of various neurologic and psychiatric disorders.
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PMID:Radiopharmaceuticals for single-photon emission computed tomography brain imaging. 1260 53


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