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1.
We recently found that patients with drug-induced parkinsonism (DIP) may have normal (group I) or abnormal (group II) putamen [123I]FP-CIT DAT (dopamine transporter) binding. In this study we reassessed clinical features and DAT binding in 19 of the original 32 patients (10 of group I and 9 of group II) after a 19–39-month follow-up period and tested the effects of chronic levodopa treatment in both cohorts of patients. In group I patients, [123I]FP-CIT SPET (single photon emission tomography) was still normal in all patients at follow-up; DAT binding and UPDRS (Unified Parkinson’s Disease Rating Scale) motor score values did not differ from baseline. In group II patients, [123I]FP-CIT SPET was still abnormal at follow-up; putamen DAT binding was significantly reduced and UPDRS III score higher compared to baseline. Levodopa treatment improved motor symptoms in three out of ten patients of group I and in eight out of nine patients of group II. No adverse psychiatric effects were observed in any of the patients. This study shows that DAT binding imaging may help to identify subjects with DIP secondary to a loss of dopamine nerve terminals in the context of a progressive degenerative parkinsonism. Patients with DIP may benefit from levodopa therapy, particularly when dopamine nerve terminal defects are present, and this should be considered in the therapeutic management of these patients.  相似文献   

2.
Summary. Mixed-type tremors pose a clinical diagnostic challenge. The aim of the study was to better characterize patients with combined postural and rest tremor. Patients were categorized into four groups: essential tremor (ET) (n = 7), combined rest + postural tremor (n = 17), PD (n = 17), and control subjects (n = 9). All underwent the University of Pennsylvania Smell Identification Test (UPSIT). The mixed-tremor group was also evaluated with SPECT imaging using the dopamine transporter (DaT) ligand 123I-labeled FP-CIT. There was no significant difference in olfaction scores between the mixed tremor and essential tremor groups (23.2 ± 6.6 vs 21.7 ± 4.9) or between these groups and controls (27.2 ± 5.0). The patients with PD had significantly lower scores than all the other groups (13.7 ± 5.4, p < 0.001). Of the 12 patients with mixed tremor evaluated by SPECT, 9 had normal findings. This study suggests that rest tremor is part of the spectrum of ET, even in patients with long-standing disease. However, in a minority of patients, there might be transformation of ET–PD. Correspondence: Ruth Djaldetti, Rabin Medical Center, Department of Neurology, Beilinson Campus, Petah Tiqwa 49100, Israel  相似文献   

3.
The in vivo assessment of brain serotonergic function might be of clinical relevance in neuropsychiatry. The loudness dependence of auditory evoked potentials (LD) has been proposed as an indirect indicator of cortical serotonergic activity, whereas single photon emission computed tomography (SPECT) and [123I]ADAM allow the selective assessment of brain serotonin transporters (SERT). The aim of this study was to investigate LD and SERT availability as independent variables of the brain serotonergic system in healthy volunteers. Fifteen (six male, nine female) subjects received both neurophysiological and imaging investigations. Evoked potentials were recorded following the application of acoustic stimuli with increasing intensities; the LD was analyzed using dipole source analysis. SPECT was performed four hours after injection of 137 ± 11.4 MBq [123I]ADAM. As a measure of SERT availability specific ADAM brainstem binding was used. LD correlated significantly with SERT availability (Pearson’s correlations: rho = −0.57, p < 0.05). The correlations remained significant after controlling for the effects of age or gender (partial correlations: rho = −0.60, p < 0.05) but were pronounced in the female group (rho = −0.83, p < 0.01). Associations between LD and SERT availability contribute to the understanding of the central serotonergic system and further validate the use of neurophysiological approaches as indirect measures of neurochemical brain activity.  相似文献   

4.
Summary. Single-photon emission computed tomography (SPECT) markers allow measuring the integrity of the brain dopaminergic system in vivo. We used dopamine transporter (DAT) SPECT with [123I]FP-CIT and dopamine D2/D3 receptor SPECT with [123I]IBZM to evaluate whether there is a reduction of DAT and/or D2/D3 receptor SPECT in treated and untreated patients with Parkinsonian syndrome (PS). We found that almost a quarter of our patients treated with anti-Parkinsonian medication prior to SPECT imaging did not show evidence of a presynaptic dopaminergic deficit while 37% of untreated patients were diagnosed as having Parkinson’s disease. 17% of treated patients had additional loss of D2/D3 receptor binding capacity in concordance with the clinical follow-up diagnoses of multiple system atrophy, progressive nuclear palsy, and vascular Parkinsonism. Apart from 38% clinically uncertain cases, SPECT was in concordance with 75% of initial clinical diagnoses. 25% were reclassified as indicated by SPECT findings and confirmed by a 1.5-year clinical follow-up. We conclude that dopamine SPECT may support establishing or refuting the clinical diagnosis and, therefore, help to make the decision for or against dopaminomimetic treatment in cases with PS.  相似文献   

5.
Abstract We used qualitative visual assessment and semiquantitative measures of striatal DAT binding using [123I]FP-CIT-SPET in 85 patients with Parkinson's disease (PD). We compared these two assessments and their correlation with PD clinical progression. SPET imaging was visually classified by a nuclear medicine physician as normal or abnormal pattern grade I, II and III, in relation to a different degree of radioligand reduction uptake. Nineteen patients presented abnormal grade I (group 1), 53 grade II (group 2) and 13 grade III (group 3). The UPDRS III motor score, the H-Y score, the rigidity and bradykinesia subscores were significantly different among the three groups. Post hoc analysis showed that all values of these clinical parameters were higher in group 3 than in 2 and 1. All clinical indices were also significantly higher in group 2 than in group 1. This means that groups 3 and 2 were clinically more severely affected. No significant differences among the 3 groups were observed for age or duration of disease. Values of the mean striatum uptake were also significantly different among the three groups. Post hoc analysis revealed significantly lower values of the mean striatum uptake in group 3 with respect to groups 2 and 1; values were also significantly lower in group 2 than in group 1. We conclude that our findings of good consistency between visual and semi-quantitative assessment may help simplify the evaluation of striatal DAT binding in PD in a clinical routine setting.  相似文献   

6.
Summary. We investigated the applicability [123I]FP-CIT SPECT for the assessment of the rate of dopaminergic degeneration in PD. Twenty early-stage PD patients (age range 43–73 yr; mean age 55.4) were examined twice, a mean of 12 months apart. The mean annual change in the ratio of specific to nonspecific [123I]FP-CIT binding to the striatum was used as the outcome measure. The mean annual decrease in striatal [123I]FP-CIT binding ratios was found to be about 8% (of the baseline mean). In order to demonstrate a significant effect (p < 0.05) of putative neuroprotective agent with 0.80 power and 50% of predicted protection within 2 years, 36 patients are required in each group, when the effects are measured by means of changes in [123I]FP-CIT binding ratios in whole striatum. Our findings indicate that [123I]FP-CIT SPECT seems to be a useful tool to investigate the progression of dopaminergic degeneration in PD and may provide an objective method of measuring the effectiveness of neuroprotective therapies. Received August 30, 2000; accepted February 19, 2001  相似文献   

7.
Ten healthy subjects and 16 patients with early Parkinson’s disease (PD) were examined with single photon emission computed tomography (SPECT) and [123I]β-CIT, a ligand for the dopamine (DA) transporter. Only drug-naive patients were examined since the expression of and binding to DA transporters may be influenced by dopaminergic medication. The main finding was a significant reduction in [123I]β-CIT binding in the ipsi- and contralateral striatal regions, especially in the putamen, which showed a mean reduction of 65% of the control mean. Discriminant function analysis of the putaminal [123I]β-CIT binding measures classified 100% of the cases in the correct group. Disease severity correlated negatively and highly significantly with the binding measures. Tremor ratings did not correlate with the SPECT measures, whereas rigidity, and to a lesser extent bradykinesia, did. Patients with unilateral PD showed a bilateral loss of striatal DA transporters. Our findings indicate that with [123I]β-CIT SPECT it is possible to diagnose PD in subjects with very mild symptoms and signs. Moreover, finding a bilateral loss of striatal DA transporters in patients with unilateral PD also suggests that it may be possible to identify subjects in the preclinical phase of the disease. Received: 12 February 1997 Received in revised form: 12 September 1997 Accepted: 16 September 1997  相似文献   

8.
Background: Dopaminergic availability is known to linearly decline in Parkinson’s disease (PD). In contrast, temporal characteristics of serotonergic markers like the serotonin transporter (SERT) in relation to clinical staging of PD and dopaminergic cell loss are less clear. This study investigated SERT availability using [123I]‐ADAM and single‐photon emission tomography (SPECT) in drug‐naive, de novo patients, i.e., in a PD stage where dopaminergic decline starts to lead to the occurence of the characteristic motor symptoms. Methods: Nine de novo patients with PD and 9 age‐matched healthy controls were studied. Measurements were repeated after 3 months of levodopa treatment in patients with PD, and dopaminergic transporter (DAT) binding was examined at baseline using [123I]‐FP‐CIT SPECT. Results: No alterations of SERT availability were found between groups, and neither correlation between SERT and DAT nor effects of levodopa treatment on SERT was found in patients with PD. Conclusions: These preliminary findings indicate that midbrain SERT is preserved in unmedicated patients at this early stage of PD, supporting the view that serotonergic decline temporally follows dopaminergic cell loss.  相似文献   

9.
We aimed to study whether either [123l] myocardial meta-iodobenzylguanidine (MIBG) myocardial scintigraphy or the odor stick identification test for Japanese (OSIT-J) is effective in differentiating Parkinson’s disease (PD) from multiple system atrophy (MSA). We compared the MIBG accumulation and olfactory score between 42 PD and 42 MSA (19 MSA-P and 23 MSA-C) patients in the early stages. [123l] MIBG myocardial scintigraphy showed higher sensitivity and the olfactory test higher specificity in differentiating PD from MSA. There were significant differences between PD and MSA-C (p = 0.0019) instead of MSA-P (p > 0.05) in the MIBG accumulation, while there were significant differences between PD and MSA-P (p = 0.0003) or MSA-C (p = 0.0003) in the OSIT-J score. Our data suggest that the olfactory test can be useful as a clinical tool with its higher specificity in differentiating PD from MSA in the early stages and, moreover, support the discrimination of PD from MSA-P.  相似文献   

10.
11.
Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor (GHS-R) acting to stimulate growth hormone release. In the previous study, we have observed the neuroprotective effects of ghrelin on dopaminergic neurons in vivo in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine -treated Parkinson’s disease mice. In order to illustrate the underlying mechanisms, in the present study, we conducted our experiment in vitro in 1-methyl-4-phenylpyridinium (MPP+)-treated MES23.5 cells that could express GHS-R1a. Ten- to 1,000-μmol/L MPP+ treatment caused decreased cell viability, with increased lactate dehydrogenase leakage. A 200-μmol/L MPP+ treatment was chosen to do the further experiments. MES23.5 cells treated with 200 μmol/L MPP+ showed decreased mitochondrial transmembrane potential, an elevated level of reactive oxidative species production and activation of caspase-3. Additionally, these cells also showed apoptotic morphological changes. Pretreatment with different doses of ghrelin (10−12–10−7 mol/L) could abolish the MPP+-induced apoptotic changes in a dose-dependent manner. These results suggested that ghrelin could antagonize MPP+-induced apoptosis in MES23.5 cells. The protective effects of ghrelin involved the restoration of mitochondria function. Juanjuan Dong and Ning Song contributed equally to this work.  相似文献   

12.
Parkinsonism in patients taking neuroleptic medications might be induced by dopamine receptor blockade alone or by dopamine blockade with nigrostriatal dysfunction. The differentiation between Parkinson's disease (PD) and drug-induced parkinsonism (DIP) is difficult to assess on clinical grounds alone. In this study, we have evaluated the clinical characteristics and striatal binding of (123)I-FP-CIT (N-omega-fluoropropyl-2beta-carboxymethoxy-3beta-{4-iodophenyl}tropane) in patients who developed DIP. A total of 20 patients (mean age, 62 +/- 13 years) who developed parkinsonism while on neuroleptic agents and 10 age-matched controls were enrolled. [123]-FP-CIT single-photon emission computed tomography (SPECT) was performed in all subjects. Neurological assessment was performed with the Motor part of the Unified Parkinson's Disease Rating Scale. [123]-FP-CIT binding of the entire striatum, caudate, and putamen was calculated. Patients were divided into two subgroups according to SPECT results for comparison of clinical characteristics. There were 9 patients who had normal scans and 11 who showed significantly diminished striatal binding, suggesting degeneration of the nigrostriatal system. Subanalyses of abnormal scans revealed significantly diminished binding in the caudate (P < 0.001 for right and left caudate) and putamen (P = 0.002 and P < 0.05 for right and left putamen, respectively). There were no differences in clinical features between patients with normal and abnormal scans. Symptoms included asymmetric tremor, bradykinesia, and rigidity in both groups. Freezing gait was present in two patients with normal scans. These results indicate that DIP is clinically indistinguishable from PD. Brain imaging with FP-CIT helps to determine whether DIP is entirely drug-induced or an exacerbation of subclinical PD.  相似文献   

13.
Summary 1-Methyl-4-phenylpyridinium (MPP+) was added directly to fresh rat brain slices and the dynamic changes in the cerebral glucose metabolic rate (CMRglc) were serially and two-dimensionally measured with [18F]2-fluoro-2-deoxy-D-glucose as a tracer. MPP+ dose-dependently increased CMRglc, reflecting enhanced glycolysis compensating for the decrease in aerobic metabolism. While the CMRglc enhancement induced by MPP+ (<10 μM) was restricted to the striatum, MPP+ (≥10 μM) induced a significant CMRglc enhancement in all brain regions. MPP+ at high concentration (1 mM) eventually initiated rapid metabolic collapse, with failure to sustain anaerobic glycolysis.  相似文献   

14.
Summary. We studied the midbrain SERT availability in patients with major depression and assessed the relation of SERT occupancy by citalopram to the treatment response. 21 non-medicated patients with major depression and 13 healthy controls were examined by [123I]-ADAM SPECT. The midbrain SERT availability (SERT V3″) was calculated using individual MRI scans. In 13/21 patients SPECT was repeated 7 days after oral medication with citalopram (10 mg/day). We found no significant difference in the mean midbrain SERT availability between the studied patients with major depression and healthy controls (0.86 ± 0.27 vs. 0.71 ± 0.44, p = 0.069). The mean SERT occupancy accounted to 61%. The degree of SERT blockade by citalopram did not correlate with the reduction in HAMD total score. Treatment with low-dosed citalopram caused individually variable occupancy of the midbrain-SERT and a rapid clinical improvement in 54% of the investigated patients.  相似文献   

15.
We assessed the status of dopamine nerve terminals in patients treated with dopamine receptor blocking agents (DRBAs) who had developed drug‐induced parkinsonism (DIP). We performed [123I]FP‐CIT SPET in 32 consecutive patients who were on DRBAs for at least 6 months and developed extrapyramidal signs. The UPDRS‐III was used to assess clinical severity. Twenty‐six age‐ and sex‐matched healthy subjects served as control group. Putamen [123I]FP‐CIT SPET binding was reduced in 14 and normal in the remaining 18 patients. There was no difference between the two groups for age, duration of DRBAs treatment, UPDRS III, tremor, rigidity, and bradykinesia subscores for upper and lower limbs. Conversely, symmetry of parkinsonian signs and presence bucco‐linguo‐masticatory dyskinesias were more frequent in individuals with normal tracer binding. Imaging of the dopamine transporter may help to identify subjects with DIP secondary to a loss of dopamine nerve terminals. © 2008 Movement Disorder Society  相似文献   

16.
Though there is considerable evidence that prefrontal repetitive transcranial magnetic stimulation (rTMS) exerts antidepressant effects, the neurobiological action of rTMS in patients with depression is poorly understood. Preclinical studies in animals and humans have demonstrated that prefrontal rTMS can induce dopamine release in mesostriatal and mesolimbic regions. We therefore investigated whether rTMS also modulates striatal dopaminergic neurotransmission in depressed patients using a dynamic [123I] iodobenzamide (IBZM) single photon emission computed tomography (SPECT) approach. Five patients with a major depressive episode (DSM-IV) underwent an acute 10 Hz rTMS challenge with 3000 stimuli over the left dorsolateral prefrontal cortex during an [123I] IBZM-SPECT bolus and constant infusion protocol. In four subjects the protocol was repeated after a three week rTMS standard treatment. Striatal IBZM binding to dopamine D2 receptors was assessed with a region-of-interest (ROI) technique. The change in striatal IBZM binding after the rTMS challenge was regarded as measure of change in endogenous striatal dopamine. Data of nine SPECT investigations showed a significant reduction by 9.6+/-6.2% in IBZM binding to striatal dopamine D2 receptors after rTMS challenge compared to baseline (p=0.01, Wilcoxon test). In this preliminary study, the reduction of IBZM binding observed after rTMS challenge is suggestive of a release in endogenous dopamine induced by prefrontal rTMS. In future, this approach can be used to differentiate specific and non-specific reward-related effects of rTMS on dopaminergic neurotransmission.  相似文献   

17.
Recent [123I]beta-CIT single-photon emission computed tomography (SPECT) studies revealed decreased serotonin transporters (SERT) density in the brain of humans with a history of MDMA ("Ecstasy") use. However, [123I]beta-CIT SPECT has until now not been validated as a method for detecting such serotonergic lesions. Therefore, the present study was undertaken. Following baseline [123I]beta-CIT SPECT scans, a rhesus monkey was treated with MDMA (5 mg/kg, s.c. twice daily for 4 consecutive days). SPECT studies 4, 10, and 31 days after MDMA treatment revealed decreases in [123I]beta-CIT binding ratios in the SERT-rich brain region studied (hypothalamic/midbrain region), with SERT density reduced by 39% in this brain region 31 days after treatment. Data obtained with SPECT studies correlated well with SERT density determined with autoradiography after sacrifice of the animal (-34%). In addition, ex vivo [123I]beta-CIT binding studies in rats 1 week after treatment with neurotoxic doses of MDMA (20 mg/kg s.c. twice daily for 4 consecutive days) revealed significant reductions in [123I]beta-CIT binding in SERT-rich regions (including the hypothalamus) when compared to saline-treated rats. The combined results of these studies indicate that SPECT imaging of SERT with [123I]beta-CIT can detect changes in SERT density secondary to MDMA-induced neurotoxicity in the hypothalamic/midbrain region, and possibly other brain regions.  相似文献   

18.
Overdiagnosis of Parkinson's disease (PD) is suggested by specialist review of community diagnosis, and in postmortem studies. In specialist centers 4 to 15% of patients entered into clinical trials as early PD do not have functional imaging support for a PD diagnosis. In a European multicenter, prospective, longitudinal study, we compared clinical diagnosis with functional SPECT imaging using [123I]FP‐CIT (DaTSCAN?, GE Healthcare). Repeat observations were performed over 3 years in patients with tremor and/or parkinsonism in whom there was initial diagnostic uncertainty between degenerative parkinsonism and nondegenerative tremor disorders. Video‐recording of clinical features was scored independently of functional imaging results by two blinded clinicians at 36 months (= gold standard clinical diagnosis). Three readers, unaware of the clinical diagnosis, classified the images as normal or abnormal by visual inspection. The main endpoint was the sensitivity and specificity of SPECT imaging at baseline compared with the gold standard. In 99 patients completing the three serial assessments, on‐site clinical diagnosis overdiagnosed degenerative parkinsonism at baseline in diagnostically uncertain cases compared with the gold standard clinical diagnosis (at 36 months), the latter giving a sensitivity of 93% and specificity of 46%. The corresponding baseline [123I]FP‐CIT SPECT results showed a mean sensitivity of 78% and a specificity of 97%. Inter‐reader agreement for rating scans as normal or abnormal was high (Cohen's = 0.94–0.97). © 2008 Movement Disorder Society  相似文献   

19.
Contrafatto D, Mostile G, Nicoletti A, Dibilio V, Raciti L, Lanzafame S, Luca A, Distefano A, Zappia M. [123I]FP‐CIT‐SPECT asymmetry index to differentiate Parkinson’s disease from vascular parkinsonism.
Acta Neurol Scand: 2012: 126: 12–16.
© 2011 John Wiley & Sons A/S. Objectives – Differential diagnosis between vascular parkinsonism (VP) and Parkinson’s Disease (PD) is often difficult, due to the overlap in clinical presentation and the lack of specificity at neuroimaging. Aim of the study was to identify a possible reliable marker at SPECT imaging useful to distinguish the two conditions. Material and methods – We studied 20 PD, 20 VP and 20 essential tremor (ET) patients as control group, who had undergone a cerebral [123I] FP‐CIT SPECT. A semiquantitative analysis was performed on DaTSCAN SPECT imaging and to establish the degree of asymmetry of the ligand uptake the Striatal Asymmetry Index (SAI) was used. Results – The binding of the ligand in the most affected side resulted significantly lower in VP than in ET patients but higher compared to PD patients. SAI was significantly higher in PD compared to VP (P < 0.001) and ET (P < 0.001) groups. We found that a cut‐off of SAI greater than 14.08 could differentiate PD from VP with a 100% specificity and a 50% sensitivity. Conclusions – SAI detected using [123I]FP‐CIT SPECT can be used to differentiate VP and PD with a good degree of certainty.  相似文献   

20.
[123I]FP-CIT (N-ω-fluoropropyl-2β-carbomethoxy-3β-{4-iodophenyl}tropane), a radioiodinated cocaine analogue, was evaluated as an agent for the in vivo labeling of dopamine (DA) transporters by biodistribution studies in rats and by single photon emission computed tomography (SPECT) studies in unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)–lesioned monkeys. In rats, intravenous injection of [123I]FP-CIT resulted in high accumulation of radioactivity in the striatum. Less pronounced uptake was seen in brain areas with high densities of serotonergic uptake sites. While striatal uptake of radioactivity after injection of [123I]FP-CIT was displaced significantly by GBR12,909 but not by fluvoxamine, the opposite was observed in brain areas known to be rich of serotonin transporters. Monkeys which were unilaterally treated with neurotoxic doses of MPTP showed severe loss of striatal [123I]FP-CIT uptake at the side of treatment. The results of this study indicate that [123I]FP-CIT, although not being a selective radioligand, binds specifically to the striatal DA transporter in vivo and thus suggest that [123I]FP-CIT promises to be a suitable radioligand for SPECT imaging of DA transporters in humans. Synapse 27:183–190, 1997. © 1997 Wiley-Liss, Inc.  相似文献   

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