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- ItemAcesso aberto (Open Access)Avaliação da Densidade do Transportador Dopaminérgico utilizando [99MTc]-TRODAT-1 E SPECT em pacientes com movimentos periódicos das pernas após teste de esforço máximo(Universidade Federal de São Paulo (UNIFESP), 2011-01-26) Cavagnolli, Daniel Alves [UNIFESP]; Mello, Marco Tulio de [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Restless legs syndrome and periodic leg movement are sleep-related movement disorders and studies have shown changes in striatal dopaminergic activity in patients with these disorders. Physical exercise has been shown to improve the symptoms of restless legs syndrome and periodic leg movement, as has treatment with dopamine agonists. However, the mechanism by which physical exercise acts as a nonpharmacological treatment in improving symptoms of restless legs syndrome and periodic leg movement remains unknown. We evaluated dopamine transporter density profiles in 16 sedentary patients (control and experimental - with periodic leg movement, groups) and the influence of acute physical exercise on its concentration after a maximal exercise test. Each patient underwent baseline polysomnography to evaluate sleep patterns and periodic leg movement index values. After obtaining the polysomnography baseline, the single photon emission computer tomography baseline was determined. Subsequently, the volunteers performed a maximal exercise test in the morning, followed by a single photon emission computer tomography two hours later and polysomnography that night, to assess the effect of acute physical exercise on dopamine transporter and sleep patterns. The results showed significant lower dopamine transporter baseline densities in the striatum region for the experimental group. The results also showed a significant reduction in the periodic leg movement rate in the experimental group and a significant increased percentage of stage-1 non-REM sleep in both groups after maximal exercise test. Significant differences between the groups were only observed for Stage 2 sleep and slow wave sleep. Our results show that patients with periodic leg movement had a lower dopamine transporter density in the left putamen region compared to the control group and an acute physical exercise (maximal exercise test) did not alter this profile, providing evidence that this improvement is the result of chronic physical exercise.
- ItemSomente MetadadadosChanges in Dopamine Transpoter During Abstinence in Crack-cocaine Users: A Study with SPECT and TRODAT-1(Elsevier B.V., 2014-05-01) Batista, Ilza Rosa [UNIFESP]; Felicio, Andre Carvalho; Jackowski, Andrea Parolin [UNIFESP]; Reis, Marilia Alves dos [UNIFESP]; Ribeiro, Wagner Silva [UNIFESP]; Laranjeira, Ronaldo [UNIFESP]; Castiglioni, Mario Luiz Vieira [UNIFESP]; Lacerda, Acioly Luiz Tavares de [UNIFESP]; Bressan, Rodrigo Affonseca [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Hosp Israelita Albert Einstein
- ItemAcesso aberto (Open Access)Clinical and molecular neuroimaging characteristics of Brazilian patients with Parkinson's disease and mutations in PARK2 or PARK8 genes(Academia Brasileira de Neurologia - ABNEURO, 2009-03-01) Barsottini, Orlando Graziani Povoas [UNIFESP]; Felício, André Carvalho [UNIFESP]; Aguiar, Patricia de Carvalho [UNIFESP]; Godeiro-Junior, Clecio [UNIFESP]; Shih, Ming C. [UNIFESP]; Hoexter, Marcelo Queiroz [UNIFESP]; Bressan, Rodrigo Affonseca [UNIFESP]; Ferraz, Henrique B. [UNIFESP]; Andrade, Luiz Augusto Franco de [UNIFESP]; Hospital Israelita Albert Einstein Instituto Israelita de Ensino e Pesquisa; Universidade Federal de São Paulo (UNIFESP)OBJECTIVE: To describe clinical and neuroimaging (SPECT) characteristics of Brazilian patients with Parkinson's disease (PD) and mutations in PARK2 or PARK8 genes. METHOD: A total of 119 patients meeting clinical criteria for PD were evaluated. RESULTS: Of all patients studied, 13 had mutations in either PARK2 (n=9) or PARK8 genes (n=4). No statistically significant differences in clinical characteristics in both groups were seen. SPECT with [99mTc] TRODAT-1 showed significant differences between patient and control and the most remarkable difference was between PARK2 and control. CONCLUSION: The study found a frequency of mutation of 10.1% and it was most commonly seen in women. These patients had long disease course and high rates of dyskinesia after L-DOPA use. PARK8 patients did not have a relevant family history of PD.
- ItemSomente MetadadadosCognitive Deficits in Machado-Joseph Disease Correlate with Hypoperfusion of Visual System Areas(Springer, 2012-12-01) Braga-Neto, Pedro [UNIFESP]; Dutra, Livia Almeida [UNIFESP]; Pedroso, Jose Luiz [UNIFESP]; Felicio, Andre C. [UNIFESP]; Alessi, Helena [UNIFESP]; Santos-Galduroz, Ruth F.; Bertolucci, Paulo Henrique F. [UNIFESP]; Castiglioni, Mario Luiz V. [UNIFESP]; Bressan, Rodrigo Affonseca [UNIFESP]; Jara de Garrido, Griselda Esther; Barsottini, Orlando Graziani Povoas [UNIFESP]; Jackowski, Andrea [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade Federal do ABC (UFABC); Univ Estadual Paulista; Univ Western AustraliaCognitive and olfactory impairments have previously been demonstrated in patients with spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD)-SCA3/MJD. We investigated changes in regional cerebral blood flow (rCBF) using single-photon emission computed tomography (SPECT) imaging in a cohort of Brazilian patients with SCA3/MJD. the aim of the present study was to evaluate the correlation among rCBF, cognitive deficits, and olfactory dysfunction in SCA3/MJD. Twenty-nine genetically confirmed SCA3/MJD patients and 25 control subjects were enrolled in the study. the severity of cerebellar symptoms was measured using the International Cooperative Ataxia Rating Scale and the Scale for the Assessment and Rating of Ataxia. Psychiatric symptoms were evaluated by the Hamilton Anxiety Scale and Beck Depression Inventory. the neuropsychological assessment consisted of Spatial Span, Symbol Search, Picture Completion, the Stroop Color Word Test, Trail Making Test (TMT), and Phonemic Verbal Fluency. Subjects were also submitted to odor identification evaluation using the 16-item Sniffin' Sticks. SPECT was performed using ethyl cysteine dimer labeled with technetium-99m. SCA3/MJD patients showed reduced brain perfusion in the cerebellum, temporal, limbic, and occipital lobes compared to control subjects (pFDR < 0.001). A significant positive correlation was found between the Picture Completion test and perfusion of the left parahippocampal gyrus and basal ganglia in the patient group as well as a negative correlation between the TMT part A and bilateral thalamus perfusion. the visuospatial system is affected in patients with SCA3/MJD and may be responsible for the cognitive deficits seen in this disease.
- ItemSomente MetadadadosConsensus Paper: Radiological Biomarkers of Cerebellar Diseases(Springer, 2015-04-01) Baldarcara, Leonardo [UNIFESP]; Currie, Stuart; Hadjivassiliou, M.; Hoggard, Nigel; Jack, Allison; Jackowski, Andrea P. [UNIFESP]; Mascalchi, Mario; Parazzini, Cecilia; Reetz, Kathrin; Righini, Andrea; Schulz, Joerg B.; Vella, Alessandra; Webb, Sara Jane; Habas, Christophe; Fed Univ Tocantins; Universidade Federal de São Paulo (UNIFESP); Univ Sheffield; Royal Hallamshire Hosp; Yale Univ; Univ Florence; Meyer Children & Careggi Hosp Florence; Childrens Hosp Buzzi; RWTH Aachen Univ Hosp; Forschungszentrum Julich; Julich Aachen Res Alliance JARA; Univ Hosp Siena; Univ Washington; CHNO Quinze VingtsHereditary and sporadic cerebellar ataxias represent a vast and still growing group of diseases whose diagnosis and differentiation cannot only rely on clinical evaluation. Brain imaging including magnetic resonance (MR) and nuclear medicine techniques allows for characterization of structural and functional abnormalities underlying symptomatic ataxias. These methods thus constitute a potential source of radiological biomarkers, which could be used to identify these diseases and differentiate subgroups of them, and to assess their severity and their evolution. Such biomarkers mainly comprise qualitative and quantitative data obtained from MR including proton spectroscopy, diffusion imaging, tractography, voxel-based morphometry, functional imaging during task execution or in a resting state, and from SPETC and PET with several radiotracers. in the current article, we aim to illustrate briefly some applications of these neuroimaging tools to evaluation of cerebellar disorders such as inherited cerebellar ataxia, fetal developmental malformations, and immune-mediated cerebellar diseases and of neurodegenerative or early-developing diseases, such as dementia and autism in which cerebellar involvement is an emerging feature. Although these radiological biomarkers appear promising and helpful to better understand ataxia-related anatomical and physiological impairments, to date, very few of them have turned out to be specific for a given ataxia with atrophy of the cerebellar system being the main and the most usual alteration being observed. Consequently, much remains to be done to establish sensitivity, specificity, and reproducibility of available MR and nuclear medicine features as diagnostic, progression and surrogate biomarkers in clinical routine.
- ItemSomente MetadadadosContributions of Neuroimaging to Understanding Sex Differences in Cocaine Abuse(Amer Psychological Assoc, 2012-02-01) Andersen, Monica L. [UNIFESP]; Sawyer, Eileen K.; Howell, Leonard L.; Emory Univ; Universidade Federal de São Paulo (UNIFESP)A consistent observation in drug abuse research is that males and females show differences in their response to drugs of abuse. in order to understand the neurobiology underlying cocaine abuse and effective treatments, it is important to consider the role of sex differences. Sex hormones have been investigated in both behavioral and molecular studies, but further evidence addressing drug abuse and dependence in both sexes would expand our knowledge of sex differences in response to drugs of abuse. Neuroimaging is a powerful tool that can offer insight into the biological bases of these differences and meet the challenges of directly examining drug-induced changes in brain function. As such, neuroimaging has drawn much interest in recent years. Specifically, positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI) technology have emerged as effective noninvasive approaches for human and animal models. Studies have revealed sex-specific changes in patterns of brain activity in response to acute cocaine injection and after prolonged cocaine use. SPECT and PET studies have demonstrated changes in the dopamine transporter but are less clear on other components of the dopaminergic system. This review highlights contributions of neuroimaging toward understanding the role of sex differences in the drug abuse field, specifically regarding cocaine, and identifies relevant questions that neuroimaging can effectively address.
- ItemSomente MetadadadosDegenerative parkinsonism in patients with psychogenic parkinsonism: A dopamine transporter imaging study(Elsevier B.V., 2010-05-01) Felicio, Andre C. [UNIFESP]; Godeiro-Junior, Clecio [UNIFESP]; Moriyama, Tais S. [UNIFESP]; Shih, Ming C. [UNIFESP]; Hoexter, Marcelo Q. [UNIFESP]; Borges, Vanderci [UNIFESP]; Silva, Sonia M. A. [UNIFESP]; Aguiar, Patricia de Carvalho [UNIFESP]; Andrade, Luiz A. F.; Bressan, Rodrigo A. [UNIFESP]; Ferraz, Henrique B. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); H Israelita Albert EinsteinObjectives: To evaluate patients with clinically established psychogenic parkinsonism (PsyP) using single-photon emission computer tomography (SPECT)with the technetium-99m labeled tracer TRODAT-1, a dopamine transporter (DAT) ligand, and investigate whether these patients have an underlying degenerative parkinsonism.Patients and methods: Five patients with PsyP were assessed using demographic data, standard clinical scales for Parkinson's Disease (PD), and a neuropsychiatric interview. DAT imaging using SPECT with TRODAT-1 was performed, and values for caudate/putamen DAT binding potentials (BP) registered. Patients with PsyP were matched with PD (n = 5) and healthy control subjects (n = 5).Results: the mean age (years-old) at first evaluation in the PsyP group was 37.4 +/- 3.7, and the mean disease duration (years) was 3.9 +/- 1.2. DAT BPs (means +/- standard deviations) on right/left caudate were, respectively, 0.69 +/- 0.18 and 0.70 +/- 0.18 in the PD group versus 1.17 +/- 0.06 and 1.12 +/- 0.10 in the control group. DAT BPs on right/left putamen were, respectively, 0.48 +/- 0.10 and 0.45 +/- 0.06 in the PD group versus 1.10 +/- 0.10 and 1.21 +/- 0.43 in the control group. Two out of five patients from the PsyP group had values for DAT BP in the putamen under the cut-off (<= 0.70) for controls, implying pre-synaptic dopaminergic deficit.Conclusions: Our data in this small group of patients suggest that DAT imaging is a tool that may help in the identification of underlying degenerative parkinsonism in PsyP. (C) 2009 Elsevier B.V. All lights reserved.
- ItemSomente MetadadadosDopamine Transporter Regulation during Four Nights of REM Sleep Deprivation Followed by Recovery - An in vivo Molecular Imaging Study in Humans(Amer Acad Sleep Medicine, 2010-02-01) Martins, R. C. S. [UNIFESP]; Andersen, Monica Levy [UNIFESP]; Garbuio, Silvério Aparecido [UNIFESP]; Bittencourt, Lia Rita Azeredo [UNIFESP]; Guindalini, Camila [UNIFESP]; Shih, M. C. [UNIFESP]; Hoexter, M. Q. [UNIFESP]; Bressan, Rodrigo Affonseca. A. [UNIFESP]; Castiglioni, M. L. V. [UNIFESP]; Tufik, Sergio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Objectives: To assess the influence of total or selective REM sleep deprivation on the dopamine transporter (DAT) densities and sleep patterns of healthy volunteers.Design: Prospective study.Setting: Evaluation of polysomnography recordings and DAT density after 4 nights of selective REM sleep deprivation followed by 3 nights of sleep recovery compared to a control group and a group that was subjected to 2 nights of total sleep deprivation. Single positron emission computed tomography and [(99m)Tc]TRODAT-1 were used to assess the cerebral DAT density in the striatum at baseline, after REM sleep deprivation and total sleep deprivation as well as after sleep recovery. Blood was collected daily to examine prolactin and estradiol levels, which were correlated with dopaminergic activity.Patients or Participants: Thirty healthy male volunteers ranging from 19 to 29 years of age were randomly assigned to one of three experimental groups after giving written informed consent (10 non-sleep deprived, 10 total sleep deprived, and 10 REM sleep deprived).Measurements and Results: Four nights of REM sleep deprivation and 2 nights of total sleep deprivation induced distinct and heterogeneous patterns of sleep recovery. No significant modulation of DAT availability was observed within groups. In the recovery nights, changes in cortisol, prolactin and estradiol concentrations were significantly correlated with specific sleep stages in the total and REM sleep deprived groups. In addition, DAT density was positively correlated with estradiol concentration and inversely associated with SWS latency only after total sleep deprivation.Conclusion: Our study demonstrates that although sleep deprivation did not promote significant alterations in DAT density within the striatum, there were significant correlations among transporter availability, hormonal concentrations and sleep parameters.
- ItemSomente MetadadadosEffects of minocycline add-on treatment on brain morphometry and cerebral perfusion in recent-onset schizophrenia(Elsevier B.V., 2015-02-01) Chaves, Cristiano; Marque, Cristiane R.; Maia-de-Oliveira, Joao P.; Wichert-Ana, Lauro; Ferrari, Thiago B.; Santos, Antonio C.; Araujo, David; Machado-de-Sousa, Joao P.; Bressan, Rodrigo A. [UNIFESP]; Elkis, Helio; Crippa, Jose A.; Guimaraes, Francisco S.; Zuardi, Antonio W.; Baker, Glen B.; Dursun, Serdar M.; Hallak, Jaime E. C.; Universidade de São Paulo (USP); Natl Sci & Technol Inst Translat Med INCT TM; Univ Fed Rio Grande do Norte; McGill Univ; Universidade Federal de São Paulo (UNIFESP); Univ AlbertaIncreasing evidence suggests that the tetracycline antibiotic minocycline has neuroprotective effects and is a potential treatment for schizophrenia. However, the mechanisms of action of minocycline in the CNS remain elusive. the aim of this study was to investigate the effects of minocycline on brain morphology and cerebral perfusion in patients with recent-onset schizophrenia after 12 months of a randomized double-blind, placebo-controlled clinical trial of minocycline add-on treatment. This study included 24 outpatients with recent-onset schizophrenia randomized for 12 months of adjuvant treatment with minocycline (200 mg/d) or placebo. MRI (1.5 T) and [Tc-99m]-ECD SPECT brain scans were performed at the end of the 12-month of trial. Between-condition comparisons of SPECT and MRI brain images were performed using statistical parametric mapping and analyzed by voxel-based morphometry (VBM). Minocycline adjuvant treatment significantly reduced positive and negative symptoms when compared with placebo. the VBM analysis of MRI scans showed that the patients in the placebo group had significant lower gray matter volumes in the midposterior cingulate cortex and in the precentral gyrus in comparison with the patients in the minocycline group. in addition, a decreased ECD uptake in the minocycline condition was observed in fronto-temporal areas. These results suggest that minocycline may protect against gray matter loss and modulate fronto-temporal areas involved in the pathophysiology of schizophrenia. Furthermore, minocycline add-on treatment may be a potential treatment in the early stages of schizophrenia and may ameliorate clinical deterioration and brain alterations observed in this period. (C) 2014 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosEvaluation of patients with Clinically Unclear Parkinsonian Syndromes submitted to brain SPECT imaging using the technetium-99m labeled tracer TRODAT-1(Elsevier B.V., 2010-04-15) Felicio, Andre C. [UNIFESP]; Godeiro-Junior, Clecio [UNIFESP]; Shih, Ming C. [UNIFESP]; Borges, Vanderci [UNIFESP]; Silva, Sonia M. A. [UNIFESP]; Aguiar, Patricia de Carvalho [UNIFESP]; Hoexter, Marcelo Q. [UNIFESP]; Barsottini, Orlando G. P.; Andrade, Luiz A. F.; Bressan, Rodrigo A. [UNIFESP]; Ferraz, Henrique B. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Hosp Israelita Albert EinsteinDespite its relatively high prevalence Parkinson's Disease (PD) is still misdiagnosed in approximately 25% of cases. in this study our aim was to evaluate patients with Clinically Unclear Parkinsonian Syndromes (CUPS) submitted to brain SPECT imaging using the technetium-99m labeled Dopamine Transporter (DAT) tracer TRODAT-1. We recruited 15 subjects with CUPS and matched them with 13 patients with probable PD and 13 healthy control subjects (HCS). A SPECT with TRODAT-1 was performed at the baseline evaluation and patients from the CUPS were followed-up for 2-years to ensure or not PD diagnosis (gold-standard). the mean +/- SD results from Right and Left striatum Binding Potential (BP) were, respectively, 1.08 +/- 0.20 and 1.04 +/- 0.16 in the HCS group, 0.47 +/- 0.16 and 0.53 +/- 0.17 in the PD group, and 0.68 +/- 0.11 and 0.84 +/- 0.17 in the CUPS group. the rate of disagreement between baseline SPECT in the CUPS group as compared to the gold standard diagnosis (clinical diagnosis of PD on follow-up) was of 20%. the sensitivity of the SPECT with TRODAT-1 was 100%, while specificity was 70%. in conclusion, our data provided further information about the role of the technetium-99m labeled tracer TRODAT-1 as a biomarker of DAT reduction that can also be used in the diagnosis of patients with CUPS. (C) 2010 Elsevier By. All rights reserved.
- ItemAcesso aberto (Open Access)Fatores associados a perfusão cerebral anormal em dependentes de cocaína(Associação Brasileira de Psiquiatria - ABP, 2001-03-01) Silveira, Dartiu Xavier da [UNIFESP]; Fernandes, Marcelo [UNIFESP]; Barbieri, Antonio [UNIFESP]; Labigalini, Eliseu [UNIFESP]; Silveira, Evelyn D [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)OBJECTIVE: To evaluate the relationship between the pattern of cocaine use and cerebral perfusion among cocaine addicts. METHOD: A sample of 30 cocaine addicts was studied using 99 m-Tc-HMPAO SPECT (single photon emission computed tomography with injection of 99 m-Tc-hexametilpropilenoamina-oxime). Their cerebral perfusion pattern was then compared with their pattern of cocaine use. RESULTS: Eighty percent of the sample presented some degree of impairment in brain perfusion, either focal or diffuse. There was no difference between sniffers and crack smokers regarding their perfusion patterns. No relationship could be established between the severity of SPECT abnormalities and the amount of drug consumption or period of abstinence. However, length of cocaine use did correlate with the severity of cerebral perfusion (Spearman correlation coefficient: r=0.45, p<0.05). CONCLUSION: This study documents the high frequency of cerebral functional impairment in cocaine addicts and establishes the relationship between length of cocaine exposure and severity of perfusion abnormalities.
- ItemSomente MetadadadosHigher dopamine transporter density in Parkinson's disease patients with depression(Springer, 2010-07-01) Felicio, Andre C. [UNIFESP]; Moriyama, Tais S. [UNIFESP]; Godeiro-Junior, Clecio [UNIFESP]; Shih, Ming C. [UNIFESP]; Hoexter, Marcelo Q. [UNIFESP]; Borges, Vanderci [UNIFESP]; Silva, Sonia M. A. [UNIFESP]; Amaro-Junior, Edson; Andrade, Luiz A. F.; Ferraz, Henrique B. [UNIFESP]; Bressan, Rodrigo A. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); HIAEDepression is a frequent non-motor symptom in Parkinson's disease (PD) with increasing rates with the progression of the disease. Molecular imaging studies have shown a reduction of dopamine transporter (DAT) density in depressed PD patients (dPD); however, DAT role in the pathophysiology of PD depression is not clear since clinical matching was inappropriate and DAT reduction could be attributed to PD severity.To further examine the role of DAT in PD depression, this study compared thoroughly matched depressed vs. non-depressed PD patients (ndPD).Twenty PD patients (n = 10 ndPD; n = 10 dPD) matched for age and disease severity were submitted to brain SPECT imaging with [(99m)Tc]-TRODAT-1, a DAT radioligand. DAT-binding potential was calculated using regions of interest bilaterally drawn in the striatum, caudate, and putamen. Depression was defined according to Beck Depression Inventory (BDI; cut-off > 18).Mean BDI scores were higher in dPD (25.0 +/- 5.6) than in ndPD patients (8.0 +/- 1.9, p < 0.0001). DAT density was greater on dPD especially in the left caudate (dPD 0.87 +/- 0.19 vs. ndDP 0.69 +/- 0.18, p = 0.02) and right putamen (dPD 0.37 +/- 0.07 vs. ndPD 0.28 +/- 0.13, p = 0.03) than in ndPD patients.Our results suggest that in vivo DAT density is increased in dPD patients as compared to ndPD, suggesting that DAT is implicated in the pathophysiology of PD depression.
- ItemSomente MetadadadosHigher nigrostriatal dopamine neuron loss in early than late onset Parkinson's disease? A [Tc-99m]-TRODAT-1 SPECT study(Wiley-Blackwell, 2007-04-30) Shih, Ming Chi; Augusto Franco de Andrade, Luiz; Amaro, Edson; Felicio, Andre Carvalho; Ferraz, Henrique Ballalai; Wagner, Jairo; Hoexter, Marcelo Queiroz; Lin, Li Fu; Fu, Ying Kai; Mari, Jair Jesus; Tufik, Sergio [UNIFESP]; Bressan, Rodrigo Affonseca; Universidade Federal de São Paulo (UNIFESP); Inst Israelita Ensino & Pesquisa Albert Einstein; Hosp Israelita Albert Einstein; Inst Nucl Energy ResEarly-onset Parkinson's disease (EOPD) is distinct from the classic late-onset PD (LOPD) because of its slower disease progression. the aim of this study was to compare dopamine neuronal loss in EOPD with that of LOPD with the same disease duration, through dopamine transporter (DAT) estimation. Fourteen patients, seven EOPD (< 50 years) and seven LOPD, matched for disease duration were scanned with [Tc-99m]-TRODAT-1-SPECT (INER-Taiwan), and were assessed with standard PD scales. EOPD patients had 34% lower striatal DAT binding potential (BP) compared with that of LOPD patients (BP = 0.29 +/- 0.12, BP = 0.44 +/- 0.12, P < 0.02) with similar PD severity. These results suggest that EOPD patients have greater dopamine density loss than LOPD patients without motor-symptom worsening. (c) 2007 Movement Disorder Society.
- ItemSomente MetadadadosIncreased dopamine transporter density in Parkinson's disease patients with social anxiety disorder(Elsevier B.V., 2011-11-15) Moriyama, Tais S. [UNIFESP]; Felicio, Andre C. [UNIFESP]; Chagas, Marcos H. N.; Tardelli, Vitor S. [UNIFESP]; Ferraz, Henrique Ballalai [UNIFESP]; Tumas, Vitor; Amaro-Junior, Edson; Andrade, Luiz Augusto Franco de [UNIFESP]; Crippa, Jose Alexandre; Bressan, Rodrigo A. [UNIFESP]; Hosp Israelita Albert Einstein; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP); CNPqSocial Anxiety Disorder (SAD) is more common among PD patients than in the general population. This association may be explained by psychosocial mechanisms but it is also possible that neurobiological mechanism underlying PD can predispose to SAD. the aim of this study was to investigate a possible dopaminergic mechanism involved in PD patients with SAD, by correlating striatal dopamine transporter binding potential (DAT-BP) with intensity of social anxiety symptoms in PD patients using SPECT with TRODAT-1 as the radiopharmaceutical. Eleven PD patients with generalized SAD and 21 PD patients without SAD were included in this study; groups were matched for age, gender, disease duration and disease severity. SAD diagnosis was determined according to DSM IV criteria assessed with SCID-I and social anxiety symptom severity with the Brief Social Phobia Scale (BSPS). Demographic and clinical data were also collected. DAT-BP was significantly correlated to scores on BSPS for right putamen (r = 0.37, p = 0.04), left putamen (r = 0.43, p = 0.02) and left caudate (r = 0.39, p = 0.03). No significant correlation was found for the right caudate (r = 0.23, p = 0.21). This finding may reinforce the hypothesis that dopaminergic dysfunction might be implicated in the pathogenesis of social anxiety in PD. (C) 2011 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosInfluence of genotype on dopamine transporter availability in human striatum and sleep architecture(Elsevier B.V., 2010-09-30) Guindalini, Camila [UNIFESP]; Martins, Raquel Cristina [UNIFESP]; Andersen, Monica L. [UNIFESP]; Tufik, Sergio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Genetic variants may modulate dopamine transporter (DAT) availability in the brain. A polymorphism within the intron 8 of the DAT1 gene was evaluated in 27 healthy men. No correlation between Int8 VNTR and either the inter-individual variability of the sleep architecture, or the DAT availability, as measured by single photon emission computed tomography (SPECT) and [(99m)Tc]TRODAT-1 was observed. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
- ItemSomente MetadadadosMethylphenidate DAT binding in adolescents with Attention-Deficit/Hyperactivity Disorder comorbid with substance use disorder - a single photon emission computed tomography with [Tc-99m] TRODAT-1 study(Elsevier B.V., 2008-04-15) Szobot, Claudia M.; Shih, Ming Chi [UNIFESP]; Schaefer, Thais; Junior, Neivo; Hoexter, Marcelo Q. [UNIFESP]; Fu, Ying Kai; Pechansky, Flavio; Bressan, Rodrigo A. [UNIFESP]; Rohde, Luis A. P.; Univ Fed Rio Grande do Sul; Univ Luterana Brasil; Universidade Federal de São Paulo (UNIFESP); Irmandade Santa Casa Misericordia; Inst Nucl Energy ResBackground: Attention-Deficit/Hyperactivity Disorder (ADHD) is highly prevalent among adolescents with Substance Use Disorders (SUD). Effects of methylphenidate (MPH) on ADHD are attributed to its properties of blocking the dopamine transporter (DAT) in the striatum. However, it has been demonstrated that drug addiction is associated with dopaminergic system changes that may affect MPH brain effects, emphasizing the need to better understand MPH actions in subjects with ADHD+SUD. Objectives: To evaluate the effect of an extended release formulation of MPH (MPH-SODAS) on DAT availability in 17 stimulant-naive ADHD adolescents with comorbid SUD (cannabis and cocaine). Methods: Subjects underwent two single photon emission computed tomography (SPECT) scans with [Tc-99m] TRODAT-1, at baseline and after 3 weeks on MPH-SODAS. Clinical assessment for ADHD relied on the Swanson, Nolan and Pelham Scale-version IV (SNAP-IV). Caudate and putamen DAT binding potential (BP) was calculated. Results: After 3 weeks on MPH-SODAS, there was a significant reduction of SNAP-IV total scores (p<0.001), and similar to 52% reductions of DAT BP at the left and right caudate. Similar decreases were found at the left and right putamen (p<0.001 for all analyses). Discussion: This study shows that the magnitude of DAT blockade induced by MPH in this population is similar to what is found in ADHD patients without SUD comorbidity, providing neurobiological support for trials with stimulants in adolescents with ADHD+SUD, an important population excluded from studies. (C) 2008 Elsevier Inc. All rights reserved.
- ItemSomente MetadadadosMolecular Imaging Genetics of Methylphenidate Response in ADHD and Substance Use Comorbidity(Wiley-Blackwell, 2011-02-01) Szobot, Claudia M.; Roman, Tatiana; Hutz, Mara H.; Genro, Julia P.; Shih, Ming Chi [UNIFESP]; Hoexter, Marcelo Q. [UNIFESP]; Junior, Neivo; Pechansky, Flavio; Bressan, Rodrigo A. [UNIFESP]; Rohde, Luis A. P.; Univ Fed Rio Grande do Sul; UFRGS; Univ Luterana Brasil; Universidade Federal de São Paulo (UNIFESP); Irmandade Santa Casa MisericordiaPurpose: Attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUDs) are highly comorbid and may share a genetic vulnerability. Methylphenidate (MPH), a dopamine transporter (DAT) blocker, is an effective drug for most ADHD patients. Although dopamine D4 receptor (DRD4) and dopamine transporter (DAT1) genes have a role in both disorders, little is known about how these genes influence brain response to MPH in individuals with ADHD/SUDs. the goal of this study was to evaluate whether ADHD risk alleles at DRD4 and DAT1 genes could predict the change in striatal DAT occupancy after treatment with MPH in adolescents with ADHD/SUDs. Methods: Seventeen adolescents with ADHD/SUDs underwent a SPECT scan with [Tc 99m] TRODAT-1 at baseline and after three weeks on MPH. Caudate and putamen DAT binding potential was calculated. Comparisons on DAT changes were made according to the subjects' genotype. Results: the combination of both DRD4 7-repeat allele (7R) and homozygosity for the DAT1 10-repeat allele (10/10) was significantly associated with a reduced DAT change after MPH treatment in right and left caudate and putamen, even adjusting the results for potential confounders (P <= 0.02; R(2) from 0.50 to 0.56). Conclusions: in patients with ADHD/SUDs, combined DRD4 7R and DAT1 10/10 could index MPH reduced DAT occupancy. This might be important for clinical trials, in terms of better understanding individual variability in treatment response. Synapse 65: 154-159, 2011. (c) 2010 Wiley-Liss, Inc.
- ItemSomente MetadadadosMolecular Imaging Studies in Parkinson Disease Reducing Diagnostic Uncertainty(Lippincott Williams & Wilkins, 2009-01-01) Felicio, Andre Carvalho [UNIFESP]; Shih, Ming Chi [UNIFESP]; Godeiro-Junior, Clecio de Oliveira [UNIFESP]; Andrade, Luiz Augusto Franco de [UNIFESP]; Bressan, Rodrigo Affonseca [UNIFESP]; Ferraz, Henrique Ballalai [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Hosp Israelita Albert EinsteinBackground: the diagnosis of Parkinson disease (PD) is based on clinical criteria but misdiagnosis is as high as 25% of cases as confirmed by anatomic-pathologic studies. Since the introduction of in vivo molecular imaging techniques using Single-Photon Emission Computed Tomography and Positron Emission Tomography, the diagnosis of PD became more reliable by assessing dopaminergic and even nondopaminergic systems.Review Summary: the purpose of this article is to critically review the current data on molecular neuroimaging focusing on the nigrostriatal circuitry and providing useful information on the role of these new imaging techniques in the management of clinically unclear cases of PD.Conclusions: Patients with essential tremor, psychogenic Parkinsonism or drug-induced Parkinsonism can be differentiated from PD in doubtful situations using molecular imaging techniques evaluating striatal dopamine transporters (DAT). However, in patients with vascular Parkinsonism, atypical Parkinsonism and Parkinsonism associated with dementia DAT scans have less diagnostic usefulness. Scans with non-DAT tracers (ie, D2 dopamine receptors) are necessary together with long-term clinical follow-up, and rescans to improve diagnostic accuracy.
- ItemAcesso aberto (Open Access)Neuroimagem do transportador de dopamina na doença de Parkinson: primeiro estudo com [99mTc]-TRODAT-1 e SPECT no Brasil(Academia Brasileira de Neurologia - ABNEURO, 2006-09-01) Shih, Ming Chi [UNIFESP]; Amaro Junior, Edson; Ferraz, Henrique Ballalai [UNIFESP]; Hoexter, Marcelo Queiroz [UNIFESP]; Goulart, Fabricio Oliveira [UNIFESP]; Wagner, Jairo; Lin, Li Fu; Fu, Ying Kai; Mari, Jair de Jesus [UNIFESP]; Lacerda, Acioly Luiz Tavares de [UNIFESP]; Tufik, Sergio [UNIFESP]; Bressan, Rodrigo Affonseca [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); HIAE Instituto Israelita de Ensino e Pesquisa Albert Einstein; Hospital Israelita Albert Einstein Departamento de Imagem; Institute of Nuclear Energy Research TaiwanBACKGROUND: Dopamine transporter (DAT) neuroimaging radiotracers were developed to estimate dopamine neuronal loss in vivo in Parkinson s disease (PD). OBJECTIVE: To evaluate DAT density in vivo using [99mTc]-TRODAT-1 and single photon computerized tomography (SPECT) in a population of Brazilian PD. METHOD: Fifteen PD patients and 15 matched healthy controls scanned with [99mTc]-TRODAT-1 (INER-Taiwan) and SPECT. Estimates of striatum DAT density were calculated using binding potential (BP). Patients were assessed with PD scales. RESULTS: PD patients had significantly lower striatal DAT-BP (mean±SD) (0.38±0.12) compared to controls (BP=0.84±0.16; p<0.01). A 100% sensitivity and 100% specificity was obtained to discriminate PD cases from controls. Negative correlations between striatal DAT-BP and PD severity (rho= -0.7, p<0.001) and motor scales (rho= -0.80, p<0.001) were found. CONCLUSION: [99mTc]TRODAT-1 SPECTs scanning was able to discriminate PD patients from controls. The technique is a powerful instrument to measure DAT density that can be used in clinical and research settings in Brazil.
- ItemSomente MetadadadosProlactinemia is uncoupled from central D-2/D-3 dopamine receptor occupancy in amisulpride treated patients(Springer, 2004-09-01) Bressan, R. A.; Erlandsson, K.; Spencer, E. P.; Ell, P. J.; Pilowsky, L. S.; Universidade Federal de São Paulo (UNIFESP); Univ London Kings Coll; UCL Med Sch; Guys & St Thomas Hosp TrustAtypical antipsychotic drugs are classically associated with lower propensity to extrapyramidal symptoms (EPS) and hyperprolactinemia than typical antipsychotic drugs. It has not been clarified why some atypical antipsychotic drugs, such as amisulpride, induce prolactin plasma concentration (PRL) elevation, but little EPS. Previous studies have found an association between striatal D-2/D-3 receptor occupancy and PRL in typical antipsychotic treated patients suggesting that PRL is a marker of central D-2/D-3 receptors blockade. Objective: We have evaluated the relationship between PRL and central (striatum, temporal cortex and thalamus) D-2/D-3 receptor occupancy in amisulpride treated schizophrenic patients. Methods: Single photon emission tomography (SPET) and [I-123]-epidepride were used to determine D-2/D-3 receptor occupancy in eight amisulpride treated patients. PRL was measured concurrently with the scans. Results: the mean PRL was 1166 (range 499-1892 mIU/1) for a mean amisulpride dose of 406 mg/day (range 150-600 mg/day). Amisulpride plasma concentration and central D-2/D-3 receptor occupancy were positively correlated (r=0.83-0.89, df=4, P<0.05). No significant correlations were observed between PRL and amisulpride (daily dose or plasma concentration, P>0.05), or between PRL and central D-2/D-3 receptor occupancy (P>0.05). Conclusions: Our findings show that amisulpride-induced hyperprolactinemia is uncoupled from central D-2/D-3 receptor occupancy. Amisulpride has poor blood-brain barrier penetration and reaches much higher concentration at the pituitary, which is outside the blood-brain barrier. Higher D-2/D-3 receptor occupancy at the pituitary gland than at central regions is a possible explanation for amisulpride PRL elevation with low EPS. Further studies evaluating pituitary D-2/D-3 receptor occupancy in vivo are necessary to confirm this hypothesis.