Characterization of the nigroestriatal system in a sample of patients with amyotrophic lateral sclerosis.

BACKGROUND: The coexistence of amyotrophic lateral sclerosis (ALS) with clinical forms of Parkinson disease (PD), although uncommon, is found to a greater degree than one would expect by chance. The pathological mechanisms of ALS and PD are still not fully understood, and the coexistence of these two diseases suggests that they could share mechanisms in common. OBJECTIVE: Here we present a sample of patients with clinically definitive or probable ALS who were evaluated with single-photon emission computed tomography SPECT/TRODAT and compared with non-ALS controls. METHODS: Patients with clinically definite or probable ALS were assessed with the amyotrophic lateral sclerosis functional rating scale (ALSFRS) to define severity and had their demographic data collected. The TRODAT results of patients with ALS were compared with those of patients with a diagnosis of PD with less than 10 years of duration, and with patients with a diagnosis of others movement disorders not associated with neurodegenerative diseases. RESULTS: A total of 75% of patients with ALS had TRODAT results below the levels considered normal; that was also true for 25% of the patients in the control group without neurodegenerative disease, and for 100% of the patients in the PD group. A statistically significant difference was found between patients with ALS and the control group without neurodegenerative disease in the TRODAT values < 0.05. CONCLUSIONS: Our study fits with the neuropathological and functional evidence that demonstrates the existence of nigrostriatal dysfunction in patients with ALS. Further research to better understand the role of these changes in the pathophysiological process of ALS needs to be performed.

ANTECEDENTES: A coexistência da esclerose lateral amiotrófica (ELA) com formas clínicas da doença de Parkinson (DP), embora incomum, é encontrada em um grau maior do que seria esperado ao acaso. Os mecanismos patológicos da ELA e da DP ainda não são totalmente compreendidos e a coexistência dessas duas doenças sugere que elas podem compartilhar mecanismos em comum. OBJETIVO: Apresentamos uma amostra de pacientes com ELA clinicamente definida ou provável que foram avaliados com tomografia computadorizada por emissão de fóton único (SPECT)/TRODAT e comparados com controles sem ELA. MéTODOS: Pacientes com ELA clinicamente definida ou provável foram avaliados com a escala funcional de esclerose lateral amiotrófica (ALSFRS) para definir a gravidade e foram coletados os seus dados demográficos. Os resultados do TRODAT de pacientes com ELA foram comparados com aqueles de pacientes com diagnóstico de DP com menos de 10 anos de duração e com pacientes com diagnóstico de outros distúrbios do movimento não associados a doenças neurodegenerativas. RESULTADOS: Um total de 75% dos pacientes com ELA apresentou resultados de TRODAT abaixo dos níveis considerados normais; 25% no grupo controle sem doença neurodegenerativa e 100% no grupo DP. Uma diferença estatisticamente significativa foi encontrada entre os pacientes com ELA e o grupo controle sem doença neurodegenerativa nos valores de TRODAT p < 0,05. CONCLUSõES: Nosso estudo está de acordo com as evidências neuropatológicas e funcionais que demonstram a existência de disfunção nigroestriatal em pacientes com ELA. Mais pesquisas para entender melhor o papel dessas mudanças no processo fisiopatológico da ELA precisam ser realizadas.

Characterization of the nigroestriatal system in a sample of patients with amyotrophic lateral sclerosis / Caracterização do sistema nigroestriatal em uma amostra de pacientes com esclerose lateral amiotrófica

Abstract Background The coexistence of amyotrophic lateral sclerosis (ALS) with clinical forms of Parkinson disease (PD), although uncommon, is found to a greater degree than one would expect by chance. The pathological mechanisms of ALS and PD are still not fully understood, and the coexistence of these two diseases suggests that they could share mechanisms in common. Objective Here we present a sample of patients with clinically definitive or probable ALS who were evaluated with single-photon emission computed tomography SPECT/TRODAT and compared with non-ALS controls. Methods Patients with clinically definite or probable ALS were assessed with the amyotrophic lateral sclerosis functional rating scale (ALSFRS) to define severity and had their demographic data collected. The TRODAT results of patients with ALS were compared with those of patients with a diagnosis of PD with less than 10 years of duration, and with patients with a diagnosis of others movement disorders not associated with neurodegenerative diseases. Results A total of 75% of patients with ALS had TRODAT results below the levels considered normal; that was also true for 25% of the patients in the control group without neurodegenerative disease, and for 100% of the patients in the PD group. A statistically significant difference was found between patients with ALS and the control group without neurodegenerative disease in the TRODAT values < 0.05. Conclusions Our study fits with the neuropathological and functional evidence that demonstrates the existence of nigrostriatal dysfunction in patients with ALS. Further research to better understand the role of these changes in the pathophysiological process of ALS needs to be performed.

Resumo Antecedentes A coexistência da esclerose lateral amiotrófica (ELA) com formas clínicas da doença de Parkinson (DP), embora incomum, é encontrada em um grau maior do que seria esperado ao acaso. Os mecanismos patológicos da ELA e da DP ainda não são totalmente compreendidos e a coexistência dessas duas doenças sugere que elas podem compartilhar mecanismos em comum. Objetivo Apresentamos uma amostra de pacientes com ELA clinicamente definida ou provável que foram avaliados com tomografia computadorizada por emissão de fóton único (SPECT)/TRODAT e comparados com controles sem ELA. Métodos Pacientes com ELA clinicamente definida ou provável foram avaliados com a escala funcional de esclerose lateral amiotrófica (ALSFRS) para definir a gravidade e foram coletados os seus dados demográficos. Os resultados do TRODAT de pacientes com ELA foram comparados com aqueles de pacientes com diagnóstico de DP com menos de 10 anos de duração e com pacientes com diagnóstico de outros distúrbios do movimento não associados a doenças neurodegenerativas. Resultados Um total de 75% dos pacientes com ELA apresentou resultados de TRODAT abaixo dos níveis considerados normais; 25% no grupo controle sem doença neurodegenerativa e 100% no grupo DP. Uma diferença estatisticamente significativa foi encontrada entre os pacientes com ELA e o grupo controle sem doença neurodegenerativa nos valores de TRODAT p< 0,05. Conclusões Nosso estudo está de acordo com as evidências neuropatológicas e funcionais que demonstram a existência de disfunção nigroestriatal em pacientes com ELA. Mais pesquisas para entender melhor o papel dessas mudanças no processo fisiopatológico da ELA precisam ser realizadas.

Striatal dopamine correlates to memory and attention in Parkinson's disease.

Parkinson's disease (PD) is clinically characterized by motor symptoms, however, specific cognitive impairments are common and poorly understood. This study was designed to assess whether cognitive performances are related to dopamine active transporter (DAT) availability in non-demented PD subjects. Fifty-four non-demented PD patients were enrolled. They underwent [99mTc] TRODAT-1 SPECT/CT and a comprehensive neuropsychological battery including attention/executive and memory tests. Multiple linear regression controlling the effect of age, disease duration and education was applied. The significance level was set at P values of < 0.02. After controlling the effect of age, disease duration and education, lower scores in Rey's Auditory-Verbal Learning Test (RAVLT)/immediate recall were significantly related with lower uptake values in the less affected striatum and more affected caudate. Lower scores in RAVLT/short-term recall were also significantly associated with lower uptake values in the more affected caudate and reduced performance in Trail Making Test part B was related with reduced DAT values in the less affected anterior putamen. Our findings suggest that reduced DAT availability in both caudate and putamen is related to reduced performances in some memory and attention/executive tasks. Nigrocaudate dysfunction is related to lower memory performance while dopamine depletion in the anterior putamen is related to poorer attention performance. If the dopaminergic defects can mostly explain all the cognitive symptoms or this phenomenon just co-occur with other anatomical and biochemical changes remains unknown. Further studies in larger patient samples are required to clarify this issue.

Is the dopaminergic loss associated with gait and postural impairments in subjects with Parkinson's disease at different motor stages?

Gait and postural control deficiencies in Parkinson's disease (PD) involve several specific motor aspects. The aim of this study was to identify and compare the main changes in gait kinematics and postural control with dopaminergic loss in the striatum region. This is a cross-sectional study that included 42 individuals with PD at different motor stages, according to the Hoehn & Yahr scale (H&Y). Motor subsection of the Movement Disorder Society-Unified Parkinson Disease Rating Scale-part III (MDS-UPDRS III) was used to evaluate general motor aspects. Gait kinematics was assessed using a three-dimensional motion capture system. Postural control was assessed by stabilometry using force platforms. Dopamine depletion was verified through 99mTc-TRODAT-1 (SPECT-CT) examination. We included 12, 15 and 15 individuals classified as H&Y I, II and III, respectively. We identified worse values of dopamine transporter uptake, MDS-UPDRS III, gait parameters (velocity, step length and stride length) and center of pressure displacement as the disease progressed. Our results indicate that higher dopaminergic loss and gait and postural control deficits occur between the H&Y levels II and III.

Impairments in gait kinematics and postural control may not correlate with dopamine transporter depletion in individuals with mild to moderate Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by the loss of dopamine, an important neurotransmitter involved in regulating movement. Nuclear medicine imaging methods such as single-photon emission computed tomography (SPECT) combined with radiotracers can obtain the density of this neurotransmitter. This reduced density leads to classic PD symptoms, such as bradykinesia, tremor and stiffness, consequently affecting walking and postural control. The aim of this study was to verify the correlation between disorders of gait kinematics and postural instability with dopamine depletion in individuals with mild to moderate PD. This is a descriptive, observational cross-sectional study. Subjects were assessed for spatiotemporal gait parameters by a three-dimensional motion capture system, for postural control by stabilometry on a force plate. Dopamine depletion was verified through 99mTc-TRODAT-1 (SPECT-CT) examination. The subjects were in the off-stage of levodopa in all analysis. We evaluated 71 individuals, 32 with mild to moderate PD (HY 2 and 2.5) and 39 healthy individuals matched for gender, age, and height. There was a significant difference between the groups regarding the spatiotemporal variables of gait, as well as in the stabilometric variables. However, there was no correlation between these disturbances and the uptake values of 99mTc-TRODAT-1. The results indicate that there is no correlation between gait impairments and postural instability of individuals with mild to moderate PD and the dopaminergic depletion measured through the 99mTc-TRODAT-1 (SPECT-CT).

Ambiente colaborativo para formação de pessoal em medicina nuclear / Collaborative environment for nuclear medicine training

OBJETIVO: Validar a proposta do desenvolvimento de um ambiente colaborativo virtual para formação de pessoal em medicina nuclear. MATERIAIS E MÉTODOS: No desenvolvimento inicial do ambiente foram levantadas as premissas, restrições e funcionalidades que deveriam ser oferecidas aos profissionais da área. O protótipo foi desenvolvido no ambiente Moodle, incluindo funcionalidades de armazenamento de dados e interação. Um estudo piloto de interação no ambiente foi realizado com uma amostra de profissionais especialistas em medicina nuclear. Análises quantitativas e de conteúdo foram realizadas a partir de um questionário semiestruturado de opinião dos usuários. RESULTADOS: A proposta do ambiente colaborativo foi validada por uma comunidade de profissionais que atuam nesta área e considerada relevante visando a auxiliar na formação de pessoal. Sugestões de melhorias e novas funcionalidades foram indicadas. Observou-se a necessidade de estabelecer um programa de formação dos moderadores no ambiente, visto que são necessárias características de interação distintas do ensino presencial. CONCLUSÃO: O ambiente colaborativo poderá permitir a troca de experiências e a discussão de casos entre profissionais localizados em instituições de diferentes regiões do País, possibilitando uma aproximação e colaboração entre esses profissionais. Assim, o ambiente pode contribuir para formação inicial e continuada de profissionais que atuam em medicina nuclear.

OBJECTIVE: To validate the proposal for development of a virtual collaborative environment for training of nuclear medicine personnel. MATERIALS AND METHODS: Organizational assumptions, constraints and functionalities that should be offered to the professionals in this field were raised early in the development of the environment. The prototype was developed in the Moodle environment, including data storage and interaction functionalities. A pilot interaction study was developed with a sample of specialists in nuclear medicine. Users' opinions collected by means of semi-structured questionnaire were submitted to quantitative and content analysis. RESULTS: The proposal of a collaborative environment was validated by a community of nuclear medicine professionals and considered as an aid in the training in this field. Suggestions for improvements and new functionalities were made. There is a need to establish a program for education of moderators specifically for this environment, considering the different interaction characteristics as the online and conventional teaching methods are compared. CONCLUSION: The collaborative environment will allow the exchange of experiences and case discussions among professionals from institutions located in different regions all over the country, enhancing the collaboration among them. Thus, the environment can contribute in the early and continued education of nuclear medicine professionals.

Molecular imaging genetics of methylphenidate response in ADHD and substance use comorbidity.

PURPOSE: 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; R² 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.

Methylphenidate 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.

BACKGROUND: 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 approximately 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.