New molecular targets for PET and SPECT imaging in neurodegenerative diseases

The pathophysiology of neurodegenerative diseases (ND) such as Alzheimer's disease (AD) and Parkinson's disease (PD) has not yet been completely elucidated. However, in the past few years, there have been great knowledge advances about intra-and extracellular proteins that may display impaired function or expression in AD, PD and other ND, such as amyloid beta (AB), alpha-synuclein, tau protein and neuroinfiammatory markers. Recent developments in the imaging techniques of positron emission tomography (PET) and single photon emission computed tomography (SPECT) now allow the non-invasive tracking of such molecular targets of known relevance to ND in vivo. This article summarizes recent findings of PET and SPECT studies using these novel methods, and discusses their potential role in the field of drug development for ND as well as future clinical applications in regard to differential diagnosis of ND and monitoring of disease progression.Brazilian Agency: CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) Brazilian agenc

Mortalidade em crianças com epilepsia severa: 10 anos de seguimento

Epilepsy is the main neurological condition in children and adolescents. Unfortunately patients with medical refractory epilepsy are more susceptible for clinical complications and death. We report a prospectively evaluated cohort of children followed for approximately 10 years. Fifty-three of 1012 patients died. Forty-two patients died due to epilepsy or its clinical complications and the main causes of death were pneumonia (in 16 cases), sepses (in 9 patients), status epilepticus (in 8 patients). In 11 patients cause of death was sudden unexpected death in epilepsy (SUDEP). Mental retardation was significantly more frequent in patients who did not die from SUDEP. SUDEP may be a significant condition associated with mortality in children and adolescents with epilepsy.Epilepsia é uma das condições neurológicas mais comuns em crianças e adolescentes. Infelizmente, pacientes com epilepsias refratárias ao tratamento medicamentoso estão mais susceptíveis a complicações clínicas e óbito. Neste trabalho reportamos, em uma análise prospectiva, um cohort de crianças acompanhadas por aproximadamente dez anos. Cinquenta e três de 1012 pacientes foram a óbito. Quarenta e dois pacientes morreram em decorrência da epilepsia ou de suas complicações clínicas; as principais causas foram pneumonia (16 casos), sepse (9 casos) e estado de mal epiléptico (8 casos). Em 11 pacientes a causa da morte foi SUDEP. A presença de retardo mental foi significantemente associada a mortalidade em crianças e adolescentes com epilepsia.Universidade de São Paulo Faculdade de Medicina de Ribeirão PretoUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

Acoplamento neurovascular e neuroimagem funcional em epilepsia

INTRODUCTION: The neural regulation of the microcirculation is done by the functional neurovascular unit that is composed of vascular, astroglial and neuronal cells. The neurovascular unit represents the interface between the Central Nervous System and the Vascular System. OBJECTIVE: This paper reviews the literature on functional neuroimaging with a particular focus on the mechanisms of the neurovascular coupling. CONCLUSIONS: Functional neuroimaging techniques as functional MRI, SPECT and PET distinguish metabolic and physiological processes underlying normal and abnormal events, based on neurovascular coupling. Although these techniques still have limitations in temporal and spatial resolution, they have considerably reduced the need for intracranial electrodes or invasive functional tests in the presurgical evaluation for intractable epilepsy. Recently, new techniques as optical approaches (measurement of intrinsic optical signals and near infrared spectroscopy) have increased both temporal and spatial resolutions. The use of such techniques in animal models has yielded experimental evidence for a neurovascular coupling in normal and epileptic conditions.INTRODUÇÃO: A regulação da microcirculação cerebral é realizada pela unidade neurovascular, que é composta por vasos sangüíneos, células astrogliais e neuronais. A unidade neurovascular representa a interface funcional entre o Sistema Nervoso Central e o sistema vascular. OBJETIVO: Este trabalho revisa a literatura sobre técnicas de neuroimagem funcional com especial enfoque nos mecanismos do acoplamento neurovascular. CONCLUSÃO: Técnicas de neuroimagem como a Ressonância Magnética funcional, SPECT e PET baseiam-se no acoplamento neurovascular para explorarem os processos metabólicos e fisiológicos subjacentes a eventos cerebrais normais e anormais. Embora estas técnicas apresentem limitações de resolução temporal e espacial, sua aplicabilidade em epilepsia tem reduzido consideravelmente a necessidade de eletrodos intracranianos e de outros métodos funcionais invasivos na avaliação pré-cirúrgica de pacientes com epilepsia intratável. Recentemente, novos procedimentos ópticos (mensuração do sinal intrínseco óptico e espectroscopia por raio infravermelho) que possuem excelente resolução espacial e temporal têm fornecido evidências experimentais do acoplamento neurovascular no cérebro normal e epiléptico

Ativação variável da ressonância magnética funcional com duas tarefas diferentes em um paciente com retardo mental

Functional MRI produces a more accurate localization of the language areas for epilepsy surgery purpose, but requires the patient cooperation. We report a 34 years-old woman with mental retardation who underwent two different verbal fluency tasks, category and word naming. We found a strong activation of the Broca’s area in the most difficult task. We suggest that a multi-task fMRI study could be successful in patients with cognitive delay.A ressonância magnética funcional permite uma localização acurada da área da linguagem para fins de cirurgia de epilepsia, mas requer a colaboração do paciente na execução da tarefa proposta, o que pode limitar a sua utilização em pacientes com retardo mental. Nós apresentamos o caso de uma mulher com 34 anos de idade, com retardo mental, que foi submetida a duas tarefas distintas de geração silenciosa de palavras, por categoria e letras. Encontramos forte ativação da área de Broca na tarefa mais complexa. Sugerimos que um estudo com múltiplas tarefas pode ser útil em pacientes com retardo mental

Translation, Cross-Cultural Adaptation, and Validation of the Portuguese Version of the Rotterdam Elderly Pain Observation Scale

INTRODUCTION: This study reports on the translation, cultural adaptation, and validation of a Portuguese version of the Rotterdam Elderly Pain Observation Scale (REPOS), a Dutch scale to assess pain in patients who cannot communicate, with or without dementia. METHODS: This is a multicenter study in pain and neurological units involving Brazil (clinical phase) and the Netherlands (training phase). We performed a retrospective cross-sectional, 2-staged analysis, translating and culturally adapting the REPOS to a Portuguese version (REPOS-P) and evaluating its psychometric properties. Eight health professionals were trained to observe patients with low back pain. REPOS consists of 10 behavioral items scored as present or absent after a 2-min observation. The REPOS score of ≥3 in combination with the Numerical Rating Scale (NRS) of ≥4 indicated pain. The Content Validity Index (CVI) in all items and instructions showed CVI values at their maximum. According to the higher correlation coefficient found between NRS and REPOS-P, it may be suggested that there was an adequate convergent validity. RESULTS: The REPOS-P was administered to 80 patients with a mean age of 60 years (SD 11.5). Cronbach's alpha coefficient showed a moderate internal consistency of REPOS-P (α = 0.62), which is compatible with the original study of REPOS. All health professionals reached high levels of interrater agreement within a median of 10 weeks of training, assuring reproducibility. Cohen's kappa was 0.96 (SD 0.03), and the intraclass correlation coefficient was 0.98 (SD 0.02), showing high reliability of REPOS-P scores between the trainer (researcher) and the trainees (healthcare professionals). The Pearson correlation coefficient was 0.95 (95% confidence interval 0.94–0.97), showing a significant correlation between the total scores of REPOS-P and NRS. CONCLUSION: The REPOS-P was a valuable scale for assessing elderly patients with low back pain by different healthcare professionals. Short application time, ease of use, clear instructions, and the brief training required for application were essential characteristics of REPOS-P

Aid in the detection of myocardial perfusion abnormality utilizing SPECT atlas and images registration: preliminary results

OBJETIVO: Criar um atlas de cintilografia de perfusão miocárdica e verificar sua aplicabilidade no auxílio computadorizado à detecção de defeitos perfusionais miocárdicos em pacientes portadores de cardiopatia isquêmica. MATERIAIS E MÉTODOS: O atlas foi criado com imagens de cintilografia de perfusão miocárdica, em condições de repouso e estresse, de 20 pacientes de ambos os gêneros com baixa probabilidade de doença arterial coronariana e julgadas normais por dois observadores experientes. Técnicas de registro de imagens e operações matemáticas sobre imagens foram utilizadas para obtenção de modelos de média e desvio-padrão da captação miocárdica percentual de cada gênero e condição fisiológica. RESULTADOS: Imagens de um paciente masculino e um feminino foram alinhadas com os atlas correspondentes, e os voxels apresentando valores de captação percentual dois desvios-padrão abaixo da média da respectiva região do atlas foram destacados nos cortes tomográficos e confirmados como defeitos de perfusão por dois observadores experientes. CONCLUSÃO: Demonstramos a criação de um atlas de cintilografia de perfusão miocárdica e obtivemos resultados promissores na sua utilização para auxílio à detecção de defeitos perfusionais. Entretanto, uma validação prospectiva com um número mais representativo de casos é necessária.OBJECTIVE: To develop an atlas of myocardial perfusion scintigraphy and evaluating its applicability in computer-aided detection of myocardial perfusion defects in patients with ischemic heart disease. MATERIALS AND METHODS: The atlas was created with rest-stress myocardial perfusion scintigraphic images of 20 patients of both genders with low probability of coronary artery disease and considered as normal by two experienced observers. Techniques of image registration and mathematical operations on images were utilized for obtaining template images depicting mean myocardial uptake and standard deviation for each gender and physiological condition. RESULTS: Myocardial perfusion scintigraphy images of one male and one female patient were aligned with the corresponding atlas template image, and voxels with myocardial uptake rates two standard deviations below the mean voxel value of the respective region in the atlas template image were highlighted on the tomographic sections and confirmed as perfusion defects by both observers. CONCLUSION: The present study demonstrated the creation of an atlas of myocardial perfusion scintigraphy with promising results of this tool as an aid in the detection of myocardial perfusion defects. However, further prospective validation with a more representative sample is recommended

Diagnostic tests in the context of the health technologies assessment: approaches, methods, and interpretation

As Avaliações de Tecnologias em Saúde (ATS) no mundo todo, predominantemente tem sido focadas em medicamentos, dispositivos médicos terapêuticos e procedimentos, sobretudo, os cirúrgicos. Apesar de sua inquestionável importância na história natural de um grande número de doenças e do impacto econômico associado ao seu uso, os testes e exames diagnósticos (TED), considerando-se suas qualidades e consequentemente a acurácia dos mesmos, tem sido pouco avaliados no contexto da ATS. Há nítida escassez de estudos que avaliam os TED tanto do ponto de vista clínico e de segurança para o paciente, quanto do econômico. O propósito desse artigo é apresentar e discutir os conceitos inerentes ao uso dos TED, as abordagens para seu emprego, as metodologias de avaliação de suas propriedades e acurácia, bem como a interpretação de resultados dos TED, sejam eles realizados individualmente, ou sob a forma de síntese de estudos de acurácia. Espera-se que esse texto possa contribuir para melhor compreensão das especificidades encontradas nos estudos dos TED e estimular sua inclusão nas ATS.The Health Technology Assessments (HTA) worldwide has been predominantly focused on drugs, medical devices and therapeutic procedures, above all, the surgeries. Despite its unquestionable importance in the natural history of a large number of diseases and of the economic impact associated with its use, the diagnostic exam and tests (DET), considering their qualities and hence the accuracy thereof, has been not evaluated in the context of the HTA. There is a clear shortage of studies that evaluate the DET, both clinician and patient safety, and economical. The purpose of this article is to present and discuss the concepts inherent in the use of DET, the approaches to your employ, the methodologies of evaluation of their properties and accuracy, as well as the interpretation of results DET studies, whether performed individually or in the form of synthesis of studies of accuracy. It is hoped that this text may contribute to better understanding of the specifics found in studies of DET and encourage their inclusion in the HTA

Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report

Objectives: Ayahuasca (AYA), a natural psychedelic brew prepared from Amazonian plants and rich in dimethyltryptamine (DMT) and harmine, causes effects of subjective well-being and may therefore have antidepressant actions. This study sought to evaluate the effects of a single dose of AYA in six volunteers with a current depressive episode. Methods: Open-label trial conducted in an inpatient psychiatric unit. Results: Statistically significant reductions of up to 82% in depressive scores were observed between baseline and 1, 7, and 21 days after AYA administration, as measured on the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS). AYA administration resulted in nonsignificant changes in Young Mania Rating Scale (YMRS) scores and in the thinking disorder subscale of the BPRS, suggesting that AYA does not induce episodes of mania and/or hypomania in patients with mood disorders and that modifications in thought content, which could indicate psychedelic effects, are not essential for mood improvement. Conclusions: These results suggest that AYA has fast-acting anxiolytic and antidepressant effects in patients with a depressive disorder