Comparação do comportamento locomotor de pacientes com doença de Parkinson, caidores e não caidores, durante o andar em terreno regular e durante a ultrapassagem de obstáculo

Introdução: Até o presente momento, não existem observações com o intuito de comparar o andar (em terreno regular e durante a ultrapassagem de obstáculo) de pacientes com doença de Parkinson (DP) caidores e não caidores. O conhecimento mais detalhado das diferenças clínicas e locomotoras entre pacientes caidores e não caidores pode servir como ferramenta importante para o melhor delineamento de intervenções com o intuito de prevenir e/ou reduzir a ocorrência de quedas na DP. Objetivo: Comparar o quadro clínico e o comportamento locomotor durante o andar em terreno regular e a ultrapassagem de obstáculo de indivíduos com DP caidores e não caidores. Método: Participaram do estudo 36 indivíduos com diagnóstico de DP idiopática. Inicialmente, a ocorrência de quedas foi registrada durante quatro meses por meio de entrevista semanal (contato pessoal e telefônico). Estes dados foram utilizados para distribuir os indivíduos em dois grupos: caidores (n=12) e não caidores (n=24). Em seguida, os pacientes realizaram, em estado “on” do medicamento, a avaliação do quadro clínico e do comportamento locomotor. A avaliação clínica incluiu a aplicação da escala de Hoehn & Yahr (estágio da doença) e da subescala motora da Unified Parkinson’s Disease Rating Scale (comprometimento motor). A avaliação do andar consistiu em caminhar, em velocidade preferida, sobre uma passarela de oito metros de comprimento em condições com e sem obstáculo. Um sistema optoeletrônico para a análise do movimento (OPTOTRAK) foi utilizado para a coleta de dados do andar. As variáveis dependentes incluíram as pontuações nas escalas clínicas e os parâmetros espaciais e temporais do andar em terreno regular e da ultrapassagem de obstáculo. Resultados: Os pacientes caidores apresentaram menores valores do que os pacientes não caidores... (Resumo completo, clicar acesso eletrônico abaixo)

Comportamento de indivíduos com doença de Parkinson no levantar da cadeira e no início da marcha: relações com o envelhecimento

Large motor dysfunctions are observed in older adults with the age advance. Parkinson’s disease (PD) patients have motor deficits to perform daily living activities. To raise from a chair, a daily task necessary to live independently, requires both large muscle recruitment and large joint range of motion to achieve the vertical position safely. Normally, we initiate gait after raise from a chair. The aim of this study was to analyze the PD patients’ behavior when rising from a chair and initiating gait and to compare it according to the age advance. In order to do that, 23 PD patients (66.61±7.64 years old) were distributed in three age groups: Young group, between 51 and 60 years of age (n=7); intermediary group, between 61 and 70 years of age (n=7); and elderly group, over 70 years of age (n=9). There were no statistical differences among groups either for the disease evolution stage or for it compromising. The task was to stand from a chair and to initiate gait forward in three attempts. The dependent variables were: spatial and temporal (first step length and duration, and stride length, duration and velocity) and angular (flexion and extension of head, shoulder, hip, knee, and ankle). The motion of standing from a chair was divided in two phases. The data was statistically treated by means of Analyses of Variance with group as the only factor. The Scheffé’s post hoc test was used to localize differences among groups and the significance level was adjusted to p≤0.017. There were statistical differences for stride...(Complete abstract click electronic access below)

Análise cinemática da marcha livre e adaptativa de pacientes com doença de Parkinson e idosos sadios: efeito da dica auditiva

Disorders in gait are identified in Parkinson’s disease patients. As a result, the capacity of walking independently and the interaction with the environment can be impairment. So, the auditory cues have been utilized as a non-pharmacological treatment to improve the locomotor impairment of the PD patients. However, these effects were observed in the regular lands and it’s not known the effects of auditory cues in gait during avoidance obstacles that could be more threaten for these patients. Yet, few studies in the literature compare the Parkinson’s disease patients with the older adults during the locomotor tasks and obstacle avoidance in association with the effects of auditory cues. The aim of the study is to compare the effects of the auditory cues in the gait and during obstacle avoidance in PD patients and older adults. 30 subjects distributed in two groups (Group 1 - 15, Parkinson’s disease patients; Group 2 - 15, healthy older adults) are going to participate of this study. After the participation approval, the assessment of clinical condition will be done by a physician. So, to investigate the locomotor pattern, it will be done a kinematic analysis. The experimental task is to walk on 8 m pathway and 18 trials will be done (6 for the free gait and 12 for adaptive gait). For the adaptive gait, two different obstacle heights will be manipulated: high obstacle (HO) and low obstacle (LO). In order to verify possible differences between the groups and the experimental condition, multivariance tests will be used with a significance level of 0.05. MANOVA revealed effect of condition and task. Thus, with DA, we observed an increase in cadence and reduced single support and stride length. When the tasks were compared, it was observed that the LO task, subjects had lower velocity and stride length... 9Complete abstract click electronic access below)

Influência da atividade física sobre o risco de quedas e o equilíbrio em pacientes com doença de Parkinson

A doença de Parkinson (DP) é uma doença neurodegenerativa que afeta principalmente o controle motor com reflexos negativos no desempenho funcional de seus pacientes. Alterações no equilíbrio podem levar à diminuição da independência e funcionalidade. Alguns estudos evidenciam os benefícios do exercício físico, como alternativa nãofarmacológica para esses pacientes. Objetivo: O presente trabalho analisou e comparou os efeitos de dois programas de atividade física sobre o risco de quedas e o equilíbrio funcional em pacientes com doença de Parkinson. O presente estudo também teve como objetivo verificar a associação entre as variáveis clínicas e comportamentais. Método: Participaram do estudo 30 pacientes com DP idiopática entre os estágios I a III na escala de estagiamento clínico de Hoehn & Yahr, sendo distribuídos em três grupos: grupo de treinamento com pesos (GTP), atividade física generalizada (GAFG) e o grupo controle (GC). O período de intervenção para o GTP e o GAFG foi de quatro meses. As avaliações foram realizadas com os participantes na fase “on” da medicação. Para avaliar o equilíbrio dinâmico juntamente com o risco de quedas foi utilizado o teste Timed Up and Go (TUG) e, para analisar o risco de quedas foi utilizada a Escala de Equilíbrio Funcional de Berg (EEFB). As avaliações clínicas foram realizadas por meio da Unified Parkinson’s Disease Rating Scale (sub-escalas funcional e motora), escala de nível de gravidade da doença de Hohen & Yahr e Mini-Exame do Estado Mental (MEEM). O teste U de Mann-Whitney foi utilizado para comparação das variáveis analisadas entre os três grupos separadamente por momento do treinamento. Resultados: Apenas em relação à EEFB foram encontradas diferenças significativas entre os grupos, com pior desempenho para o grupo controle (GC). Conclusão: Foi possível observar que: os pacientes... (Resumo completo, clicar acesso eletrônico abaixo)

Controle motor em pacientes com doença de Parkinson: terapia do espelho, foco de atenção e tarefa dupla

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Resolution of tremor fluoxetine-induced in an elderly patient

Aim: To report a possible case of tremor fluoxetine-induced treated as Parkinson’s disease in an elderly female patient noncompliant with the pharmacotherapy, with uncontrolled hypertension and using fluoxetine to treat depression. Presentation of Case: Patient complained of sleepiness in the morning, agitation, anxiety, insomnia and mental confusion. Her greatest concern was about bilateral hand tremors which, in her view became, worse after biperiden was prescribed. Therefore, she stopped taking it. The initial medication was: omeprazole, losartan, biperiden, fluoxetine, atenolol + chlorthalidone, acetylsalicylic acid, atorvastatin and diazepam. Pharmacotherapeutic follow up was performed in order to check the necessity, safety and effectiveness of treatment. Discussion: During the analysis of pharmacotherapy, the patient showed uncontrolled blood pressure and had difficulty complying with the treatment. Thus, in view of the complaints expressed by the patient, our first hypothesis was a possible serotonin syndrome related to fluoxetine use. We proposed a change in the fluoxetine regime and discontinuation of biperiden. As tremors persisted, we suggested the replacement of fluoxetine by sertraline, since a possible tremor fluoxetine-induced could explain the complaint. This approach solved the drug-related problem identified. Conclusion: Tremors reported by the patient was identified as an iatrogenic event related to fluoxetine, which was solved by management of serotonin-reuptake inhibitors.

A computer-controlled color vision test for children based on the Cambridge Colour Test

The present study aimed at providing conditions for the assessment of color discrimination in children using a modified version of the Cambridge Colour Test (CCT, Cambridge Research Systems Ltd., Rochester, UK). Since the task of indicating the gap of the Landolt C used in that test proved counterintuitive and/or difficult for young children to understand, we changed the target Stimulus to a patch of color approximately the size of the Landolt C gap (about 7 degrees Of Visual angle at 50 cm from the monitor). The modifications were performed for the CCT Trivector test which measures color discrimination for the protan, deutan and tritan confusion lines. Experiment I Sought to evaluate the correspondence between the CCT and the child-friendly adaptation with adult subjects (n = 29) with normal color vision. Results showed good agreement between the two test versions. Experiment 2 tested the child-friendly software with children 2 to 7 years old (n = 25) using operant training techniques for establishing and maintaining the subjects` performance. Color discrimination thresholds were progressively lower as age increased within the age range tested (2 to 30 years old), and the data-including those obtained for children-fell within the range of thresholds previously obtained for adults with the CCT. The protan and deutan thresholds were consistently lower than tritan thresholds, a pattern repeatedly observed in adults tested with the CCT. The results demonstrate that the test is fit for assessment of color discrimination in young children and may be a useful tool for the establishment of color vision thresholds during development.

Chromatic discrimination losses in multiple sclerosis patients with and without optic neuritis using the Cambridge Colour Test

We assessed chromatic discrimination in multiple sclerosis (MS) patients both with (ON) and without (no ON) a history of optic neuritis using the Cambridge color test (CCT). Our goal was to determine the magnitude and chromatic axes of any color vision losses in both patient groups, and to evaluate age-related changes in chromatic discrimination in both patient groups compared to normals. Using the CCT, we measured chromatic discrimination along the protan, deutan and tritan axes in 35 patients with MS (17 ON eyes) and 74 age matched controls. Color thresholds for both patient groups were significantly higher than controls` along the protan and tritan axes (P < 0.001). In addition, the ON and no-ON groups differed significantly along all three-color axes (p < 0.001). MS patients presented a progressive color discrimination impairment with age (along the deutan and tritan axes) that was almost two times faster than controls, even in the absence of ON. These findings suggest that demyelinating diseases reduce sensitivity to color vision in both red-green and blue-yellow axes, implying impairment in both parvocellular and koniocellular visual pathways. The CCT is a useful tool to help characterize vision losses in MS and the relationship between these losses and degree of optic nerve involvement.

Hypoactivity of the central dopaminergic system and autistic-like behavior induced by a single early prenatal exposure to lipopolysaccharide

The aim of the present study was to evaluate the behavioral patterns associated with autism and the prevalence of these behaviors in males and females, to verify whether our model of lipopolysaccharide (LPS) administration represents an experimental model of autism. For this, we prenatally exposed Wistar rats to LPS (100 mu g/kg, intraperitoneally, on gestational day 9.5), which mimics infection by gram-negative bacteria. Furthermore, because the exact mechanisms by which autism develops are still unknown, we investigated the neurological mechanisms that might underlie the behavioral alterations that were observed. Because we previously had demonstrated that prenatal LPS decreases striatal dopamine (DA) and metabolite levels, the striatal dopaminergic system (tyrosine hydroxylase [TH] and DA receptors D1a and D2) and glial cells (astrocytes and microglia) were analyzed by using immunohistochemistry, immunoblotting, and real-time PCR. Our results show that prenatal LPS exposure impaired communication (ultrasonic vocalizations) in male pups and learning and memory (T-maze spontaneous alternation) in male adults, as well as inducing repetitive/restricted behavior, but did not change social interactions in either infancy (play behavior) or adulthood in females. Moreover, although the expression of DA receptors was unchanged, the experimental animals exhibited reduced striatal TH levels, indicating that reduced DA synthesis impaired the striatal dopaminergic system. The expression of glial cell markers was not increased, which suggests that prenatal LPS did not induce permanent neuroinflammation in the striatum. Together with our previous finding of social impairments in males, the present findings demonstrate that prenatal LPS induced autism-like effects and also a hypoactivation of the dopaminergic system. (c) 2012 Wiley Periodicals, Inc.

Normative Data for Healthy Middle-Aged and Elderly Performance on the Addenbrooke Cognitive Examination-Revised

Objective: To provide normative data for healthy middle-aged and elderly Brazilians' performance on the Addenbrooke Cognitive Examination-Revised (ACE-R) and to investigate the effects of age, sex, and schooling on test performance. Background: The ACE-R is a brief cognitive battery that assesses various aspects of cognition. Its 5 subdomains (Attention and Orientation, Memory, Verbal Fluency, Language, and Visuospatial Abilities) are commonly impaired in Alzheimer disease or frontotemporal dementia. Methods: We evaluated 144 cognitively healthy volunteers (50% men, 50% women) aged 50 to 93 years, with 4 to 24 years of schooling. We divided the participants into 4 age groups, each of which was then stratified into 3 groups according to years of education. We assessed all participants with the ACE-R, the Mattis Dementia Rating Scale, and the Cornell Scale for Depression in Dementia. Results: Years of education affected all ACE-R subscores. Age influenced the Verbal Fluency subscore (P < 0.001) and the ACE-R total score (P < 0.05). Sex affected the Attention and Orientation (P = 0.037) and Mini-Mental State Examination subscores (P = 0.048), but not the ACE-R total score (P > 0.05). Conclusions: The performance of healthy middle-aged and elderly individuals on the ACE-R battery is strongly influenced by education and, to a lesser extent, by age. These findings are of special relevance in countries with populations that have marked heterogeneity in educational levels.

Subgroup-specific structural variation across 1,000 medulloblastoma genomes

Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4 alpha. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-beta signalling in Group 3, and NF-kappa B signalling in Group 4, suggest future avenues for rational, targeted therapy.

Memory-rescuing effects of cannabidiol in an animal model of cognitive impairment relevant to neurodegenerative disorders

Rationale Cannabidiol, the main nonpsychotropic constituent of Cannabis sativa, possesses a large number of pharmacological effects including anticonvulsive, sedative, hypnotic, anxiolytic, antipsychotic, anti-inflammatory, and neuroprotective, as demonstrated in clinical and preclinical studies. Many neurodegenerative disorders involve cognitive deficits, and this has led to interest in whether cannabidiol could be useful in the treatment of memory impairment associated to these diseases. Objectives We used an animal model of cognitive impairment induced by iron overload in order to test the effects of cannabidiol in memory-impaired rats. Methods Rats received vehicle or iron at postnatal days 12-14. At the age of 2 months, they received an acute intraperitoneal injection of vehicle or cannabidiol (5.0 or 10.0 mg/kg) immediately after the training session of the novel object recognition task. In order to investigate the effects of chronic cannabidiol, iron-treated rats received daily intraperitoneal injections of cannabidiol for 14 days. Twenty-four hours after the last injection, they were submitted to object recognition training. Retention tests were performed 24 h after training. Results A single acute injection of cannabidiol at the highest dose was able to recover memory in iron-treated rats. Chronic cannabidiol improved recognition memory in iron-treated rats. Acute or chronic cannabidiol does not affect memory in control rats. Conclusions The present findings provide evidence suggesting the potential use of cannabidiol for the treatment of cognitive decline associated with neurodegenerative disorders. Further studies, including clinical trials, are warranted to determine the usefulness of cannabidiol in humans suffering from neurodegenerative disorders.

Validity of the Brazilian version of the freezing of gait questionnaire

Objective: To validate the freezing of gait questionnaire (FOG-Q) for a Brazilian population of Parkinson's disease (PD) patients. Methods: One hundred and seven patients with a diagnosis of PD were evaluated by shortened UPDRS motor scale (sUPDRm), Hoehn and Yahr (HY), Schwab and England scale (SE), Berg balance scale (BBS), falls efficacy scale international (FES-I), gait and balance scale (GABS), and the FOG-Q Brazilian version. Results: 47.7% of PD patients had FOG episodes; this group had worse scores on sUPDRSm, FOGQ, FES-I, BBS, GABS and FOG item of UPDRS when compared to the PD group without FOG. The internal consistency was 0.86, intra-rater 0.82 and inter-rater 0.78. The FOG-Q Brazilian version was significantly correlated with items related to gait and balance. The ROC curve was 0.94, the sensitivity was 0.90 and specificity was 0.92. Conclusion: Our study suggests that the FOG-Q Brazilian version is a reliable and valid instrument for assessing FOG in PD patients.

Olfactory impairment in familial ataxias

The main clinical manifestations of the spinocerebellar ataxias (SCAs) result from the involvement of the cerebellum and its connections. Cerebellar activity has been consistently observed in functional imaging studies of olfaction, but the anatomical pathways responsible for this connection have not yet been elucidated. Previous studies have demonstrated olfactory deficit in SCA2, Friedreich's ataxia and in small groups of ataxia of diverse aetiology. The authors used a validated version of the 16-item smell identification test from Sniffin' Sticks (SS-16) was used to evaluate 37 patients with genetically determined autosomal dominant ataxia, and 31 with familial ataxia of unknown genetic basis. This data was also compared with results in 106 Parkinson's disease patients and 218 healthy controls. The SS-16 score was significantly lower in ataxia than in the control group (p<0.001, 95% CI for beta=0.55 to 1.90) and significantly higher in ataxia than in Parkinson's disease (p<0.001, 95% CI for beta=-4.58 to -3.00) when adjusted for age (p=0.001, 95% CI for beta=-0.05 to -0.01), gender (p=0.19) and history of tobacco use (p=0.41). When adjusted for general cognitive function, no significant difference was found between the ataxia and control groups. This study confirms previous findings of mild hyposmia in ataxia, and further suggests this may be due to general cognitive deficits rather than specific olfactory problems.

NADPH Oxidase and Neurodegeneration

NADPH oxidase (Nox) is a unique, multi-protein, electron transport system that produces large amounts of superoxide via the reduction of molecular oxygen. Nox-derived reactive oxygen species (ROS) are known to be involved in a variety of physiological processes, including host defense and signal transduction. However, over the past decade, the involvement of (Nox)-dependent oxidative stress in the pathophysiology of several neurodegenerative diseases has been increasingly recognized. ROS produced by Nox proteins contribute to neurodegenerative diseases through distinct mechanisms, such as oxidation of DNA, proteins, lipids, amino acids and metals, in addition to activation of redox-sensitive signaling pathways. In this review, we discuss the recent literature on Nox involvement in neurodegeneration, focusing on Parkinson and Alzheimer diseases.