La lévodopa est-elle néfaste pour la cognition dans la maladie de Parkinson? : étude pilote

Introduction et objectifs : Alors que l'effet moteur de la lévodopa (L-dopa) dans la maladie de Parkinson (MP) est clair et établi, son effet sur la cognition demeure incertain. Les troubles cognitifs ont un impact important sur la qualité de vie et les études évaluant l'effet cognitif de ce médicament donnent des résultats encore divergents. L’objectif primaire de cette étude pilote est d’observer l’impact des doses cliniques de lévodopa sur la cognition. Un second objectif sera d'établir une courbe dose-réponse pour observer les différences potentielles. Méthodes : Cinq patients avec MP ont été évalués à l’aide de 2 tests cognitifs (CPT-II et Stroop) et 2 tests moteurs (Finger Tapping et UPDRS-III) en OFF (sevrage minimal de 12 heures) et en ON avec des doses croissantes de lévodopa (commençant à 50mg avec une augmentation de dose de 50mg par visite) jusqu’à l'observation d'une performance cognitive optimale ou d'effets secondaires. Une administration répétée des tests cognitifs a été faite à la première visite pour limiter l’effet d’apprentissage. Résultats : Le temps de réaction (RT) mesuré en millisecondes au CPT-II a augmenté (médiane 3.03%) après la prise de médicament alors que les erreurs ont légèrement diminué (médiane -9.92%). Au Stroop, l’effet d’interférence évalué selon les changements au temps d’inhibition mesuré en secondes était légèrement moindre sans changement dans les erreurs. Avec les doses prescrites, le RT a augmenté de 3,50% et le nombre d’erreurs est resté stable alors que les doses inférieures ont eu une moindre augmentation du RT tout en diminuant les erreurs. Dans le Stroop, les doses faibles ont amélioré le temps de près de 19% alors que les doses prescrites ont quant à elles diminué les erreurs. Malgré une certaine variabilité, la courbe dose-réponse indique que les erreurs diminuaient aux doses faibles et fortes dans le CPT-II alors que le RT augmentait généralement, ce qui pourrait indiquer un style de performance plus prudent. L’effet de la lévodopa sur l’interférence dans le Stroop variait légèrement sans tendances fixes mis à part le bénéfice observé par les doses faibles. Une importante variabilité a été observée dans les évaluations motrices entre les sujets ainsi qu'au sein du même sujet. Conclusion : Ces résultats indiquent qu’en général, le médicament ne semble pas avoir d’effet néfaste important sur l’attention et les fonctions exécutives évaluées auprès de ce groupe de patients parkinsoniens. L'effet cognitif des doses plus faibles semble leur être bénéfique et meilleur que les doses cliniquement prescrites. La relation dose-réponse démontre un effet cognitif variable de la lévodopa entre les doses, n'indiquant toutefois pas de tendances claires.

Utilidad del [99m] Tc TRODAT-1 en el diagnóstico de la Enfermedad de Parkinson: revisión sistemática de la literatura

Propósito de la revisión: la enfermedad de Parkinson (EP) es un trastorno degenerativo caracterizado clínicamente por presentar temblor en reposo, rigidez y bradicinesia. El propósito es determinar la utilidad de la molécula TRODAT-1 en el diagnóstico de la EP. Metodología: se realizó una búsqueda en las bases de datos: PUBMED, COCHRANE, MEDLINE, LILACS y SCIELO en un período de 10 años desde enero de 1998 a enero de 2008. Se obtuvieron 26 artículos, estos se analizaron y se seleccionaron 10 artículos, de los cuales sólo 6 respondían a las necesidades del estudio, de acuerdo a los criterios de inclusión. De los 6 artículos analizados, 4 fueron clasificados como evidencia grado (+) y los 2 restantes evidencia grado (-) de acuerdo con las guías NICE. Todos los artículos revisados reportan una disminución importante en la captación del TRODAT-1 a nivel estriatal, su utilidad en el diagnóstico de EP en estadios tempranos, bajo costo y seguridad. Sólo tres reportan valores de sensibilidad y especificidad, pero su nivel de calidad no permite hacer una comparación de los mismos. Conclusiones: se propone realizar estudios de prueba diagnóstica comparados con el diagnóstico clínico de la enfermedad, que tengan un acuerdo en la forma de plantear las mediciones semicuantitativas de las unidades de captación utilizando las mismas fórmulas para hacerlos comparables.

Prediction of Parkinson’s disease tremor onset using radial basis function neural networks

The possibility of using a radial basis function neural network (RBFNN) to accurately recognise and predict the onset of Parkinson’s disease tremors in human subjects is discussed in this paper. The data for training the RBFNN are obtained by means of deep brain electrodes implanted in a Parkinson disease patient’s brain. The effectiveness of a RBFNN is initially demonstrated by a real case study.

A fuzzy logic controller for intestinal levodopa infusion in Parkinson’s disease

The aim of this work is to evaluate the fuzzy system for different types of patients for levodopa infusion in Parkinson Disease based on simulation experiments using the pharmacokinetic-pharmacodynamic model. Fuzzy system is to control patient’s condition by adjusting the value of flow rate, and it must be effective on three types of patients, there are three different types of patients, including sensitive, typical and tolerant patient; the sensitive patients are very sensitive to drug dosage, but the tolerant patients are resistant to drug dose, so it is important for controller to deal with dose increment and decrement to adapt different types of patients, such as sensitive and tolerant patients. Using the fuzzy system, three different types of patients can get useful control for simulating medication treatment, and controller will get good effect for patients, when the initial flow rate of infusion is in the small range of the approximate optimal value for the current patient’ type.

Efeitos das técnicas breath-stacking e espirometria de incentivo nos volumes da caixa torácica em pacientes com Doença de Parkinson

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Déficits de memória induzidos por baixas doses de reserpina em ratos: possível relação com prejuízos no processamento emocional na Doença de Parkinson

We have recently verified that the monoamine depleting drug reserpine at doses that do not modify motor function - impairs memory in a rodent model of aversive discrimination. In this study, the effects of reserpine (0.1-0.5 mg/kg) on the performance of rats in object recognition, spatial working memory (spontaneous alternation) and emotional memory (contextual freezing conditioning) tasks were investigated. While object recognition and spontaneous alternation behavior were not affected by reserpine treatment, contextual fear conditioning was impaired. Together with previous studies, these results suggest that mild monoamine depletion would preferentially induce deficits in tasks involved with emotional contexts. Possible relationships with cognitive and emotional processing deficits in Parkinson disease are discussed

Estudo dos efeitos comportamentais do neuropeptídeos em camundongos submetidos a modelos animais de Parkinson

Neuropeptide S (NPS) is the endogenous ligand of a G-protein coupled receptor. Preclinical studies have shown that NPSR receptor activation can promote arousal, anxiolytic-like behavioral, decrease in food intake, besides hyperlocomotion, which is a robust but not well understood phenomenon. Previous findings suggest that dopamine transmission plays a crucial role in NPS hyperactivity. Considering the close relationship between dopamine and Parkinson Disease (PD), and also that NPSR receptors are expressed on dopaminergic nuclei in the brain, the current study attempted to investigate the effects of NPS in motor deficits induced by intracerebroventricular (icv) administration of 6-OHDA and systemic administration of haloperidol. Motor deficits induced by 6-OHDA and haloperidol were evaluated on Swiss mice in the rota-rod and catalepsy test. Time on the rotating rod and time spent immobile in the elevated bar were measured respectively in each test. L-Dopa, a classic antiparkinsonian drug, and NPS were administrated in mice submitted to one of the animal models of PD related above. 6-OHDA injection evoked severe motor impairments in rota-rod test, while the cataleptic behavior of 6-OHDA injected mice was largely variable. The administration of L-Dopa (25 mg/kg) and NPS (0,1 and 1 nmol) reversed motor impairments induced by 6-OHDA in the rota-rod. Haloperidolinduced motor deficits on rota-rod and catalepsy tests which were reversed by L-Dopa (100 e 400 mg/kg), but not by NPS (0,1 and 1 nmol) administration. The association of L-Dopa 10 mg/kg and NPS 1 nmol was also unable to counteract haloperidol-induced motor deficits. To summarize, 6-OHDA-, but not haloperidol-, induced motor deficits were reversed by the central administration of NPS. These data suggest that NPS possibly facilitates dopamine release in basal ganglia, what would explain the overcome of motor performance promoted by NPS administration in animals pretreated with 6-OHDA, but not haloperidol. Finally, the presented findings point, for the first time, to the potential of NPSR agonist as an innovative treatment for PD.

Eletromiografia de superfície da musculatura supra-hióidea durante a deglutição de idosos sem doenças neurológicas e idosos com Parkinson

OBJETIVO: investigar as diferenças entre os achados eletromiográficos dos músculos supra-hióideos direito e esquerdo durante a deglutição de um líquido e um pastoso fino, em sujeitos idosos com doença de Parkinson e idosos sem doença neurológica. MÉTODOS: 30 sujeitos de ambos os sexos participaram deste estudo, 15 idosos sem doença neurológica e os demais com doença de Parkinson. Todos foram submetidos a um protocolo de avaliação clínica e avaliação eletromiográfica de superfície. RESULTADOS: foram constatadas diferenças significantes nos valores entre os sujeitos (f=14.4 e p= 0.000) e entre os lados (f=4.4 e p=0.0037). em relação ao tempo de duração da contração muscular durante a deglutição as diferenças foram significantes apenas entre as consistências (f=8.2 e p=0.005). CONCLUSÃO: a amplitude eletromiográfica foi menor nos sujeitos com doença de Parkinson e maior nos músculos supra-hiódeos do lado direito em ambos os grupos. A duração da contração muscular não diferiu significativamente entre os sujeitos com doença de Parkinson e idosos sem doença neurológica e foi menor para a consistência líquida.

Mensuração da qualidade de vida de indivíduos com a doença de Parkinson por meio do questionário PDQ-39

INTRODUÇÃO: A doença de Parkinson (DP) é caracterizada por uma degeneração progressiva seletiva de neurônios localizados na pars compacta da substância negra. Ela compõe-se por um conjunto de quatro sintomas motores: tremor, rigidez, bradicinesia e instabilidade postural. OBJETIVO: O estudo objetivou investigar os fatores relacionados à queda na percepção da qualidade de vida de indivíduos com DP. MATERIAIS E MÉTODOS: Participaram deste estudo 25 indivíduos com diagnóstico de doença de Parkinson, classificados entre os estágios um e cinco da escala de estadiamento de Hoen e Yahr, tendo a sua qualidade de vida avaliada segundo o Parkinson Disease Questionary-39 (PDQ-39). RESULTADOS: Os 25 indivíduos (12 homens e 13 mulheres) apresentaram idade média de 71,2 ± 8,5 anos, variando entre 53 a 85 anos, e tempo de evolução da doença de 6,54 ± 7,71, variando entre 1 e 39 anos de doença. Verificou-se que as piores percepções sobre a qualidade de vida estão relacionadas ao domínio mobilidade, com média de 55% de comprometimento, e ao domínio atividade de vida diária, com 52,78% de comprometimento. Ficou também constatada uma alta correlação entre o escore total do PDQ-39 com os domínios atividade de vida diária, bem-estar emocional e mobilidade. CONCLUSÕES: A partir dos resultados obtidos, é possível constatar que carências de origem motora associadas aos sinais e sintomas e às complicações secundárias da DP interferem negativamente sobre a percepção da qualidade de vida dos indivíduos.

Adaptação para a língua Portuguesa e aplicação de protocolo de avaliação das disartrias de origem central em pacientes com Doença de Parkinson

OBJETIVO: traduzir e adaptar protocolo desenvolvido por pesquisadores alemães, adequando-o às características fonéticas e linguísticas do português falado no Brasil. Caracterizar os componentes de fala mais alterados na população com doença de Parkinson, comparando-os com grupo de sujeitos normais na mesma faixa etária. MÉTODOS: realizou-se a tradução e adaptação do protocolo. Posteriormente foram avaliados 21 pacientes com diagnóstico neurológico de Doença de Parkinson nos estágios Hoehn &Yarh, entre 2 e 3, e 10 sujeitos normais. O protocolo incluía avaliação da respiração, fonação, ressonância, articulação, prosódia e a análise acústica dos parâmetros vocais. RESULTADOS: o protocolo mostrou-se de fácil aplicação clínica. Nos sujeitos com doença de Parkinson foram observadas alterações predominantes na fonação (85,9%) e articulação (42,9%). CONCLUSÃO: o estudo demonstrou ser o protocolo uma ferramenta eficiente para a avaliação da disartria em pacientes com doença de Parkinson.

Efeito da fadiga no andar de pacientes com doença de Parkinson: relação com o nível de atividade física

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influência do fortalecimento muscular no equilíbrio e qualidade de vida em indivíduos com doença de Parkinson

This study aimed to evaluate the effect of muscle strengthening in the balance, mobility and quality of life (QoL) in individuals with Parkinson's disease (PD), and to check the correlation between muscle strengthening and QoL. Nine subjects belonging to both sexes, diagnosed with PD, participated in this study. Initially, they went through an evaluation of their balance and functional mobility through the Berg Balance Scale (BBS), the ­Timed Up and Go (TUG) test, and a QoL test through the Parkinson's Disease Questionnaire (PDQ-39). The subjects also performed a test for determining the maximum load (one-repetition maximum) for the muscle groups trained. After the normality and homogeneity of the data were verified, the Student's t-test and Spearman correlation test were carried out. A significance level of p<0.05 was considered. We verified an improvement in balance (p=0.008) and QoL (p=0.013), and a negative correlation between balance and QoL (evaluation: r=-0.65 and p=0.05, revaluation: r=-0.82 and p=0.005). It was concluded that muscle strengthening was efficient in the improvement of balance and QoL in individuals with PD.

Pausas em justificativas e conclusões nos discursos de um sujeito com doença de Parkinson e de um sujeito sem lesão neurológica

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Equilíbrio funcional em indivíduos com doença de Parkinson e sua relação com a qualidade de vida

Introduction: Parkinson’s Disease (PD) is characterized by a set of four motor symptoms: tremor, rigidity, bradykinesia and postural instability. These defi cits may predispose individuals to limitations resulting from falls and their secondary consequences. Objective: To evaluate the functional balance and quality of life (QoL) in individuals with PD and determine whether there is correlation between performance on tests of balance with the QoL. Method: The project was referred to the Ethics Committee in Research of Universidade Estadual Paulista “Julio de Mesquita Filho” Campus de Marília and was approved under protocol number 1806/09. Participated in this study with individuals diagnosed with PD between levels one and four in the Hoen and Yahr scale. The subjects were evaluated according to functional balance and QoL, respectively by the instruments: Functional Balance Scale Berg (EEFB), Time Up and Go test (TUG), and Parkinson’s Disease Questionnaire-39 (PDQ-39). To perform the statistical analysis used the GraphPad Prism 5. To perform the correlation analysis for the variables passed normality by the Shapiro-Wilk. Since the variables were non-parametric test was used Spearman. During the analysis the statistical signifi cance level was considered p ≤ 0, 05. Results: We studied 25 individuals aged between 54 and 85 years (71.20 ± 8.50), time of diagnosis between one and 39 years (6.54 ± 7.71) disease. Moderate correlation was found between the EEFB with QoL (r =- 0.6), and TUG with QoL (r = 0.6836). Among the aspects of QoL balance showed a higher correlation with the domains “mobility” (TUG r = 0, 6768; EEFB r = -0.6155) and “Activities of daily living” (TUG r = 0, 7357, and EEFB r = -0.6521). Conclusion: Patients with Parkinson’s disease show defi cits in balance and QoL. The balance disorders have a high correlation among themselves and show how aspects of QoL.

Long duration exercise program in individuals with parkinson´s disease: effects on functional capacity

The aim of this study was to investigate the effects of long duration exercise program on physical fitness components of functional capacity in individuals with Parkinson disease (PD) and to evaluate ongoing effects of exercise after 8 to 10-week follow-up without exercise. Twenty-four individuals with PD were randomly assigned to two groups: generalized exercise program and stretching exercise program (control group). The generalized exercise program provided training in physical fitness components of functional capacity. The stretching exercise program was characterized by low intensity and volume, mainly with static exercises. Both groups were evaluated before (BI) and after the 4-month (AI) exercise program. In addition, the individuals of generalized exercise program were also evaluated after 8-month exercise program and after 8 to 10- week follow-up without exercise. The generalized exercise program improved flexibility (BI - 38.50±12.42 cm; AI - 44.00±12.74 cm) and agility (BI - 30.59±7.54 s; AI - 28.56±8.20 s) while the stretching exercise program worsened coordination (BI - 23.27±6.58 s; AI - 28.06±7.37 s) and aerobic resistance (BI- 13.64±3.76 min; AI - 17.27±5.15 min) and improved balance (BI - 44.00±7.79 pts; AI - 46.57±6.53 pts). Lower-limb strength and UPDRS-motor scale scores were better at 8 months (14.75±2.92 rep and 26.25±13.97 pts, respectively) compared to baseline (13.13±2.59 rep and 31.63±12.82 pts, respectively) and 4 months (13.50±1.93 rep and 30.38±14.52 pts, respectively) for generalized exercise program. However, the benefits of 8 months of exercise were lost after 8 to 10-week follow-up without exercise (lower-limb strength - 12.43±3.15 rep and UPDRS-motor scale - 32.57±14.05 pts). In conclusion, generalized exercise program improved the functional capacity in individuals with PD, differently of stretching exercise program. In addition, a long duration exercise program promoted benefits for functional capacity and disease progression in individuals with PD. However, benefits were lost after a short period without exercise.