12-month results from a novel test battery used in a duodenal levodopa infusion trial

A novel test battery consisting of self-assessments and motor tests (tapping and spiral drawing) for patients with Parkinson’s disease (PD) was developed for a hand computer with touch screen in a telemedicine setting. Tests are performed four times per day in the home environment during weeklong test periods. Results are processed into scores for different dimensions of the symptom state and an ‘overall score’ reflecting the global condition of a patient during a test period. The test battery was validated in a separate study recently submitted to Mov Disord. This test battery is currently being used in an open longitudinal trial (DAPHNE, EudraCT No. 2005- 002654-21) by sixty-five patients with advanced PD at nine clinics around Sweden. On inclusion, the patients were either receiving treatment with duodenal levodopa/carbidopa infusion (Duodopa®) (n=36), or they were candidates for receiving this treatment (n=29). We now present interim results for the first twelve months. Test periods were performed in three-month intervals. During most of the periods, UPDRS ratings were performed in afternoons at the start of the week. In twenty of the patients, scores were available during individually optimized oral polypharamacy, before receiving infusion and at least one test period after having started infusion treatment. Usability and compliance with performing tests, this far are good, both with patients and clinical staff. Correlations between test periods 2 and 3 during infusion treatment (three months apart) are stronger for overall test score than for total UPDRS, indicating good reliability. The correlation between overall test score and UPDRS for all test periods is adequate (r=-0.6). In an exact Wilcoxon signed rank test, where the endpoint is the change from the first to the twelve month test period (n=25), there was no change in test results in any of the test battery dimensions for the patients already receiving infusion when included. However, in the patients entering the study before receiving infusion, there was a significant change (improvement) from the baseline to the twelve month test period in dimensions; ‘off’, ‘dyskinesia’ and ‘satisfied’ and in the ‘overall score’ (n=15). The mean improvement in overall score after infusion was 29% (p=0.015). We conclude that the test battery is able to measure a functional improvement with infusion that is sustained over at least twelve months.

Administração repetida de baixas doses de reserpina: um possível modelo para o estudo de déficits cognitivos e motores associados à Doença de Parkinson

Parkinson's disease (PD) is one of the most common neurodegenerative brain disorders and is characterized primarily by a progressive degeneration of dopaminergic neurons nigroestriatais. The main symptoms of this disease are motor alterations (bradykinesia, rigidity, tremor at rest), which can be highly disabling in advanced stages of the condition. However, there are symptomatic manifestations other than motor impairment, such as changes in cognition, mood and sensory systems. Animal models that attempt to mimic clinical features of PD have been used to understand the behavioral and neural mechanisms underlying neurophysiological disturbance of this disease. However, most models promote an intense and immediate motor impairment, consistent with advanced stages of the disease, invalidating these studies for the evaluation of its progressive nature. The administration of reserpine (a monoamine depletor) in rodents has been considered an animal model for studying PD. Recently we found that reserpine (in doses lower than those usually employed to produce the motor symptoms) promotes a memory deficit in an aversive discrimination task, without changing the motor activity. It was suggested that the administration of this drug in low doses can be useful for the study of memory deficits found in PD. Corroborating this data, in another study, acute subcutaneous administration of reserpine, while preserving motor function, led to changes in emotional context-related (but not neutral) memory tasks. The goal of this research was to study the cognitive and motor deficits in rats repeatedly treated with low doses of reserpine, as a possible model that simulates the progressive nature of the PD. For this purpose, 5-month-old male Wistar rats were submitted to a repeated treatment with vehicle or different doses of reserpine on alternate days. Cognitive and motor parameters and possible changes in neuronal function were evaluated during treatment. The main findings were: repeated administration of 0.1 mg / kg of reserpine in rats is able to induce the gradual appearance of motor signs compatible with progressive features found in patients with PD; an increase in striatal levels of oxidative stress and changes in the concentrations of glutamate in the striatum were observed five days after the end of treatment; in animals repeatedly-treated with 0. 1 mg/kg, cognitive deficits were observed only after the onset of motor symptoms, but not prior to the onset of these symptoms; 0.2 mg / kg reserpine repeated treatment has jeopardized the cognitive assessment due to the presence of severe motor deficits. Thus, we suggest that the protocol of treatment with reserpine used in this work is a viable alternative for studies of the progressive appearance of parkinsonian signs in rats, especially concerning motor symptoms. As for the cognitive symptoms, we suggest that more studies are needed, possibly using other behavioral models, and / or changing the treatment regimen

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.

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.

The role of vision in Parkinson's disease locomotion control: Free walking task

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

Assistência Odontológica em Crianças com Paralisia Cerebral e Perspectivas Tecnológicas de Reabilitação

The improvement of oral health and quality of life is closely related to transdisciplinary dialogue, technological development and social responsibility. In patients with cerebral palsy, the lesion of motor areas of the brain compromises the development and function of the craniofacial complex. Considering all the ethiopathogenic conditions, the treatment of such patients involves great difficulties. The dentist and other professionals related to their rehabilitation need to deal with difficulty in chewing, respiration, phonation, besides the poor oral hygiene resulted from abnormal involuntary movements of facial and masticatory musculature, tongue, and upper limb. It is also relevant the lack of understanding about the importance of oral health care due to mental deficits of these individuals. This study aims to review some aspects of oral health in patients with cerebral palsy proposing rehabilitation associated to technology. Few studies concerned about the effectiveness of therapies for oral rehabilitation in patients with cerebral palsy. Laser therapy, electromyography, electrostimulation and LED therapy should be analyzed as options for treatment of patients with cerebral palsy. Following research projects should focus more attention on the dynamic and oral function of these patients to achieve positive repercussions in their overall health. © ArquiMed, 2010.

Effects of resistance training on the performance of activities of daily living in patients with Alzheimer's disease

Aim: The objective of this study was to investigate the effects of resistance training in activities of daily living performance in Alzheimer's disease (AD) patients. Methods: An exploratory and longitudinal study, lasting for 16weeks, with the participation of 34 patients divided equally in: the training group (TG), who participated in a resistance training protocol (three sets of 20 repetitions in five exercises); and the social gathering group (SGG), who participated in a social interaction protocol (i.e. group dynamics, writing and reading activities). Results: We observed significant differences between the groups in moving around the house, climbing stairs, standing up from the floor and putting on socks tests. Conclusion: This study showed that resistance training improves agility, lower limb strength, balance and flexibility in AD patients, while SGG protocol is important to improve the agility. © 2012 Japan Geriatrics Society.

Motor intervention in children with school learning difficulties

This study sought to evaluate motor development in children aged 6 to 11 years with learning difficulties and school characteristics of delayed motor development, before and after application of a motor intervention program. The sample consisted of 28 children with a mean age of 107.21 ± 16.56 months, who were evaluated by the Motor Development Scale and received motor intervention for 6 months, followed by reassessment. We observed a statistically significant difference between the average of the motor activity ratios in all areas of the evaluation and reevaluation. Also verified in the evaluation were the concentration ratios of children with motor activity greater than or equal to 80 and there was a revaluation increase in this concentration on re-evaluation, the areas with the greatest increase in concentration and significant differences being: Body Schema, Space and temporal Organization. In the overall evaluation of MDS, most children presented the classification of low normal. However, in the reassessment most have evolved into the average normal, only 4 of themremaining in the same classification. Therefore, in this study, children with learning disabilities also showed motor deficits and the intervention applied contributed to an increase in the motor ratios with consequent improvement in motor development. Besides psychopedagogical asistance, it is essential to reassess them and if necessary apply the intervention in the motor development of children with learning difficulties.

Análise cinemática da oscilação corporal de idosos com doença de Parkinson: efeitos da restrição visual

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

A interferência da tarefa dupla, motora e cognitiva, no andar de pacientes com doença de Parkinson

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Equilíbrio dinâmico em idosos com doença de Parkinson

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Exercício, funcionalidade e distúrbios do sono em pacientes com doença de Parkinson

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeito de dica auditiva na marcha livre e adaptativa em pacientes com doença de Parkinson

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

Desempenho motor de alunos com paralisia cerebral frente à adaptação de recursos pedagógicos

Pós-graduação em Educação - FFC

Análise comportamental e histológica de um modelo animal da doença de Parkinson em camundongos suíços

A Doença de Parkinson (DP) é uma das doenças neurodegenerativas mais comuns relacionadas com a idade, e apresenta sintomatologia com alterações motoras clássicas que estão relacionadas com a degeneração dos neurônios dopaminérgicos da SNpc e a diminuição de dopamina no estriado. Modelos animais da DP são instrumentos importantes utilizados por pesquisadores para uma maior compreensão de mecanismos patológicos envolvidos na doença e para a avaliação de possíveis intervenções terapêuticas. Tais modelos devem mimetizar algum aspecto da doença, como a degeneração dos neurônios dopaminérgicos nigrais. Neste contexto, o modelo da DP induzido pela injeção da neurotoxina 6- hidroxidopamina (6-OHDA) já se encontra bem estabelecido em ratos, mas necessita ainda de melhor caracterização das alterações comportamentais e lesões no sistema nigro-estriatal em camundongos de diferentes linhagens a fim de que haja interpretações confiáveis quando o modelo for usado em testes terapêuticos. O presente estudo teve como objetivo melhorar a caracterização do modelo unilateral da DP com 6-OHDA em camundongos suíços, avaliando alterações comportamentais e o efeito sobre os neurônios dopaminérgicos da SNpc. Nesta investigação utilizou-se uma única injeção intraestriatal unilateral de 6-OHDA, em duas diferentes concentrações da toxina: 5µg/µl e 10µg/µl. Os nossos resultados mostraram que ambas as concentrações utilizadas causaram perda severa de neurônios dopaminérgicos na SNpc, com uma média de 74,5% e 89,5% de per da, respectivamente. Esta perda apresentou uma correlação alta com o comportamento rotatório induzido por apomorfina e uma correlação baixa com a ambulação no teste do campo aberto. Desta forma, injeções intraestriatais de 5µg/µl ou 10µg/µl de 6-OHDA, em camundongos suíços, reproduzem de forma efetiva o modelo animal unilateral da DP com 6-OHDA, podendo ser utilizadas de forma confiável em experimentos que visem a investigação de terapias farmacológicas, celulares e/ou de neuroproteção para a DP.