FundaÃÃo de Amparo à Pesquisa do Estado do Cearà / Pacientes com doenÃa de Parkinson (DP) desenvolvem freqÃentemente flutuaÃÃes motoras com perda de beneficio terapÃutico. A levodopa permanece como agente dopaminÃrgico mais efetivo, entretanto, apÃs alguns anos de tratamento observa-se geralmente flutuaÃÃes motoras e discinesias. A ocorrÃncia destas complicaÃÃes à responsÃvel por incapacidade e constituem desafio terapÃutico. PublicaÃÃes recentes tÃm sugerido que a amantadina, inicialmente prescrita como uma substÃncia com atividade antiviral, poderia reduzir as discinesias em pacientes com DP. A disfunÃÃo orofarÃngea tambÃm à freqÃentemente observada em pacientes com DP e à posteriormente uma causa de aspiraÃÃo silenciosa que conduz a pneumonia e eventualmente morte. Neste estudo, avaliamos o efeito da amantadina nas discinesias e flutuaÃÃes motoras induzidas por levodopa em pacientes com DP. Utilizamos desenho duplo-cego, randomizado e controlado por placebo. Durante o estudo foram randomizados 20 pacientes, tendo 16 completado o protocolo conforme o planejado. No grupo tratado com amantadina, foi observada reduÃÃo da duraÃÃo da discinesia (p=0.037). NÃo foram relatadas, nem observadas reaÃÃes adversas apÃs uso da amantadina. Neste estudo observou-se uma reduÃÃo das dicinesias nos pacientes tratados com amantadina. Foram avaliados 15 pacientes com DP e portadores de discinesia induzida por levodopa, 12 pacientes com DP sem discinesias, e 7 controles. Os pacientes com DP e discinesia apresentaram eficiÃncia de deglutiÃÃo semelhante ao grupo controle. A eficiÃncia da deglutiÃÃo foi significativamente menor no grupo de pacientes com DP sem discinesia do que no grupo controle (p=0,02). EpisÃdios de aspiraÃÃo foram observados em apenas um paciente. De acordo com este estudo, a presenÃa de discinesia nÃo foi associada a piora da funÃÃo orofarÃngea dos pacientes com DP, o que reforÃa o conceito que outros sistemas diferentes do dopaminÃrgico possam estar envolvidos na gÃnese da disfunÃÃo orofarÃngea na DP / Patients presenting with ParkinsonÂs disease (PD) frequently develop motor fluctuations and loss of therapeutic benefit. Levodopa is the most effective dopaminergic agent, however, after some years of treatment motor fluctuations and dyskinesias are commonly observed. These complications are a source of disability and a therapeutic challenge. Previous studies have shown that amantadine, initially prescribed as an anti-viral substance, potentially reduce dyskinesia in PD patients. Oropharyngeal dysfunction are also frequently seen in PD patients. The latter is a cause of unsuspected aspiration leading to pneumonia and eventually death. Presently, we evaluated the effects of amantadine on daytime fluctuations and dyskinesia in PD. We performed a double-blind, randomized, placebo-controlled study. Twenty PD cases were randomized and 16 finished the study. In those treated with amantadine, a reduction of the duration of dyskinesia was observed (P=0,037). In this study, adverse drug reactions were not registered. We conclude that a reduction of dyskinesia was associated with the use of amantadine in PD patients. We have also studied the oropharyngeal function through videofluorocopy. We evaluated 15 patients with PD presenting dyskinesia, 12 cases with PD without dyskinesia and 7 age-matched control. Patients with PD and dyskinesias had oropharyngeal swallowing efficiency similar to control. Patients with PD and without dyskinesia had a significant reduction of oropharyngeal swallowing efficiency in relation to control (P=0,02). Silent aspiration was observed in only one case. According to this study, dyskinesia was not associated with worsening of oropharyngeal function in PD which reinforce the concept that other systems different from dopamine may be involved in the genesis of oropharyngeal dysfunction in PD.

Abstract Parkinson's disease (PD) is known to affect both the extrapyramidal system and the autonomic nervous system even in the early phases of the disease. This study was designed to evaluate cardiovascular autonomic regulation in early PD by measuring heart rate (HR) variability from 24-hour ECG recordings. The dynamics of blood pressure (BP), HR and sweating in patients with and without wearing-off were assessed during clinical observations after a morning dose of levodopa. In patients with wearing-off the tests were repeated after selegiline withdrawal. The power spectral components of HR variability and the SD1 value of the Poincaré analysis that quantifies the short-term beat-to-beat variability were suppressed at night in the PD patients. During the daytime only the SD1 of the Poincaré was suppressed. The results indicate impairment of parasympathetic cardiovascular regulation in untreated patients with PD. The dysfunction was more pronounced at night and in patients with more severe PD. The patients with wearing-off had fluctuation of BP during the observation period, BP increasing when the motor performance worsened and vice versa (p < 0.001). The patients without wearing-off did not show fluctuation of BP. Sweating increased during the observation period, and reached its maximum level at the time of the highest UPDRS motor score phase (off-stage) in patients with wearing-off, but in the patients without wearing-off no changes in sweating were observed. Sweating of the hands was significantly higher in PD patients with motor fluctuations than in those without. Selegiline withdrawal decreased systolic BP significantly during the on-stage in a supine position as well as during the orthostatic test. The initial drop of BP in the orthostatic test was significantly smaller after selegiline withdrawal. The HR and sweating remained unaffected. The results show that the autonomic nervous system is affected in the early phases of PD. The dysfunction becomes more pronounced with the disease progression. Wearing-off type motor fluctuations are associated with fluctuation of BP and sweating and these fluctuations may represent autonomic dysfunction caused by PD, the effect of PD medication, or both. Selegiline withdrawal seems to alleviate the orthostatic reaction in patients with advanced PD.