RESUMO
Pramipexole is a nonergolinic dopamine agonist, with high affinity for the D2 subfamily of dopamine receptors. Pramipexole is efficacious for the symptomatic treatment of early Parkinson's Disease (PD) and its early use, before that of levodopa can delay the emergence of levodopa-related motor complication. Dosage should be increased gradually from a starting dose of 0.375 mg/day up to a maximum of 4.5 mg/day in equally divided doses taken three times per day with pramipexole immediate-release or equivalent daily dosages once-daily with pramipexole extended-release. Pramipexole can also improve depressive symptoms and possibly health-related quality of life in PD. Nonetheless, its use is not devoid of tolerability problems. While peripheral adverse drug reactions, such as nausea, vomiting or orthostatic hypotension, can be effectively treated and usually pose few problems to most patients, neuropsychiatric events can seriously limit the use of pramipexole in some cases. Indeed, excessive daytime somnolence, impulse-control disorders, hallucinations or delusions can severely affect patients, causing important personal or social handicap. Patients should be informed about the risk of such neuropsychiatric complications and their presence should be actively detected at each consultation. More effort will have to be put into further studying the risk-benefit ratio of pramipexole and other dopamine agonists in the treatment of early PD.
Assuntos
Antiparkinsonianos/uso terapêutico , Benzotiazóis/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Animais , Antiparkinsonianos/farmacocinética , Benzotiazóis/farmacocinética , Ensaios Clínicos como Assunto , Humanos , PramipexolRESUMO
OBJECTIVE: In a previous study we showed that simultaneous electromyographic (EMG) recording of the mentalis, flexor digitorum superficialis and extensor digitorum brevis (SINBAR EMG montage) detected the highest rates of rapid eye movement (REM) sleep phasic EMG activity in subjects with REM sleep behavior disorder (RBD). As a next step, in the present study we evaluated the usefulness of the SINBAR EMG montage to detect the movements and vocalizations occurring in RBD. METHODS: Polysomnographic studies with synchronized audiovisual monitoring of 11 patients with idiopathic RBD were analyzed. Phasic EMG activity in REM sleep was scored and quantified in 3-s mini-epochs while the video was reviewed to detect motor events and vocalizations. RESULTS: A total of 64.8% (11,562 out of 17,848) of all mini-epochs contained phasic EMG activity, whereas 28.8% (5135 out of 17,848) contained movements or vocalizations. Using the SINBAR EMG montage, 94.4% of the mini-epochs containing behavioral events were linked to phasic EMG activity. The sensitivity of the SINBAR EMG montage was 94.4%, specificity was 47.2%, negative predictive value was 95.4% and positive predictive value was 41.9%. Isolated EMG recording of the mentalis did not show phasic EMG activity in 35.5% of the behavioral events seen in the video. CONCLUSIONS: The SINBAR EMG montage is a useful approach for the diagnosis of RBD showing that simultaneous EMG recording of the mentalis, flexor digitorum superficialis and extensor digitorum brevis muscles detected the majority (94.4%) of the motor and vocal manifestations occurring in RBD. For clinical purposes, this means that it is efficient to screen the video when increased phasic EMG activity is seen on the polysomnography.
Assuntos
Eletromiografia/métodos , Movimento/fisiologia , Transtorno do Comportamento do Sono REM/diagnóstico , Transtorno do Comportamento do Sono REM/fisiopatologia , Sono REM/fisiologia , Voz/fisiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/diagnóstico , Transtornos dos Movimentos/fisiopatologia , Músculo Esquelético/fisiologia , Polissonografia , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Gravação de VideoteipeRESUMO
Excessive daytime sleepiness is common in Parkinson's disease and has been associated with Parkinson's disease-related dementia. Narcoleptic features have been observed in Parkinson's disease patients with excessive daytime sleepiness and hypocretin cell loss has been found in the hypothalamus of Parkinson's disease patients, in association with advanced disease. However, studies on cerebrospinal fluid levels of hypocretin-1 (orexin A) in Parkinson's disease have been inconclusive. Reports of sleep studies in Parkinson's disease patients with and without excessive daytime sleepiness have also been disparate, pointing towards a variety of causes underlying excessive daytime sleepiness. In this study, we aimed to measure cerebrospinal fluid hypocretin-1 levels in Parkinson's disease patients with and without dementia and to study their relationship to dementia and clinical excessive daytime sleepiness, as well as to describe potentially related sleep architecture changes. Twenty-one Parkinson's disease patients without dementia and 20 Parkinson's disease patients with dementia, along with 22 control subjects without sleep complaints, were included. Both Epworth sleepiness scale, obtained with the help of the caregivers, and mini-mental state examination were recorded. Lumbar cerebrospinal fluid hypocretin-1 levels were measured in all individuals using a radio-immunoassay technique. Additionally, eight Parkinson's disease patients without dementia and seven Parkinson's disease patients with dementia underwent video-polysomnogram and multiple sleep latencies test. Epworth sleepiness scale scores were higher in Parkinson's disease patients without dementia and Parkinson's disease patients with dementia than controls (P < 0.01) and scores >10 were more frequent in Parkinson's disease patients with dementia than in Parkinson's disease patients without dementia (P = 0.04). Cerebrospinal fluid hypocretin-1 levels were similar among groups (controls = 321.15 +/- 47.15 pg/ml; without dementia = 300.99 +/- 58.68 pg/ml; with dementia = 309.94 +/- 65.95 pg/ml; P = 0.67), and unrelated to either epworth sleepiness scale or mini-mental state examination. Dominant occipital frequency awake was slower in Parkinson's disease patients with dementia than Parkinson's disease patients without dementia (P = 0.05). Presence of slow dominant occipital frequency and/or loss of normal non-rapid eye movement sleep architecture was more frequent among Parkinson's disease patients with dementia (P = 0.029). Thus, excessive daytime sleepiness is more frequent in Parkinson's disease patients with dementia than Parkinson's disease patients without dementia, but lumbar cerebrospinal fluid hypocretin-1 levels are normal and unrelated to severity of sleepiness or the cognitive status. Lumbar cerebrospinal fluid does not accurately reflect the hypocretin cell loss known to occur in the hypothalamus of advanced Parkinson's disease. Alternatively, mechanisms other than hypocretin cells dysfunction may be responsible for excessive daytime sleepiness and the sleep architecture alterations seen in these patients.