Daytime alertness in Parkinson's disease: potentially dose-dependent, divergent effects by drug class.

Many patients with idiopathic Parkinson's disease experience difficulties maintaining daytime alertness. Controversy exists regarding whether this reflects effects of antiparkinsonian medications, the disease itself, or other factors such as nocturnal sleep disturbances. In this study we examined the phenomenon by evaluating medicated and unmedicated Parkinson's patients with objective polysomnographic measurements of nocturnal sleep and daytime alertness. Patients (n = 63) underwent a 48-hour laboratory-based study incorporating 2 consecutive nights of overnight polysomnography and 2 days of Maintenance of Wakefulness Testing. We examined correlates of individual differences in alertness, including demographics, clinical features, nocturnal sleep variables, and class and dosage of anti-Parkinson's medications. Results indicated that, first, relative to unmediated patients, all classes of dopaminergic medications were associated with reduced daytime alertness, and this effect was not mediated by disease duration or disease severity. Second, the results showed that increasing dosages of dopamine agonists were associated with less daytime alertness, whereas higher levels of levodopa were associated with higher levels of alertness. Variables unrelated to the Maintenance of Wakefulness Test defined daytime alertness including age, sex, years with diagnosis, motor impairment score, and most nocturnal sleep variables. Deficits in objectively assessed daytime alertness in Parkinson's disease appear to be a function of both the disease and the medications and their doses used. The apparent divergent dose-dependent effects of drug class in Parkinson's disease are anticipated by basic science studies of the sleep/wake cycle under different pharmacological agents.

Phasic muscle activity in sleep and clinical features of Parkinson disease.

OBJECTIVE: The absence of atonia during rapid eye movement (REM) sleep and dream-enactment behavior (REM sleep behavior disorder [RBD]) are common features of sleep in the alpha-synucleinopathies. This study examined this phenomenon quantitatively, using the phasic electromyographic metric (PEM), in relation to clinical features of idiopathic Parkinson disease (PD). Based on previous studies suggesting that RBD may be prognostic for the development of later parkinsonism, we hypothesized that clinical indicators of disease severity and more rapid progression would be related to PEM. METHODS: A cross-sectional convenience sample of 55 idiopathic PD patients from a movement disorders clinic in a tertiary care medical center underwent overnight polysomnography. PEM, the percentage of 2.5-second intervals containing phasic muscle activity, was quantified separately for REM and non-REM (NREM) sleep from 5 different electrode sites. RESULTS: Higher PEM rates were seen in patients with symmetric disease, as well as in akinetic-rigid versus tremor-predominant patients. Men had higher PEM relative to women. Results occurred in all muscle groups in both REM and NREM sleep. INTERPRETATION: Although our data were cross-sectional, phasic muscle activity during sleep suggests disinhibition of descending motor projections in PD broadly reflective of more advanced and/or progressive disease. Elevated PEM during sleep may represent a functional window into brainstem modulation of spinal cord activity and is broadly consistent with the early pathologic involvement of non-nigral brainstem regions in PD, as described by Braak.

Daytime REM sleep in Parkinson's disease.

BACKGROUND: Previous studies have demonstrated both clinical and neurochemical similarities between Parkinson's disease (PD) and narcolepsy. The intrusion of REM sleep into the daytime remains a cardinal feature of narcolepsy, but the importance of these intrusions in PD remains unclear. In this study we examined REM sleep during daytime Maintenance of Wakefulness Testing (MWT) in PD patients. METHODS: Patients spent 2 consecutive nights and days in the sleep laboratory. During the daytime, we employed a modified MWT procedure in which each daytime nap opportunity (4 per day) was extended to 40 min, regardless of whether the patient was able to sleep or how much the patient slept. We examined each nap opportunity for the presence of REM sleep and time to fall asleep. RESULTS: Eleven of 63 PD patients studied showed 2 or more REM episodes and 10 showed 1 REM episode on their daytime MWTs. Nocturnal sleep characteristics and sleep disorders were unrelated to the presence of daytime REM sleep, however, patients with daytime REM were significantly sleepier during the daytime than those patients without REM. Demographic and clinical variables, including Unified Parkinson's Disease Rating Scale motor scores and levodopa dose equivalents, were unrelated to the presence of REM sleep. CONCLUSIONS: A sizeable proportion of PD patients demonstrated REM sleep and daytime sleep tendency during daytime nap testing. These data confirm similarities in REM intrusions between narcolepsy and PD, perhaps suggesting parallel neurodegenerative conditions of hypocretin deficiency.