Sleep
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To determine whether thalamocortical signaling between the thalamus and the neocortex decreases from wakefulness to nonrapid eye movement (NREM) sleep. ⋯ Results of this study provide evidence of a functional deafferentation of the neocortex during nonrapid eye movement (NREM) sleep in humans. This deafferentation likely accounts for increased sensory awareness thresholds during NREM sleep. Decreased thalamocortical connectivity in regions such as the posterior cingulate/precuneus also are observed in coma and general anesthesia, suggesting that changes in thalamocortical connectivity may act as a universal "control switch" for changes in consciousness that are observed in coma, general anesthesia, and natural sleep.
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Obstructive sleep apnea (OSA) is strongly associated with cardiovascular disease, including stroke and acute coronary syndromes. Plasminogen activator inhibitor-1 (PAI-1), the principal inhibitor of tissue-type plasminogen activator (t-PA), has a pronounced circadian rhythm and is elevated in both OSA and cardiovascular disease and may be an important link between the two conditions. Endothelial dysfunction is one of the underlying pathophysiological mechanisms of cardiovascular disease, and may be altered in OSA. Our primary aim was to compare circadian variability of PAI-1 and t-PA in patients with OSA and normal controls by determining the amplitude (peak level) and mesor (rhythm adjusted mean) of PAI-1 and t-PA in serial blood samples over a 24-h period. The secondary aim was to measure markers of endothelial function (brachial and radial artery flow) in patients with OSA compared with normal controls. ⋯ The presence of obstructive sleep apnea adversely affects circadian fibrinolytic balance with higher mean plasminogen activator inhibitor-1 activity and antigen, and significantly lower mean tissue-type plasminogen activator activity compared with controls. This perturbation may be an important mechanism for increased cardiovascular events in patients with obstructive sleep apnea. Intermittent hypoxia and changes in circadian clock gene activity in obstructive sleep apnea may be responsible for these findings and warrant further study. Favorable changes in fibrinolytic balance may underlie the reduction in cardiovascular events observed with the treatment of obstructive sleep apnea.
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Obstructive sleep apnea (OSA) is a significant public health problem caused by repeated episodes of upper airway closure that occur only during sleep. Attempts to treat OSA pharmacologically have been unsuccessful because there has not been identification of a target operating at cranial motor nuclei, blockade of which can reactivate pharyngeal muscle activity throughout sleep. Increasing potassium conductance is a common mechanism by which state-dependent neuromodulators reduce motoneuron excitability. Therefore, we aimed to determine if potassium channel blockade is an effective strategy to reactivate the pharyngeal musculature throughout sleep. ⋯ These findings establish proof-of-principle that targeted blockade of certain potassium channels at the hypoglossal motor pool is an effective strategy for reversing upper airway hypotonia and causing sustained reactivation of genioglossus throughout nonrapid eye movement and rapid eye movement sleep. These findings identify an important new direction for translational approaches to the pharmacological treatment of obstructive sleep apnea.
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Randomized Controlled Trial Multicenter Study Comparative Study
Pregabalin versus pramipexole: effects on sleep disturbance in restless legs syndrome.
To compare pregabalin versus placebo and pramipexole for reducing restless legs syndrome (RLS)-related sleep disturbance. ⋯ This study demonstrated improvements in objective and subjective measures of sleep maintenance and sleep architecture with pregabalin compared with placebo and pramipexole. Effects of pregabalin on periodic limb movement arousal index were comparable to pramipexole.
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Randomized Controlled Trial
Continuous positive airway pressure improves sleep and daytime sleepiness in patients with Parkinson disease and sleep apnea.
Obstructive sleep apnea (OSA), common in Parkinson disease (PD), contributes to sleep disturbances and daytime sleepiness. We assessed the effect of continuous positive airway pressure (CPAP) on OSA, sleep, and daytime sleepiness in patients with PD. ⋯ Therapeutic continuous positive airway pressure versus placebo was effective in reducing apnea events, improving oxygen saturation, and deepening sleep in patients with Parkinson disease and obstructive sleep apnea. Additionally, arousal index was reduced and effects were maintained at 6 weeks. Finally, 3 weeks of continuous positive airway pressure treatment resulted in reduced daytime sleepiness measured by multiple sleep latency test. These results emphasize the importance of identifying and treating obstructive sleep apnea in patients with Parkinson disease.