Overnight S100B in Parkinson's Disease: A glimpse into sleep-related neuroinflammation.

Calcium-binding protein B (S100B), a primary product of astrocytes, is a proposed marker of Parkinson's Disease (PD) pathophysiology, diagnosis and progression. However, it has also been implicated in sleep disruption, which is very common in PD. To explore the relationship between S100B, disease severity, sleep symptoms and polysomnography (PSG) findings, overnight changes in serum S100B levels were investigated for the first time in PD. 17 fully treated, non-demented, moderately advanced PD patients underwent PSG and clinical assessment of sleep symptoms. Serum S100B samples were collected immediately before and after the PSG. Results are shown as median [interquartile range]. Night and morning S100B levels were similar, but uncorrelated (rs=-0.277, p=0.28). Morning S100B levels, as opposed to night levels, positively correlated with the Unified Parkinson's Disease rating scale (UPDRS) subsections I and II (rs=0.547, p=0.023; rs=0.542, p=0.025). Compared to those with overnight S100B reduction, patients with overnight S100B elevation had higher H&Y scores (2.5 [0.87] vs. 2 [0.25], p=0.035) and worse total Pittsburgh Sleep Quality Index (PSQI) and Parkinson's Disease Sleep Scores (10 [3.2] vs. 8 [4.5], p=0.037; 92.9 [39] vs. 131.4 [28], p=0.034). Correlation between morning S100B levels and total UPDRS score was strengthened after controlling for total PSQI score (rs=0.531, p=0.034; partial rs=0.699, p=0.004, respectively). Overnight S100B variation and morning S100B were associated with PD severity and perceived sleep disruption. S100B is proposed as a putative biomarker for sleep-related neuroinflammation in PD. Noradrenergic-astrocytic dysfunction is hypothesized as a possible mechanism underlying these findings.

Changes in lung volume and upper airway using MRI during application of nasal expiratory positive airway pressure in patients with sleep-disordered breathing.

Nasal expiratory positive airway pressure (nEPAP) delivered with a disposable device (Provent, Ventus Medical) has been shown to improve sleep-disordered breathing (SDB) in some subjects. Possible mechanisms of action are 1) increased functional residual capacity (FRC), producing tracheal traction and reducing upper airway (UA) collapsibility, and 2) passive dilatation of the airway by the expiratory pressure, carrying over into inspiration. Using MRI, we estimated change in FRC and ventilation, as well as UA cross-sectional area (CSA), in awake patients breathing on and off the nEPAP device. Ten patients with SDB underwent nocturnal polysomnography and MRI with and without nEPAP. Simultaneous images of the lung and UA were obtained at 6 images/s. Image sequences were obtained during mouth and nose breathing with and without the nEPAP device. The nEPAP device produced an end-expiratory pressure of 4-17 cmH(2)O. End-tidal Pco(2) rose from 39.7 ± 5.3 to 47.1 ± 6.0 Torr (P < 0.01). Lung volume changes were estimated from sagittal MRI of the right lung. Changes in UA CSA were calculated from transverse MRI at the level of the pharynx above the epiglottis. FRC determined by MRI was well correlated to FRC determined by N(2) washout (r = 0.76, P = 0.03). nEPAP resulted in a consistent increase in FRC (46 ± 29%, P < 0.001) and decrease in ventilation (50 ± 15%, P < 0.001), with no change in respiratory frequency. UA CSA at end expiration showed a trend to increase. During wakefulness, nEPAP caused significant hyperinflation, consistent with an increase in tracheal traction and a decrease in UA collapsibility. Direct imaging effects on the UA were less consistent, but there was a trend to dilatation. Finally, we showed significant hypoventilation and rise in Pco(2) during use of the nEPAP device during wakefulness and sleep. Thus, at least three mechanisms of action have the potential to contribute to the therapeutic effect of nEPAP on SDB.