Psychosis in Parkinson's Disease: Current Treatment Options and Impact on Patients and Caregivers.

Parkinson's disease (PD) is the second most common neurodegenerative disease seen in older adults after Alzheimer's disease, with increasing prevalence worldwide. Parkinson's disease psychosis (PDP) is a common, non-motor feature of PD, which increases caregiver stress and is a risk-factor for nursing home placement. In this paper we review PDP epidemiology, features, diagnosis, and treatment. PDP most often presents with sequential development of minor and then increasingly complex visual hallucinations mediated by dopaminergic-serotonergic interactions activating the mesolimbic pathway, with contributions from other structures and neurotransmitters. Appropriate evaluation of differential diagnoses for psychosis is vital before diagnosing PDP. Initial treatment should involve non-pharmacologic approaches. If these are unsuccessful and PDP symptoms significantly impact the patient's and or their caregivers' quality of life and functions, then pharmacotherapy is indicated. Pimavanserin is a recently FDA-approved pharmacologic treatment for PDP with a better profile of balanced effectiveness and safety compared to previous use of atypical antipsychotics. Early diagnosis and safer, more effective treatments for PDP should help reduce caregiver burden and enable caregivers to continue to provide care at home versus institutionalization.

Positive pressure ventilation compresses pulmonary acinar microvessels but not their supply vessels.

Pulmonary alveolar septal capillaries receive their perfusion from a web of larger surrounding acinar vessels. Using 4 µm diam. Latex particles, we showed that positive pressure ventilation narrowed the acinar vessels as evidenced by venous 4 µm particle concentrations and perfusate flows <50% of particle concentrations in negative pressure ventilated lungs. We aimed to understand the effects of positive and negative pressure ventilation on flows of larger particles through the lung. Isolated, ventilated rat lungs (air, transpulmonary pressures of 15/5 cm H2O, 25 breaths/min) were perfused with a hetastarch solution at Ppulm art/PLA pressures of 10/0 cm H2O. Red latex 7 µm (2.5 mg, 4.8 × 106) or 15 µm (2.5 mg, 5.5 × 105) particles were infused into each lung during positive or negative pressure ventilation. An equal number of green particles was infused 20 min later. Flows through lungs infused with 7 µm and 15 µm particles were not different from flows through lungs infused with 4 µm particles (p = 0.811). Venous particle concentrations of 7 µm particles relative to infused particles were lower in positive pressure lungs (0.03 ±â€¯0.03%) compared to negative pressure lungs (0.17 ±â€¯0.12%) (p = 0.041). Venous particle concentrations of 15 µm particles were not different between positive (2.3 ±â€¯1.9%) and negative (3.3 ±â€¯1.8%) pressure ventilation (p = 0.406). Together with our previous study, we conclude that 4 µm and 7 µm particles both enter acinar vessels but that the 7 µm particles are too large to flow through those vessels. In contrast, we conclude that 15 µm particles bypass the acinar vessels, flowing instead through larger intrapulmonary vessels to enter the venous outflow. These findings suggest that intrapulmonary vessels are organized as a web that allows bypass of the acinar vessels by large particles and, that these bypass vessels are not compressed by positive pressure ventilation.

Negative pressure ventilation enhances acinar perfusion in isolated rat lungs.

We compared acinar perfusion in isolated rat lungs ventilated using positive or negative pressures. The lungs were ventilated with air at transpulmomary pressures of 15/5 cm H2O, at 25 breaths/min, and perfused with a hetastarch solution at Ppulm art/PLA pressures of 10/0 cm H2O. We evaluated overall perfusability from perfusate flows, and from the venous concentrations of 4-µm diameter fluorescent latex particles infused into the pulmonary circulation during perfusion. We measured perfusion distribution from the trapping patterns of those particles within the lung. We infused approximately 9 million red fluorescent particles into each lung, followed 20 min later by an infusion of an equal number of green particles. In positive pressure lungs, 94.7 ± 2.4% of the infused particles remained trapped within the lungs, compared to 86.8 ± 5.6% in negative pressure lungs ( P ≤ 0.05). Perfusate flows averaged 2.5 ± 0.1 mL/min in lungs ventilated with positive pressures, compared to 5.6 ± 01 mL/min in lungs ventilated with negative pressures ( P ≤ 0.05). Particle infusions had little effect on perfusate flows. In confocal images of dried sections of each lung, red and green particles were co-localized in clusters in positive pressure lungs, suggesting that acinar vessels that lacked particles were collapsed by these pressures thereby preventing perfusion through them. Particles were more broadly and uniformly distributed in negative pressure lungs, suggesting that perfusion in these lungs was also more uniformly distributed. Our results suggest that the acinar circulation is organized as a web, and further suggest that portions of this web are collapsed by positive pressure ventilation.

Arterio-venous anastomoses in isolated, perfused rat lungs.

Several studies have suggested that large-diameter (>25 µm) arterio-venous shunt pathways exist in the lungs of rats, dogs, and humans. We investigated the nature of these pathways by infusing specific-diameter fluorescent latex particles (4, 7, 15, 30, or 50 µm) into isolated, ventilated rat lungs perfused at constant pressure. All lungs received the same mass of latex (5 mg), which resulted in infused particle numbers that ranged from 1.7 × 107 4 µm particles to 7.5 × 104 50 µm particles. Particles were infused over 2 min. We used a flow cytometer to count particle appearances in venous effluent samples collected every 0.5 min for 12 min from the start of particle infusion. Cumulative percentages of infused particles that appeared in the samples averaged 3.17 ± 2.46% for 4 µm diameter particles, but ranged from 0.01% to 0.17% for larger particles. Appearances of 4 µm particles followed a rapid upslope beginning at 30 sec followed by a more gradual downslope that lasted for up to 12 min. All other particle diameters also began to appear at 30 sec, but followed highly irregular time courses. Infusion of 7 and 15 µm particles caused transient but significant perfusate flow reductions, while infusion of all other diameters caused insignificant reductions in flow. We conclude that small numbers of bypass vessels exist that can accommodate particle diameters of 7-to-50 µm. We further conclude that our 4 µm particle data are consistent with a well-developed network of serial and parallel perfusion pathways at the acinar level.