Are standing osmotic gradients the main driver of cerebrospinal fluid production? A computational analysis

Background: The mechanisms of cerebrospinal fluid (CSF) production by the ventricular choroid plexus (ChP) have not been fully deciphered. One prominent hypothesized mechanism is trans-epithelial water transport mediated by accumulation of solutes at the luminal ChP membrane that produces local osmotic gradients. However, this standing osmotic gradient hypothesis has not been systematically tested. Methods: To assess the plausibility of the standing gradient mechanism serving as the main driver of CSF production by the ChP, we developed a three-dimensional (3D) and a one-dimensional (1D) computational model to quantitatively describe the associated processes in the rat ChP inter-microvillar spaces and in CSF pools between macroscopic ChP folds (1D only). The computationally expensive 3D model was used to examine the applicability of the 1D model for hypothesis testing. The 1D model was employed to predict the rate of CSF produced by the standing gradient mechanism for 200,000 parameter permutations. Model parameter values for each permutation were chosen by random sampling from distributions derived from published experimental data. Results: Both models predict that the CSF production rate by the standing osmotic gradient mechanism is below 10% of experimentally measured values that reflect the contribution of all actual production mechanisms. The 1D model indicates that increasing the size of CSF pools between ChP folds, where diffusion dominates solute transport, would increase the contribution of the standing gradient mechanism to CSF production. Conclusions: The models suggest that the effect of standing osmotic gradients is too small to contribute substantially to CSF production. ChP motion and movement of CSF in the ventricles, which are not accounted for in the models, would further reduce this effect, making it unlikely that standing osmotic gradients are the main drivers of CSF production

Discordance between physical symptoms versus perception of severity by women with nausea and vomiting in pregnancy (NVP)

BACKGROUND: Nausea and vomiting in pregnancy (NVP) is a multifaceted condition that affects more than half of pregnant women and can range in severity from mild nausea to severe dehydration. Presently physicians evaluate mostly physical symptoms of NVP in trying to assess the severity of the condition. The objective of this study was to investigate how factors, other than the physical morbidity of nausea and vomiting, influence self-perception of NVP by affected women. METHODS: Five hundred women with NVP calling a 1–800 NVP Healthline were asked to rate their NVP severity and report their nausea duration and number of vomiting/retching episodes. RESULTS: Nausea and vomiting/retching correlated significantly but very poorly with self-assessment of NVP severity. There was also a correlation between nausea duration and vomiting/retching frequency however the correlations were weak and overall physical symptoms could only explain 14% of the variability of women's feelings and perceptions through multivariate analysis. CONCLUSIONS: Physical symptoms weakly correlate with self-assessment of NVP severity. Other aspects of this condition, most probably psychosocial, influence women's perception of NVP severity