A Lumped Parameter Modelling Study of Idiopathic Intracranial Hypertension: Does the CSF Formation Rate vary with the Capillary Transmural Pressure?

Abstract

Studies simultaneously measuring the intracranial pressure (ICP) and sagittal sinus pressures in idiopathic intracranial hypertension (IIH), suggest either a reduction in the CSF outflow resistance or the CSF formation rate. A study maintaining the ICP at zero showed a significantly elevated CSF formation rate. The purpose of this study is to define the most feasible explanation for these findings. A lumped parameter model originally developed to study normal pressure hydrocephalus was extended to investigate IIH. The model was used to estimate the CSF formation rate and the capillary transmural pressure (TMP), utilizing the data from 4 experiments published within the literature. When the CSF formation rates of these 4 studies were plotted against the estimated capillary transmural pressures, a straight line with an R2 of 0.999 was returned. The model suggests the CSF formation rate in IIH varies with the capillary TMP. A reduced capillary TMP secondary to a reduced blood flow in IIH moderates the ICP. The variation in formation rate is most likely a function of the blood brain barrier (BBB) breakdown known to occur in this disease. Drugs which stabilize the BBB may trigger IIH.