A Lumped Parameter Model Suggests That Infusion Studies Overestimate the Cerebrospinal Fluid Outflow Resistance in Normal Pressure Hydrocephalus

Background/objectives: Cerebrospinal infusion studies indicate that cerebrospinal fluid outflow resistance (Rout) is elevated in normal pressure hydrocephalus (NPH). These studies assume that the cerebrospinal formation rate (CSFfr) does not vary during the infusion. If the CSFfr were to increase during the infusion then the Rout would be overestimated. Previous estimates of the CSFfr in NPH have suggested a low figure. More recent estimates of the CSFfr suggest that it is increased, indicating it probably varies with measurement technique. This would bring the estimation of Rout into doubt. A previous paper using a lumped parameter model suggested the CSFfr could vary with the capillary transmural pressure (TMP) in this disease, suggesting a possible solution to this problem. The current study investigates the possibility that the intracranial pressure manipulation occurring during an infusion study may vary the capillary TMP and CSFfr. Methods: A lumped parameter model previously developed to describe the hydrodynamics of NPH was modified to investigate the effect of CSF pressure manipulation during infusion studies and to describe how the CSFfr could vary depending on the technique used. Results: The model indicates the capillary transmural pressure is normal in NPH and increases during an infusion study. CSF drainage at the end of an infusion study similarly increases the capillary TMP and, presumably, the CSFfr by increasing the interstitial fluid production. Conclusions: The model suggests that infusion studies and draining CSF increases the CSFfr in NPH compared to earlier techniques. Allowing for an increase in the CSFfr suggests that infusion overestimates the Rout by between 23 and 33%. This study indicates that further research may be required into the utility and accuracy of infusion studies and their ability to diagnose NPH.