Intracranial pressure elevation alters CSF clearance pathways

Vegard Vinje,Karen-Helene Støverud,Anders Eklund,Kent-Andre Mardal,Marie E Rognes

doi:10.1186/s12987-020-00189-1

Vegard Vinje, Karen-Helene Støverud + Show 3 more

Open Access

https://doi.org/10.1186/s12987-020-00189-1

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Abstract

BackgroundInfusion testing is a common procedure to determine whether shunting will be beneficial in patients with normal pressure hydrocephalus. The method has a well-developed theoretical foundation and corresponding mathematical models that describe the CSF circulation from the choroid plexus to the arachnoid granulations. Here, we investigate to what extent the proposed glymphatic or paravascular pathway (or similar pathways) modifies the results of the traditional mathematical models.MethodsWe used a compartment model to estimate pressure in the subarachnoid space and the paravascular spaces. For the arachnoid granulations, the cribriform plate and the glymphatic circulation, resistances were calculated and used to estimate pressure and flow before and during an infusion test. Finally, different variations to the model were tested to evaluate the sensitivity of selected parameters.ResultsAt baseline intracranial pressure (ICP), we found a very small paravascular flow directed into the subarachnoid space, while 60% of the fluid left through the arachnoid granulations and 40% left through the cribriform plate. However, during the infusion, 80% of the fluid left through the arachnoid granulations, 20% through the cribriform plate and flow in the PVS was stagnant. Resistance through the glymphatic system was computed to be 2.73 mmHg/(mL/min), considerably lower than other fluid pathways, giving non-realistic ICP during infusion if combined with a lymphatic drainage route.ConclusionsThe relative distribution of CSF flow to different clearance pathways depends on ICP, with the arachnoid granulations as the main contributor to outflow. As such, ICP increase is an important factor that should be addressed when determining the pathways of injected substances in the subarachnoid space. Our results suggest that the glymphatic resistance is too high to allow for pressure driven flow by arterial pulsations and at the same time too small to allow for a direct drainage route from PVS to cervical lymphatics.

Highlights

Infusion testing is a common procedure to determine whether shunting will be beneficial in patients with normal pressure hydrocephalus
Our model extends on previous models [27, 28] of cerebrospinal fluid (CSF) pressure, flow and compliance within the intracranial compartment, by computing paravascular spaces (PVS) pressure and by including additional outflow pathways
According to our models of CSF clearance, outflow predominantly occurred through the arachnoid granulations, both during baseline and plateau intracranial pressure (ICP)

Summary

Introduction

Infusion testing is a common procedure to determine whether shunting will be beneficial in patients with normal pressure hydrocephalus. The method has a well-developed theoretical foundation and corresponding mathematical models that describe the CSF circulation from the choroid plexus to the arachnoid granulations. Infusion testing is a standard procedure to assess whether patients with normal pressure hydrocephalus (a type of dementia) would benefit from shunt surgery. Paravascular spaces (PVS), extensions of the Virchow– Robin spaces, play an active role in a brain-wide CSF circulation in conduits that run in parallel with the vasculature. The purpose of this circulation is to clear solutes from deep inside the brain, taking the role of the lymphatic system within the central nervous system which is absence of lymphatic vessels. The glymphatic pathway enters the extracellular space (ECS) through AQP-4 channels or inter-endfeet gaps, and from there eventually reaches the venous PVS

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