The Pathogenesis of Normal Pressure Hydrocephalus: A Theoretical Analysis

Abstract

Hydrocephalus is an abnormal accumulation of cerebrospinal fluid (CSF) in the cerebral ventricles, usually caused by impaired absorption of the fluid into the bloodstream. Despite obstructed absorption and continued secretion of CSF into the ventricles at a near normal rate, the ventricular CSF pressure (VCSFP) is often normal. We attempt to understand how hydrocephalus can exist with normal VCSFP by exploring the role of the brain parenchyma in absorbing CSF in hydrocephalus. We test three theories: (1) the ventricular wall is impermeable to CSF; (2) ventricular CSF seeps into the parenchyma, from which it is efficiently absorbed; and (3) ventricular CSF seeps into the parenchyma but is absorbed inefficiently. We model the brain as a thick spherical shell consisting of a porous, elastic, solid matrix, containing interstitial fluid and blood. We modify the equations of poroelasticity, which describe flow of fluid through porous solids, to allow for parenchymal absorption. For each of the three theories we calculate the steady state changes in VCSFP and in parenchymal fluid pressure caused by an incremental defect in CSF absorption. We also calculate the-steady state changes in fluid content, tissue volume, tissue displacement, and stresses caused by a small increment of VCSFP. We conclude that only the second theory-seepage of CSF with efficient parenchymal absorption-accounts for the clinical features of normal pressure hydrocephalus. These features include sustained ventricular dilatation despite normal VCSFP, increased periventricular fluid content, and localized periventricular white matter damage.

Neuroendoscopic foraminoplasty for bilateral idiopathic occlusion of foramina of monro

“…It is not clear why such patients of idiopathic hydrocephalus that probably have had this pathology congenitally, may present so late in adulthood. Some adaptational mechanisms, parenchymal absorption, could be suggested as a reason for such a late presentation by attenuation of the severity of hydrocephalus (9). Specifically, CSF absorption in hydrocephalus by a transparenchymal pathway into the cerebral vasculature was reported in a murine model (3).…”

Calculation of intracranial pressure in human brain using Darcy's and Biot's models

“…Similarly to Levine's (1999) work, Darcy's flow through the brain parenchyma is studied considering the brain as a fully saturated medium. The brain geometry is simplified and considered as athick sphere with internal ( R i ¼ 2cm) and external radius ( R e ¼ 8cm).…”

“…This assumptionleads to the spherically symmetric problem where the analytical solution is sought under applied boundary conditions. Levine's (1999) analyticalformulation is further extended to consider the CSF seepage towards the parenchyma through the ventricles. CSF is known to be produced by the choroid plexus at am aximumr ate of 10 2 8 m 3 /s ( c max ); most of it goes to the aqueduct of Sylvius, whereasthe rest flows through the brain parenchymatothe resorption region in the subarachnoid spaces( SAS ;Welch 1963;Levine 1999;Linninger et al 2009).…”

Ventricle Equilibrium Position in Healthy and Normal Pressure Hydrocephalus Brains Using an Analytical Model

“…Hence, the relative pressure between intracranial CSF pressure (ICP) and the venous sinuses instead of the level of venous blood pressure is the prominent factor for ventricle enlargement. There is a delicate balance of Starling forces of hydrostatic and osmotic pressure across the brain capillaries [15,20]. The mentioned components together affect the pathophysiology of ventricular expansion.…”

“…Due to the difficulty in performing experimental studies, interest in analytical and numerical approaches has increased [12][13][14]. Among these approaches, Levine highlighted the role of interstitial fluid (ISF) absorption as a source of compliance in a spherical model of brain [15]. In brief, the numerical and analytical studies that apply or predict a pressure gradient larger than 1 mm Hg do not help answer the NPH unclear mechanism.…”