New Concepts of Cerebrospinal Fluid Physiology and Development of Hydrocephalus

Abstract

The goal of this review is the presentation of the new (Bulat-Klarica-Orešković) hypothesis of cerebrospinal fluid (CSF) physiology and the ensuing new concept of hydrocephalus development in light of this hypothesis. The widely accepted classic hypothesis of CSF physiology and the traditional concept of hydrocephalus are contradicted by numerous experimental and clinical data, which consequently results in unsatisfying clinical treatment and patient recovery. Therefore, the newly presented concept of hydrocephalus development and possible future treatments are discussed. A new definition suggests that hydrocephalus is a pathological state in which CSF is excessively accumulated inside the cranial part of the CSF system, predominantly in one or more brain ventricles as a consequence of impaired hydrodynamics of intracranial fluids between CSF, brain, and blood compartments.

Impaired folate 1-carbon metabolism causes formate-preventable hydrocephalus in glycine decarboxylase–deficient mice

“…Potential mechanisms underlying the development of ventriculomegaly and hydrocephalus could therefore include consequences of FOCM suppression or glycine accumulation in CSF or neural tissues. For example, it is proposed that altered osmolality of CSF (a potential effect of excess glycine) could result in net movement of water into the ventricles, leading to abnormal CSF hydrodynamics (16). Alternatively, FOCM is required for provision of 1-carbon groups for key cellular processes including nucleotide biosynthesis and methylation reactions, whose disturbance could plausibly lead to agenesis is associated with development of both communicating and noncommunicating forms of hydrocephalus in mice, as seen in genetic mutants for Msx1, Pax6, and Rfx3 or overexpression of Sox3 (17,18).…”

Decreased Cerebrospinal Fluid Flow Is Associated With Cognitive Deficit in Elderly Patients

“…The increase of intracranial pressure during the cardiac cycle causes a flow from the blood and brain interstitial fluid to the CSF, and a net CSF flow toward its extracerebral compartment and venous blood (Oreskovic et al, 2017a). Since this CSF flow is important for protein clearance from the brain (Puy et al, 2016), it is possible that impaired CSF flow could be associated with cognitive decline (Coblentz et al, 1973; Sohn et al, 1973; Rubenstein, 1998).…”

Uncertainty quantification of parenchymal tracer distribution using random diffusion and convective velocity fields

“…representing e.g. capillary absorption [53] or direct outflow to lymph nodes [64]. We assume that the parenchymal domain contains no tracer initially: c(0, x, ω) = 0.…”

“…Over the last decade, there has been a significant renewed interest in the waterscape of the brain; that is, the physiological mechanisms governing cerebrospinal fluid (CSF) and interstitial fluid (ISF) flow in (and around) the brain parenchyma. A number of new theories have emerged including the glymphatic system [37,39], the intramural periarterial drainage (IPAD) theory [18,5], and the Bulat-Klarica-Oreskovic hypothesis [53], along with critical evaluations [34,11,68]. A great deal of uncertainty and a number of open questions relating to the roles of diffusion, convection and clearance within the brain parenchyma remain.…”

“…Bedussi et al [15] observed tracers move towards the ventricular system, ultimately leaving the brain via the cribriform plate and the nose. A continuous pathway alongside capillaries to the paravenous space has been suggested [31], and capillaries continuously filtrate and absorb water inside the brain parenchyma [53]. In addition, substances may leave the parenchyma crossing the blood-brain barrier, or possibly directly to lymph nodes [35].…”