Abnormal Accumulation Of Cerebrospinal Fluid Research Articles

MT1-MMP deficiency leads to defective ependymal cell maturation, impaired ciliogenesis, and hydrocephalus.

Hydrocephalus is characterized by abnormal accumulation of cerebrospinal fluid (CSF) in the ventricular cavity. The circulation of CSF in brain ventricles is controlled by the coordinated beating of motile cilia at the surface of ependymal cells (ECs). Here, we show that MT1-MMP is highly expressed in olfactory bulb, rostral migratory stream, and the ventricular system. Mice deficient for membrane-type 1-MMP (MT1-MMP) developed typical phenotypes observed in hydrocephalus, such as dome-shaped skulls, dilated ventricles, corpus callosum agenesis, and astrocyte hypertrophy, during the first 2 weeks of postnatal development. MT1-MMP-deficient mice exhibited reduced and disorganized motile cilia with the impaired maturation of ECs, leading to abnormal CSF flow. Consistent with the defects in motile cilia morphogenesis, the expression of promulticiliogenic genes was significantly decreased, with a concomitant hyperactivation of Notch signaling in the walls of lateral ventricles in Mmp14-/- brains. Inhibition of Notch signaling by γ-secretase inhibitor restored ciliogenesis in Mmp14-/- ECs. Taken together, these data suggest that MT1-MMP is required for ciliogenesis and EC maturation through suppression of Notch signaling during early brain development. Our findings indicate that MT1-MMP is critical for early brain development and loss of MT1-MMP activity gives rise to hydrocephalus.

Parameter-robust multiphysics algorithms for Biot model with application in brain edema simulation

In this paper, we develop parameter-robust numerical algorithms for Biot model and apply the algorithms in brain edema simulations. By introducing an intermediate variable, we derive a multiphysics reformulation of the Biot model. Based on the reformulation, the Biot model is viewed as a generalized Stokes subproblem combining with a reaction–diffusion subproblem. Solving the two subproblems together or separately leads to a coupled or a decoupled algorithm. We conduct extensive numerical experiments to show that the two algorithms are robust with respect to the key physical parameters. The algorithms are applied to study the brain swelling caused by abnormal accumulation of cerebrospinal fluid in injured areas. The effects of the key physical parameters on brain swelling are carefully investigated. It is observed that the permeability has the biggest influence on intracranial pressure (ICP) and tissue deformation; the Young’s modulus and the Poisson ratio do not affect the maximum value of ICP too much but have big influence on the tissue deformation and the developing speed of brain swelling.

Systematic analysis and identification of unexpected interactions from the neuroprotein drug interactome in hydrocephalus pharmacological intervention.

Hydrocephalus is a neurological condition caused by an abnormal accumulation of cerebrospinal fluid; pharmacological intervention of the disease has been found to elicit a variety of adverse drug reactions (ADRs) in central nervous system (CNS) by unexpectedly targeting certain functional neuroproteins. Here, a systematic neuroprotein drug interactome (SNDI) is created for 11 hydrocephalus drugs/metabolites plus 20 control drugs across 518 druggable pockets on the surface of 472 CNS neuroproteins via a large-scale molecular docking approach. Heuristic clustering analysis of the SNDI profile divides the 31 investigated drug ligands into a distinct panel and a background panel; the former consists of two hydrocephalus drugs (Furosemide and Triamterene) and their respective metabolites (Furosemide glucuronide and Hydroxytriamterene) that are inferred to have generally high affinity towards the whole array of neuroprotein pockets. A total of 13 neuroproteins are enriched in gene ontology semantic mining as putative unexpected targets of the distinct panel, and their intermolecular interactions with hydrocephalus drugs/metabolites are investigated in detail using dynamics simulation and energetics analysis. We also perform kinase assay and viability test to substantiate the interactome analysis. It is found that the Furosemide and Triamterene have significant cytotoxic effects on normal human astrocytes, in which the Triamterene can inhibit the neurokinase ROCK2, a representative of putative unexpected targets, with a high activity, which is comparable with the sophisticated ROCK2 inhibitor Fasudil.

Congenital Hydrocephalus in Arar, Northern Saudi Arabia

Background: Congenital hydrocephalus, an important cause of neurologic morbidity and mortality in children, is a medical condition characterized by an abnormal accumulation of cerebrospinal fluid in the brain. Objectives: To estimate the prevalence and the recent progresses in diagnosis of hydrocephalus as well as the changes in epidemiology and treatment outcomes of the disease. Methods: This is a descriptive study involved all neonates born in Maternity and child hospital in Arar city, Northern Saudi Arabia, KSA, during the period from 1 January to 31 December 2017. Among 6000 delivered infant in 2017; there was 23 cases of hydrocephalus. Data was collected by using predesigned questionnaire which include questions designed to fulfill the study objectives. Results: the prevalence of hydrocephalus among studied infants was 0.38%. Consanguinity between parents was reported among 60.9% of the cases. Other congenital anomalies reported, cardiac anomalies 39.1%, spina bifida 17.4% and cleft palate 8.7%. Cause of hydrocephalus was 65.2% hereditary and 34.8% infection (secondary cause). Swelling of the eyelid, increased vascular clarity on the skull, transparent skin in the head, the child's tendency to sleep, disorientation, irritability and nervousness, high crying, weakness of feeding and vomiting, delayed child skills, convulsions, increased size of the head, the sun's sign in the eye and the child is always looking down were the symptoms reported by the cases. 56.5% of the cases had shunt insertion and 43.4% had ordinary medical treatment. 30.4% of the shunt cases were complicated (17.4% had shunt blockage with infection and fever, 13% shunt blockage and 69.6% had other complications). Outcome of the case; 39.1% were stable, 13% worsen and 47.8% died (34.7% died by complications, 8.7% during operation and 4.3% did not receive treatment). Conclusion: The prevalence of hydrocephalus is comparable to that of other countries. More research is recommended because it is probable that the real prevalence of congenital hydrocephalus was underestimated and no account of how often abortions are performed among mothers of hydrocephalic fetuses. So more efforts from the ministry of health is needed.

A mutation in Ccdc39 causes neonatal hydrocephalus with abnormal motile cilia development in mice.

Pediatric hydrocephalus is characterized by an abnormal accumulation of cerebrospinal fluid (CSF) and is one of the most common congenital brain abnormalities. However, little is known about the molecular and cellular mechanisms regulating CSF flow in the developing brain. Through whole-genome sequencing analysis, we report that a homozygous splice site mutation in coiled-coil domain containing 39 (Ccdc39) is responsible for early postnatal hydrocephalus in the progressive hydrocephalus (prh) mouse mutant. Ccdc39 is selectively expressed in embryonic choroid plexus and ependymal cells on the medial wall of the forebrain ventricle, and the protein is localized to the axoneme of motile cilia. The Ccdc39prh/prh ependymal cells develop shorter cilia with disorganized microtubules lacking the axonemal inner arm dynein. Using high-speed video microscopy, we show that an orchestrated ependymal ciliary beating pattern controls unidirectional CSF flow on the ventricular surface, which generates bulk CSF flow in the developing brain. Collectively, our data provide the first evidence for involvement of Ccdc39 in hydrocephalus and suggest that the proper development of medial wall ependymal cilia is crucial for normal mouse brain development.

Learning Based Segmentation of CT Brain Images: Application to Postoperative Hydrocephalic Scans.

Hydrocephalus is a medical condition in which there is an abnormal accumulation of cerebrospinal fluid (CSF) in the brain. Segmentation of brain imagery into brain tissue and CSF [before and after surgery, i.e., preoperative (pre-op) versus postoperative (post-op)] plays a crucial role in evaluating surgical treatment. Segmentation of pre-op images is often a relatively straightforward problem and has been well researched. However, segmenting post-op computational tomographic (CT) scans becomes more challenging due to distorted anatomy and subdural hematoma collections pressing on the brain. Most intensity- and feature-based segmentation methods fail to separate subdurals from brain and CSF as subdural geometry varies greatly across different patients and their intensity varies with time. We combat this problem by a learning approach that treats segmentation as supervised classification at the pixel level, i.e., a training set of CT scans with labeled pixel identities is employed. Our contributions include: 1) a dictionary learning framework that learns class (segment) specific dictionaries that can efficiently represent test samples from the same class while poorly represent corresponding samples from other classes; 2) quantification of associated computation and memory footprint; and 3) a customized training and test procedure for segmenting post-op hydrocephalic CT images. Experiments performed on infant CT brain images acquired from the CURE Children's Hospital of Uganda reveal the success of our method against the state-of-the-art alternatives. We also demonstrate that the proposed algorithm is computationally less burdensome and exhibits a graceful degradation against a number of training samples, enhancing its deployment potential.

Influence of the hole geometry on the flow distribution in ventricular catheters for hydrocephalus.

Background Hydrocephalus is a medical condition consisting of an abnormal accumulation of cerebrospinal fluid within the brain. A catheter is inserted in one of the brain ventricles and then connected to an external valve to drain the excess of cerebrospinal fluid. The main drawback of this technique is that, over time, the ventricular catheter ends up getting blocked by the cells and macromolecules present in the cerebrospinal fluid. A crucial factor influencing this obstruction is a non-uniform flow pattern through the catheter, since it facilitates adhesion of suspended particles to the walls. In this paper we focus on the effects that tilted holes as well as conical holes have on the flow distribution and shear stress.Methods We have carried out 3D computational simulations to study the effect of the hole geometry on the cerebrospinal fluid flow through ventricular catheters. All the simulations were done with the OpenFOAM® toolbox. In particular, three different groups of models were investigated by varying (i) the tilt angles of the holes, (ii) the inner and outer diameters of the holes, and (iii) the distances between the so-called hole segments.ResultsThe replacement of cylindrical holes by conical holes was found to have a strong influence on the flow distribution and to lower slightly the shear stress. Tilted holes did not involve flow distribution changes when the hole segments are sufficiently separated, but the mean shear stress was certainly reduced.ConclusionsThe authors present new results about the behavior of the fluid flow through ventricular catheters. These results complete earlier work on this topic by adding the influence of the hole geometry. The overall objective pursued by this research is to provide guidelines to improve existing commercially available ventricular catheters.

Investigating cerebral oedema using poroelasticity

Cerebral oedema can be classified as the tangible swelling produced by expansion of the interstitial fluid volume. Hydrocephalus can be succinctly described as the abnormal accumulation of cerebrospinal fluid (CSF) within the brain which ultimately leads to oedema within specific sites of parenchymal tissue. Using hydrocephalus as a test bed, one is able to account for the necessary mechanisms involved in the interaction between oedema formation and cerebral fluid production, transport and drainage. The current state of knowledge about integrative cerebral dynamics and transport phenomena indicates that poroelastic theory may provide a suitable framework to better understand various diseases. In this work, Multiple-Network Poroelastic Theory (MPET) is used to develop a novel spatio-temporal model of fluid regulation and tissue displacement within the various scales of the cerebral environment. The model is applied through two formats, a one-dimensional finite difference – Computational Fluid Dynamics (CFD) coupling framework, as well as a two-dimensional Finite Element Method (FEM) formulation. These are used to investigate the role of endoscopic fourth ventriculostomy in alleviating oedema formation due to fourth ventricle outlet obstruction (1D coupled model) in addition to observing the capability of the FEM template in capturing important characteristics allied to oedema formation, like for instance in the periventricular region (2D model).

VP-shunt dysfunction caused by malaria CNS infection

Malaria is a widespread mosquito-borne infectious disease with over 300 million cases and roughly 900 thousand deaths in 2013. Cerebral involvement of malaria causes 50 % of all infection-associated deaths, especially in children below the age of 5 years. Hydrocephalus is a medical condition with abnormal accumulation of cerebrospinal fluid in physiological cavities and ventricles. Standard treatment is the implantation of a cerebrospinal fluid shunt device. A common problem associated with shunt treatment especially in pediatric patients is infection and consecutive shunt dysfunction caused by bacteriae or high protein levels clogging the valve. In these cases, Staphylococcus aureus and Staphylococcus epidermidis are predominantly found in CSF cultures. We present a case of a 2-year old boy from Saudi Arabia with a ventriculoperitoneal (VP)-shunt-dependent congenital hydrocephalus who suffered from cerebral malaria and developed consecutive shunt failure. To the best of our knowledge, shunt failure caused by malaria CNS infection with Plasmodium falciparum has not yet been reported in the literature and should be considered as a rare cause of VP-shunt failure in patients with atypical VP-shunt infections living in or traveling from endemic areas.

A Medical Perspective Regarding the Use of Biomaterials for the Treatment of Hydrocephalus in Children

Hydrocephalus is a medical condition consisting of an abnormal accumulation of cerebrospinal fluid in the ventricles of the brain. This may cause increased intracranial pressure, progressive enlargement of the head, followed by ischemia, convulsions, tunnel vision, and mental disability and even death. This affection usually appears due to the blockage of cerebrospinal fluid (CSF) flow in the ventricles or in the subarachnoid space surrounding the brain. In a person without hydrocephalus, CSF continuously circulates through and around the brain, its ventricles and the spinal cord and is continuously drained away into the circulatory system. Alternatively, the condition may result from an overproduction of the CSF, from a congenital malformation blocking normal drainage of the fluid, or from complications of head injuries or infections.In the treatment of hydrocephalus, the implementation of perfectly tolerable materials enables surgeons to carry out a progressive drainage of excess cerebrospinal fluid towards other cavities of the body. By today’s standards silicone based biomaterials are the sum of all progress in biomaterial science, immunology and pathology. Lack of an immune signature, chemical and biological stability, perfect adhesion resistance and many more ultrastructure-related features come as perfect proof for the impact material science has on medicine. Future biomaterials, coated with antibiotics or antibodies are now closer than ever to be implemented in medicine.

Neglected case of hydrocephalus in a five-year-old child

Introduction: Hydrocephalus is abnormal accumulation of cerebrospinal fluid (csF) in the ventricles of the brain. It is of two types: congenital and acquired. case report: A child, five-year-old, presented to the emergency department with a severe neglected hydrocephalus which was not the complaint of the parents. conclusion: Neglected hydrocephalus will leave an irreversible brain damage to the child. the best way to avoid that negligence is to spread health education in all areas with special focus in rural regions.

Assessment of hydrocephalus in children based on digital image processing and analysis

Abstract Hydrocephalus is a pathological condition of the central nervous system which often affects neonates and young children. It manifests itself as an abnormal accumulation of cerebrospinal fluid within the ventricular system of the brain with its subsequent progression. One of the most important diagnostic methods of identifying hydrocephalus is Computer Tomography (CT). The enlarged ventricular system is clearly visible on CT scans. However, the assessment of the disease progress usually relies on the radiologist’s judgment and manual measurements, which are subjective, cumbersome and have limited accuracy. Therefore, this paper regards the problem of semi-automatic assessment of hydrocephalus using image processing and analysis algorithms. In particular, automated determination of popular indices of the disease progress is considered. Algorithms for the detection, semi-automatic segmentation and numerical description of the lesion are proposed. Specifically, the disease progress is determined using shape analysis algorithms. Numerical results provided by the introduced methods are presented and compared with those calculated manually by a radiologist and a trained operator. The comparison proves the correctness of the introduced approach.

Prevalence of congenital hydrocephalus in the Hashemite kingdom of Jordan: A hospital-based study

Background: Congenital hydrocephalus, an important cause of neurologic morbidity and mortality in children, is a medical condition characterized by an abnormal accumulation of cerebrospinal fluid in the brain. It can be caused by abnormal brain development, obstruction of the cerebral aqueduct flow, Chiari malformations, and Dandy-Walker malformation. The prevalence of congenital hydrocephalus is 2.2 to 18 per 10,000 live births. Objectives: To determine the prevalence of congenital hydrocephalus among livebirths in the Hashemite Kingdom of Jordan (HKJ). Methods: Clinical data were collected from medical records of all livebirths with congenital hydrocephalus born at Al Bashir Hospital, Amman/The Hashemite Kingdom of Jordan in 2004-2005 and 2008-2011. Descriptive analysis was carried out using the Statistical Package for the Social Science (SPSS 20). Results: The prevalence of hydrocephalus was 0.092% with a relative predominance among males. Conclusion: The study concluded that the prevalence of congenital hydrocephalus is comparable to that of developed countries. The efforts made by the Ministry of Health seem to have paid off. More research on stillbirths is recommended.

Increased CSF osmolarity reversibly induces hydrocephalus in the normal rat brain.

BackgroundHydrocephalus is a central nervous system (CNS) disorder characterized by the abnormal accumulation of cerebrospinal fluid (CSF) in cerebral ventricles, resulting in their dilatation and associated brain tissue injury. The pathogenesis of hydrocephalus remains unclear; however, recent reports suggest the possible involvement of abnormal osmotic gradients. Here we explore the kinetics associated with manipulating CSF osmolarity on ventricle volume (VV) in the normal rat brain.MethodsCSF was made hyper-osmotic by introducing 10KD dextran into the lateral ventricle, either by acute injection at different concentrations or by chronic infusion at a single concentration. The induction and withdrawal kinetics of dextran infusion on VV were explored in both contexts.ResultsAcute intraventricular injection of dextran caused a rapid increase in VV which completely reversed within 24 hours. These kinetics are seemingly independent of CSF osmolarity across a range spanning an order of magnitude; however, the magnitude of the transient increase in VV was proportional to CSF osmolarity. By contrast, continuous intraventricular infusion of dextran at a relatively low concentration caused a more gradual increase in VV which was very slow to reverse when infusion was suspended after five days.ConclusionWe conclude that hyperosmolar CSF is sufficient to produce a proportional degree of hydrocephalus in the normal rat brain, and that this phenomenon exhibits hysteresis if CSF hyperosmolarity is persistent. Thus pathologically-induced increases in CSF osmolarity may be similarly associated with certain forms of clinical hydrocephalus. An improved understanding of this phenomenon and its kinetics may facilitate the development of novel therapies for the treatment of clinical hydrocephalus.

The Extracellular Space in the Edematous Human Cerebral Cortex: An Electron Microscopic Study Using Cortical Biopsies

In a vascular anomaly showing moderate edema, the extracellular space appeared apparently normal, exhibiting a membrane to membrane space of about 20 nm in width. In congenital hydrocephalus, this space appeared notably enlarged and occupied by an electron transparent, nonproteinaceous interstitial edema fluid, due to abnormal accumulation of cerebrospinal fluid. In brain trauma, the distended extracellular space contained either electron-lucid nonproteinaceous or electron-dense proteinaceous edema fluid. Hemorrhagic foci, fibrinoid material, and non-nervous invading cells, such as macrophages and monocytes, were also found. In brain tumors, the widened extracellular space showed electron-dense proteinaceous edema fluid and bundles of fibrinoid material. The enlarged extracellular space found in congenital hydrocephalus, vascular anomalies, brain trauma, and tumors is closely related to the clinical symptoms exhibited by the patients under study.

A novel microdevice for the treatment of hydrocephalus: design and fabrication of an array of microvalves and microneedles

We present an implantable, microfabricated device for the treatment of hydrocephalus. Hydrocephalus is a medical condition, in which an abnormal accumulation of cerebrospinal fluid (CSF, a water-like fluid that circulates around and protects the brain and spinal cord.) occurs in the brain. The novel microdevice presented here mimics the function of natural one-way valves, arachnoid villi, found in the human brain. Hence, we name it microfabricated arachnoid villi (MAV). The MAV consists of an array of one-way microvalves and hollow microneedles. The one-way microvalves control flow based on pressure differential. A Parylene microvalve array with a dome petal geometry was designed and fabricated. Initial flow tests demonstrated the desired low cracking pressure of the valve and a sufficient mechanical stability. The hollow microneedle array was designed to pierce the dura mater membrane (A tough fibrous membrane covering the brain and the spinal cord and lining the inner surface of the skull.) and provide a conduit for CSF. An SU-8 microneedle array was designed and successfully microfabricated. The innovative MAV may open a new era in the treatment of hydrocephalus.

High-pressure hydrocephalus: A novel analytical modeling approach

Hydrocephalus is an abnormal accumulation of cerebrospinal fluid (CSF) within ventricles and subarachnoid space (SAS) as a result of disturbances in secretion or absorption procedures. It is believed that arachnoid villi cells, which are microscopic projections of pia-arachnoid mater that extend into venous channels in sagittal sinus, are the main sites for CSF absorption, but it is tempting to speculate that a significant portion of CSF is removed from the SAS by nasal lymphatic vessels around olfactory nerve. Thus, in this paper, we propose an analytical model of CSF–lymphatic-blood circulation, in which these two output pathways for CSF absorption have been considered. Mathematical relations governing the pressures in different interacting compartments of the brain are considered. In addition, for increasing the similarity of our model to the physiological conditions, the bulk flow mechanism, which is supposed to occur during CSF absorption, has been considered in our model. We used our model to simulate hydrocephalus. The results indicate that the lymphatic disorders have more considerable effect in decreasing CSF absorption, compared to the disturbances in arachnoid villi cells. Based on our modeling, we believe that disorders in lymphatic pathway may be a cause of high-pressure hydrocephalus. Surely experimental studies are required to validate our hypothesis.

Eye Movement Disorders in Hydrocephalus and Increased Intracranial Pressure

Hydrocephalus is an abnormal accumulation of cerebrospinal fluid that causes enlargement of cerebral ventricles and increased intracranial pressure. Hydrocephalus and increased intracranial pressure are associated with many neurologic disorders in children and adults. There are numerous ocular findings described in patients with increased intracranial pressure. The purpose of this paper is to discuss several eye movement disorders associated with hydrocephalus and increased intracranial pressure.

PEDIATRIC NEUROANESTHESIA: Hydrocephalus

Hydrocephalus, one of the most common adult and pediatric neurosurgical disorders, is an abnormal accumulation of cerebrospinal fluid in the ventricular system as a result of obstruction to the flow of cerebrospinal fluid. Causes of hydrocephalus include congenital obstruction, hemorrhage, infection, cysts and tumors, and associated neural tube deformities (i.e., myelomeningocele, Arnold-Chiari malformation). Treatment of hydrocephalus involves surgical implantation of shunt systems to drain the cerebrospinal fluid. Anesthetic considerations involve attention to the possibility of increased intracranial pressure and prevention of aspiration through rapid-sequence intravenous induction and modest hyperventilation until the ventricles have been decompressed.

The Pathogenesis of Normal Pressure Hydrocephalus: A Theoretical Analysis

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.