Intraventricular infusion of hyperosmolar dextran induces hydrocephalus: a novel model of hydrocephalus.

Circulation theory conceives brain as a plastic bag with an inability to get rid of the excess water through the brain tissues. However, the brain is permeable to water due to the presence of aquaporin channels (Agre 2004) and other ion channels.  Aquaporin channels allow water to go through the brain tissues from the ventricles into the bloodstream. The fact that brain is permeable to water makes the brain to be conceived as a tea bag instead of a plastic bag. Tea bag by itself cannot hold any water and the presence of tealeaves are essential to keeping water in the ventricles. Osmotic gradients resulting from large macromolecules such as proteins draw water towards these large macromolecules in water-permeable tissues. This paper demonstrates that infusion of excess macromolecules is sufficient to cause hydrocephalus without any obstruction to the CSF pathways.

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

Osmotic gradients resulting from large macromolecules such as proteins draw water towards these large macromolecules in water-permeable tissues. This paper demonstrates that infusion of macromolecules and increasing osmotic load in the ventricular fluid results in dose-dependent hydrocephalus in acute and chronic experiments in rat model. The data demonstrate increase in the size of the ventricles occurs within half an hour of infusing macromolecules into the ventricles establishing the role of osmotic gradients in the genesis of hydrocephalus.

In other words, more tealeaves in the ventricles mean more hydrocephalus.

Normal macromolecular clearance out of the ventricles is delayed in hydrocephalus.

There is substantial evidence that demonstrates the role of osmotic gradients due to excess macromolecules in the CSF in the development of hydrocephalus Clearance of these excess macromolecules can therefore be expected to relieve hydrocephalus. This paper demonstrates that the infused macromolecules are transported from the ventricles along the paravascular pathways to be eventually cleared into the bloodstream. These infused labeled macromolecules are transported into these paravascular spaces and then taken up by the cells of the blood vessels in the brain. These cells form the blood brain barrier. The labeled macromolecules are then expelled out of the brain in to the blood stream. Macromolecular transport is slow and there is accumulation of macromolecules around the blood vessels in the presence of hydrocephalus compared to normals.

New concepts in the pathogenesis of hydrocephalus.

 Hydrocephalus results in cognitive and physical handicap and can present at any age as a result of a wide variety of different diseases. The pathophysiology of hydrocephalus is unclear. While circulation theory is widely accepted as a hypothesis for the development of hydrocephalus, there is a lack of adequate proof in clinical situations and in experimental settings. Brain disorders that results in excess macromolecules in the ventricular CSF will change the osmotic gradient and result in hydrocephalus.

This review encompasses several key findings that have been noted to be important in the genesis of hydrocephalus, including but not limited to the drainage of CSF through the olfactory pathways and cervical lymphatics, the paravascular pathways and the role of venous system. We propose that as osmotic gradients play an important role in the water transport into the ventricles, the transport of osmotically active macromolecules play a critical role in the genesis of hydrocephalus. Therefore, we can view hydrocephalus as a disorder of macromolecular clearance, rather than circulation.

A proposed role for efflux transporters in the pathogenesis of hydrocephalus.

Efflux transporters, especially p-glycoprotein, located along the blood brain barrier play an important role in clearance of macromolecules (endobiotics and xenobiotics) from the brain to the blood. These efflux transporters can be viewed as vacuum cleaners that pick up these macromolecules and throw them out of the brain into the bloodstream. 

In support of this concept, hydrocephalus occurs in the HTx rat, which has p-glycoprotein missing in the paravascular pathways but is expressed normally in other parts of the brain. P-glycoprotein is a key candidate mechanism, due to its location along pathways of macromolecular clearance, and its broad specificity to a variety of different macromolecules.

This article proposes the existing evidence for the role of efflux transporters in the pathogenesis of hydrocephalus and its relevance to the pathogenesis of hydrocephalus as a macromolecular transport disorder.

Dynamic Disequilibrium of Macromolecular Transport as Possible Mechanism for Hydrocephalus Associated With Long-Term Spaceflight.

 Hydrocephalus associated with long term spaceflight (HALS) for missions lasting over five months is well described but poorly understood. While structural changes of the brain due to microgravitational forces affecting the circulation of cerebrospinal fluid (CSF) have been described as one potential cause, we propose an alternative hypothesis based on dynamic disequilibrium of macromolecular transport across the blood brain barrier. We propose that factors altering physiology under conditions of spaceflight such as microgravity, hypercapnia, venous hypertension, medications, and dietary substances contribute to increased protein load in the ventricles and/or contribute to impairment of transport out of the ventricles that results in HALS. Individual variation in the genetic expression of efflux transporters (p-glycoprotein) has been shown to correlate with the presence and degree of hydrocephalus in animal studies. We describe the evidence behind this concept and propose how these factors can be studied in order to determine the underlying pathogenesis which is imperative in order to cure or prevent HALS 

Noninvasive measurement of cerebrospinal fluid flow using an ultrasonic transit time flow sensor: a preliminary study.

Mechanical failure—which is the primary cause of CSF shunt malfunction—is not readily diagnosed, and the specific reasons for mechanical failure are not easily discerned. Prior attempts to measure CSF flow noninvasively have lacked the ability to either quantitatively or qualitatively obtain data. To address these needs, this preliminary study evaluates an ultrasonic transit time flow sensor in pediatric and adult patients with external ventricular drains (EVDs)

We found that the Transonic flow sensor accurately measures CSF output within ± 15% or ± 2 ml/hr, diagnoses the blockage or lack of flow, and records real-time continuous flow data in patients with EVDs. Calculations of a wide variety of diagnostic parameters can be made from the waveform recordings, including resistance and compliance of the ventricular catheters and the compliance of the brain.

Strategic Placement of Bedside Ventriculostomies Using Ultrasound Image Guidance: Report of three Cases

The blind free-hand technique for external ventricular drain (EVD) placement sometimes requires multiple attempts, and catheter location is often less than ideal. Our institution has adapted an intraoperative ultrasound-guided ventriculostomy technique for the placement of EVDs at the bedside. Our experience with ultrasound at the bedside has proven to be invaluable in certain circumstances. We present three cases of strategic EVD catheter trajectories that were made possible at the bedside with the use of ultrasound.

Ultrasound-guided bedside EVD placement allows EVD trajectories to be customized based on realtime information to accommodate for distorted and dynamic anatomy of the brain and its ventricles.

Bedside External Ventricular Drain Placement: Can Multiple Passes Be Predicted on the Computed Tomography Scan Before the Procedure?

Bedside external ventricular drain (EVD) placement is less than perfect and often requires multiple passes to achieve cerebrospinal fluid flow. We conducted this prospective study to understand why multiple passes are necessary and whether this affects the incidence of hemorrhage.

We compared the number of passes in 47 EVD placement procedures to the incidence of hemorrhage after the procedure. We also analyzed computed tomography scans before the procedure to identify variables that correlate with multiple passes.

There was no statistical relationship between the number of passes and hemorrhage (P > 0.99). Subarachnoid hemorrhage, intraventricular hemorrhage, and midline shift were not found to be statistically significant in relation to the number of passes. The presence of midline shift and rostral hematoma significantly correlated with multiple passes.

Use of Grotenhuis Perforator in Endoscopic Third Ventriculostomy and Cyst Fenestration

We performed a retrospective review of consecutive patients at our institution who underwent endoscopic third ventriculostomy (E3 V) or fenestration of intraventricular cysts using the Grotenhuis endoscopic perforator. The procedure was performed on 23 patients between 2001 and 2006, and included 20 E3Vs and three intraventricular cyst fenestrations. The Grotenhuis perforator was effective in accomplishing a fenestration with multiple attempts. When the floor of the third ventricle was translucent, the perforator was effective with the least amount of effort. The instrument was less effective and additional instruments were necessary in patients with arachnoid cysts or when the floor of the third ventricle was thick. The main advantage in using the Grotenhuis perforator was in displacing the floor of the third ventricle away from the basilar artery during perforation. No basilar artery injury or other serious complications occurred in patients who underwent E3 V or cyst fenestration using the Grotenhuis perforator.

Radiation risk due to shunted hydrocephalus and the role of MR imaging compatible programmable valves

Diagnostic radiology is a double-edged sword: While providing critical information that forms the basis of treatment, it adds to the risk associated with cumulative radiation given to the patient. Shunted hydrocephalus exemplifies this conundrum. Hydrocephalus is a common neurosurgical condition that affects individuals of all ages, and the most common method for managing hydrocephalus is the surgical implantation of a shunt system to divert the flow of CSF from the ventricles. The integrity of the tubing is checked by a series of x-rays of the head, chest, and abdomen; the size of the ventricles is assessed by CT of the head. This need for confirming the suspicion of a shunt malfunction by diagnostic radiology increases the risk for longterm effects of ionizing radiation.

A visit to the emergency department will result in nearly the same amount of radiation that any healthy individual gets from background radiation (estimated at 3 mSv) during a year. Despite this diligence in managing shunt problems, 2 of 3 patients who are investigated are not found to have shunt malfunction. Of the programmable valves used in shunts today, only a few are MR imaging–safe. These MR imaging safe–programmable valves avoid the need for radiation exposure after diagnostic MR imaging.

Evidence-based perioperative protocol for ventriculoperitoneal shunt infection reduction at a single institution.

Ventriculoperitoneal shunt infections are common and result in significant morbidity, mortality, and health care expenditure. The objective of this study was to create an evidence-based perioperative shunt infection prevention protocol and analyze its efficacy by comparing the incidence of shunt infection before and after implementation at one institution.

A perioperative ventriculoperitoneal shunt surgery protocol was developed based on a systematic literature review with the goal of reducing infection rates. Patients undergoing shunt surgery at Upstate Medical University Hospital, from before and after implantation of the perioperative shunt surgery protocol, were retrospectively analyzed and compared.

Although shunt infection rates preprotocol and post-protocol were not significantly different, a trend toward fewer shunt infections was observed with protocol implementation.