In 2000 I was asked by Dr. David McLone to write a chapter on the classification of hydrocephalus for the fourth edition of Pediatric Neurosurgery: Surgery of the Developing Nervous System
]. I had been working with the School of Engineering at Case Western Reserve University on the application of engineering principles to the study of ventricular volume regulation. This process involved the use of a mathematical model which attempted to predict what would happen to the volume of the ventricles and the pressures within those compartments produced by creating resistance elements in the pathways between the CSF compartments. Previous work on such a model was reviewed and particularly the theoretical discussion by Spertell regarding brain viscoelasticity [9
]. Our multi-compartmental model led to testable hypotheses which could explain what would happen if the sagittal sinus pressure was raised or what would happen if one created a resistance element at the basal cisterns. Figure is a demonstration of the CSF system as interacting compartments each with its own pressure and volume related to the flow of CSF [10
]. Based on this diagram experiments could be performed on animal models of hydrocephalus that would challenge the results of the mathematics from the mathematical model. The diagram led to the need to measure the pressures and volumes in the individual compartments and to attempt to define the resistances between the various compartments. The result of this thought process became a circuit diagram of the CSF pathway as a hydraulic analog of an electrical circuit [12
]. Figure is an artist’s rendering of this circuit diagram analogous to an electrical circuit. Visualizing the flow of CSF in this way serves as a template to assess the possible treatment options that are available to treat an individual patient. What followed has been a 30-year study of hydrocephalus based on this model. It became evident to me that this model would be useful in the classification of hydrocephalus and formed the basis of the book chapter that was produced [13
Multicompartmental model of ventricular volume regulation. Used with permission from Karger (Rekate et al. 1988)
Artist’s concept of circuit diagram of cerebral blood flow and CSF production and flow. Used with permission from Barrow Neurological Institute (Rekate et al. 2008)
Review of the inconsistencies in the criteria that were being used for the selection of patients for endoscopic third ventriculostomy led to the unassailable conclusion that simply classifying hydrocephalus as communicating or non-communicating at a time when the actual point of the obstruction or restriction of CSF flow could be determined in most cases had become inadequate. Other questions that remained to be answered and could not be using the simple classification of Dandy included why some patients who developed hydrocephalus in infancy or had arachnoid cysts treated with shunts in infancy develop severely increased intracranial pressure with no expansion of the ventricles or cyst at the time of shunt failure. A more sophisticated classification was now available but not generally known or accepted. Techniques for the study of CSF dynamics had improved dramatically since the studies of Dandy. Tools such as magnetic resonance imaging (MRI), Cine MRI flow studies, cisternography utilizing dye studies and especially long-term studies of the outcomes of treatment decisions make it possible to accurately define a point of restriction of flow.
I was then invited at the inaugural meeting of the International Society for Hydrocephalus and CSF Research by meeting president Dr. Petra Klinge to give a talk on the subject of the definition and classification of hydrocephalus. In preparation for this talk I wrote an article published in the open access on-line journal Cerebrospinal Fluid Research
entitled “A Contemporary Definition and Classification of Hydrocephalus: A Straw Man to Produce Debate.” At the time of the presentation at the meeting and during the experience in Hannover, I called on the participants to challenge and discuss the classification [13
Following the “roll-out” of the concepts a large number of recognized experts in hydrocephalus treatment and research were contacted, and two meetings were held. The first occurred in Los Angeles at the 40th annual meeting of the International Society for Pediatric Neurosurgery. The second meeting was held in Phoenix in January of 2010. The participants in the process of producing a consensus statement are listed in the addendum at the end of this discussion (“Appendix
”). At the end of these discussions a consensus was reached and agreed to by all. The results of these meetings were presented at the International Hydrocephalus Symposium in Crete in May 2010 and at the International Society for Research in Hydrocephalus and Spina Bifida in June as well as the Hydrocephalus Association Convention in July of that year. There was widespread support for the classification and enthusiasm that it would serve as a platform for research and structure to analyze research using animal models.
The structure of the consensus was that the first level of classification of hydrocephalus would be based on the point where the flow of CSF is restricted. The potential sites of restriction of flow as seen in Fig. would be the foramina of Monro, the aqueduct of Sylvius, the basal cisterns, the arachnoid granulations, and outflow of venous blood from the dural venous sinuses. It was also recognized that hydrocephalus could exist and progress without a point of obstruction or increased resistance to flow. This would truly be communicating hydrocephalus.
The primary classification of point of obstruction would then be modified by the etiology of the inciting condition, the chronicity or rapidity of onset, and the age of the person or experimental animal. It is expected that the point of obstruction will be sought in both experimental animals as well as patients in clinical studies so that likes can be compared.
Exploring the hydraulic circuit using animal models
The collaboration between the Division of Neurosurgery, the department of Systems and Design Engineering and the Electronics Design Center at Case Western Reserve University began with weekly meetings for several hours in which engineering and physiological concepts were discussed and important literature researched. The plan was to develop a mathematical model of ventricular volume regulation and cerebrospinal fluid (CSF) dynamics which would include actually measured parameters such as starting CSF volumes, intracranial pressures (ICP) and rate of CSF production as well as presumed but so far unmeasured parameters such as the resistance elements within the CSF system such as the resistance at the aqueduct of Sylvius. We would then manipulate the model to see what changes would occur in predicted volumes and pressures of the CSF compartments. Initially the expectation was that intracranial pulsation would play a major role in the process, but at that time there was no model available that could be used to add an alternating current (AC) circuit to the model. We decided that we would begin by testing the issues related to the bulk flow model and would move on to the AC or pulse-wave model at a later time.
The model thus created included a fixed volume of the intracranial compartment, a spinal compartment that was outside the fixed volume constraint and six CSF compartments and the brain and spinal cord dealt with as a single entity. It was essential that the research be able to study and lead to the understanding of not only hydrocephalus but also normal pressure hydrocephalus (NPH) and pseudotumor cerebri (PC) [10
Resistance elements within the CSF pathways
The first step in the experimental design here was to actually measure the significance of the proposed resistance elements within the CSF pathways. Utilizing a canine model of hydrocephalus and with normal controls, we instrumented the compartments to measure the pressure differentials across various presumed points of obstruction. We cannulated the lateral ventricles, third ventricle and cisterna magna in both normal and hydrocephalic dogs and infused artificial CSF into one of the lateral ventricles while measuring the pressure in the various components. In these experiments we found that no pressure differential could be measured anywhere in the system. This inability to measure pressure differentials within the intracranial compartment also was found when there was a known point of obstruction in the hydrocephalic animals.
We then implanted a balloon in the cortical subarachnoid space of the dog and applied a wave form to it with multiple ICP transducers intracranially and found that the pulse wave was transmitted undiminished and instantaneously to all transducers intracranially [16
]. While one of the potential explanations is that our transducers which were both strain gauge and fluid-coupled types were not sufficiently sensitive to measure the pressure differentials. They had a sensitivity of plus or minus 1 mmHg. The alternative explanation and the one that is most defensible is that the brain is a viscoelastic substance and in this set of experiments was acting as a fluid chamber where changes in pressure are transmitted instantaneously and fully to all areas.
Measurable pressure differentials were found in only one context. If one of the lateral ventricles is drained to a subatmospheric pressure, a pressure differential of 12 mmHg can be accurately measured [17
]. This condition mirrors the situation of “post-shunt ventricular asymmetry” seen in children who are shunted and have an intact septum pellucidum whose shunted ventricle is uniformly smaller than the contralateral ventricle [18
]. Anatomic studies of the foramen of Monro have shown that this phenomenon is due to the fact that the septum pellucidum is drawn toward the shunted or drained ventricle and comes to rest on the head of the caudate nucleus leading to a functional and reversible obstruction to flow [17
The intracisternal kaolin model utilized in our experiments led to hydrocephalus by obstructing the outflow of CSF from the outlet foramina of the fourth ventricle. The condition was found using ventriculography to be accompanied by, in nearly all animals, syringomyelia as well making this a model of what Oi would call hydromyelic hydrocephalus [20
Obstruction between the spinal and cortical subarachnoid spaces is rarely diagnosed but is probably the cause of many or most cases of NPH [21
]. Older studies utilizing protein labeled with a radioisotope tracer showed that the dye injected into the spinal subarachnoid space in patients quickly entered the ventricles but its clearance into the cortical subarachnoid space was dramatically delayed suggesting a blockage between the SSAS and CSAS. Di Rocco performed autopsies on patients who had responded to shunting for NPH and who died subsequently of other causes. He found dense arachnoidal thickening around the brainstem in the posterior fossa [21
McAllister has studied this extraventricular obstructive hydrocephalus using a rat model of hydrocephalus where the kaolin is injected through the skull base into the lower CSAS. Hydrocephalus in these animals develops quite slowly and is usually mild but does occur [23
Blockage between the SSAS and CSAS results from either subarachnoid hemorrhage or infection. It frequently involves the area around the brainstem selectively, and this form of hydrocephalus has been shown to be amenable to endoscopic third ventriculostomy [24
]. This point of obstruction is also the explanation for the successful management of NPH utilizing endoscopic third ventriculostomy (ETV) [25
Venous hypertension causing hydrocephalus
Increased pressure in the dural venous sinuses that occurs in adults results in PC and not hydrocephalus [26
]. Drainage of CSF into the dural venous sinuses requires a gradient between the ICP and sagittal sinus pressure of 5–7 mmHg [27
]. If the pressure in the sagittal sinus is elevated, the ICP must elevate as well in order for CSF to be absorbed. If the volume of the skull is fixed, the ICP goes up until CSF can be absorbed. If on the other hand the skull is not of a fixed volume, the ICP is in communication with atmospheric pressure. This occurs in the case of small babies and in the case of patients undergoing large craniectomies for stroke or trauma. In this situation the ICP cannot go above the atmospheric pressure, and the patient develops hydrocephalus.
Exploring this phenomenon, Olivero occluded the superior sagittal sinus of normal and craniectomized rabbits. The rabbits whose skull was intact developed intracranial hypertension without ventriculomegaly. The craniectomized rabbits however developed hydrocephalus [29
True communicating hydrocephalus: Hydrocephalus without a point of obstruction
Much of my fascination with the study of the physics of CSF and hydrocephalus was stimulated by the experiments of Di Rocco and colleagues who produced hydrocephalus in experimental animals by implanting a balloon in the ventricle and augmenting the pulse wave. There was no source of obstruction to the flow of CSF in these animals [30
In order to study whether it was possible to produce hydrocephalus in experimental animals without a point of obstruction and without the augmentation of the pulsation, we did prolonged infusions of artificial CSF into normal and hydrocephalic dogs to simulate the overproduction of CSF by choroid plexus papillomas. In these experiments the normal dogs did develop modest ventriculomegaly, but the dogs that had been previously made hydrocephalic with kaolin developed severe ventriculomegaly [33