Recent advances in the understanding and treatment of hydrocephalus

Recent Advances in the Understanding and Treatment of Hydrocephalus Harold L. Rekate Advances in the management of patients with hydrocephalus and other abnormalities of cerebrospinal fluid dynamics and intracranial pressure have come from a variety of sources including an improved understanding of the pathophysiology of the various subtypes of the problem, development of alternative methods of treating the condition without reliance on implantable shunting devices, use of neuroendoscopy, and the development of newer types of shunt valves. The purpose of this review is t o put into perspective the relative importance of each of these advances to the overall management of our patients.

Copyright 9 1997 by W.B. Saunders Company

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ATHOLOGISTS were studying hydrocephalus at postmortem before the twentieth century, 1,2 but the study of the pathophysiology of the hydrocephalic process began in earnest in this century with the pioneering work of Walter Dandy and his coworkers at Johns Hopkins University. 3 They discovered that the choroid plexus was the source of the production of cerebrospinal fluid (CSF), described the anatomy of the CSF pathways, and classified the types of hydrocephalus as communicating and noncommunicating (obstructive) by the injection of supravital dyes into some portion of the CSF pathways and attempted recovery from other areas. 4 Much of Dandy's work has subsequently been revised. 4,5 For instance, we now know that 20% to 50% of CSF is actually made up of brain extracellular fluid created as a by-product of cerebral metabolism. 6 Concomitant with these studies, Dandy made significant attempts to treat the hydrocephalic condition using techniques that were suggested by the laboratory experiments. Extirpation of the choroid plexuses of the lateral ventricle performed via open craniotomy was advocated as early as 1918. 7 Over the subsequent decades, many procedures were performed to treat hydrocephalus, however, responses were sporadic and often short-lived. For an excellent review of the history of the treatment of hydrocephalus, the reader is directed to the article by Pudenz. 8 It was the development of the valveregulated shunt at the beginning of the second half of the twentieth century that resulted in the expectation that children born with hydrocephalus could have effective treatment and had the possibility of living productive lives) At the time of the development of the valveregulated shunt, diagnostic studies to evaluate the presence or absence of hydrocephalus, its severity, and its anatomic basis were both primitive and, in many cases, invasive and dangerous. Physical

examination, plain skull radiographs showing marked splaying of the sutures, and transillumination of the infant's skull were the mainstays of making the original diagnosis. At that point, the diagnosis of hydrocephalus carried with it at least a 50% mortality with half of the remaining patients being profoundly retarded.~~ There was little enthusiasm for proceeding to more invasive studies. Cerebral angiograms enabled the physician to identify the size of the lateral ventricles, the presence or absence of subdural blood or fluid, and occasionally, the actual cause of the hydrocephalus if it was due to a mass lesion. Ventriculography using air or, in some cases, positive contrast agents was used when the actual anatomy of the CSF pathways needed to be defined. Because the valve regulated shunt gave the promise of successful treatment of hydrocephalus and there were essentially no other forms of treatment available, animal models were not developed and randomized trials were not performed. 9 Owing to the invasiveness of the needed diagnostic studies, mild and moderate degrees of hydrocephalus often went unrecognized. Centers in which large numbers of patients were treated and consistent attempts made to follow and document the results of treatment were established and succeeded or failed based on the enthusiasm of the neurosurgeon involved. These centers became "living laboratories" where individual experiences led to the constant changes in our understanding of the process itself and its treatment. This consolidation of From the Department of Pediatric Neurosurgery, Barrow Neurologic Institute, Mercy Healthcare Arizona, Phoenix; and the Department of Neurosurgery, University of Arizona School of Medicine, Tucson, A Z Address reprint requests to Harold L. Rekate, MD, Barrow Neurologic Institute, 2910 N. Third Ave, Phoenix, AZ 85013. Copyright 9 1997 by W.B. Saunders Company 1071-9091/97/0403-000355.00/0

Seminars in Pediatric Neurology, Vol 4, No 3 (September), 1997: pp 167-178

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the care of children with shunts became the inciting event for the development of the subspecialty of pediatric neurosurgery. The need for those who were actively pursuing improvements in the care of children with hydrocephalus led to a national conference and a monograph derived from the discussions of a majority of the neurosurgeons involved in the treatment of hydrocephalus in a systematic way. The ideas expressed in the monograph, Workshop in Hydrocephalus edited by Dr. Kenneth Shulman, defined the problems that new forms of therapy in previously hopeless situations may create, u These problems have been the source of much debate and somewhat less scientific study. The monograph represented the state of knowledge regarding hydrocephalus from the time of its publication in 1965 until the development of modern neurodiagnostic testing with the installation of the first computerized axial tomographic (CAT) scan in the United States in 1973. The need to have a forum for neurosiargeons actively involved in hydrocephalus treatment culminated with the establishment of the Section of Pediatric Neurological Surgery of the American Association of Neurological Surgeons in 1972 as the first subspecialty group within American neurosurgery. There have been many advances in the treatment of hydrocephalus in the last quarter century in terms of advanced imaging techniques, basic science research into pathophysiologic mechanisms, the development of new technologies, and most recently the submission of our individual prejudices to the rigors of randomized prospective trials. It is the author's intention to describe the importance of these new advances to the management of hydrocephalus and therefore the lives of our patients and point out the areas where further study is needed. UNDERSTANDING OF PATHOPHYSIOLOGY For the most part and in most situations it is accepted that hydrocephalus is understandable as a

physical phenomenon analogous to the creation of a dam or the filling of a water balloon. CSF is produced within the ventricles of the brain by two processes. The first method of formation, as described above, is CSF production by an energyrequiting process by the choroid plexuses within the ventricles of the brain. CSF produced in this manner differs chemically from the serum from which it is derived.12 The second method of formation of CSF is the production of brain extracellular

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fluid (ECF) within the parenchyma of the brain and spinal cord. The process is a by-product of cerebral and spinal cord metabolism and requires no added energy of its own. 6 The chemical content of brain ECF is identical to that of CSF, and ECF is removed from the brain by bulk flow into the CSF and thence to the cortical subarachnoid space where it is absorbed into the venous sinuses. Unless perturbed by the use of certain drugs that have been shown to decrease CSF production, the rate of CSF production remains constant at about 0.3 mL/min or 400 to 450 mL/day in the older child and the adult. It should also be noted that CSF is also produced by the spinal cord ECF and travels through the central c~/nal rostrally to exit into the fourth ventricle by bulk flow where it mixes with the CSF produced intracranially. Milhorat 13 has produced hydromyelia in experimental animals by placing a constricting band around the upper portion of the spinal cord. This experiment confirms that at least in some situations the source of the CSF distending the spinal cord in hydromyelia is produced within the spinal cord itself.13 CSF produced within the ventricular system passes through a series of channels and pathways until it finally reaches the cortical subarachnoid space where it is absorbed into the sagittal sinus primarily through specialized organs at the interface between the subarachnoid space and the venous sinuses called arachnoid villi. McComb and Hyman 14 have shown that the process of CSF absorption is passive and not energy dependent. The pressure differential between the cortical subarachnoid space and the sagittal sinus is about 5 torr mm Hg). The arachnoid villi are acting as a differential pressure valve with an opening pressure of 5 mm Hg between the cortical subarachnoid space and the sagittal sinus. 15,16The inlet and outlet fluids anatomically retain the same relationship to each other regardless of position. Therefore, the natural valve is a ventriculo-sagittal sinus shunt with a medium pressure "slit" valve (closing pressure 60 to 90 turn H20), which does not have a tendency to siphon owing to the anatomic relationships. No flow of CSF occurs when intracranial pressure (ICP) is lower that 5 mm Hg (70 mm H20). Beyond this point, CSF absorption increases in proportion to the ICP creating an effective "controller" of ICP. 15 Shunts to the sagittal sinus have been performed but are technically more

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difficult and carry with them some increased risk relative to more standard shunt systems. CSF is also absorbed in other ways. It can be shown in animal models and presumed in humans to exit into the paranasal sinuses and the conjunctiva of the eye. 17Tracers in CSF can be recovered in paracervical lymphatics, and a great deal of effort has gone into the tracing of this pathway. It has also been postulated that CSF may travel out along the cranial nerves and spinal nerves to be absorbed into the systemic circulation. These alternative pathways of CSF absorption function minimally if at all under the state of normal CSF dynamics but can be recruited to adapt for conditions of increased intracranial pressure.18 Two other pathways of CSF absorption have been suggested but remain very controversial. It seems unlikely that CSF can be absorbed in significant amounts by transmission through the pial surface of the brain or spinal cord, and attempts to measure extrachoroidal/extraependymal CSF have been unsuccessful. Finally, the concept of "transependymal reabsorption of CSF" has been evoked to explain stabilization of ventriculomegaly in patients with complete obstruction of the CSF pathways. Capillaries and veins are "Collapsible tubes" and when the intraparenchmal pressure increases to the point that it is significantly higher than the capillaries and veins within it those vessels will collapse and cease to be a conduit for removal of CSE18 The rate of CSF production and direct current flow is very small compared with the vascular component (approximately 3,000 times greater). Even the aqueduct of Sylvius, the narrowest channel within the CSF pathway, does not create a measurable resistance within the CSF system? 9,2~ Within the limits of sensitivity of the measuring devices we have available in our physiology laboratories, there does not seem to be a measurable difference in pressure between the lateral ventricle and its penultimate terminus, the cortical subarachnoid space. 19,2~Obviously, the flow of CSF is not a DC current. Each cardiac contraction adds a large volume of blood to the intracranial compartment and it is this increase in cerebral blood volume that creates the pulsations. As seen on cine magnetic resonance imaging (MRI) of the CSF pathways, large volumes of CSF are displaced across the aqueduct and foramen magnum with each cardiac cycle with a net flow of the above-mentioned 0.3 mL/minute.

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The arachnoid villus is therefore the only resistor or "dam" in the CSF system, which has a measurable resistance. 19,2~This function seems to be quite important for the maintenance of normal anatomic relationships within the CSF pathways. The brain is a viscoelastic substance and may be physically distorted by changes in its environment. For example, the placement of ventricular shunts leads not to normalization of the ventricular system but in most cases to subnormally small ventricles, which sometimes appear nonvisible on imaging studies and may be associated with the symptomatic "slit ventricle syndrome. 21'' A second example of the importance of the "dam effect" of the arachnoid granulations can be inferred from the anatomic changes seen in the context of "spontaneous intracranial hypotension." This condition consists of incapacitating headaches of relatively sudden onset which may be associated with a variety of cranial nerve deficits. 22,23 It is thought to result from a rupture of a spinal arachnoid diverticulum extradurally. Intracranial pressures in this condition have been reported as low as minus 25 mm Hg in the erect position. MRI reveals diffuse dural enhancement presumably from the pulling away of the subarachnoid spaces from the dura. There is also frequently a "settling" of the brain with anatomic distortions being created in relation to the tentorium and the Foramen Magnum (Hindbrain hernia or Chiari I malformtion). There is a case report of spontaneous reassencion of the cerebellar tonsils with resolution of the syndrome itself. 24 The system that has just been described is relatively straightforward and lends itself to a mathematical description using equations derived from fluid mechanical analogs of Ohm's law of electrical circuit. Together with the Department of Systems and Control Engineering and the Electronics Design Center at Case Institute (Case Western Reserve University School [CWRU] of Engineering, Cleveland, OH), and our neurophysiology laboratory first at the CWRU School of Medicine and subsequently at the Barrow Neurological Institute, Phoenix, AZ, studied clinical abnormalities of CSF dynamics and laboratory models of hydrocephalus in an attempt to create an interactive mathematical and physiological model that would predict clinical behavior from a variety of clinical manipulations. 25,26 We were never able to create a computer program that would allow the inputting of baseline data (ventricular volumes, ICP, and

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shunt valve characteristics), which would reliably predict the behavior of the system in terms of rate of change of ventricular volume or ICE We were able to use the information derived from this process to design experiments that would lead to improved understanding of the hydrocephalic process and eventually to make some important clinical observations, which resulted in some changes of both understanding and treatment paradigms. 25,26 Very early, it became clear that the system was not nearly as simple as would be expected by the physics described above. It was obvious from the early attempts to validate the model that the two most vexing points of difficulty in understanding the process, that of normal pressure hydrocephalus (NPH) and pseudotumor cerebri (PC) could not be explained by the first pass of the model. The problem revolved around the differences between an electrical circuit and the flow of water. In the electrical model, if one increases the resistance at one point in the circuit, there are two possible outcomes. The first possibility is that the upstream/ downstream voltage difference would increase (analogous to increasing the upstream pressure to maintain a constant flow). The second possibility is that the rate of flow (amperage) would decrease maintaining the voltage constant. Which of these happened or, frequently, in what percentages did each occur depending on the type of equipment that was being powered by the circuit. When dealing with the brain and CSF dynamics the question becomes, "When the resistance across the CSF pathway increases significantly, will the result be an increase in the ICP with little or no increase in the volumes of the ventricles (pseudotumor cerebri) or will the rate of flow decrease substantially leading to an increase in ventricular volume (hydrocephalus)?" The critical problem is then reduced to "What determines the percentage of stored energy produced by blocking the CSF pathways goes to increasing ICP and what percentage goes toward ventricular dilatation? Normally, both things happen simultaneously. Understanding the many enigmatic conditions affecting these relationships required a definition of the factors, which determined how this energy was distributed. With great effort, we found that the factor that determined the distribution of the energy between ventricular dilatation and increased ICP related to the "stiffness" of the human brain. The stiffer the brain the more of the energy would go to increasing

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ICE and the more "flaccid" the brain the more the ventricular dilatation would predominate. 27 Our first mathematical manipulation of this factor used the term Kb assuming that the brain stiffness was an intrinsic factor of the living brain and was a constant over the period of study within an individual patient. Soon thereafter, we found that brain stiffness was not a constant but a rapidly changing variable that we have termed brain turgor and other authors have looked at as brain compliance. 27,28 Because compliance is generally understood to mean the change in volume per unit change in pressure in neurophysiology, the entire craniospinal axis is studied; therefore we prefer the term turgor because it relates only to the brain itself, which is critical to the understanding of the enigmatic conditions. Using the above-mentioned thought process and laboratory experiments, we have been able to study CSF dynamics in novel ways leading to improved understanding of enigmatic conditions and leading to novel but effective new treatment paradigms. Several of these are described briefly below. 1. Pseudotumor cerebri (PC) is a condition of increased CSF pressure and resistance to outflow, which can be treated successfully with lumboperitoneal shunting. This occurs in the context of a very high brain turgor and high resistance to CSF outflow or high cerebral venous pressures. We have studied PC patients using retrograde venography and measurement of venous pressures. 29 In the standard type of idiopathic pseudotumor cerebri of obese young women, the pressure in the cerebral veins is very high (measured as high as 45 mm Hg in one patient), and this is due to very high right atrial pressures as a result of the obesity. The high venous pressures result in poor CSF absorption because the ICP must be 5 mm Hg greater than venous sinus pressure to be absorbed. These increased venous pressures are also transmitted back into the substance of the brain, which leads to high brain turgor in a positive feedback loop which responds well to weight loss by diet, gastric stapling, or the use of the newer powerful anorexics. 29 2. The "floppy brain syndrome." We have identified a small subset of patients whose ventricles remain dilated and who remain in poor clinical condition following shunt revision. ICP monitoring has shown that these patients experience

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ICE which is quite low while they are still exhibiting signs consistent with increased ICE In these patients with shunts that are proven to be working, the placement of a lose venous tourniquet around the neck will result in increasing cerebral venous pressures, increase brain turgor, and result in the extra CSF being forced out of the ventricles through the shunt resulting in marked improvement in the clinical condition of the patient as well as decreasing the size of the cerebral ventricles. One patient with a chronic form of this condition forgot to put his neck wrap on after showering and presented in extremis to the emergency room with massive ventriculomegaly and bilateral decerebrate posturing. The neck wrap was reapplied on the way to the operating room for surgery, and he awoke fully in the elevator. CT scan performed 20 minutes later revealed that the ventricles had returned to normal size. 27 3. Diffuse pediatric head injury is a condition that is common in children following high-energy head injuries in which imaging studies show no mass lesions but only obliteration of the cisterns in children with a low Glascow Coma Score. These children usually show very high ICPs, which initially show response to treatment with standard forms of therapy but eventually escape from this treatment. These children frequently die as a result of uncontrolled intracranial hypertension several days later. The condition seemed analogous to PC and we began treating refractory cases (essentially hopeless cases) as if they were PC using controlled lumbar drainage. 3~ In the patients that were selected, the use of the lumbar drain was very effective in the immediate and lasting decrease in ICP allowing discontinuation of other treatment modalities and excellent outcomes in a significant number of the patients. We now use controlled lumbar drainage in children preferentially to barbiturate coma because of the propensity of the last modality to result in hypotension requiring pressors. 31 At the microscopic and submicroscopic level, several investigators are attempting to define in animal models the effects of hydrocephalus on the developing organism and on the young animal as well as to understand the process of the reestablishment of the volume of the brain itself following the performance of a s h u n t . 32,33 In two of these models,

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the rat/maze model of Miyazawa and S a t o , 34 and the swimming rabbit model of Wehby et al (M Wehby personal communication), behavioral abilities and neurodevelopment may be tested as well as structural and biochemical changes. Using these models as well as other established animal models, these investigators have studied the differences between the hydrocephalic animal and control animals as well as "early" versus "late" shunted animals. What seems apparent from these works is that severe anatomic and neurochemical changes can be demonstrated in experimental animals using these techniques with disruption of neural cytoarchitecture and loss of neurotransmitters, but if the animals undergo "early" shunting, nearly all of the changes are reversible and the early shunted animals perform well on behavioral testing. On the other hand, "late" shunted animals show poor improvement in their cerebral microanatomy and do poorly on behavioral testing. It is interesting that in all of these models the "late" shunted animals also share the fact that there has been no reconstitution in the cerebral mantle thickness. This is consistent with the observations of Young et a135 that the prognosis for developmental outcome in clinical hydrocephalus related not to the severity of the hydrocephalus, but to its reversibility. Patients in whom the size of the cerebral ventricles decresed significantly following shunting did well, whereas those in whom the brain did not respond did significantly poorer. The message here is that hydrocephalus that is severe and chronic may eventually get to a point that it becomes irreversible. Future studies in both the laboratory and in the clinical setting will need to be done to be able to predict where the "point of no return" is and how clinicians can assure intervention before that point. DEVELOPMENT OF NEW TECHNOLOGY

Neuroendoscopy As stated above, endoscopes have been used from very early in the twentieth century to treat hydrocephalus. L'Espinasse 36 used large cystoscopes within massively dilated ventricles to coagulate and revolve the choroid plesuses in an attempt to control the hydrocephalus process. This procedure was later advocated by Scal"ff. 37 After the development of valve systems, these procedures, which carried a poor success rate and high mortal-

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ity, were abandoned for the most part. Recently there has been an explosion of interest in and enthusiasm for neuroendoscopic intervention in hydrocephalus. As early as 1978, Vries 38 revived the concept of using the endoscope to avoid shunting by performing a third ventriculostomy. At this time the use of endoscopy was becoming routine in orthopedics, general surgery, Obstetrics and gynecology, and pulmonary and gastrointestinal medicine. As a result of this rapid increase in popularity, the technology of endoscopes advanced rapidly as well. Both fiberoptic and lens scopes are now available with excellent resolution providing vision at multiple angles. The scopes are now fully sterilizable and are linked to imaging systems that also have excellent resolution. Steerable scopes allow the surgeon to navigate the scope to intraventricular spaces which would otherwise be unapproachable. Surgical techniques are quite different using the endoscope than they are when using surgical techniques through open surgery. The learning curve is quite steep. Teaching yourself how to manipulate long instruments while using a TV monitor to guide the action takes experience. Indications for neuroendoscopy are presently being established and just as in other areas of minimally invasive surgery, the possibilities are just beginning to be explored. Patients who present beyond infancy with obstructive hydrocephalus, such as from late diagnosis of aqueductal stenosis or from the so-called "tectal glioma," are ideal candidates for definitive treatment of the hydrocephalus using endoscopic third ventriculostomy. Success in shunt avoidance in this setting is probably 80%. 39 When newborns are treated in this way for noncommunicating hydrocephalus, the success rate is quite poor (about 10%). 40 The reasons that this dichotomy exists is poorly understood and is probably related to the fact that the fontanel and sutures are open in the babies and intraventricular pressure is in equilibrium with atmospheric pressure preventing the attaining of a sufficient pressure head to distend the subarachnoid spaces and cause the CSF to be absorbed. It has also been suggested that in patients with infantile hydrocephalus, the CSF pathways (arachnoid villi) may be poorly developed. Although some babies definitely do respond to endoscopic third ventriculostomy, most neurosurgeons who perform significant amounts of intraventricular surgery using the endoscope do not

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recommend the procedure in children under 6 months of age and some in children under 2 years of age. Piatt and Carson 41 have shown that complex shunt systems have poorer survival than do simple (one ventricular catheter) shunts. The fenestration of noncommunicating compartments is an ideal indication for neuroendoscopic intervention. Creating holes in the septum pellucidum in patients with non or poor communication between the ventricles, fenestrating intraventricular cysts, and communicating arachnoid cysts into the cisternal spaces can be performed using neuroendoscopy if the working space is large enough to manipulate the scope within it. Controlled trials are not yet available but considering the dismal performance of shunts containing multiple ventricular catheters, this procedure may be very helpful in the lifetime management of shunt-dependent patients. One of the most frustrating problems related to hydrocephalus management involves the management of the "isolated fourth ventricle." Placing ventricular catheters in the fourth ventricle is very difficult and potentially quite dangerous. Recently, experience is being gained using the endoscope to place stints within the aqueduct of Sylvius to allow the free communication between the third and fourth ventricles. This can be done from a far frontal approach through the foramen of Monro or in a flexed-prone position through the fourth ventricle itself into the third ventricle (KM Manwaring, personal communication). Procedures such as these are aided greatly by the adjunctive use of frameless stereotaxis. When the anatomy is distorted and landmarks are difficult to find, it is possible to become lost in the ventricular system and the various forms of frameless stereotaxis are ideal for preventing this form of difficulty. Neuroendoscopy has been found to be extremely useful in expanding the concept of shunt independence. Before the widespread availability of the technique, there was much discussion about whether or not a patient once shunted could ever do without the shunt. Opinions ran a large gamut from that of Foltz who believed that "Once a shunt, always a shunt" to others who believed that shunts could be removed in a large percentage of patients regardless of the size of the cerebral ventricles and regardless of the etiology of the hydrocephalus. 42,43 Epstein et a144,45 believed that shunting created a dependency on the shunt and attempted to prevent

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such dependency using head wrapping and shunts that contained "on-off" switches to drain only enough CSF to keep the ventricles from enlarging. In 1982, a study from CWRU in Cleveland reported on the systematic attempt to remove shunts as no longer needed. 46 The results of that study showed that in patients with communicating hydrocephalus as shown by the injection of indigo carmine dye into the lateral ventricle through the shunt reservoir and recovering it via lumbar puncture, 50% of patients could have their shunts removed as not needed albeit with a significant enlargement of the ventricular system. Except in the subset of cases with hydrocephalus secondary to spina bifida (Chiari II malformation), patients became ill from 4 to 24 hours following the clamping or tying off of the shunt or they showed minimal or no signs of increased ICE In the former case, the shunts were reconstituted, and in the latter they were removed. However, patients with spina bifida could seem asymptomatic and yet be damaged by the shunt not working. Four such patients were found out of a total spinabifida population of 20 undergoing this evaluation. These patients suffered respiratory arrest 12 hours to 5 years after it was known that they no longer had working shunts. Two patients died and two patients were left with severe motor and cognitive deficits, which unfortunately left them dependent for activities of daily living. These results led us to conclude that testing for shunt independence in the context of spina bifida was extremely dangerous and except in extreme circumstances not worth the risk. 46 Walker et al developed an approach to the symptomatic slit ventricle syndrome, which involved the externalization of the shunt system, impeding its flow, and if the ventricles became large enough to navigate within to perform an endoscopic third ventriculostomy in an attempt to remove the shunt as not needed (ML Walker, personal communication). An earlier study presenting an algorithm for the treatment of severe headaches in patients with shunts had emphasized the importance of determining the reason for the problem in attempting to deal with these headaches. 47 Although few in number, patients with symptomatic slit ventricle syndrome could be incapacitated by the complaints and used a great many resources in terms of imaging studies and surgical procedures. We decided to offer these patients an opportunity to prove that they needed the shunts in the

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first place and if they did exhibit increased ICP and the ventricles could be expanded to a large enough size to be able to navigate with the scope, an endoscopic third ventriculostomy would be attempted. Fifty-four patients have been entered into this protocol to date. The result of the study is that some patients were able to tolerate the removal of the shunt with no further intervention as seen in the previously mentioned shunt independence study. 46 Other patients required shunt re-insertion. However, 32 of these patients (60%) were able to have their shunts removed following endoscopic third ventriculostomy. One of the patients whose shunt was removed presented 1 year later with signs and symptoms of overt hydrocephalus and no flow was found on cine-MRI. She underwent a second exploration of the third ventricle revealing that the basillar artery had herniated through the first fenestration. A second ventriculostomy was performed successfully again leaving her shunt independent. 48 In a very recent work, Teo and J o n e s 49 reported their experiences with endoscopy in the spina bifida population. They had little success with the use of this technique as the first form of treatment of the patients, but an almost 80% success rate when patients who had shunts presented with shunt failure. One caveat here is that the patients were selected for the appropriateness of such intervention on the basis of CT scan criteria. Some patients do not dilate up the third ventricle despite rather massive dilatation of the lateral ventricles. The authors suggest that MR imaging may give more information with which to judge who is and who is not a reasonable candidate for the procedure based on the anatomy of the third ventricle. In light of the experiences reported above, it is essential to observe these patients very carefully to guard against the late deterioration discussed in these patients following the procedure and shunt removal.

Design of Shunt Systems Initially, all shunts manufactured for the control of hydrocephalus were differential pressure valves with differing closing or opening pressures. Each had its own pressure flow characteristics, and each equilibrated at a somewhat different rate. They all shared the fact that when the patient changed from the recumbent to the erect position, there was a tremendous drop in the ICP. 5~ This was especially noticeable after the peritoneum became the receptacle of choice for the distal end of the shunt, and

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the phenomenen is due to the siphoning effect created by the differences in the height of the head over the abdomen in the face of a continuous column of water. Portnoy 51 recognized this problem and in 1975 reported his experiences using an "anti-siphon device" (ASD). This device must be implanted under freely moving skin. It contains a diaphragm that collapses when the pressure within the shunt system becomes negative relative to sensed atmospheric pressure. The valve only reopened when the pressure within the shunt again rose to higher than atmospheric pressure. Problems have been reported with the system, 52-s4 but it was successful in relieving incapacitating slit ventricle symptoms. Since the introduction of the ASD, several devices with similar construction have been released. The Siphon Control Device ([SCD] PS Medical Corporation, Goleta, CA) and the Delta valve of various pressure ranges also are developed and marketed by PS Medical. The SCD differs from the ASD in that the valve is closed at rest and must be opened by positive pressure within the system. This adds some resistance to the system as a whole and adding it in series with an existing shunt system will turn a low-pressure valve into a medium-pressure system and so forth. The Delta valve (PS Medical) is a more efficient, smaller version of the SCD incorporated with a differential pressure valve in a single system. In vivo testing has demonstrated that the Delta Valve equilibrates rapidly but does not permit extreme low pressures in the erect position and is probably ideal in situations, such as normal pressure hydrocephalus, in which a low-pressure valve is needed; however, one that siphons is likely to leave the patient at severe risk for life-threatening subdural hematoma. Another attempt to prevent the overdrainage problem is the Orbis-Sigma Valve (Cordis Corp., Miami, FL). This valve is termed a flow-control valve. The pressure-flow characteristics of this form of shunt are such that it is able to prevent overdrainage over a wide range of pressures by restricting the flow to that of CSF production (20 mL/h). This is accomplished by incorporating a resistance element, which changes with the changes in the differential pressure across the valve mechanism. The result is that the valve has a unique pressure-flow relationship with no flow at lowpressure differentials (below 70 mL H20 differen-

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tial pressure). From 70 mL n20 to 400 mL H20, the flow through the valve remains constant at about 20 mL/hr. Above 400 mL H20, the valve opens fully with very high flow rates possible. My personal experiences with these various valve systems in patients in whom ICP has been monitored either through the shunt or via a separately placed parenchymal ICP monitoring device has shown that older patients with differential pressure valves develop very negative ICPs ( - 1 5 to - 2 5 mm Hg) very quicklyY When a siphon control device and antisiphon device are linked to a differential pressure valve, or a Delta valve is used, the ICP falls quickly but does not allow extremely negative ICP ( - 5 to 0 mm Hg). In the case of the Orbis Sigma valve, the rate of fall of ICP when assuming the erect position is quite slow, but when equilibration is reached, the nadir reaches - 7 to l0 mm Hg. These results are predicted using the mathematical model developed by Drake et al. 56 The ASD, SCD, Delta valve, and Orbis Sigma valve have all been developed to prevent the complications of overdrainage, have all been advocated in the literature, 21,51 and have been found to be successful in most cases. 47 Very little in the treatment of hydrocephalus is more controversial than the overdrainage syndromes, and little agreement exists even as to the incidence and nomenclature. There are two distinct forms of overdrainage. The acute form is produced when patients with very large ventricles are shunted using differential pressure valves. In infants this can lead to secondary craniosynostosis, especially of the sagittal suture, resulting in very abnormally shaped heads. In some cases, it prevents the subsequent growth of the skull when the child's brain has filled in the space resulting in secondary microcephaly and possibly cephalocranial disproportion. This form of overdrainage is especially severe and dangerous in older patients with normal pressure hydrocephalus (NPH). The subdural hematomas in this condition are frequently associated with neurological deterioration and sometimes death. Both in the infant with an open fontanel and in the NPH, the dilemma is very vexing. The likelihood of successful treatment is improved with the use of low-pressure shunts, 57 whereas the complication rates are significantly higher. The second form the overdrainage can take is termed the slit ventricle syndrome (SVS) or slit -

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ventricle syndromes because there are several The actual incidence of this condition is unknown with estimates ranging from nearly nonexistent with never a need to treat, to a relatively common condition needing treatment in as many as 15% of older children and adults with shuntdependent hydrocephalus and small ventricles on imaging studies. SVS should be distinguished from radiographic slit ventricles seen in more than 80% of chronically shunted children and believed by some to be the goal of hydrocephalus management. The cause of the headaches in these patients is multifactorial and in most we never find out the actual cause because most of these patients are treated empirically either with shunt valve upgrade or by the incorporation of a device that retards siphoning. Some authors have reported success with the use of antimigraine medication with its effect on cerebral blood volume. 58 It is only in the patients who continue to have recurrent and incapacitating headaches that further workup with ICP monitoring is required. This also may be a group of patients, which may be candidates for shunt removal after ICP monitoring with or without endoscopic third ventriculostomy.48 Is there a reason to chose one valve system over another? It seems that most shunted children and adults do very well with whatever valve system is used. There are certain instances in which certain valve systems are more appropriate than others. 59 The most compelling situation seems to be the older patient with normal pressure hydrocephalus or the older patient whose shunt has been delayed for a variety of reasons. In these patients the incorporation of an ASD, SCD, or Delta valve would seem to be the strategy most likely to result in adequate ventricular decompression with the fewest complications. The only randomized prospective trial comparing the functioning of one form of shunt with another has recently been completed by Drake and Kestle (unpublished data). This trial was performed at a number of centers in Canada, the United States, and Europe and was presented at the 1997 annual meeting of the AANS in Denver, CO. It showed no discernable differences in the 1-year survival rate of newly implanted shunt systems comparing the Delta valve, The Orbis sigma Valve, and all other valve systems presumed to be differential pressure valves. It should be noted that this study was heavily weighted c a u s e s . 21,47

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toward infants where the effects of siphoning would be expected to be minimized. The study showed no differences in any of the parameters studied except that the OS valves led to reexpansion of the brain in a slower fashion. At this point, the decision as to which shunt should be used will be driven by the familiarity of the individual neurosurgeon and possibly in the near future by economic considerations. Programmable valves for the treatment of hydrocephalus are devices containing multiple differential pressure valves that can be selected without surgical intervention. Two such systems are available worldwide. The first is the Sophy valve (Sophysa Corp., Orsay, Cedex, France), which has four positions. The programming is done using the application of a bar magnet allowing the rotation of a bar, which rotates into place selecting the resistance of the valve. This valve is available in Europe, but at this time there does not seem to be any energy to obtain Food and Drug Administration approval for its sale in the United States. The second valve mechanism is the Codman Medos (Hakim) Programmable Valve (Codman Corporation). Clinical trials have been performed in the United States, but as of the writing of this review, the results have not been released and approval has not been granted. Data from other countries have been encouraging as to the ability to adjust the pressure noninvasively leading to an improvement in the clinical condition of the patients. What these new advanced technology devices will eventually add to the treatment of the patient with hydrocephalus remains to be determined. PREVENTION OF COMPLICATIONS

The actual surgical procedure to put in a shunt is not difficult, and in most cases the performance of a primary shunt should take less than 1 hour. As such, it may be one of the most underrated procedures in neurosurgery. Grave, intraoperative immediate complications are quite rare. The actual complication rate of the surgical procedure is high. In the as yet unpublished study by Drake and Kestle mentioned above, the infection rate for first shunt was 8% with little in the way of variation among centers. Published infection rates range widely in the literature from less than 1% to as high a s 2 1 % . 60-62 Most of the patients in the studies were infants, and considering the analysis of Pople et al63 who showed the

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increased infection risk in children under the age of 6 months, this rate of infection seems reasonable. Also, the 1-year failure rate was 38%. It is, for the most part, the complications of shunting, which lead to the dangers for the child and the cost to the system of the delivery of health care. It has been shown that shunt infection in babies under the age of 6 months with hydrocephalus is associated with a significant deterioration in intellectual potential.64,65 It is in this very important aspect of the treatment of hydrocephalus where the least progress has been made and the most compelling need for improvement is needed. The advantages derived from the prevention of shunt infections and failures if it were possible would overhelm any increase in costs from new technology in shunt development. Better understanding of the causes of shunt malfunction and shunt failure is needed as well as potential new strategies to deal with these issues. When such strategies are suggested, it will become vitally important to perform randomized prospective trials of the new form of management versus standard techniques so that the real effects can be ascertained. ACCESS: THE MOST IMPORTANT CHALLENGE FACING THOSE WHO HAVE AND THOSE WHO TREAT HYDROCEPHALUS

Very few children with hydrocephalus survived before the development of the valve-regulated shunt. Patients treated in those early days who have survived are now in the fifth decade of life. Hydrocephalus in and of itself is no longer considered a lethal disease. Unfortunately, this perception is not entirely correct. Sgouros et al66 evaluated the course of patients who had once been observed in a children's hospital but whose care became the responsibility of an adult hospital when the patients became adults. The complication rate leading to death and serious neurological deterioration was surprisingly quite high. The transition of the child to adulthood carries with it potentially great risks .66 The first risk involves the attainment of an independent lifestyle. A poll of its adult members by the Hydrocephalus Association revealed that one quarter of its adult affected members had suffered a shunt failure that resulted in coma, Young adults living alone, especially those that have not had a shunt failure in a long period of time, tend to ignore the premonitory symptoms of

HAROLD L. REKATE

shunt failure until the symptoms become severe. Such patients are occasionally found dead or in a coma having suffered imperfectly reversible neurological deficits as a result of the delays in finding care. These patients must prepare for independence with a clear understanding of how and where they can obtain care quickly and also ideally have some method available to have some minimal surveillance built into their daily lives. An even more challenging aspect of the care of patients with shunt dependent hydrocephalus relates to medical economics. It is very likely that most young adult patients with shunts in the United States lack health insurance after they are no longer the responsibility of their parents. This is a critical issue because patients without health insurance are unlikely to seek care until the problems related to shunt function are far along and the possibility of serious complications great. The presence of a shunt will always be a preesisting condition preventing adults with hydrocephalus from making employment decisions to work anywhere that does not accept preexisting conditions. Their only option then is to live without hospitalization insurance and run the risks of both bankruptcy and serious neurological deterioration. Long-term patients with shunt-dependent hydrocephalus who have hospitalization insurance fall victim to the constant changes in the places of the delivery of health care and the ways that the patient must access that care. These changes jeopardize the patient's ability to obtain care quickly enough to have a good result. For many families and patients, the need to become familiar with each of the aspects that they must understand to obtain care efficiently, and how to be able to assess the quality and responsiveness of that system can be an overwhelming challenge. Fewer people have choices. This lack of choice and failure of the system to provide an efficient and effective care that is essential for the survival of these individuals who have grown up with such hope creates an unacceptable risk that a functional adult will die or become totally dependent. Many families truly need active advocacy for their needs. For one reason or another, they do not have the resources to actually fight for the responsive medical care that they so desperately need. The physician or system that cares for these patients must understand the risk that these patients experience in the times of rapid change. Each

ADVANCES IN HYDROCEPHALUS TREATMENT

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f o l l o w - u p visit m u s t b e u s e d to m a k e sure t h a t t h e p a t i e n t s or t h e i r c a r e t a k e r s u n d e r s t a n d the i m p o r t a n c e o f o b t a i n i n g m e d i c a l care p r o m p t l y a n d b e g i v e n i n s t r u c t i o n s o n h o w to a c c e s s t h a t care.

Finally, the n e e d s o f t h e p a t i e n t s m u s t b e a d d r e s s e d b y the h e a l t h care s y s t e m in g e n e r a l so that they m a y r e c e i v e c o n t i n u o u s m e d i c a l care h o p e f u l l y b y a s y s t e m that u n d e r s t a n d s t h e i r u n i q u e needs.

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