Idiopathic hydrocephalus in children and idiopathic intracranial hypertension in adults: two manifestations of the same pathophysiological process?

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1 See the corresponding editorial in this issue, pp J Neurosurg (6 Suppl Pediatrics) 107: , 2007 Idiopathic hydrocephalus in children and idiopathic intracranial hypertension in adults: two manifestations of the same pathophysiological process? GRANT A. BATEMAN, M.B.B.S., F.R.A.N.Z.C.R., 1,2 ROBERT L. SMITH, M.B.B.S., F.R.A.C.P., 2,3 AND SABBIR H. SIDDIQUE, M.B.B.S., F.R.A.N.Z.C.R. 1 1 Department of Medical Imaging, John Hunter Hospital; 2 Newcastle University Faculty of Health, Callaghan Campus; and 3 Department of Pediatric Neurology, John Hunter Children s Hospital, Newcastle, Australia Object. Both idiopathic intracranial hypertension (IIH) in adults and idiopathic hydrocephalus in children have been shown to involve elevations in venous pressure that resolve once the cerebrospinal fluid pressure is reduced. It has been assumed that the venous pressure elevations in both conditions are not hemodynamically significant, but measurement of venous collateral flow in IIH has shown these pressure elevations to be of consequence. The authors used the same methodology to see if the venous pressure elevations noted in childhood hydrocephalus are important. Methods. Fourteen patients with idiopathic childhood hydrocephalus underwent magnetic resonance imaging with flow quantification. The degree of ventricular enlargement, total blood inflow, and superior sagittal/straight sinus outflow was measured. The degree of collateral venous flow was calculated for each venous territory. The findings were compared with findings in 14 age-matched controls. Results. In children with hydrocephalus the cerebral blood inflow was normal, but the superior sagittal sinus (SSS) and straight sinus outflows were reduced by 27% and 38%, respectively, compared with measurements in controls (p = 0.03 and 0.002). These findings suggest that approximately 150 ml of blood per minute was returning via collateral channels from that portion of the brain drained by the SSS, and 60 ml/minute was returning from collaterals in the deep venous territory. Conclusions. Similarly to patients with IIH, children with hydrocephalus show a significant elevation in collateral venous flow, indicating that the same venous pathophysiological process may be operating in both conditions. Whether or not the ventricles dilate may depend on the differences in brain compliance between adults and children. (DOI: /PED-07/12/439) KEY WORDS aqueduct stenosis communicating hydrocephalus idiopathic intracranial hypertension pediatric neurosurgery I N children, it is well established that communicating hydrocephalus can be caused by venous hypertension. In achondroplasia and craniosynostosis, hydrocephalus is caused by a fixed venous outflow obstruction. 18 Superior sagittal sinus venography demonstrates a narrow or interrupted sinus and venous collateral flow through emissary veins and spinal venous plexuses. The hydrocephalus resolves with venous bypass surgery. 18 Similarly, Shulman and Ransohoff 22 found in 15 children with hydrocephalus but without osseous dysplasia, that there was also an elevation in SSS pressure with a loss of the driving force across the arachnoid villi similar to what was seen in patients with Abbreviations used in this paper: CSF = cerebrospinal fluid; ICP = intracranial pressure; IIH = idiopathic intracranial hypertension; MR = magnetic resonance; SD = standard deviation; SSS = superior sagittal sinus. J. Neurosurg: Pediatrics / Volume 107 / December, 2007 osseous dysplasia. This finding suggested that an elevation in venous pressure may be associated with many other forms of childhood hydrocephalus as well. Sainte-Rose et al. 18 noted, however, that in most forms of childhood hydrocephalus (those without dysplasia) the SSS pressure fell to the same values as jugular venous pressure following CSF removal. This suggested that the increased SSS pressure may have been due to a reversible compression/collapse of the sinuses caused by the intracranial hypertension. The authors asserted that if a high CSF pressure was the cause of the venous pressure elevation, the venous pressure elevation could not also be the cause of the CSF pressure elevation. They believed that the raised venous pressure was therefore not significant in the causation of hydrocephalus. 18 This reasoning leads to a conundrum that is, elevated venous pressure can cause hydrocephalus and also be caused by hydrocephalus. Although the differentiation be- 439

2 G. A. Bateman, R. L. Smith, and S. H. Siddique tween a reversible and fixed obstruction appears at first to be academic, it is actually of utmost importance because, as Sainte-Rose et al. 18 suggest, in the former instance, in which the collapse is the consequence of the increased CSF pressure, it would not be appropriate to insert a venous bypass. Partly as a consequence of such assertions, current practice emphasizes investigating and treating venous outflow obstruction predominantly in children in whom osseous dysplasia is suspected. In adults, elevated venous sinus pressures cause IIH rather than hydrocephalus (that is, raised CSF pressure but nondilated ventricles). 11 It has been noted that the difference in outcome from raised venous pressure (hydrocephalus or IIH) is related to patient age and depends on whether the cranial sutures are patent or closed. 16 Similar to childhood hydrocephalus, as described in the literature previously discussed, IIH may occur in patients with fixed venous outflow obstruction (for example, from thrombosis or fixed stenosis) 4 or with dynamic stenoses from collapse of the transverse sinuses. 12 It has also been suggested that those patients with IIH and fixed stenoses should be treated with stent insertion 9 and those with dynamic stenoses should not be treated because the stenoses are not significant. 15 These opinions seem to echo those that have been expressed about childhood hydrocephalus. In order to study the relevance of venous sinus pressure in IIH and hydrocephalus an MR imaging based surrogate marker of elevated venous pressure has been developed. It was noted that a fixed stenosis or thrombosis of a sinus caused a reduction in flow through this sinus and increased flow in collateral vessels. 1 A measure of this collateral flow could be used as a noninvasive marker of the raised venous pressure. This concept will be discussed with reference to Fig. 1, which shows the MR venogram of a child with achondroplasia and obstruction of the major sinuses at the skull base. There are multiple large venous collateral channels taking blood, around the occlusions, via the face and through emissary veins. This collateral flow must be associated with a reduction in the major sinus flow. Indeed, Hirabuki et al. 10 measured a 32% reduction in SSS flow in five patients with achondroplasia and hydrocephalus compared with controls, suggesting that fixed stenoses produce significant collateral flow. An attempt could be made to directly measure the flow in each collateral vein, but this would be tedious and inaccurate because many of the smaller veins would be missed. The same result can be obtained, however, by subtracting the major venous sinus outflow from the arterial inflow. This method is both easier to perform and likely to be a more accurate way of estimating the collateral flow. Using this methodology, it has been recently shown that patients with IIH and dynamic stenoses have evidence of significant collateral flow, a finding that suggests that the dynamic stenoses in IIH are hemodynamically important. 1 With these considerations in mind, the same methodology has now been used to test the hypotheses that the venous hemodynamics in childhood hydrocephalus are similar to those of IIH in adults and that both of these conditions encourage the development of collateral outflow pathways. Clinical Material and Methods Study Population Fourteen patients found to have symptomatic idiopathic FIG. 1. An MR venogram obtained in a child with hydrocephalus secondary to achondroplasia. Note the obstruction of the major venous sinuses at the skull base (large arrow) and the collateral veins passing through the face and emissary veins (smaller arrows). ventricular dilation at a tertiary referral hospital were prospectively entered into the study. There were seven male and seven female patients of mean age 8 5 (SD) years (range 6 months 16 years). Patients with hydrocephalus secondary to tumor, hemorrhage, or infection were excluded but idiopathic aqueduct stenosis was not excluded. Five patients had evidence of aqueduct stenosis diagnosed initially on planar imaging but confirmed later by means of aqueduct flow quantification. The control group consisted of 14 children who were undergoing cranial MR examinations for conditions thought not likely to involve cerebral pathological conditions (for instance, investigation of middle ear or pituitary abnormalities). Controls were excluded if pathological cerebral structural conditions were subsequently identified. The controls consisted of six boys and eight girls (mean age 8 5 years). As is common in MR imaging examinations of children, sedation was used to complete the diagnostic and experimental components of the examination in both the patient and control groups; sedation was used in the examinations of nine members of the study group and seven members of the control group. Informed consent was obtained from the parents or guardians of the patients and where appropriate from the children themselves as well. The hospital ethics committee approved the study protocol. MR Imaging and Analysis In all cases MR images were obtained using a 1.5-tesla superconducting magnet (Magnetom Vision, Siemens). Standard T1-weighted sagittal, T2-weighted and fluid atten- 440 J. Neurosurg: Pediatrics / Volume 107 / December, 2007

3 Venous pathophysiology of childhood hydrocephalus uated inversion recovery axial images, and MR flow quantification sequences were obtained. The ventricle/cerebral index (Evans index) was obtained as the ratio of maximum width of both anterior horns of the ventricles to the diameter of the inner table of the skull along the line of measurement of the anterior horn transverse dimension, expressed as a percentage. A retrospectively cardiac gated phase contrast flow quantification sequence was used with TR 29 msec, TE 7 msec, flip angle 30, slice thickness 6 mm, matrix , field of view 200, and number of excitations 1; this is a standard sequence available on this scanner. The velocity encoding values of 20 cm/second, 40 cm/second, and 150 cm/second were used. The lowest velocity encoding value was selected to maximize the measurement of the aqueduct flow, the middle value was used for the venous sinuses, and the highest one was used to maximize the arterial measurements. The arterial plane of section was selected to intersect the vertical portion of the petrous internal carotid arteries and to pass through the clivus to the basilar artery as described in the literature. 3 The venous plane was selected to pass through the SSS 2 cm above the confluence of sinuses and then pass through the straight sinus. The aqueduct flow was measured perpendicular to the middle portion of the aqueduct. The planar imaging, as well as the flow quantification raw data, was archived on magnetooptical disc. Regions of interest were placed around the carotid arteries, basilar artery, the SSS, straight sinus, and aqueduct in each patient. Care was taken to exclude aliasing by retrospectively manipulating the baselines of each resultant graph. The addition of the flow from the three arteries gave the total supratentorial blood inflow. The SSS and straight sinus outflow was obtained from the region of interest placed around each of these vessels. The percentage of the arterial inflow represented by the SSS and straight sinus outflow was calculated. Means and SDs were obtained for each group of patients. Differences between the groups were tested using a nonpaired Student t-test. Results The ventricular size and blood flow data for patients with communicating and obstructive hydrocephalus are summarized in Table 1, and the pooled data are summarized in Table 2. Clinical and Morphological Findings J. Neurosurg: Pediatrics / Volume 107 / December, 2007 TABLE 1 Comparison of clinical characteristics in communicating and obstructive hydrocephalus* Variable Of the 14 patients with hydrocephalus, nine presented with communicating hydrocephalus and five with aqueduct stenosis, the aqueduct occlusion being confirmed as a lack of flow on the aqueduct MR flow quantification. All patients were symptomatic at presentation with most suffering from headaches and some visual symptoms. Of the children with communicating hydrocephalus, five had long-standing hydrocephalus that had initially been treated conservatively (that is, an acute deterioration had occurred just before the MR imaging), two had previously been treated by means of shunt insertion but presented acutely with shunt malfunction, and two presented acutely with previously undiagnosed hydrocephalus. Of the five with obstructive hydrocephalus, three had an acute first-time presentation, one presented after a failed third ventriculostomy, and one presented after a shunt failure. The mean Evans index was increased by 19 percentage points in comparison with controls (50% compared with 31%, p ), with all patients in the hydrocephalus group showing ventricular dilation. Hemodynamic Findings Type of Hydrocephalus Communicating Obstructive p Value no. of patients 9 5 NA age (yrs) 8 (5) 7 (6) 0.64 Evans index (%) 51 (12) 49 (7) 0.73 cerebral inflow (ml/min) 1290 (290) 910 (250) 0.03 SSS outflow (ml/min) 530 (230) 310 (170) 0.09 ST outflow (ml/min) 140 (30) 90 (30) 0.02 SSS outflow as percentage of inflow 40 (11) 34 (14) 0.36 (%) ST outflow as percentage of inflow 11 (2) 11 (4) 0.72 (%) * Values other than numbers of patients are given as means with SDs in parentheses. Abbreviations: NA = not applicable; ST = straight sinus. p The cerebral inflow appears to be significantly less in the patients with obstructive hydrocephalus compared with the patients with communicating hydrocephalus, but the obstructive hydrocephalus sample size is small, and a closer examination of the data for these patients shows that four of the five patients had inflows in the expected normal range for their ages and one had a very low inflow. If this patient were excluded, there would be no significant difference between the groups. Nevertheless, there was no significant difference in the percentage venous return for the deep or superficial systems between the children with obstructive hydrocephalus and those with communicating hydrocephalus. The reduction in the percentage return compared with controls for the communicating group was significant for both the SSS and the straight sinus (p = 0.01 and p = 0.003, respectively); similarly the patients with obstructive hydrocephalus showed a significant reduction compared with controls (p = and p = 0.02, respectively). To improve TABLE 2 Comparison of clinical characteristics of all patients with hydrocephalus and age-matched controls* Patients w/ Variable Controls Hydrocephalus p Value no. of patients NA age (yrs) 8 (5) 8 (5) 0.80 Evans index (%) 31 (3) 50 (10) cerebral inflow (ml/min) 1200 (200) 1160 (330) 0.65 SSS outflow (ml/min) 620 (160) 450 (230) 0.03 ST outflow (ml/min) 200 (66) 125 (40) SSS outflow as percentage 51 (8) 38 (12) of inflow (%) ST outflow as percentage 16 (4) 11 (3) of inflow (%) * Values other than numbers of patients are given as means with SDs in parentheses. p

4 G. A. Bateman, R. L. Smith, and S. H. Siddique the statistics, the data obtained in the patients with hydrocephalus were pooled. When all patients with hydrocephalus were considered as a single group, there was no significant difference in the arterial inflow volumes between these patients and those in the control group, but a 27% reduction in SSS outflow and a 38% reduction in straight sinus flow were noted in the hydrocephalus group compared with the control group (p = 0.03 and p = 0.002, respectively). The reduction in the percentage return was significant for both the SSS and the straight sinus (p = and p = , respectively). Discussion Shulman and Ransohoff 22 measured the SSS pressure in a group of 15 children with communicating or noncommunicating hydrocephalus and found a mean pressure of 17 mm Hg compared with a jugular bulb pressure of 2.6 mm Hg, indicating elevated venous sinus pressure. In some of these cases, sinograms showed elongation and tapering of the lateral sinuses just proximal to the jugular foramen with enlarged parietal and mastoid emissary channels, suggesting the probable site of apparent venous obstruction. Sainte- Rose et al. 18 showed that, in patients without dysplasia involving the skull base, these stenoses were reversible once the CSF pressure was lowered. They went on to suggest that these stenoses were secondary to venous compression and did not require venous bypass. In our study we sought to establish whether the dynamic stenoses found in childhood hydrocephalus are hemodynamically significant by measuring the degree of collateral flow they induce. Blood Flow Cerebral blood inflow can be measured using MR imaging based flow quantification. Koudijs et al. 13 performed phase-contrast flow quantification in seven healthy children (mean age 8.8 years) using a technique identical to that used in this study and found a median flow of 1200 ml/minute. Their finding correlates well with that of the current study, in which a mean flow rate of 1200 ml/minute was found. The normal SSS flow rates for children vary with age. 10 Flows of 500 ml/minute occur in 2-year-old children, and the flow increases with age to peak at 600 ml/minute at 6 to 8 years of age and then gradually decreases. 10 These findings closely match the data from the controls in this study. It may be inferred from the findings reported in the literature that normally about 50% of the arterial inflow returns via the SSS outflow. No normal data have been reported in the literature regarding the straight sinus flow in children. The findings of the current study suggests that normally the straight sinus returns 16% of the inflow. In idiopathic intracranial hypertension, venous sinus pressure gradients have been shown to be elevated to approximately 10 times the normal values, 12 and these elevated pressures open collateral vessels. Collateral flow has been previously measured as a reduced percentage of the SSS outflow compared with inflow, with a 15% shortfall in the percentage return in the SSS territory (p ) and a 5% reduction in the straight sinus territory (p ) in IIH. 2 In the current study, the total arterial inflow in the patients with hydrocephalus was normal; indicating that the blood flowing into the capillary bed of the brain drained by the sagittal and straight sinuses was also probably normal (or another area of the brain would have to have been hyperemic to make up the shortfall). It is apparent from Table 2 that there is a shortfall in the percentage return in the SSS territory of about 13% and a shortfall of 5% in the straight sinus flow, indicating a similar increase in collateral flow in our study population and patients with IIH. To put this observation into perspective, there is approximately 150 ml/minute ( ml/minute) of arterial inflow not drained by the SSS and approximately 60 ml/minute ( ml/minute) of collateral flow originating from the deep system. Both of these figures suggest that a hemodynamically significant outflow stenosis must be operating. Interestingly, Hirabuki et al. 10 noted a 32% reduction in SSS flow in five patients with achondroplasia, fixed outflow obstruction, and hydrocephalus; in our study there was an overall 27% reduction in SSS flow. This comparison suggests that there is no significant hemodynamic difference between fixed and dynamic stenoses in children with hydrocephalus. As with the pressure data already discussed, 18,22 there was also no apparent difference in collateral flow between communicating and noncommunicating hydrocephalus, suggesting that the same venous pathophysiological condition may occur in both groups. The Initiator of Hydrocephalus: Resistance to CSF Absorption or Venous Pressure There is a significant elevation in venous pressure in idiopathic childhood hydrocephalus, but most of the literature suggests that an elevation in the resistance to CSF resorption (approximately three times normal) is the cause of this syndrome, 20,21 indicating a significant discrepancy between the findings in this study and those reported in the CSF resorption literature. Davson et al. 7 produced a mathematical model describing the relationship between ICP and the formation and reabsorption of CSF. They showed that ICP = R out FR CSF P SSS (Eq. 1) where R out is the resistance of CSF outflow, FR CSF is the rate of formation of CSF, and P SSS is the SSS pressure. 7 This equation suggests that the elevation in CSF pressure noted in childhood must come about because of an elevation in the CSF production rate, an elevation in the resistance to CSF resorption, an elevation in SSS pressure, or some combination of these factors. Shulman et al. 22 simultaneously measured the CSF and SSS pressure in 15 patients with childhood hydrocephalus and found a mean CSF/SSS gradient of 1.2 mm Hg. Sainte-Rose et al. 18 also found a minimal pressure gradient, the normal range for this gradient being 2 to 6 mm Hg. 5 Rearranging Davson s equation we find that the CSF/SSS pressure gradient is equal to the product of the CSF production rate and the resistance to flow across the arachnoid granulations. That is, ICP P SSS = R out FR CSF. (Eq. 2) The rate of CSF production has been shown to be normal in childhood hydrocephalus, and it is also relatively independent of the ICP. 6,17 Putting these results into Equation 2, we find that the R out must also be normal in children with hydrocephalus. This finding conflicts with results reported in the literature, which suggest that there is an elevated R out. 20,21 This discrepancy can be explained if the assumptions inherent in calculating the R out by using CSF infusion 442 J. Neurosurg: Pediatrics / Volume 107 / December, 2007

5 Venous pathophysiology of childhood hydrocephalus tests are understood. The R out value is calculated to be the slope of the graph obtained when mock CSF is infused into the spinal canal at varying rates or pressures and the resultant CSF pressure is plotted against the infusion rate. Ekstedt 8 states that the slope of this regression line is the R out but also notes that the slope could theoretically be explained by an elevation in the SSS pressure occurring during the course of the test. The requirement that the SSS pressure not change during the course of the test appears to be routinely ignored. Ekstedt concludes, whether or not the assumption of a rectilinear extrapolation is true can only be proved when the SSS pressure is measured directly during a CSF hydrodynamic experiment. Shulman and Ransohoff 22 and Sainte-Rose et al. 18 showed that, in childhood hydrocephalus associated with venous sinus compression, the venous pressures were directly related to the CSF pressure changes. Therefore, during infusion testing, an elevation in venous pressure will occur as a direct consequence of the elevation in CSF pressure, which is part of the infusion test. This occurrence will artifactually elevate the estimation of R out. Thus, direct pressure measurements indicate that the SSS pressure elevation is the major variable bringing about the elevation in CSF pressure in most cases of childhood hydrocephalus, despite the SSS pressure elevation itself being secondary to the CSF pressure elevation. This apparent contradiction can be explained if one accepts that a positive feedback loop exists in the venous outflow pathways of patients with dynamic stenoses. 1 The elevated compliance of the venous outflow in some children allows the CSF pressure to directly elevate the venous pressure and the venous pressure (because it sets the CSF pressure) then feeds back in a loop. 1 Stevens et al. 26 have studied an identical concept using IIH modeling based on electrical circuit theory, and the results of their study have confirmed the plausibility of this explanation. Brain Compliance and Ventricular Enlargement If venous obstruction can cause both hydrocephalus and IIH, then why do the ventricles enlarge in the one condition but not the other? The answer appears to be related to brain compliance. Compliance, or the pressure/volume index, is essentially a measure of the degree of stiffness of the walls delimiting the container surrounding the CSF. Sklar et al. 24 noted, it is apparent that changes in the pressure volume elasticity function (compliance) can alter the course of developing hydrocephalus and that elasticity changes may actually cause the ventricular enlargement. Shapiro et al. 20 found that childhood hydrocephalus is associated with an increase in brain compliance (twice normal) and the viscoelastic properties of the brain were altered in a way that allowed volume to be added to the ventricular system without altering the intracranial pressure in a significant way. 21 In fact, it is even possible for children to develop a low-pressure hydrocephalic state with continuous symptoms and ventricular enlargement despite CSF pressures that are lower than normal. 14 If compliance were the cause of the ventricular enlargement, one could hypothesize that, in older children and adults (whose ventricles do not dilate), there is normal compliance. This hypothesis appears to be correct. Sklar et al. 23 noted that the elasticity of the brain was normal in eight patients with IIH. Thus, patients with IIH are protected from developing J. Neurosurg: Pediatrics / Volume 107 / December, 2007 ventriculomegaly because of the elasticity of their brains. 24 Indeed, the shift to normal brain compliance with aging may occur even in children with hydrocephalus after long-term shunt treatment. When shunts malfunction, two groups of shunt-dependent children emerge. In the first group, the symptoms evolve rapidly with little enlargement of the ventricles despite significantly elevated CSF pressures (slitventricle syndrome); in the second there is more subtle deterioration with lower CSF pressures but enlarged ventricles (similar to standard childhood hydrocephalus). 19 The development of slit-ventricle syndrome occurs secondary to isolation of the ventricle into which the shunt was placed or obstruction of the shunt tube. 25 Despite an elevation in CSF pressure, the ventricles do not increase in size, but the patients respond to lumboperitoneal shunt placement. 25 It would appear that slit-ventricle syndrome is essentially the childhood equivalent of IIH with a nonfunctioning shunt tube. The brain compliance in children with slit-ventricle syndrome has been shown to be normal, 19 and this appears to protect them from ventricular enlargement. Diagnosis and Treatment Upon the basis of the preceding discussion it is suggested that an elevation in venous pressure may be important in the pathophysiological mechanisms of idiopathic childhood hydrocephalus. Although shunt placement provides symptomatic relief for these children, it probably does not change the underlying pathophysiological condition. As with IIH in adults, 9 direct treatment of the venous outflow obstruction may provide a more physiological basis for the treatment of children with hydrocephalus. It is suggested that all children with hydrocephalus should have an MR venogram as part of the workup for hydrocephalus. Ultimately, whether the first line of treatment in these patients should include correction of the stenoses or shunt placement will depend on the morbidity rates and long-term success of the differing procedures required. Conclusions Similarly to adults with IIH, children with idiopathic hydrocephalus show a significant elevation in collateral venous flow, indicating that elevated sinus compliance and venous collapse may be the underlying causes in both conditions. Whether or not the ventricles dilate in these diseases may depend on the differences in the brain compliance noted between adults and children. References 1. Bateman GA: Arterial inflow and venous outflow in idiopathic intracranial hypertension associated with venous outflow stenoses. J Clin Neurosci:[epub ahead of print], Bateman GA: Association between arterial inflow and venous outflow in idiopathic and secondary intracranial hypertension. J Clin Neurosci 13: , Bateman GA: Pulse-wave encephalopathy: a comparative study of the hydrodynamics of leukoaraiosis and normal-pressure hydrocephalus. Neuroradiology 44: , Bateman GA: Vascular hydraulics associated with idiopathic and secondary intracranial hypertension. AJNR Am J Neuroradiol 23: , Benabid AL, De Rougemont J, Barge M: [Cerebral venous pres- 443

6 G. A. Bateman, R. L. Smith, and S. H. Siddique sure, sinus pressure and intracranial pressure.] Neurochirurgie 20: , Blomquist HK, Sundin S, Ekstedt J: Cerebrospinal fluid hydrodynamic studies in children. J Neurol Neurosurg Psychiatry 49: , Davson H, Welch K, Segal MB: Physiology and Pathophysiology of the Cerebrospinal Fluid. New York: Churchill Livingstone, 1987, pp Ekstedt J: CSF hydrodynamic studies in man. 1. Method of constant pressure CSF infusion. J Neurol Neurosurg Psychiatry 40: , Higgins JN, Cousins C, Owler BK, Sarkies N, Pickard JD: Idiopathic intracranial hypertension: 12 cases treated by venous sinus stenting. J Neurol Neurosurg Psychiatry 74: , Hirabuki N, Watanabe Y, Mano T, Fujita N, Tanaka H, Ueguchi T, et al: Quantification of flow in the superior sagittal sinus performed with cine phase-contrast MR imaging of healthy and achondroplastic children. AJNR Am J Neuroradiol 21: , Karahalios DG, Rekate HL, Khayata MH, Apostolides PJ: Elevated intracranial venous pressure as a universal mechanism in pseudotumor cerebri of varying etiologies. Neurology 46: , King JO, Mitchell PJ, Thompson KR, Tress BM: Manometry combined with cervical puncture in idiopathic intracranial hypertension. Neurology 58:26 30, Koudijs SM, van der Grond J, Hoogendoorn MLC, Hulshoff Pol HE, Schnack HG, Witkamp TD, et al: MRI, volumetry, 1H spectroscopy, and cerebropetal blood flowmetry in childhood idiopathic anatomic megalencephaly. J Magn Res Imag 24: , Pang D, Altschuler E: Low-pressure hydrocephalic state and viscoelastic alterations in the brain. Neurosurgery 35: , Rohr A, Döner L, Stingele R, Buhl R, Alfke K, Jansen O: Reversibility of venous sinus obstruction in idiopathic intracranial hypertension. AJNR Am J Neuroradiol 28: , Rosman NP, Shands KN: Hydrocephalus caused by increased intracranial venous pressure: a clinicopathological study. Ann Neurol 3: , Rubin RC, Henderson ES, Ommaya AK, Walker MD, Rall DP: The production of cerebrospinal fluid in man and its modification by acetazolamide. J Neurosurg 25: , Sainte-Rose C, LaCombe J, Pierre-Kahn A, Renier D, Hirsch JF: Intracranial venous sinus hypertension: cause or consequence of hydrocephalus in infants? J Neurosurg 60: , Shapiro K, Fried A: Pressure-volume relationships in shuntdependent childhood hydrocephalus. The zone of pressure instability in children with acute deterioration. J Neurosurg 64: , Shapiro K, Fried A, Marmarou A: Biomechanical and hydrodynamic characterization of the hydrocephalic infant. J Neurosurg 63:69 75, Shapiro K, Marmarou A, Shulman K: Abnormal brain biomechanics in the hydrocephalic child. From: Concepts in Pediatric Neurosurgery, 1982, vol 2. Pediatr Neurosurg 19: , Shulman K, Ransohoff J: Sagittal sinus pressure in hydrocephalus. J Neurosurg 23: , Sklar FH, Beyer CW Jr, Clark WK: Physiological features of the pressure-volume function of brain elasticity in man. J Neurosurg 53: , Sklar FH, Diehl JT, Beyer CW Jr, Clarke WK: Brain elasticity changes with ventriculomegaly. J Neurosurg 53: , Sood S, Barrett RJ, Powell T, Ham SD: The role of lumbar shunts in the management of slit ventricles: does the slit-ventricle syndrome exist? J Neurosurg 103 (2 Suppl): , Stevens SA, Previte M, Lakin WD, Thakore NJ, Penar PL, Hamschin B: Idiopathic intracranial hypertension and transverse sinus stenosis: a modeling study. Mat Med Biol 24:85 109, 2007 Manuscript submitted July 24, Accepted August 28, Address correspondence to: Grant A. Bateman, M.B.B.S., Department of Medical Imaging, John Hunter Hospital, Locked Bag 1, Newcastle Region Mail Center, Newcastle 2310, Australia. grant.bateman@hnehealth.nsw.gov.au. 444 J. Neurosurg: Pediatrics / Volume 107 / December, 2007