In vitro testing of explanted shunt valves in hydrocephalic patients with suspected valve malfunction.

Diagnosis of symptomatic valve malfunction in hydrocephalic patients treated with VP-Shunt (VPS) might be difficult. Clinical symptoms such as headache or nausea are nonspecific, hence cerebrospinal fluid (CSF) over- or underdrainage can only be suspected but not proven. Knowledge concerning valve malfunction is still limited. We aim to provide data on the flow characteristics of explanted shunt valves in patients with suspected valve malfunction. An in vitro shunt laboratory setup was used to analyze the explanted valves under conditions similar to those in an implanted VPS. The differential pressure (DP) of the valve was adjusted stepwise to 20, 10, 6, and 4 cmH2O. The flow rate of the explanted and the regular flow rate of an identical reference valve were evaluated at the respective DPs. Twelve valves of different types (Codman CertasPlus valve n = 3, Miethke Shuntassistant valve n = 4, Codman Hakim programmable valve n = 3, DP component of Miethke proGAV 2.0 valve n = 2) from eight hydrocephalic patients (four male), in whom valve malfunction was assumed between 2016 and 2017, were replaced with a new valve. Four patients suffered from idiopathic normal pressure (iNPH), three patients from malresorptive and one patient from obstructive hydrocephalus. Post-hoc analysis revealed a significant difference (p < 0.001) of the flow rate between each explanted valve and their corresponding reference valve, at each DP. In all patients, significant alterations of flow rates were demonstrated, verifying a valve malfunction, which could not be objectified by the diagnostic tools used in the clinical routine. In cases with obscure clinical VPS insufficiency, valve deficiency should be considered.

A counterforce to diversion of cerebrospinal fluid during ventriculoperitoneal shunting: the intraperitoneal pressure. An observational study.

BACKGROUND: Intraperitoneal pressure (IPP) counteracts the diversion of cerebrospinal fluid (CSF) from the cranial to the peritoneal compartment during ventriculoperitoneal shunting. Animal studies suggest that the intrinsic IPP exceeds the intraperitoneal hydrostatic pressure. The intrinsic IPP in mobile patients is relevant for shunt therapy, but data about it is not available. METHODS: The IPP was measured indirectly in 25 mobile subjects (13 female) by applying a standard intravesical pressure measurement technique. Measurements were carried out in reference to the navel (supine position) and the xiphoid (upright position). Results were adjusted for the intraperitoneal hydrostatic pressure and correlated afterward with general body measures. RESULTS: The corrected mean (SD) IPP measured in the supine position was 4.4 (4.5) cm H2O, and the mean (SD) upright IPP was 1.6 (7.8) cm H2O (p = 0.02). A positive correlation was found between the body mass index (BMI) and the IPP in the upright (r = 0.51) and supine (r = 0.65) body positions, and between the abdominal circumference and the IPP in the supine position (r = 0.63). CONCLUSIONS: The intrinsic IPP in mobile subjects exceeds the intraperitoneal hydrostatic pressure. Thus, the intrinsic IPP counteracts the diversion of CSF into the peritoneal compartment. The intrinsic IPP is correlated with mobile patients' general body measures.

Pressure Measurement Techniques for Abdominal Hypertension: Conclusions from an Experimental Model.

Introduction. Intra-abdominal pressure (IAP) measurement is an indispensable tool for the diagnosis of abdominal hypertension. Different techniques have been described in the literature and applied in the clinical setting. Methods. A porcine model was created to simulate an abdominal compartment syndrome ranging from baseline IAP to 30 mmHg. Three different measurement techniques were applied, comprising telemetric piezoresistive probes at two different sites (epigastric and pelvic) for direct pressure measurement and intragastric and intravesical probes for indirect measurement. Results. The mean difference between the invasive IAP measurements using telemetric pressure probes and the IVP measurements was -0.58 mmHg. The bias between the invasive IAP measurements and the IGP measurements was 3.8 mmHg. Compared to the realistic results of the intraperitoneal and intravesical measurements, the intragastric data showed a strong tendency towards decreased values. The hydrostatic character of the IAP was eliminated at high-pressure levels. Conclusion. We conclude that intragastric pressure measurement is potentially hazardous and might lead to inaccurately low intra-abdominal pressure values. This may result in missed diagnosis of elevated abdominal pressure or even ACS. The intravesical measurements showed the most accurate values during baseline pressure and both high-pressure plateaus.

High-resolution mechanical imaging of glioblastoma by multifrequency magnetic resonance elastography.

OBJECTIVE: To generate high-resolution maps of the viscoelastic properties of human brain parenchyma for presurgical quantitative assessment in glioblastoma (GB). METHODS: Twenty-two GB patients underwent routine presurgical work-up supplemented by additional multifrequency magnetic resonance elastography. Two three-dimensional viscoelastic parameter maps, magnitude |G*|, and phase angle φ of the complex shear modulus were reconstructed by inversion of full wave field data in 2-mm isotropic resolution at seven harmonic drive frequencies ranging from 30 to 60 Hz. RESULTS: Mechanical brain maps confirmed that GB are composed of stiff and soft compartments, resulting in high intratumor heterogeneity. GB could be easily differentiated from healthy reference tissue by their reduced viscous behavior quantified by φ (0.37±0.08 vs. 0.58±0.07). |G*|, which in solids more relates to the material's stiffness, was significantly reduced in GB with a mean value of 1.32±0.26 kPa compared to 1.54±0.27 kPa in healthy tissue (P = 0.001). However, some GB (5 of 22) showed increased stiffness. CONCLUSION: GB are generally less viscous and softer than healthy brain parenchyma. Unrelated to the morphology-based contrast of standard magnetic resonance imaging, elastography provides an entirely new neuroradiological marker and contrast related to the biomechanical properties of tumors.

In vitro performance and principles of anti-siphoning devices.

BACKGROUND: Anti-siphon devices (ASDs) of various working principles were developed to overcome overdrainage-related complications associated with ventriculoperitoneal shunting. OBJECTIVE: We aimed to provide comparative data on the pressure and flow characteristics of six different types of ASDs (gravity-assisted, membrane-controlled, and flow-regulated) in order to achieve a better understanding of these devices and their potential clinical application. METHODS: We analyzed three gravity-dependent ASDs (ShuntAssistant [SA], Miethke; Gravity Compensating Accessory [GCA], Integra; SiphonX [SX], Sophysa), two membrane-controlled ASDs (Anti-Siphon Device [IASD], Integra; Delta Chamber [DC], Medtronic), and one flow-regulated ASD (SiphonGuard [SG], Codman). Defined pressure conditions within a simulated shunt system were generated (differential pressure 10-80 cmH2O), and the specific flow and pressure characteristics were measured. In addition, the gravity-dependent ASDs were measured in defined spatial positions (0-90°). RESULTS: The flow characteristics of the three gravity-assisted ASDs were largely dependent upon differential pressure and on their spatial position. All three devices were able to reduce the siphoning effect, but each to a different extent (flow at inflow pressure: 10 cmH2O, siphoning -20 cmH2O at 0°/90°: SA, 7.1 ± 1.2*/2.3 ± 0.5* ml/min; GCA, 10.5 ± 0.8/3.4 ± 0.4* ml/min; SX, 9.5 ± 1.2*/4.7 ± 1.9* ml/min, compared to control, 11.1 ± 0.4 ml/min [*p < 0.05]). The flow characteristics of the remaining ASDs were primarily dependent upon the inflow pressure effect (flow at 10 cmH2O, siphoning 0 cmH2O/ siphoning -20cmH2O: DC, 2.6 ± 0.1/ 4 ± 0.3* ml/min; IASD, 2.5 ± 0.2/ 0.8 ± 0.4* ml/min; SG, 0.8 ± 0.2*/ 0.2 ± 0.1* ml/min [*p < 0.05 vs. control, respectively]). CONCLUSION: The tested ASDs were able to control the siphoning effect within a simulated shunt system to differing degrees. Future comparative trials are needed to determine the type of device that is superior for clinical application.

The Frankfurt horizontal plane as a reference for the implantation of gravitational units: a series of 376 adult patients.

BACKGROUND: The in-line combination of adjustable differential pressure valves with fixed gravitational units is increasingly recommended in the literature. The spatial positioning of the gravitational unit is thereby decisive for the valve opening pressure. We aimed at providing data on factors contributing to primary overdrainage and underdrainage of cerebrospinal fluid (CSF), with special attention paid to the implantation angle of the gravitational unit. METHODS: Weretrospectively analyzed the postoperative course of 376 consecutive patients who received a ventriculoperitoneal shunt with a proGAV valve. The incidence of both primary CSF overdrainage and underdrainage was correlated with the implantation angle of the gravitational unit in regard to the Frankfurt horizontal plane and the patients' general parameters. RESULTS: Primary overdrainage was found in 41 (10.9 %) patients. Primary underdrainage was found in 113 (30.1 %) patients. A mean deviation of 10° (±7.8) for the gravitational unit in regard to the vertical line to the Frankfurt horizontal plane was found. In 95 % of the cases the deviation was less than 25°. No significant correlation between the implantation angle and the incidence of overdrainage or underdrainage of CSF was found. The patients' age and having single hydrocephalus entities were identified as factors significantly predisposing patients to overdrainage or underdrainage. CONCLUSION: The implantation of the gravitational unit of the proGAV valve within a range of at least 10° in regard to the vertical line to the Frankfurt horizontal plane does not seem to predispose patients to primary overdrainage or underdrainage in ventriculoperitoneal shunting. The plane may serve as a useful reference for the surgeon's orientation.

Feasibility of telemetric ICP-guided valve adjustments for complex shunt therapy.

OBJECT: The advances in shunt valve technology towards modern adjustable differential pressure (DP) valves and adjustable gravitational assisted valves result in an increasing complexity of therapeutical options. Modern telemetric intracranial pressure (ICP) sensors may be helpful in their application for diagnostic purposes in shunt therapy. We present our first experiences on telemetric ICP-guided valve adjustments in cases with the combination of an adjustable DP valve and adjustable gravitational unit. METHODS: Four consecutive cases were evaluated in a retrospective review who had received a proGAV adjustable, gravitational assisted DP valve with secondary in-line implantation of an adjustable shunt assistant (proSA), together with a telemetric ICP sensor (Neurovent-P-tel) between December 2010 and June 2012 in our institution. The measured ICP values and the corresponding valve adjustments were analyzed in correlation with the clinical course and the cranial imaging of the patients. RESULTS: No surgery-related complications were observed after implantation of the proSA and the telemetric ICP sensor additional to the proGAV. ICP values could actively be influenced by adjustments of the respective valve units. An increase of the position depending resistance of the proSA resulted in significant attenuated negative ICP values for the standing position, while adjustments of the proGAV could be detected not only in a supine position but also in a standing position. A clinical improvement could be achieved in all cases. CONCLUSION: The combination of adjustability in the differential pressure valve and the gravitational unit reveals a complex combination which may be difficult to adapt only according to clinical information. Telemetric ICP-guided valve adjustments seem to be a promising tool as an objective measure according to different body positions. Further investigations are needed to select the patients for these costly implants.

Large-scale referencing of the telemetric neurovent-P-tel intracranial pressure sensor in a porcine model.

The Neurovent-P-tel sensor is a promising device for telemetric intracranial pressure (ICP) measurements in cases of complex hydrocephalus. Data on its accuracy within a broad ICP range are missing. We applied a porcine model for large-scale manipulation of the ICP values. The telemetric ICP sensor was referenced against ICP values measured directly from a water column within a riser tube. A total of 34 comparative ICP measurements within an ICP range from 2 cm H2O to 31 mm Hg were performed. The mean difference between both measurement techniques was 0.4 mm Hg. The limits of agreement, where 95% of differences between both methods are expected, were from -2.4 to 3.1 mm Hg. The telemetric Neurovent-P-tel sensor system provides good accuracy within a broad range exceeding normal ICP values and might be useful in clinical practice.

Differential pressure in shunt therapy: investigation of position-dependent intraperitoneal pressure in a porcine model.

OBJECT: The differential pressure between the intracranial and intraperitoneal cavities is essential for ventriculoperitoneal shunting. A determination of the pressure in both cavities is decisive for selecting the appropriate valve type and opening pressure. The intraperitoneal pressure (IPP)-in contrast to the intracranial pressure-still remains controversial with regard to its normal level and position dependency. METHODS: The authors used 6 female pigs for the experiments. Two transdermal telemetric pressure sensors (cranial and caudal) were implanted intraperitoneally with a craniocaudal distance of 30 cm. Direct IPP measurements were supplemented with noninvasive IPP measurements (intragastral and intravesical). The IPP was measured with the pigs in the supine (0°), 30°, 60°, and vertical (90°) body positions. After the pigs were euthanized, CT was used to determine the intraperitoneal probe position. RESULTS: With pigs in the supine position, the mean (± SD) IPP was 10.0 ± 3.5 cm H2O in a mean vertical distance of 4.5 ± 2.8 cm to the highest level of the peritoneum. The difference between the mean IPP of the cranially and the caudally implanted probes (Δ IPP) increased according to position, from 5.5 cm H2O in the 0° position to 11.5 cm H2O in the 30° position, 18.3 cm H2O in the 60° position, and 25.6 cm H2O in the vertical body position. The vertical distance between the probe tips (cranially implanted over caudally implanted) increased 3.4, 11.2, 19.3, and 22.3 cm for each of the 4 body positions, respectively. The mean difference between the Δ IPP and the vertical distance between both probe tips over all body positions was 1.7 cm H2O. CONCLUSIONS: The IPP is subject to the position-dependent hydrostatic force. Normal IPP is able to reduce the differential pressure in patients with ventriculoperitoneal shunts.

Patients benefit from low-pressure settings enabled by gravitational valves in normal pressure hydrocephalus.

OBJECTIVE: The ability of siphon regulatory devices to improve overdrainage control despite low-pressure settings of the valve for the horizontal body position has been described previously. We aim to provide a systematic investigation on the ability of gravitational units as siphon regulatory devices to improve clinical outcome in shunt therapy. METHODS: We analyzed retrospectively postoperative complications, type and frequency of valve adjustments and the clinical outcome using Black's outcome scale at different time points of all iNPH patients operated in our center between January 2007 and December 2010. They had received either a proGAV® valve with an integrated gravitational unit, or a programmable Codman Hakim® valve without an integrated siphon regulatory device. RESULTS: The postoperative course of 55 proGAV® and 45 programmable Codman Hakim® patients was analyzed. The latest documented valve setting of the proGAV® group and Codman Hakim® group was median 50mm H2O and 120 mm H2O, respectively. Overdrainage occurred among both groups in 20% of the patients, while surgical intervention for overdrainage-related complications was seen to be necessary only in 7% of the cases in the Codman Hakim® group. Clinical outcome differed in an increasing manner over the observation period (median 4 points after 3, 12 months and at final presentation in the proGAV®; median 4 points after 3 and 12 months and 3 points at final presentation in Codman Hakim® group (p=0.001)). CONCLUSION: Adjustable and gravity-assisted valves like the proGAV® improve overdrainage control and enable thus low-pressure settings for the horizontal body position. We observed an improved and more sustainable functional outcome for iNPH patients with an adjustable and gravity-assisted valve compared to iNPH patients without an integrated siphon regulatory device.

MR elastography in a murine stroke model reveals correlation of macroscopic viscoelastic properties of the brain with neuronal density.

The aim of this study was to investigate the influence of neuronal density on viscoelastic parameters of living brain tissue after ischemic infarction in the mouse using MR elastography (MRE). Transient middle cerebral artery occlusion (MCAO) in the left hemisphere was induced in 20 mice. In vivo 7-T MRE at a vibration frequency of 900 Hz was performed on days 3, 7, 14 and 28 (n = 5 per group) after MCAO, followed by the analysis of histological markers, such as neuron counts (NeuN). MCAO led to a significant reduction in the storage modulus in the left hemisphere relative to contralateral values (p = 0.03) without changes over time. A correlation between storage modulus and NeuN in both hemispheres was observed, with correlation coefficients of R = 0.648 (p = 0.002, left) and R = 0.622 (p = 0.003, right). The loss modulus was less sensitive to MCAO, but correlated with NeuN in the left hemisphere (R = 0.764, p = 0.0001). In agreement with the literature, these results suggest that the shear modulus in the brain is reduced after transient ischemic insult. Furthermore, our study provides evidence that the in vivo shear modulus of brain tissue correlates with neuronal density. In diagnostic applications, MRE may thus have diagnostic potential as a tool for image-based quantification of neurodegenerative processes.

Evaluation of a new large animal model for controlled intracranial pressure changes induced by capnoperitoneum.

BACKGROUND: A standardized large animal model for controlled ICP manipulation within a relevant range and repetitive ICP measurements is missing. We sought to develop such a model on the base of controlled IPP changes induced by capnoperitoneum. METHODS: We utilized six female pigs (mean body weight 59.5 ± 18.4 kg) for experiments. A ventricular catheter connected with a burr hole reservoir was implanted. ICP was measured directly as cm H2O within a riser tube after percutaneous cannulation of the reservoir. A noninvasive intraperitoneal pressure (IPP) measurement was established (intravesical). Animals were placed in lateral position and a capnoperitoneum was induced. Measurements of ICP, IPP, MAP and respiratory parameters were performed at baseline IPP and after CO2 insufflation to IPP levels of 20 and 30 mmHg. RESULTS: Baseline IPP in lateral position referenced to median line was 9.8 (±2) mm Hg, while corresponding ICP was 10 (±2.2) mm Hg. After IPP elevation to 20 mmHg, ICP increased to 18.8 (±1.9) mm Hg. At 30 mmHg IPP, ICP increased to 22.8 (±2.8) mm Hg. Except peak airway pressure, all other parameters were kept constantly. Mean ICP variation in the individual subject was 13.4 (±2.5) mm Hg, while a ICP range from minimum 9 to maximum 31 mmHg was documented. CONCLUSIONS: We report a large animal model that allows (1) repeated measurement of the ICP and (2) manipulation of the ICP within a large pressure range by controlled IPP changes due to capnoperitoneum.

Shunting with gravitational valves--can adjustments end the era of revisions for overdrainage-related events?: clinical article.

OBJECT: Overdrainage of CSF remains an unsolved problem in shunt therapy. The aim of the present study was to evaluate treatment options on overdrainage-related events enabled by the new generation of adjustable gravity-assisted valves. METHODS: The authors retrospectively studied the clinical course of 250 consecutive adult patients with various etiologies of hydrocephalus after shunt insertion for different signs and symptoms of overdrainage. Primary and secondary overdrainage were differentiated. The authors correlated the incidence of overdrainage with etiology of hydrocephalus, opening valve pressure, and patient parameters such as weight and size. Depending on the severity of overdrainage, they elevated the opening pressure, and follow-up was performed until overdrainage was resolved. RESULTS: The authors found 39 cases (15.6%) involving overdrainage-related problems--23 primary and 16 secondary overdrainage. The median follow-up period in these 39 patients was 2.1 years. There was no correlation between the incidence of overdrainage and any of the following factors: sex, age, size, or weight of the patients. There was also no statistical significance among the different etiologies of hydrocephalus, with the exception of congenital hydrocephalus. All of the "complications" could be resolved by readjusting the opening pressure of the valve in one or multiple steps, avoiding further operations. CONCLUSIONS: Modern adjustable and gravity-assisted valves enable surgeons to set the opening pressure relatively low to avoid underdrainage without significantly raising the incidence of overdrainage and to treat overdrainage-related clinical and radiological complications without surgical intervention.

Alteration of brain viscoelasticity after shunt treatment in normal pressure hydrocephalus.

INTRODUCTION: Normal pressure hydrocephalus (NPH) represents a chronic neurological disorder with increasing incidence. The symptoms of NPH may be relieved by surgically implanting a ventriculoperitoneal shunt to drain excess cerebrospinal fluid. However, the pathogenesis of NPH is not yet fully elucidated, and the clinical response of shunt treatment is hard to predict. According to current theories of NPH, altered mechanical properties of brain tissue seem to play an important role. Magnetic resonance elastography (MRE) is a unique method for measuring in vivo brain mechanics. METHODS: In this study cerebral MRE was applied to test the viscoelastic properties of the brain in 20 patients with primary (N = 14) and secondary (N = 6) NPH prior and after (91 ± 16 days) shunt placement. Viscoelastic parameters were derived from the complex modulus according to the rheological springpot model. This model provided two independent parameters µ and α, related to the inherent rigidity and topology of the mechanical network of brain tissue. RESULTS: The viscoelastic parameters µ and α were found to be decreased with -25% and -10%, respectively, compared to age-matched controls (P < 0.001). Interestingly, α increased after shunt placement (P < 0.001) to almost normal values whereas µ remained symptomatically low. CONCLUSION: The results indicate the fundamental role of altered viscoelastic properties of brain tissue during disease progression and tissue repair in NPH. Clinical improvement in NPH is associated with an increasing complexity of the mechanical network whose inherent strength, however, remains degraded.

In vivo viscoelastic properties of the brain in normal pressure hydrocephalus.

Nearly half a century after the first report of normal pressure hydrocephalus (NPH), the pathophysiological cause of the disease still remains unclear. Several theories about the cause and development of NPH emphasize disease-related alterations of the mechanical properties of the brain. MR elastography (MRE) uniquely allows the measurement of viscoelastic constants of the living brain without intervention. In this study, 20 patients (mean age, 69.1 years; nine men, 11 women) with idiopathic (n = 15) and secondary (n = 5) NPH were examined by cerebral multifrequency MRE and compared with 25 healthy volunteers (mean age, 62.1 years; 10 men, 15 women). Viscoelastic constants related to the stiffness (µ) and micromechanical connectivity (α) of brain tissue were derived from the dynamics of storage and loss moduli within the experimentally achieved frequency range of 25-62.5 Hz. In patients with NPH, both storage and loss moduli decreased, corresponding to a softening of brain tissue of about 20% compared with healthy volunteers (p < 0.001). This loss of rigidity was accompanied by a decreasing α parameter (9%, p < 0.001), indicating an alteration in the microstructural connectivity of brain tissue during NPH. This disease-related decrease in viscoelastic constants was even more pronounced in the periventricular region of the brain. The results demonstrate distinct tissue degradation associated with NPH. Further studies are required to investigate the source of mechanical tissue damage as a potential cause of NPH-related ventricular expansions and clinical symptoms.