Toward the "Perfect" Shunt: Historical Vignette, Current Efforts, and Future Directions.

As a concept, drainage of excess fluid volume in the cranium has been around for more than 1000 years. Starting with the original decompression-trepanation of Abulcasis to modern programmable shunt systems, to other nonshunt-based treatments such as endoscopic third ventriculostomy and choroid plexus cauterization, we have come far as a field. However, there are still fundamental limitations that shunts have yet to overcome: namely posture-induced over- and underdrainage, the continual need for valve opening pressure especially in pediatric cases, and the failure to reinstall physiologic intracranial pressure dynamics. However, there are groups worldwide, in the clinic, in industry, and in academia, that are trying to ameliorate the current state of the technology within hydrocephalus treatment. This chapter aims to provide a historical overview of hydrocephalus, current challenges in shunt design, what members of the community have done and continue to do to address these challenges, and finally, a definition of the "perfect" shunt is provided and how the authors are working toward it.

A Soft Robotic Actuator System for In Vivo Modeling of Normal Pressure Hydrocephalus.

OBJECTIVE: The intracranial pressure (ICP) affects the dynamics of cerebrospinal fluid (CSF) and its waveform contains information that is of clinical importance in medical conditions such as hydrocephalus. Active manipulation of the ICP waveform could enable the investigation of pathophysiological processes altering CSF dynamics and driving hydrocephalus. METHODS: A soft robotic actuator system for intracranial pulse pressure amplification was developed to model normal pressure hydrocephalus in vivo. Different end actuators were designed for intraventricular implantation and manufactured by applying cyclic tensile loading on soft rubber tubing. Their mechanical properties were investigated, and the type that achieved the greatest pulse pressure amplification in an in vitro simulator of CSF dynamics was selected for application in vivo. A hydraulic actuation device based on a linear voice coil motor was developed to enable automated and fast operation of the end actuators. The combined system was validated in an acute ovine pilot in vivo study. RESULTS: in vitro results show that variations in the used materials and manufacturing settings altered the end actuator's dynamic properties, such as the pressure-volume characteristics. In the in vivo model, a cardiac-gated actuation volume of 0.125 mL at a heart rate of 62 bpm caused an increase of 205% in mean peak-to-peak amplitude but only an increase of 1.3% in mean ICP. CONCLUSION: The introduced soft robotic actuator system is capable of ICP waveform manipulation. SIGNIFICANCE: Continuous amplification of the intracranial pulse pressure could enable in vivo modeling of normal pressure hydrocephalus and shunt system testing under pathophysiological conditions to improve therapy for hydrocephalus.

The influence of upright posture on craniospinal, arteriovenous, and abdominal pressures in a chronic ovine in-vivo trial.

INTRODUCTION: Most investigations into postural influences on craniospinal and adjacent physiology have been performed in anesthetized animals. A comprehensive study evaluating these physiologies while awake has yet been completed. METHODS: Six awake sheep had telemetric pressure sensors (100 Hz) implanted to measure intracranial, intrathecal, arterial, central venous, cranial, caudal, dorsal, and ventral intra-abdominal pressure (ICP, ITP, ABP, CVP, IAPcr, IAPcd, IAPds, IAPve, respectively). They were maneuvered upright by placing in a chair for two minutes; repeated 25 times over one month. Changes in mean and pulse pressure were calculated by comparing pre-chair, P0, with three phases during the maneuver: P1, chair entrance; P2, chair halftime; P3, prior to chair exit. Statistical significance (p ≤ .05) was assessed using repeated measures ANOVA. RESULTS: Significant mean pressure changes of (P1 - P0) and (P3 - P0) were measured at - 12.1 ± 3.1 and - 14.2 ± 3.0(p < .001), 40.8 ± 10.5 and 37.7 ± 3.5(p = .019), 9.7 ± 8.3 and 6.2 ± 5.3(p = .012), 22.3 ± 29.8 and 12.5 ± 12.1(p = .042), and 11.7 ± 3.9 and 9.0 ± 5.2(p = .014) mmHg, for ICP, ITP, IAPds, IAPcr, IAPca, respectively. For pulse pressures, significant changes of (P1 - P0) and (P3 - P0) were measured at - 1.3 ± 0.7 and - 2.0 ± 1.1(p < .001), 4.7 ± 2.3 and 1.4 ± 1.4(p < .001), 15.0 ± 10.2 and 7.3 ± 5.5(p < .001), - 0.7 ± 1.8 and - 1.7 ± 1.7(p < .001), - 1.3 ± 4.2 and - 1.4 ± 4.7(p = .006), and 0.3 ± 3.9 and - 1.0 ± 1.3(p < .001) mmHg, for ICP, ITP, ABP, IAPds, IAPcr, IAPca, respectively. CONCLUSIONS: Pressures changed posture-dependently to differing extents. Changes were most pronounced immediately after entering upright posture (P1) and became less prominent over the chair duration (P2-to-P3), suggesting increased physiologic compensation. Dynamic changes in IAP varied across abdominal locations, motivating the abdominal cavity not to be considered as a unified entity, but sub-compartments with individual dynamics.

Influence of head-over-body and body-over-head posture on craniospinal, vascular, and abdominal pressures in an acute ovine in-vivo model.

INTRODUCTION: Optimal shunt-based hydrocephalus treatments are heavily influenced by dynamic pressure behaviors between proximal and distal ends of shunt catheters. Posture-dependent craniospinal, arterial, venous, and abdominal dynamics thereby play an essential role. METHODS: An in-vivo ovine trial (n = 6) was conducted to evaluate communication between craniospinal, arterial, venous, and abdominal dynamics. Tilt-testing was performed between -13° and + 13° at 10-min intervals starting and ending at 0° prone position. Mean pressure, pulse pressure, and Pearson correlation (r) to the respective angle were calculated. Correlations are defined as strong: |r|≥ 0.7, mild: 0.3 <|r|< 0.7, and weak: |r|≤ 0.3. Transfer functions (TFs) between the arterial and adjacent compartments were derived. RESULTS: Strong correlations were observed between posture and: mean carotid/femoral arterial (r = - 0.97, r = - 0.87), intracranial, intrathecal (r = - 0.98, r = 0.94), jugular (r = - 0.95), abdominal cranial, dorsal, caudal, and intravesical pressure (r = - 0.83, r = 0.84, r = - 0.73, r = 0.99) while mildly positive correlation exists between tilt and central venous pressure (r = 0.65). Only dorsal abdominal pulse pressure yielded a significant correlation to tilt (r = 0.21). TFs followed general lowpass behaviors with resonant peaks at 4.2 ± 0.4 and 11.5 ± 1.5 Hz followed by a mean roll-off of - 15.9 ± 6.0 dB/decade. CONCLUSIONS: Tilt-tests with multi-compartmental recordings help elucidate craniospinal, arterial, venous, and abdominal dynamics, which is essential to optimize shunt-based therapy. Results motivate hydrostatic influences on mean pressure, with all pressures correlating to posture, with little influence on pulse pressure. TF results quantify the craniospinal, arterial, venous, and abdominal compartments as compliant systems and help pave the road for better quantitative models of the interaction between the craniospinal and adjacent spaces.

Venous dynamics in anesthetized sheep govern postural-induced changes in cerebrospinal fluid pressure comparable to those in humans.

Sheep are popular large animals in which to model human disorders and to study physiological processes such as cerebrospinal fluid dynamics. However, little is known about vascular compensatory mechanisms affecting cerebrospinal fluid pressures during acute postural changes in sheep. Six female white Alpine sheep were anesthetized to investigate the interactions of the vascular and cerebrospinal fluid system by acquiring measurements of intracranial pressure and central and jugular venous pressure during passive postural changes induced by a tilt table. The cross-sectional area of the common jugular vein and venous blood flow velocity was recorded. Anesthetized sheep showed bi-phasic effects of postural changes on intracranial pressure during tilting. A marked collapse of the jugular vein was observed during head-over-body tilting; this is in accordance with findings in humans. Active regulatory effects of the arterial system on maintaining cerebral perfusion pressure were observed independent of tilting direction. Conclusion: Anesthetized sheep show venous dynamics in response to posture-induced changes in intracranial pressure that are comparable with those in humans.

The Sheep as a Comprehensive Animal Model to Investigate Interdependent Physiological Pressure Propagation and Multiparameter Influence on Cerebrospinal Fluid Dynamics.

The present study aims to develop a suitable animal model for evaluating the physiological interactions between cerebrospinal fluid (CSF) dynamics, hemodynamics, and abdominal compartment pressures. We seek to contribute to the enhanced recognition of the pathophysiology of CSF-dependent neurological disorders like hydrocephalus and the improvement of available treatment options. To date, no comprehensive animal model of CSF dynamics exists, and establishing an accurate model will advance our understanding of complex CSF physiology. Persisting knowledge gaps surrounding the communication and pressure propagation between the cerebrospinal space and adjacent anatomical compartments exacerbate the development of novel therapies for neurological diseases. Hence, the need for further investigation of the interactions of vascular, craniospinal, and abdominal pressures remains beyond dispute. Moreover, the results of this animal study support the optimization of in vitro test benches for medical device development, e.g., ventriculoperitoneal shunts. Six female white alpine sheep were surgically equipped with pressure sensors to investigate the physiological values of intracranial, intrathecal, arterial, central venous, jugular venous, vesical pressure, and four differently located abdominal pressures. These values were measured simultaneously during the acute animal trial with sheep under general anesthesia. Both carotid and femoral arterial blood pressure indicate a reliable and comparable representation of the systematic blood pressure. However, the jugular venous pressure and the central venous pressure in sheep in dorsal recumbency do not correlate well under general anesthesia. Furthermore, there is a trend for possible comparability of lateral intraventricular and lumbar intrathecal pressure. Nevertheless, animal body position during measurements must be considered since different body constitutions can alter the horizontal line between the cerebral ventricles and the lumbar subarachnoid space. While intra-abdominal pressure measurement in the four different abdominal quadrants yielded greater inter-individual variability, intra-vesical pressure measurements in our setting delivered comparable values for all sheep. We established a novel and comprehensive ovine animal model to investigate interdependent physiologic pressure propagation and multiparameter influences on CSF dynamics. The results of this study will contribute to further in vitro bench testing, the derivation of novel quantitative models, and the development of a pathologic ovine hydrocephalus model.

Intercompartmental communication between the cerebrospinal and adjacent spaces during intrathecal infusions in an acute ovine in-vivo model.

INTRODUCTION: The treatment of hydrocephalus has been a topic of intense research ever since the first clinically successful use of a valved cerebrospinal fluid shunt 72 years ago. While ample studies elucidating different phenomena impacting this treatment exist, there are still gaps to be filled. Specifically, how intracranial, intrathecal, arterial, and venous pressures react and communicate with each other simultaneously. METHODS: An in-vivo sheep trial (n = 6) was conducted to evaluate and quantify the communication existing within the cranio-spinal, arterial, and venous systems (1 kHz sampling frequency). Standardized intrathecal infusion testing was performed using an automated infusion apparatus, including bolus and constant pressure infusions. Bolus infusions entailed six lumbar intrathecal infusions of 2 mL Ringer's solution. Constant pressure infusions were comprised of six regulated pressure steps of 3.75 mmHg for periods of 7 min each. Mean pressure reactions, pulse amplitude reactions, and outflow resistance were calculated. RESULTS: All sheep showed intracranial pressure reactions to acute increases of intrathecal pressure, with four of six sheep showing clear cranio-spinal communication. During bolus infusions, the increases of mean pressure for intrathecal, intracranial, arterial, and venous pressure were 16.6 ± 0.9, 15.4 ± 0.8, 3.9 ± 0.8, and 0.1 ± 0.2 mmHg with corresponding pulse amplitude increases of 2.4 ± 0.3, 1.3 ± 0.3, 1.3 ± 0.3, and 0.2 ± 0.1 mmHg, respectively. During constant pressure infusions, mean increases from baseline were 14.6 ± 3.8, 15.5 ± 4.2, 4.2 ± 8.2, and 3.2 ± 2.4 mmHg with the corresponding pulse amplitude increases of 2.5 ± 3.6, 2.5 ± 3.0, 7.7 ± 4.3, and 0.7 ± 2.0 mmHg for intrathecal, intracranial, arterial, and venous pulse amplitude, respectively. Outflow resistances were calculated as 51.6 ± 7.8 and 77.8 ± 14.5 mmHg/mL/min for the bolus and constant pressure infusion methods, respectively-showing deviations between the two estimation methods. CONCLUSIONS: Standardized infusion tests with multi-compartmental pressure recordings in sheep have helped capture distinct reactions between the intrathecal, intracranial, arterial, and venous systems. Volumetric pressure changes in the intrathecal space have been shown to propagate to the intraventricular and arterial systems in our sample, and to the venous side in individual cases. These results represent an important step into achieving a more complete quantitative understanding of how an acute rise in intrathecal pressure can propagate and influence other systems.

Infectious Wildlife Diseases in Austria-A Literature Review From 1980 Until 2017.

This literature review examines infectious wildlife disease research in Austria. We analyzed 226 research papers, published between 1980 and 2017. We determined that wildlife disease papers increased significantly from 0.8 ± 0.8 publications per year in the first decade (1980-1989) when compared to 2008-2017 with an average of 12.9 ± 4.1 publications per year. We illustrate information about the most investigated diseases and highlight the lack of research into certain wildlife pathogens. A special emphasis was given to diseases with zoonotic potential. The review showed that research focused on a few select species like the red fox (Vulpes vulpes), red deer (Cervus elaphus), and wild boar (Sus scrofa), all game species. Moreover, diseases affecting livestock and human health were seen more often. The review also found that only a low number of publications actually stated disease prevalence and confidence interval data. The reported diseases identified were classified according to their notifiable status and the distribution at the wildlife-human and wildlife-livestock interface. Furthermore, we try to argue why research into some diseases is prioritized, and why other diseases are underrepresented in current Austrian research. While spatiotemporal indicators could not be assessed due to the variability in methodologies and objectives of various studies, the information provided by this review offers the first comprehensive evaluation of the status of infectious wildlife disease research in Austria. Therefore, this study could assist investigators to identify further areas of priorities for research and conservation efforts and for wildlife management professionals to inform policy and funding strategies. With this review, we want to encourage research in the field of wildlife diseases in Austria to enhance current knowledge in the prevention of further loss in biodiversity and to find new measures to promote "One Health" on a global scale.