Spinal subarachnoid space pressure measurements in an in vitro spinal stenosis model: implications on syringomyelia theories

Full explanation for the pathogenesis of syringomyelia (SM), a neuropathology characterized by the formation of a cystic cavity (syrinx) in the spinal cord (SC), has not yet been provided. It has been hypothesized that abnormal cerebrospinal fluid (CSF) pressure, caused by subarachnoid space (SAS) flow blockage (stenosis), is an underlying cause of syrinx formation and subsequent pain in the patient. However, paucity in detailed in vivo pressure data has made theoretical explanations for the syrinx difficult to reconcile. In order to understand the complex pressure environment, four simplified in vitro models were constructed to have anatomical similarities with post-traumatic SM and Chiari malformation related SM. Experimental geometry and properties were based on in vivo data and incorporated pertinent elements such as a realistic CSF flow waveform, spinal stenosis, syrinx, flexible SC, and flexible spinal column. The presence of a spinal stenosis in the SAS caused peak-to-peak cerebrospinal fluid CSF pressure fluctuations to increase rostral to the stenosis. Pressure with both stenosis and syrinx present was complex. Overall, the interaction of the syrinx and stenosis resulted in a diastolic valve mechanism and rostral tensioning of the SC. In all experiments, the blockage was shown to increase and dissociate SAS pressure, while the axial pressure distribution in the syrinx remained uniform. These results highlight the importance of the properties of the SC and spinal SAS, such as compliance and permeability, and provide data for comparison with computational models. Further research examining the influence of stenosis size and location, and the importance of tissue properties, is warranted.     

Sustained high-pressure in the spinal subarachnoid space while arterial expansion is low may be linked to syrinx development

Syringomyelia (a spinal cord cyst) usually develops as a result of conditions that cause cerebrospinal fluid (CSF) obstruction. The mechanism of syrinx formation and enlargement remains unclear, though previous studies suggest that the fluid enters via the perivascular spaces (PVS) of the penetrating arteries of the spinal cord, and that alterations in the CSF pulse timing and pressure could contribute to enhanced PVS inflow. This study uses an idealised computational model of the PVS to investigate the factors that influence peri-arterial fluid flow. First, we used three sample patient-specific models to explore whether changes in subarachnoid space (SAS) pressures in individuals with and without syringomyelia could influence PVS inflow. Second we conducted a parametric study to determine how features of the CSF pulse altered perivascular fluid, including alterations to timing and magnitude of the peak SAS pressure, the timing of reversal from high to low pressure (diastolic phase), and the area under the pressure–time curve. The model for the patient with syringomyelia had higher net CSF inflow to the PVS than the two subjects without syringomyelia. In the parametric study, only increasing the area under the high pressure region of the SAS pulse substantially increased PVS inflow, when coupled with a temporal shift in arterial and SAS pulses. This suggests that a period of sustained high SAS pressure while arterial diameter is low may increase net CSF pumping into the PVS.     

The presence of arachnoiditis affects the characteristics of CSF flow in the spinal subarachnoid space: a modelling study

Syringomyelia is a neurological disorder characterised by high pressure fluid-filled cysts within the spinal cord. As syringomyelia is associated with abnormalities of the central nervous system that obstruct cerebrospinal fluid (CSF) flow, it is thought that changes in CSF dynamics play an important role in its pathogenesis. Using three-dimensional computational models of the spinal subarachnoid space (SAS), this study aims to determine SAS obstructions, such as arachnoiditis, change in CSF dynamics in the SAS. The geometry of the SAS was reconstructed from a series of MRI images. CSF is modelled as an incompressible Newtonian fluid with a dynamic viscosity of 1 mPa s. Three computational models simulated CSF flow in either the unobstructed SAS, or with the SAS obstructed by a porous region simulating dorsal or circumferential arachnoiditis. The permeability of this porous obstruction was varied for the model with dorsal arachnoiditis. The results show that arachnoiditis increases flow resistance in the SAS and this is accompanied by a modest increase in magnitude and/or shift in timing (with respect to the cardiac cycle) of the CSF pressure drop across the region of arachnoiditis. This study suggests that syrinx formation may be related to a change in temporal CSF pulse pressure dynamics.     

Hydrodynamic modeling of cerebrospinal fluid motion within the spinal cavity

The fluid that resides within cranial and spinal cavities, cerebrospinal fluid (CSF), moves in a pulsatile fashion to and from the cranial cavity. This motion can be measured hy magnetic resonance imaging (MRI) and may he of clinical importance in the diagnosis of several brain and spinal cord disorders such as hydrocephalus, Chiari malformation, and syringomyelia. In the present work, a geometric and hydrodynamic characterization of an anatomically relevant spinal canal model is presented. We found that inertial effects dominate the flow field under normal physiological flow rates. Along the length of the spinal canal, hydraulic diameter was found to vary significantly from 5 to 15 mm. The instantaneous Reynolds number at peak flow rate ranged from 150 to 450, and the Womersle number ranged from 5 to 17. Pulsatile flow calculations are presented for an idealized geometric representation of the spinal cavity. A linearized Navier-Stokes model of the pulsatile CSF flow was constructed based on MRI flow rate measurements taken on a healthy volunteer. The numerical model was employed to investigate effects of cross-sectional geometry and spinal cord motion on unsteady velocity, shear stress, and pressure gradientfields. The velocity field was shown to be blunt, due to the inertial character of the flow, with velocity peaks located near the boundaries of the spinal canal rather than at the midpoint between boundaries. The pressure gradient waveform was found to be almost exclusively dependent on the flow waveform and cross-sectional area. Characterization of the CSF dynamics in normal and diseased states may be important in understanding the pathophysiology of CSF related disorders. Flow models coupled with MRI flow measurements mnay become a noninvasive tool to explain the abnormal dynamics of CSF in related brain disorders as well as to determine concentration and local distribution of drugs delivered into the CSF space.     

Evaluation by fluid/structure-interaction spinal-cord simulation of the effects of subarachnoid-space stenosis on an adjacent syrinx

A finite-element numerical model was constructed of the spinal cord, pia mater, filum terminale, cerebrospinal fluid in the spinal subarachnoid space (SSS), and dura mater. The cord was hollowed out by a thoracic syrinx of length 140 mm, and the SSS included a stenosis of length 30 mm opposite this syrinx. The stenosis severity was varied from 0% to 90% by area. Pressure pulse excitation was applied to the model either at the cranial end of the SSS, simulating the effect of cranial arterial pulsation, or externally to the abdominal dura mater, simulating the effect of cough. A very short pulse was used to examine wave propagation; a pulse emulating cardiac systole was used to examine the effects of fluid displacement. Additionally, repetitive sinusoidal excitation was applied cranially. Bulk fluid flow past the stenosis gave rise to prominent longitudinal pressure dissociation ("suck") in the SSS adjacent to the syrinx. However, this did not proportionally increase the longitudinal motion of fluid in the syrinx. The inertia of the fluid in the SSS, together with the compliance of this space, gave a resonance capable of being excited constructively or destructively by cardiac or coughing impulses. The main effect of mild stenosis was to lower the frequency of this resonance; severe stenosis damped out to-and-fro motions after the end of the applied excitation. Syrinx fluid motion indicated the fluid momentum and thus the pressure developed when the fluid was stopped by the end of the syrinx; however, the tearing stress in the local cord material depended also on the instantaneous local SSS pressure and was therefore not well predicted by syrinx fluid motion. Stenosis was also shown to give rise to a one-way valve effect causing raised SSS pressure caudally and slight average cord displacement cranially. The investigation showed that previous qualitative predictions of the effects of suck neglected factors that reduced the extent of the resulting syrinx fluid motion and of the cord tearing stress, which ultimately determines whether the syrinx lengthens.     

Syringomyelia hydrodynamics: an in vitro study based on in vivo measurements

A simplified in vitro model of the spinal canal, based on in vivo magnetic resonance imaging, was used to examine the hydrodynamics of the human spinal cord and subarachnoid space with syringomyelia. In vivo magnetic resonance imaging (MRI) measurements of subarachnoid (SAS) geometry and cerebrospinal fluid velocity were acquired in a patient with syringomyelia and used to aid in the in vitro model design and experiment. The in vitro model contained a fluid-filled coaxial elastic tube to represent a syrinx. A computer controlled pulsatile pump was used to subject the in vitro model to a CSF flow waveform representative of that measured in vivo. Fluid velocity was measured at three axial locations within the in vitro model using the same MRI scanner as the patient study. Pressure and syrinx wall motion measurements were conducted external to the MR scanner using the same model and flow input. Transducers measured unsteady pressure both in the SAS and intra-syrinx at four axial locations in the model A laser Doppler vibrometer recorded the syrinx wall motion at 18 axial locations and three polar positions. Results indicated that the peak-to-peak amplitude of the SAS flow waveform in vivo was approximately tenfold that of the syrinx and in phase (SAS approximately 5.2 +/- 0.6 ml/s, syrinx approximately 0.5 +/- 0.3 ml/s). The in vitro flow waveform approximated the in vivo peak-to-peak magnitude (SAS approximately 4.6 +/- 0.2 ml/s, syrinx approximately 0.4 +/- 0.3 ml/s). Peak-to-peak in vitro pressure variation in both the SAS and syrinx was approximately 6 mm Hg. Syrinx pressure waveform lead the SAS pressure waveform by approximately 40 ms. Syrinx pressure was found to be less than the SAS for approximately 200 ms during the 860-ms flow cycle. Unsteady pulse wave velocity in the syrinx was computed to be a maximum of approximately 25 m/s. LDV measurements indicated that spinal cord wall motion was nonaxisymmetric with a maximum displacement of approximately 140 microm, which is below the resolution limit of MRI. Agreement between in vivo and in vitro MR measurements demonstrates that the hydrodynamics in the fluid filled coaxial elastic tube system are similar to those present in a single patient with syringomyelia. The presented in vitro study of spinal cord wall motion, and complex unsteady pressure and flow environment within the syrinx and SAS, provides insight into the complex biomechanical forces present in syringomyelia.     

Mechanical indicators of injury severity are decreased with increased thecal sac dimension in a bench-top model of contusion type spinal cord injury

The cerebrospinal fluid (CSF) is thought to protect the spinal cord from physiologic loading; however, it is unclear whether this protective role extends to traumatic events in which bone fragments enter the canal at high velocity. A synthetic model of the spinal neural anatomy, with mechanical properties similar to native tissues, was constructed to determine if the thickness of the CSF layer (0, 12.8, 19.2 and 24.8 mm, 10 mm cord) and the velocity (1.2, 2.4, 3.7 and 4.8 m/s) of a 20 g impactor affect mechanical predictors of spinal cord injury (SCI) severity. Cord compression was directly proportional to impact velocity, inversely proportional to CSF dimension and zero for the largest dura size. The cord was compressed by more than 18% of its original diameter for the "no CSF" condition and the small dura size for all velocities. Impact loads were directly proportional to velocity, and inversely proportional to the thickness of the CSF layer. Peak cord tension increased with dura size and velocity. Peak CSF pressure decreased with distance from the impact epicenter for all dura sizes; attenuation was proportional to the velocity and greatest for the smallest dura. Increased CSF dimension led to reduced CSF pressure near the impact epicenter but had little effect at the remote sites. The results suggest that a thicker CSF layer may reduce the stress induced in the cord, and therefore metrics of SCI risk may be improved by incorporating thecal sac dimensions. Computational, synthetic, cadaveric and animal models may better simulate the biomechanics of human SCI if fluid interaction is incorporated.     

Fluid–structure interaction simulation of the brain–skull interface for acute subdural haematoma prediction

Traumatic brain injury is a leading cause of disability and mortality. Finite element-based head models are promising tools for enhanced head injury prediction, mitigation and prevention. The reliability of such models depends heavily on adequate representation of the brain–skull interaction. Nevertheless, the brain–skull interface has been largely simplified in previous three-dimensional head models without accounting for the fluid behaviour of the cerebrospinal fluid (CSF) and its mechanical interaction with the brain and skull. In this study, the brain–skull interface in a previously developed head model is modified as a fluid–structure interaction (FSI) approach, in which the CSF is treated on a moving mesh using an arbitrary Lagrangian–Eulerian multi-material formulation and the brain on a deformable mesh using a Lagrangian formulation. The modified model is validated against brain–skull relative displacement and intracranial pressure responses and subsequently imposed to an experimentally determined loading known to cause acute subdural haematoma (ASDH). Compared to the original model, the modified model achieves an improved validation performance in terms of brain–skull relative motion and is able to predict the occurrence of ASDH more accurately, indicating the superiority of the FSI approach for brain–skull interface modelling. The introduction of the FSI approach to represent the fluid behaviour of the CSF and its interaction with the brain and skull is crucial for more accurate head injury predictions.

     

Models of the pulsatile hydrodynamics of cerebrospinal fluid flow in the normal and abnormal intracranial system

Images obtained from magnetic resonance imaging have helped to ascertain that both the cerebrospinal fluid (CSF) and brain move in a pulsatile manner within the cranium. However, these images are not able to reveal any quantitative information on the physiological forces that are associated with pulsatile motion. Understanding both the pressure and velocity flow field of CSF in the ventricles is important to help understand the mechanics of hydrocephalus. Four separate fluid structure interaction models of the ventricular system in the sagittal plane were created for this purpose. The first model was of a normal brain. The second and third models were pathological brain models with aqueductal stenosis at various locations along the fluid pathway. The fourth model was of a hydrocephalic brain. Results revealed the hydrodynamics of CSF pulsatile flow in the ventricles of these models. Most importantly, it has also revealed the different changes in CSF pulsatile hydrodynamics caused by the various locations of fluid flow obstructions.     

A one-dimensional model of the spinal cerebrospinal-fluid compartment

Modeling of the cerebrospinal fluid (CSF) system in the spine is strongly motivated by the need to understand the origins of pathological conditions such as the emergence and growth of fluid-filled cysts in the spinal cord. In this study, a one-dimensional (1D) approximation for the flow in elastic conduits was used to formulate a model of the spinal CSF compartment. The modeling was based around a coaxial geometry in which the inner elastic cylinder represented the spinal cord, middle elastic tube represented the dura, and the outermost tube represented the vertebral column. The fluid-filled annuli between the cord and dura, and the dura and vertebral column, represented the subarachnoid and epidural spaces, respectively. The system of governing equations was constructed by applying a 1D form of mass and momentum conservation to all segments of the model. The developed 1D model was used to simulate CSF pulse excited by pressure disturbances in the subarachnoid and epidural spaces. The results were compared to those obtained from an equivalent two-dimensional finite element (FE) model which was implemented using a commercial software package. The analysis of linearized governing equations revealed the existence of three types of waves, of which the two slower waves can be clearly related to the wave modes identified in previous similar studies. The third, much faster, wave emanates directly from the vertebral column and has little effect on the deformation of the spinal cord. The results obtained from the 1D model and its FE counterpart were found to be in good general agreement even when sharp spatial gradients of the spinal cord stiffness were included; both models predicted large radial displacements of the cord at the location of an initial cyst. This study suggests that 1D modeling, which is computationally inexpensive and amenable to coupling with the models of the cranial CSF system, should be a useful approach for the analysis of some aspects of the CSF dynamics in the spine. The simulation of the CSF pulse excited by a pressure disturbance in the epidural space, points to the possibility that regions of the spinal cord with abnormally low stiffness may be prone to experiencing large strains due to coughing and sneezing.     

Global/local head models to analyse cerebral blood vessel rupture leading to ASDH and SAH

Blunt and rotational head impacts due to vehicular collisions, falls and contact sports cause relative motion between the brain and skull. This increases the normal and shear stresses in the (skull/brain) interface region consisting of cerebrospinal fluid (CSF) and subarachnoid space (SAS) trabeculae. The relative motion between the brain and skull can explain many types of traumatic brain injuries (TBI) including acute subdural hematomas (ASDH) and subarachnoid hemorrhage (SAH) which is caused by the rupture of bridging veins that transverse from the deep brain tissue to the superficial meningeal coverings. The complicated geometry of the SAS trabeculae makes it impossible to model all the details of the region. Investigators have compromised this layer with solid elements, which may lead to inaccurate results. In this paper, the failure of the cerebral blood vessels due to the head impacts have been investigated. This is accomplished through a global/local modelling approach. Two global models, namely a global solid model (GSM) of the skull/brain and a global fluid model (GFM) of the SAS/CSF, were constructed and were validated. The global models were subjected to two sets of impact loads (head injury criterion, HIC = 740 and 1044). The relative displacements between the brain and skull were determined from GSM. The CSF equivalent fluid pressure due to the impact loads were determined by the GFM. To locally study the mechanism of the injury, the relative displacement between the brain and skull along with the equivalent fluid pressure were implemented into a new local solid model (LSM). The strains of the cerebral blood vessels were determined from LSM. These values were compared with their relevant experimental ultimate strain values. The results showed an agreement with the experimental values indicating that the second impact (HIC = 1044) was strong enough to lead to severe injury. The global/local approach provides a reliable tool to study the cerebral blood vessel ruptures leading to ASDH and/or SAH.     

The effect of cerebrospinal fluid thickness on traumatic spinal cord deformation

A spinal cord injury may lead to loss of motor and sensory function and even death. The biomechanics of the injury process have been found to be important to the neurological damage pattern, and some studies have found a protective effect of the cerebrospinal fluid (CSF). However, the effect of the CSF thickness on the cord deformation and, hence, the resulting injury has not been previously investigated. In this study, the effects of natural variability (in bovine) as well as the difference between bovine and human spinal canal dimensions on spinal cord deformation were studied using a previously validated computational model. Owing to the pronounced effect that the CSF thickness was found to have on the biomechanics of the cord deformation, it can be concluded that results from animal models may be affected by the disparities in the CSF layer thickness as well as by any difference in the biological responses they may have compared with those of humans.     

Three-dimensional cerebrospinal fluid flow within the human ventricular system

Cerebrospinal fluid (CSF) is a Newtonian fluid and can, therefore, be modelled using computational fluid dynamics (CFD). Previous modelling of the CSF has been limited to simplified geometric models. This work describes a geometrically accurate three dimensional (3D) computational model of the human ventricular system (HVS) constructed from magnetic resonance images (MRI) of the human brain. It is an accurate and full representation of the HVS and includes appropriately positioned CSF production and drainage locations. It was used to investigate the pulsatile motion of CSF within the human brain. During this investigation CSF flow rate was set at a constant 500 ml/day, to mimic real life secretion of CSF into the system, and a pulsing velocity profile was added to the inlets to incorporate the effect of cardiac pulsations on the choroid plexus and their subsequent influence on CSF motion in the HVS. Boundary conditions for the CSF exits from the ventricles (foramina of Magendie and Lushka) were found using a “nesting” approach, in which a simplified model of the entire central nervous system (CNS) was used to examine the effects of the CSF surrounding the ventricular system (VS). This model provided time varying pressure data for the exits from the VS nested within it. The fastest flow was found in the cerebral aqueduct, where a maximum velocity of 11.38 mm/s was observed over five cycles. The maximum Reynolds number recorded during the simulation was 15 with an average Reynolds number of the order of 0.39, indicating that CSF motion is creeping flow in most of the computational domain and consequently will follow the geometry of the model. CSF pressure also varies with geometry with a maximum pressure drop of 1.14 Pa occurring through the cerebral aqueduct. CSF flow velocity is substantially slower in the areas that are furthest away from the inlets; in some areas flow is nearly stagnant.     

Three-dimensional cerebrospinal fluid flow within the human ventricular system

Cerebrospinal fluid (CSF) is a Newtonian fluid and can, therefore, be modelled using computational fluid dynamics (CFD). Previous modelling of the CSF has been limited to simplified geometric models. This work describes a geometrically accurate three dimensional (3D) computational model of the human ventricular system (HVS) constructed from magnetic resonance images (MRI) of the human brain. It is an accurate and full representation of the HVS and includes appropriately positioned CSF production and drainage locations. It was used to investigate the pulsatile motion of CSF within the human brain. During this investigation CSF flow rate was set at a constant 500 ml/day, to mimic real life secretion of CSF into the system, and a pulsing velocity profile was added to the inlets to incorporate the effect of cardiac pulsations on the choroid plexus and their subsequent influence on CSF motion in the HVS. Boundary conditions for the CSF exits from the ventricles (foramina of Magendie and Lushka) were found using a "nesting" approach, in which a simplified model of the entire central nervous system (CNS) was used to examine the effects of the CSF surrounding the ventricular system (VS). This model provided time varying pressure data for the exits from the VS nested within it. The fastest flow was found in the cerebral aqueduct, where a maximum velocity of 11.38 mm/s was observed over five cycles. The maximum Reynolds number recorded during the simulation was 15 with an average Reynolds number of the order of 0.39, indicating that CSF motion is creeping flow in most of the computational domain and consequently will follow the geometry of the model. CSF pressure also varies with geometry with a maximum pressure drop of 1.14 Pa occurring through the cerebral aqueduct. CSF flow velocity is substantially slower in the areas that are furthest away from the inlets; in some areas flow is nearly stagnant.     

A computational model of the cerebrospinal fluid system incorporating lumped-parameter cranial compartment and one-dimensional distributed spinal compartment

The dynamic transmission of pressure through the cerebro-circulatory system may play a role in the genesis of pathological conditions of the brain and spinal cord. This study aims to lay down the foundations for computer modelling of the cerebrospinal (CSF) pressure dynamics in the cranio-spinal cavity as a single entity. The cerebro-vascular system was modelled as a set of resistors and capacitors. The model of the CSF space comprised a lumped cranial compartment and a distributed spinal compartment. Apart from simulating normal (baseline) conditions, the effects of jugular vein compression, and thoracic pressure elevation by coughing were investigated by applying pressure waveforms at the appropriate points in the model. The Chiari malformation was simulated by assigning high resistance to the circulation of the CSF between the cranium and the spine. The model was capable of reproducing physiologically plausible results for all forms of excitation. The spinal cavity behaved effectively as a lumped compartment, except for the cough excitation where wave-type behaviour was evident. In that case, the Chiari obstruction resulted in prolonged periodic straining of the spinal cord. This result can be of significance for understanding the mechanism of the formation of cysts in the spinal cord.     

Poro-elastic modeling of Syringomyelia – a systematic study of the effects of pia mater,central canal,median fissure,white and gray matter on pressure wave propagation and fluid movement within the cervical spinal cord

Syringomyelia, fluid-filled cavities within the spinal cord, occurs frequently in association with a Chiari I malformation and produces some of its most severe neurological symptoms. The exact mechanism causing syringomyelia remains unknown. Since syringomyelia occurs frequently in association with obstructed cerebrospinal fluid (CSF) flow, it has been hypothesized that syrinx formation is mechanically driven. In this study we model the spinal cord tissue either as a poro-elastic medium or as a solid linear elastic medium, and simulate the propagation of pressure waves through an anatomically plausible 3D geometry, with boundary conditions based on in vivo CSF pressure measurements. Then various anatomic and tissue properties are modified, resulting in a total of 11 variations of the model that are compared. The results show that an open segment of the central canal and a stiff pia (relative to the cord) both increase the radial pressure gradients and enhance interstitial fluid flow in the central canal. The anterior median fissure, anisotropic permeability of the white matter, and Poisson ratio play minor roles.     

A coupled hydrodynamic model of the cardiovascular and cerebrospinal fluid system

Coupling of the cardiovascular and cerebrospinal fluid (CSF) system is considered to be important to understand the pathophysiology of cerebrovascular and craniospinal disease and intrathecal drug delivery. A coupled cardiovascular and CSF system model was designed to examine the relation of spinal cord (SC) blood flow (SCBF) and CSF pulsations along the spinal subarachnoid space (SSS). A one-dimensional (1-D) cardiovascular tree model was constructed including a simplified SC arterial network. Connection between the cardiovascular and CSF system was accomplished by a transfer function based on in vivo measurements of CSF and cerebral blood flow. A 1-D tube model of the SSS was constructed based on in vivo measurements in the literature. Pressure and flow throughout the cardiovascular and CSF system were determined for different values of craniospinal compliance. SCBF results indicated that the cervical, thoracic, and lumbar SC each had a signature waveform shape. The cerebral blood flow to CSF transfer function reproduced an in vivo-like CSF flow waveform. The 1-D tube model of the SSS resulted in a distribution of CSF pressure and flow and a wave speed that were similar to those in vivo. The SCBF to CSF pulse delay was found to vary a great degree along the spine depending on craniospinal compliance and vascular anatomy. The properties and anatomy of the SC arterial network and SSS were found to have an important impact on pressure and flow and perivascular fluid movement to the SC. Overall, the coupled model provides predictions about the flow and pressure environment in the SC and SSS. More detailed measurements are needed to fully validate the model.     

Hydrodynamic and Longitudinal Impedance Analysis of Cerebrospinal Fluid Dynamics at the Craniovertebral Junction in Type I Chiari Malformation

Elevated or reduced velocity of cerebrospinal fluid (CSF) at the craniovertebral junction (CVJ) has been associated with type I Chiari malformation (CMI). Thus, quantification of hydrodynamic parameters that describe the CSF dynamics could help assess disease severity and surgical outcome. In this study, we describe the methodology to quantify CSF hydrodynamic parameters near the CVJ and upper cervical spine utilizing subject-specific computational fluid dynamics (CFD) simulations based on in vivo MRI measurements of flow and geometry. Hydrodynamic parameters were computed for a healthy subject and two CMI patients both pre- and post-decompression surgery to determine the differences between cases. For the first time, we present the methods to quantify longitudinal impedance (LI) to CSF motion, a subject-specific hydrodynamic parameter that may have value to help quantify the CSF flow blockage severity in CMI. In addition, the following hydrodynamic parameters were quantified for each case: maximum velocity in systole and diastole, Reynolds and Womersley number, and peak pressure drop during the CSF cardiac flow cycle. The following geometric parameters were quantified: cross-sectional area and hydraulic diameter of the spinal subarachnoid space (SAS). The mean values of the geometric parameters increased post-surgically for the CMI models, but remained smaller than the healthy volunteer. All hydrodynamic parameters, except pressure drop, decreased post-surgically for the CMI patients, but remained greater than in the healthy case. Peak pressure drop alterations were mixed. To our knowledge this study represents the first subject-specific CFD simulation of CMI decompression surgery and quantification of LI in the CSF space. Further study in a larger patient and control group is needed to determine if the presented geometric and/or hydrodynamic parameters are helpful for surgical planning.     

Physical characteristics in the new model of the cerebrospinal fluid system

It is unknown which factors determine the changes in cerebrospinal fluid (CSF) pressure inside the craniospinal system during the changes of the body position. To test this, we have developed a new model of the CSF system, which by its biophysical characteristics and dimensions imitates the CSF system in cats. The results obtained on a model were compared to those in animals observed during changes of body position. A new model was constructed from two parts with different physical characteristics. The "cranial" part is developed from a plastic tube with unchangeable volume, while the "spinal" part is made of a rubber baloon, with modulus of elasticity similar to that of animal spinal dura. In upright position, in the "cranial" part of the model the negative pressure appears without any measurable changes in the fluid volume, while in "spinal" part the fluid pressure is positive. All of the observed changes are in accordance to the law of the fluid mechanics. Alterations of the CSF pressure in cats during the changes of the body position are not significantly different compared to those observed on our new model. This suggests that the CSF pressure changes are related to the fluid mechanics, and do not depend on CSF secretion and circulation. It seems that in all body positions the cranial volume of blood and CSF remains constant, which enables a good blood brain perfusion.     

Hsp40 function in yeast prion propagation: Amyloid diversity necessitates chaperone functional complexity

It has been estimated that cerebrospinal fluid (CSF) contains approximately 80 proteins that significantly increase or decrease in response to various clinical conditions. Here we have evaluated the CSF protein PrPC (cellular prion protein) for possible increases or decreases following spinal cord injury. The physiological function of PrPC is not yet completely understood; however, recent findings suggest that PrPC may have neuroprotective properties. Our results show that CSF PrPC is decreased in spinal cord injured patients 12 hours following injury and is absent at 7 days. Given that normal PrPC has been proposed to be neuroprotective we speculate that the decrease in CSF PrPC levels may influence neuronal cell survival following spinal cord injury.