Precise location of the ventricular catheter tip in ventriculoperitoneal shunt placement guided by 3D printed individualized guide.

OBJECTIVE: Improper placement of the ventricular catheter tip is the most common cause of shunting disorders after ventriculoperitoneal shunt (VPS) placement surgery. Here, through two illustrative cases, we described a novel method of precise ventricular catheter tip location. METHODS: Three-dimensional (3D) Slicer software was used to define the ventricle puncture path and determine the ventricle catheter tip location preoperatively, and the 3D individualized guide model was printed. RESULTS: The ventricular puncture was performed under the guidance of the 3D guide to achieve precise ventricle catheter tip location intraoperatively. CONCLUSIONS: This technique is safe, simple, efficient and cost-effective, which facilitates its clinical implementation and promotion.

Consideration of Kinase Inhibitors for the Treatment of Hydrocephalus.

Hydrocephalus is a devastating condition characterized by excess cerebrospinal fluid (CSF) in the brain. Currently, the only effective treatment is surgical intervention, usually involving shunt placement, a procedure prone to malfunction, blockage, and infection that requires additional, often repetitive, surgeries. There are no long-term pharmaceutical treatments for hydrocephalus. To initiate an intelligent drug design, it is necessary to understand the biochemical changes underlying the pathology of this chronic condition. One potential commonality in the various forms of hydrocephalus is an imbalance in fluid-electrolyte homeostasis. The choroid plexus, a complex tissue found in the brain ventricles, is one of the most secretory tissues in the body, producing approximately 500 mL of CSF per day in an adult human. In this manuscript, two key transport proteins of the choroid plexus epithelial cells, transient receptor potential vanilloid 4 and sodium, potassium, 2 chloride co-transporter 1, will be considered. Both appear to play key roles in CSF production, and their inhibition or genetic manipulation has been shown to affect CSF volume. As with most transporters, these proteins are regulated by kinases. Therefore, specific kinase inhibitors are also potential targets for the development of pharmaceuticals to treat hydrocephalus.

Does preventive external ventricular drainage benefit patients with mild ventricular hemorrhage?

External ventricular drainage (EVD) is the routine intraventricular hemorrhage (IVH) treatment. Neurological deterioration and symptomatic hydrocephalus are often the default indications for EVD insertion. However, the outcome of preventive EVD is unclear in patients with mild IVH. This study aimed to determine whether EVD is beneficial in patients with mild IVH. This study aimed to determine whether EVD is beneficial in patients with mild IVH. Data from IVH patients treated conservatively or with EVD at two hospitals from January 2017 to December 2022 were analyzed retrospectively. Patients with a Glasgow Coma Scale (GCS) score of 12-14 and a modified Graeb score (mGS) ≥ 5 at admission were included. The primary outcome was poor functional status, defined as a modified Rankin Scale (mRS) score of 3-6 at 90 days. Secondary outcomes included the distribution of mRS score categories, the resolution time of intraventricular blood clots, and complications. Forty-nine patients were enrolled in the study: 21 patients in the EVD group, 28 in the non-EVD group, and 13 in the EVD group who received urokinase injections. ICH volume was an independent predictor of poor functional status. Currently, no evidence supports that preventive EVD benefits patients with mild IVH.

Cerebrospinal Fluid Production and Absorption and Ventricular Enlargement Mechanisms in Hydrocephalus.

Cerebrospinal fluid (CSF) production and absorption concept significantly changed in the early 2010s from "third circulation theory" and "classical bulk flow theory" to a whole new one as follows: First, CSF is mainly produced from interstitial fluid excreted from the brain parenchyma, and CSF produced from the choroid plexus plays an important role in maintaining brain homeostasis. Second, CSF is not absorbed in the venous sinus via the arachnoid granules, but mainly in the dural lymphatic vessels. Finally, the ventricles and subarachnoid spaces have several compensatory direct CSF pathways at the borders attached to the choroid plexus, e.g., the inferior choroidal point of the choroidal fissure, other than the foramina of Luschka and Magendie. In idiopathic normal pressure hydrocephalus (iNPH), the lateral ventricles and basal cistern are enlarged simultaneously due to the compensatory direct CSF pathways. The average total intracranial CSF volume increased from about 150 mL at 20 years to about 350 mL at 70 years due to the decrease in brain volume with aging and further increased above 400 mL in patients with iNPH. CSF movements are composed of a steady microflow produced by the rhythmic wavy movement of motile cilia on the ventricular surface and dynamic pulsatile flow produced by the brain and cerebral artery pulsation, respiration, and head movement. Pulsatile CSF movements might totally decrease with aging, but it in the ventricles might increase at the foramina of Magendie and Luschka dilation. Aging CSF dynamics are strongly associated with ventricular dilatation in iNPH.

An Analysis of Temporal Trend of Incidence of Post-Resection Cerebrospinal Fluid Diversion in Pediatric Posterior Fossa Tumor Patients and the Predictive Factors.

Objective: We aim to find the temporal trend of incidence of post-resection cerebrospinal fluid (CSF) diversion (ventriculoperitoneal [VP] shunt/endoscopic third ventriculostomy [ETV]) in pediatric posterior fossa tumor (pPFT) patients with no pre-resection CSF diversion and the possible clinical predictors. Methods: We reviewed 108 operated children (age ≤16 years) with PFTs, from 2012 to 2020, at a tertiary care center. Patients with preoperative CSF diversion (n = 42), lesions within cerebellopontine cistern (n = 8), and those lost to follow-up (n = 4) were excluded. Life table, Kaplan-Meier curve, univariate and multivariate analyses were used to determine CSF-diversion-free survival and independent predictive factors, with significance defined as P < 0.05. Results: The median (IQR) age was 9 (7) years (M: F: 2.5:1). Mean (±SD) duration of follow-up was 32.43 ± 21.3 months. 38.9% of patients (n = 42) needed post-resection CSF diversion. Of these, 64.3% (n = 27) were done in early (≤ 30 days), 23.8% (n = 10) in intermediate (>30 days to ≤6 months), and 11.9% (n = 5) in late (≥6 months) postoperative period (P-value < 0.001). Preoperative papilledema (HR: -5.8, 95%CI: 1.7-5.8), periventricular lucency (PVL) (HR: 6.2, 95%CI: 2.3-16.6), and wound complication (HR: 3.8, 95%CI: 1.7-8.3) were found on univariate analysis as significant risk factors for early post-resection CSF diversion. On multivariate analysis, PVL on preoperative imaging (HR: -4.2, 95%CI: 1.2-14.7, P = 0.02) was identified as an independent predictor. Preoperative ventriculomegaly, raised intracranial pressure and intraoperative visualization of CSF egress from the aqueduct were not found to be significant factors. Conclusion: Significantly high incidence of post-resection CSF diversion in pPFTs occurs in early (≤30 days) postoperative period, with preoperative papilledema, PVL, and wound complication being its significant predictive factors. Postoperative inflammation, causing edema and adhesion formation can be one of the important factors for post-resection hydrocephalus in pPFTs.

LRP2 contributes to planar cell polarity-dependent coordination of motile cilia function.

Motile cilia are protruding organelles on specialized epithelia that beat in a synchronous fashion to propel extracellular fluids. Coordination and orientation of cilia beating on individual cells and across tissues is a complex process dependent on planar cell polarity (PCP) signaling. Asymmetric sorting of PCP pathway components, essential to establish planar polarity, involves trafficking along the endocytic path, but the underlying regulatory processes remain incompletely understood. Here, we identified the endocytic receptor LRP2 as regulator of PCP component trafficking in ependyma, a multi-ciliated cell type that is involved in facilitating flow of the cerebrospinal fluid in the brain ventricular system. Lack of receptor expression in gene-targeted mice results in a failure to sort PCP core proteins to the anterior or posterior cell side and, consequently, in the inability to coordinate cilia arrangement and to aligned beating (loss of rotational and translational polarity). LRP2 deficiency coincides with a failure to sort NHERF1, a cytoplasmic LRP2 adaptor to the anterior cell side. As NHERF1 is essential to translocate PCP core protein Vangl2 to the plasma membrane, these data suggest a molecular mechanism whereby LRP2 interacts with PCP components through NHERF1 to control their asymmetric sorting along the endocytic path. Taken together, our findings identified the endocytic receptor LRP2 as a novel regulator of endosomal trafficking of PCP proteins, ensuring their asymmetric partition and establishment of translational and rotational planar cell polarity in the ependyma.

Novel concepts in the pathogenesis of hydrocephalus.

PURPOSE: Hydrocephalus is a multifactorial neurological disorder and one of the most common neurosurgical conditions characterized by excessive cerebrospinal fluid (CSF) accumulation within the brain's ventricles. It can result in dilatation of the ventricular system caused by the inadequate passage of CSF from its point of production within the ventricles to its point of absorption into the systemic circulation. Recent findings on the genetics and molecular studies of hydrocephalus have the potential to improve treatment and quality of life. METHODS: Review of literature on the novel studies of the pathogenesis of hydrocephalus. CONCLUSION: Molecular studies on the pathogenesis of hydrocephalus have provided a means to improve the treatment and follow-up of patients with hydrocephalus.

Is ventricular lavage a novel treatment of neonatal posthemorrhagic hydrocephalus? a meta analysis.

INTRODUCTION: Intraventricular hemorrhage (IVH) may produce obliterative arachnoiditis, which disrupts the flow and absorption of cerebrospinal fluid (CSF), resulting in posthemorrhagic hydrocephalus (PHH). PHH gives a high risk of neurofunctional impairment. Ventricular lavage is the treatment of choice for PHH in neonates with IVH for decades. It is developing with the combination of fibrinolytic therapy, also called drainage, irrigation, and fibrinolytic therapy (DRIFT), and with the use of neuroendoscopic apparatus, also called neuroendoscopic lavage (NEL). METHODS: This review is a meta-analysis using the PRISMA method guideline, including the clinical studies comparing ventricular lavage (VL) with standard treatment of PHH between 2000 and 2021. RESULTS: VL group reduced the shunt dependency compared to standard treatment (OR = 0.22; 95CI 0.05 to 0.97; p = 0.05). VL group has less infection risk compared to the standard treatment group (RR = 0.20; 95CI 0.07 to 0.59; p < 0.05). The severe neurofunctional outcome is similar between the two groups (OR = 0.99; 95CI 0.13 to 7.23; p = 0.99). The early approach treatment group may give better neurofunctional outcomes compared to the late approach (OR = 0.14; 95CI 0.06 to 0.35; p < 0.05). CONCLUSION: VL reduce the shunt dependency on the PHH, decreasing the shunt's related infection rate. The early ventricular lavage may give benefit for the neurocognitive outcome.

Thermal and Postural Effects on Fluid Mixing and Irrigation Patterns for Intraventricular Hemorrhage Treatment.

Intraventricular hemorrhage is characterized by blood leaking into the cerebral ventricles and mixing with cerebrospinal fluid. A standard treatment method involves inserting a passive drainage catheter, known as an external ventricular drain (EVD), into the ventricle. EVDs have common adverse complications, including the occlusion of the catheter, that may lead to permanent neural damage or even mortality. In order to prevent such complications, a novel dual-lumen catheter (IRRAflow®) utilizing an active fluid exchange mechanism has been recently developed. However, the fluid dynamics of the exchange system have not been investigated. In this study, convective flow in a three-dimensional cerebral lateral ventricle with an inserted catheter is evaluated using an in-house lattice-Boltzmann-based fluid-solid interaction solver. Different treatment conditions are simulated, including injection temperature and patient position. Thermal and gravitational effects on medication distribution are studied using a dye simulator based on a recently-introduced (pseudo)spectral convection-diffusion equation solver. The effects of injection temperature and patient position on catheter performance are presented and discussed in terms of hematoma irrigation, vortical structures, mixing, and medication volume distribution. Results suggest that cold-temperature injections can increase catheter efficacy in terms of dye distribution and irrigation potential, both of which can be further guided by patient positioning.

Outcomes of Combined Endoscopic Surgery and Fibrinolytic Treatment Protocol for Intraventricular Hemorrhage: A Randomized Controlled Trial.

BACKGROUND: Intraventricular fibrinolysis (IVF) and endoscopic surgery (ES) are the new promising treatment strategies to enhance the rate of hematoma clearance, which might improve functional outcome. This study investigated and compared the outcomes among these interventions. METHODS: A randomized (1:1) double-blinded trial was carried out between August 2018 and December 2021. The intervention and control groups comprised patients receiving IVF and/or ES and external ventricular drainage (EVD), respectively. All participants had experienced primary or secondary intraventricular hemorrhage (IVH) from spontaneous intracerebral hemorrhage with obstructive hydrocephalus complications. The primary outcome was modified Rankin Scale score 180 days post treatment. Interim assessments were planned for every 50 participants enrolled to ensure safety and efficacy. RESULTS: After enrollment of 110 participants (55 participants in each group), there was a difference in 30-day mortality (2 [3.6%] vs. 13 [32.7%] in the EVD group, P = 0.002), reaching the predetermined boundaries for termination of the trial. We demonstrated a better favorable outcome (modified Rankin Scale score 0-3) at 180 days in the intervention group, compared with the control group (35 [63.6%] vs. 24 [43.6%], P = 0.04). Participants in the intervention group experienced a higher IVH removal rate (91% [9.0] vs. 69.5% [38.0], P < 0.01) and had lower shunt conversion (1 [1.8%] vs. 16 [29.3%], P < 0.01). Treatment complications were comparable between the two groups. CONCLUSIONS: This study demonstrated that combined ES and IVF is safe and effective for the treatment of IVH. In addition, it concluded that aggressive but safe procedures used to remove IVH could improve clinical outcome in patients with IVH.

The choroid plexus: a missing link in our understanding of brain development and function.

Studies of the choroid plexus lag behind those of the more widely known blood-brain barrier, despite a much longer history. This review has two overall aims. The first is to outline long-standing areas of research where there are unanswered questions, such as control of cerebrospinal fluid (CSF) secretion and blood flow. The second aim is to review research over the past 10 years where the focus has shifted to the idea that there are choroid plexuses located in each of the brain's ventricles that make specific contributions to brain development and function through molecules they generate for delivery via the CSF. These factors appear to be particularly important for aspects of normal brain growth. Most research carried out during the twentieth century dealt with the choroid plexus, a brain barrier interface making critical contributions to the composition and stability of the brain's internal environment throughout life. More recent research in the twenty-first century has shown the importance of choroid plexus-generated CSF in neurogenesis, influence of sex and other hormones on choroid plexus function, and choroid plexus involvement in circadian rhythms and sleep. The advancement of technologies to facilitate delivery of brain-specific therapies via the CSF to treat neurological disorders is a rapidly growing area of research. Conversely, understanding the basic mechanisms and implications of how maternal drug exposure during pregnancy impacts the developing brain represents another key area of research.

Development of the brain ventricular system from a comparative perspective.

The brain ventricular system (BVS) consists of brain ventricles and channels filled with cerebrospinal fluid (CSF). Disturbance of CSF flow has been linked to scoliosis and neurodegenerative diseases, including hydrocephalus. This could be due to defects of CSF production by the choroid plexus or impaired CSF movement over the ependyma dependent on motile cilia. Most vertebrates have horizontal body posture. They retain additional evolutionary innovations assisting CSF flow, such as the Reissner fiber. The causes of hydrocephalus have been studied using animal models including rodents (mice, rats, hamsters) and zebrafish. However, the horizontal body posture reduces the effect of gravity on CSF flow, which limits the use of mammalian models for scoliosis. In contrast, fish swim against the current and experience a forward-to-backward mechanical force akin to that caused by gravity in humans. This explains the increased popularity of the zebrafish model for studies of scoliosis. "Slit-ventricle" syndrome is another side of the spectrum of BVS anomalies. It develops because of insufficient inflation of the BVS. Recent advances in zebrafish functional genetics have revealed genes that could regulate the development of the BVS and CSF circulation. This review will describe the BVS of zebrafish, a typical teleost, and vertebrates in general, in comparative perspective. It will illustrate the usefulness of the zebrafish model for developmental studies of the choroid plexus (CP), CSF flow and the BVS.

An early analysis of Codman® CerebroFlo® Endexo coated ventricular catheters in the setting of intraventricular hemorrhage.

Intraventricular hemorrhages (IVH) are a potentially fatal diagnosis that must be managed properly to avoid devastating complications. While existing catheters have offered relative success, their reactive composition makes them prone to eventual obstruction and thrombotic activation. This problematic outcome has led to emergence of the Codman® CerebroFlo® EVD Catheter (Integra LifeSciences, Princeton, NJ, USA). This catheter is the first of its kind to incorporate the Endexo additive, a slightly reactive, surface modifying molecule that prevents protein adhesion and biomatter accumulation. Despite the promising early outcomes, there are no PubMed articles characterizing this device, with minimal literature highlighting its clinical value. Through a contemporary literature review, the authors will characterize the technological principles, indications, and advantages of this novel device. The authors reported the early findings of this catheter, with studies showing 99% reduction in thrombotic activity with an additional 89% reduction in catheter obstruction compared to its competitors. Areas of uncertainty regarding this device are discussed, with its lack of antibiotic coating being a possible area for clinical concern. In conclusion, the CerebroFlo® catheter is a novel and effective tool in the management of IVH that should be widely considered for the management of IVH.

[Metallic foreign bodies of brain ventricles]. / Metallicheskie inorodnye tela zheludochkov golovnogo mozga.

Head injuries are often associated with intracranial foreign bodies that require decision making on the need for certain surgical treatment. Intraventricular foreign bodies are rare, so the question of surgical tactics is still open. OBJECTIVE: To summarize the experience of treating the wounded with intraventricular foreign bodies. MATERIAL AND METHODS: Treatment outcomes in victims with foreign bodies in lateral ventricles are presented. Searching in the e-Library, PubMed, Google Scholar databases included the following keywords: «penetrating wounds¼, «foreign bodies¼, «cerebral ventricles¼, «gunshot injury¼, «ventricular foreign bodies¼. We analyzed data on the treatment of victims with intraventricular foreign bodies. RESULTS: Three victims underwent surgery, and foreign bodies were removed from the occipital horn of the lateral ventricle, third ventricle and temporal horn of the lateral ventricle. Conservative approach was preferred in 1 case. Follow-up ranged from 1 month to 7 years, GOS score - 3-4 points. Disability was due to severe injury and not associated with surgical treatment per se. We found 16 publications matching the searching criteria. Treatment methods varied from standard surgical approaches to stereotactic management. The indication for removal of foreign bodies was their migration through the ventricular system and occlusive hydrocephalus. None patient had neurological aggravation. CONCLUSION: Intraventricular foreign bodies are rare and present certain difficulties in choosing the method and timing of treatment. Indications for their removal are migration, occlusive hydrocephalus and infectious complications. The method of removal is determined depending on location, magnetic properties, nature of injury, surgical preferences and other factors.

Measurements of cerebrospinal fluid production: a review of the limitations and advantages of current methodologies.

Cerebrospinal fluid (CSF) is an essential and critical component of the central nervous system (CNS). According to the concept of the "third circulation" originally proposed by Cushing, CSF is mainly produced by the choroid plexus and subsequently leaves the cerebral ventricles via the foramen of Magendie and Luschka. CSF then fills the subarachnoid space from whence it disperses to all parts of the CNS, including the forebrain and spinal cord. CSF provides buoyancy to the submerged brain, thus protecting it against mechanical injury. CSF is also transported via the glymphatic pathway to reach deep interstitial brain regions along perivascular channels; this CSF clearance pathway promotes transport of energy metabolites and signaling molecules, and the clearance of metabolic waste. In particular, CSF is now intensively studied as a carrier for the removal of proteins implicated in neurodegeneration, such as amyloid-ß and tau. Despite this key function of CSF, there is little information about its production rate, the factors controlling CSF production, and the impact of diseases on CSF flux. Therefore, we consider it to be a matter of paramount importance to quantify better the rate of CSF production, thereby obtaining a better understanding of CSF dynamics. To this end, we now review the existing methods developed to measure CSF production, including invasive, noninvasive, direct, and indirect methods, and MRI-based techniques. Depending on the methodology, estimates of CSF production rates in a given species can extend over a ten-fold range. Throughout this review, we interrogate the technical details of CSF measurement methods and discuss the consequences of minor experimental modifications on estimates of production rate. Our aim is to highlight the gaps in our knowledge and inspire the development of more accurate, reproducible, and less invasive techniques for quantitation of CSF production.

Study protocol for ACTIVE study: safety and feasibility evaluation of external ventricular drainage with ACTIVE fluid exchange in intraventricular hemorrhage-a phase 2, multi-center, randomized controlled trial.

BACKGROUND: Primary intraventricular hemorrhage (IVH) or IVH secondary to intracerebral (ICH) and subarachnoid hemorrhage (SAH) are known to have a very poor prognosis, with an expected mortality between 50 and 80% (Hinson et al. Current Neurology and Neuroscience Reports 10:73-82, 2010). Clearance of IVH might improve patient outcome. METHODS: The study is designed as an investigator-initiated, comparative, prospective, multi-center, 1:1 randomized phase 2 trial evaluating the efficacy and safety of active irrigation in external ventricular drainage (intervention arm-IRRAflow) compared to passive external ventricular drainage (control arm-EVD). The trial will enroll 58 patients with primary or secondary IVH. Major eligibility criteria include age ≥18 years of age, IVH documented on head CT or MRI scan (Graeb score ≥3), need of cerebrospinal fluid drainage, deterioration of consciousness or medical sedation at the time of enrollment, and indication for active treatment evaluated by the treating physicians. Exclusion criteria included patients with fixed and dilated pupils and pregnant or nursing women. The primary endpoint of the study is catheter occlusion evaluated by time to first observed occlusion from VC placement. Secondary endpoints include clearance of ventricular blood as measured by head CT scan, rates of catheter-related infection and shunt dependency, length of intensive care unit stay, functional status-Extended Glascow Outcome Scale (eGOS) and modified Rankin scale (mRS) at discharge to rehabilitation and 90 days-and mortality rates at 30 days and 90 days. DISCUSSION: With no standardized treatment for IVH and a poor prognosis, new treatments are needed. IVH patients often need CSF drainage to treat hydrocephalus and to decrease ICP. Standard treatment with passive external ventricular drainage is related to an increased risk of infections which is found in up to 22% of treated cases. The passive VC is known to have a risk of occlusion and is seen in 19-47% of the cases. We hypothesize that the use of active fluid change using the IRRAflow system will be safe and feasible and will reduce the occlusion and infection rates in patients with IVH. TRIAL REGISTRATION: ClicalTrials.gov NCT05204849. Registered 15 December 2021. Updated 24 January 2022.

Isolated Fetal Ventriculomegaly- Postnatal Outcomes and Proposed New Prognostication Classification.

Background: Outcome of Isolated ventriculomegaly diagnosed antenatally depends on size of ventricles and associated malformations. There is scarcity of literature on the guidelines for prognostication based on outcomes as per the ventricle size. Aim: The aim of this work was to study outcome of antenatally detected isolated ventriculomegaly in terms of medical termination, postnatal neuro-developmental milestones, and mortality; and also to propose a new prognostication classification. Methods: Prospective and retrospective observational study on antenatal mothers with isolated ventriculomegaly diagnosed in fetus. Outcomes in terms of termination of pregnancy, postnatal mortality, need of surgery, and morbidity were recorded. Patients were categorized into four groups: Group 1--ventricle size <10 mm, II--11-15 mm, III--16-20 mm, and IV > 20 mm and neuro-developmental milestones were co-related. Association with chromosomal anomalies, congenital heart disease, and maternal infection were also analyzed. Results: 521 antenatal females were referred with fetal anomalies with 163 having CNS malformations. Isolated ventriculomegaly was seen in only 44. Patients of groups 1 and 2 had 100% normal neuro-developmental milestones without any intervention. Group 3 patients had normal neurodevelopmental milestones in 60% only while shunt surgery was required in 40% of patients. All patients of group 4 had poor outcome with only 50% survival. No association with chromosomal anomalies and heart disease was found. Conclusions: Prognosis of isolated ventriculomegaly depends upon size of ventricles and its progressive increase on serial ultrasounds. New proposed classification is simple and would be useful for the treating surgeons to explain the prognosis to parents so as to relieve them of anxiety.

Human intracranial pulsatility during the cardiac cycle: a computational modelling framework.

BACKGROUND: Today's availability of medical imaging and computational resources set the scene for high-fidelity computational modelling of brain biomechanics. The brain and its environment feature a dynamic and complex interplay between the tissue, blood, cerebrospinal fluid (CSF) and interstitial fluid (ISF). Here, we design a computational platform for modelling and simulation of intracranial dynamics, and assess the models' validity in terms of clinically relevant indicators of brain pulsatility. Focusing on the dynamic interaction between tissue motion and ISF/CSF flow, we treat the pulsatile cerebral blood flow as a prescribed input of the model. METHODS: We develop finite element models of cardiac-induced fully coupled pulsatile CSF flow and tissue motion in the human brain environment. The three-dimensional model geometry is derived from magnetic resonance images (MRI) and features a high level of detail including the brain tissue, the ventricular system, and the cranial subarachnoid space (SAS). We model the brain parenchyma at the organ-scale as an elastic medium permeated by an extracellular fluid network and describe flow of CSF in the SAS and ventricles as viscous fluid movement. Representing vascular expansion during the cardiac cycle, a prescribed pulsatile net blood flow distributed over the brain parenchyma acts as the driver of motion. Additionally, we investigate the effect of model variations on a set of clinically relevant quantities of interest. RESULTS: Our model predicts a complex interplay between the CSF-filled spaces and poroelastic parenchyma in terms of ICP, CSF flow, and parenchymal displacements. Variations in the ICP are dominated by their temporal amplitude, but with small spatial variations in both the CSF-filled spaces and the parenchyma. Induced by ICP differences, we find substantial ventricular and cranial-spinal CSF flow, some flow in the cranial SAS, and small pulsatile ISF velocities in the brain parenchyma. Moreover, the model predicts a funnel-shaped deformation of parenchymal tissue in dorsal direction at the beginning of the cardiac cycle. CONCLUSIONS: Our model accurately depicts the complex interplay of ICP, CSF flow and brain tissue movement and is well-aligned with clinical observations. It offers a qualitative and quantitative platform for detailed investigation of coupled intracranial dynamics and interplay, both under physiological and pathophysiological conditions.