Ventriculosinus shunt: a pilot study to investigate new technology to treat hydrocephalus and mimic physiological principles of cerebrospinal fluid drainage

Sune Munthe Department of Neurosurgery, Odense University Hospital, Odense;
Department of Clinical Research and BRIDGE (Brain Research Inter-Disciplinary Guided Excellence), University of Southern Denmark, Odense; and

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Christian Bonde Pedersen Department of Neurosurgery, Odense University Hospital, Odense;
Department of Clinical Research and BRIDGE (Brain Research Inter-Disciplinary Guided Excellence), University of Southern Denmark, Odense; and

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Frantz Rom Poulsen Department of Neurosurgery, Odense University Hospital, Odense;
Department of Clinical Research and BRIDGE (Brain Research Inter-Disciplinary Guided Excellence), University of Southern Denmark, Odense; and

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Mikkel Schou Andersen Department of Neurosurgery, Odense University Hospital, Odense;
Department of Clinical Research and BRIDGE (Brain Research Inter-Disciplinary Guided Excellence), University of Southern Denmark, Odense; and

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Svend Erik Børgesen CSF-Dynamics A/S, Kongens Lyngby, Denmark

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OBJECTIVE

Devices draining CSF to the intracranial venous sinus for the treatment of hydrocephalus have been tested in the past, and while clinically effective, have not shown efficacy in the long term. The majority of these devices become obstructed within 3 months due to endothelial overgrowth. In this study, the authors investigated a newly developed ventriculosinus (VS) shunt outlet device with the objective of showing it would remain patent for at least 6 months.

METHODS

Twelve patients in need of shunting for hydrocephalus underwent an operation using the investigational device and were followed for 6 months to record patency of the shunt.

RESULTS

In 10 patients, the shunt was patent at 6 months, with the outlet device remaining unobstructed. In the remaining 2 patients, one died just before reaching the 6-month endpoint, and in the other the outlet was misplaced during surgery and therefore ceased to function after 3 months. No occlusion of the internal jugular vein or thrombus formation was noted in any of the 12 cases.

CONCLUSIONS

These findings indicate that the outlet device can remain patent and has the capability to mimic physiological drainage by diverting CSF to the intracranial sinus. Additional confirmation of its potential as part of a new VS shunt system and ultimately as a viable alternative for ventriculoperitoneal and ventriculoatrial shunting to reduce complication rates requires further clinical trials.

ABBREVIATIONS

APTT = activated partial thromboplastin time; ICP = intracranial pressure; IJV = internal jugular vein; INR = international normalized ratio; NPH = normal pressure hydrocephalus; PEEK = polyetheretherketone; Rout = resistance to CSF outflow; VAP = venous access port; VS = ventriculosinus.

OBJECTIVE

Devices draining CSF to the intracranial venous sinus for the treatment of hydrocephalus have been tested in the past, and while clinically effective, have not shown efficacy in the long term. The majority of these devices become obstructed within 3 months due to endothelial overgrowth. In this study, the authors investigated a newly developed ventriculosinus (VS) shunt outlet device with the objective of showing it would remain patent for at least 6 months.

METHODS

Twelve patients in need of shunting for hydrocephalus underwent an operation using the investigational device and were followed for 6 months to record patency of the shunt.

RESULTS

In 10 patients, the shunt was patent at 6 months, with the outlet device remaining unobstructed. In the remaining 2 patients, one died just before reaching the 6-month endpoint, and in the other the outlet was misplaced during surgery and therefore ceased to function after 3 months. No occlusion of the internal jugular vein or thrombus formation was noted in any of the 12 cases.

CONCLUSIONS

These findings indicate that the outlet device can remain patent and has the capability to mimic physiological drainage by diverting CSF to the intracranial sinus. Additional confirmation of its potential as part of a new VS shunt system and ultimately as a viable alternative for ventriculoperitoneal and ventriculoatrial shunting to reduce complication rates requires further clinical trials.

In Brief

The objective of this study was to investigate the patency of a novel drain outlet for a hydrocephalus shunt designed for shunting CSF to the intracranial sinus. The option to shunt to the venous sinus is closer to the physiological norm than the current methods and could avoid the many complications of standard ventriculoperitoneal shunts. The key finding was that the device remained patent and shows promise as a future technology for patients with hydrocephalus.

The complication rates associated with shunting CSF for the treatment of hydrocephalus remain unacceptably high despite many attempted technical improvements since shunts were first invented in the 1950s. Modifications have been made in recent decades with features intended to compensate for the changes between intracranial pressure (ICP) and receiving sites such as adjustable valves or antigravitational features, but even recent reviews fail to register the impact of these enhancements on shunt failure rates. Current technology does not address a fundamental issue: the choice of drainage sites (most commonly the peritoneum and atrium) is "unphysiological" and the fluctuating pressure differences between these sites and ICP will therefore always be a challenge to manage mechanically.

Shunting implies intervention in a complex, multidimensional system involving physiological variables such as CSF production, CSF outflow, pressure, cerebral compliance, cardiac output, body position, and physical activity. When shunting CSF to the intraperitoneal cavity, for example, which is standard practice for most hydrocephalus shunt operations, the flow in the shunt is entirely dependent on the pressure difference between the intracranial and intraabdominal compartments. The intraabdominal pressure fluctuates greatly in the short term as well as the long term and depends on posture and physical activity such as breathing, walking, lifting, etc.,1 as well as obesity, among other factors.2 When taking all these factors and their delicate balance into consideration, the diversion of CSF to the peritoneal cavity or right atrium of the heart by means of a drain with a predetermined flow or pressure restriction is highly artificial; the known risks of complications and side effects are therefore considered somewhat inevitable. However, because this intervention is the standard of care for managing the condition, the inherent complications are reluctantly tolerated as an unfortunate necessity.

Manufacturers have attempted to overcome the limitations of shunts with the introduction of antisiphoning devices (more accurately, devices with valves to compensate for siphoning), programmable shunts (adjustable valves), or self-adjusting CSF flow-regulating shunt devices. This has not, however, resulted in significant reductions of reoperations or in extended revision-free periods after shunt implantation.3 In their Cochrane review, Garegnani et al.4 concluded: "Standard shunt valves for hydrocephalus compared to anti-siphon or self-adjusting CSF flow-regulating valves may cause little to no difference on the main outcomes."

In fact, the frequency of reoperations within the first 6 months following shunt implantation is generally reported to be 25%–30%.46 A recent report cites a particularly poor outcome of 32.6% shunt failures 30 days after insertion in patients older than 50 years in the US.5 The 5-year survival rate for any type of CSF shunt investigated is only approximately 50%, inevitably resulting in many repeated surgeries.6 There is a lack of accurate comprehensive data to be found on shunt revision surgeries across different geographical regions, but the annual figures available from the Danish national health database that captures all procedures in the country show a 58% revision and removal rate of hydrocephalus shunts (2021).7

Unwaveringly high failure and complication rates and the absence of breakthrough devices are compelling reasons for exploring new methods for diverting CSF. This study builds on an earlier 2002 Danish study8 in which 150 patients were operated on using ventriculosinus (VS) shunts and showed immediate clinical benefit until issues were discovered with the outlet. The outlet, which at the time was a simple silicone catheter, had drifted to the side of the vein and had become enveloped by endothelial growth within 3 months. The invention of a new outlet device specifically designed to overcome these earlier failings and intended for placement in the jugular foramen provided the opportunity to examine the method of VS shunting. The primary objective of the study was to test the new experimental outlet device for patency for 6 months.

Methods

Approval and Ethical Consideration

All experiment protocols were approved by the Regional Committee on Health Research Ethics for the Capital Region of Denmark as well as the Danish Medicines Agency. The Regional Committee on Health Research Ethics for the Capital Region of Denmark is based on the second Declaration of Helsinki and all procedures were conducted in accordance with those guidelines and regulations. Informed consent was obtained from all participants. The study was conducted following the Guidelines for Good Clinical Practice and was monitored by an independent good clinical practice monitor.

Study Design and Patient Population

The study was a prospective interventional single-arm, single-center open-label pilot study performed at Odense University Hospital, Denmark, on adult patients (≥ 18 years old) in need of shunting for hydrocephalus. Twelve patients were included. Inclusion criteria were the following: 1) a need for shunting, 2) MR or CT venography showing venous cross flow between the right and left transverse sinus, 3) normal lung perfusion scintigraphy, and 4) normal blood coagulation status (international normalized ratio [INR], activated partial thromboplastin time [APTT], thrombocyte count). Exclusion criteria were pregnancy and failing to meet the above inclusion criteria. The primary endpoint was that the device should remain patent for at least 6 months and the secondary endpoint was clinical outcome based on gait, cognitive dysfunction, and urinary incontinence.

There were four defined time points in the study (Table 1): 1) preoperative with medical examinations as per inclusion criteria, 2) surgery using the investigational device and accessories as described below, 3) 3-month follow-up at the outpatient clinic in which the patency of the device was tested, and 4) 6-month follow-up at the outpatient clinic in which the patency of the device was tested and MRI/CT and lung scintigraphy were also performed.

TABLE 1.

Overview of visits

Visit DescriptionVisit 1 (preop)Visit 2 (op)Visit 3 (3-mo FU)Visit 4 (6-mo FU)Notes
Obtain informed consentx
Record DOB & medical historyxAge, hydrocephalus type
Physical/neurological examxxxDevelopment of hoarseness was verified at 3 mos to ensure that presence of VAP in jugular foramen did not cause nerve irritation
Blood testxNormal blood coagulation status (INR, APTT, thrombocytes)
CSF testsxx
ICP, Rout, CSF tap test (all recorded if already done)x
Urine pregnancy test if applicablexxx
Lung scintigraphyxxPerformed preop to ensure no signs of pulmonary thrombus & at 6 mos at end of study
MR venogram/CT scanxxMR venography was performed to show cross venous flow btwn rt & lt transverse sinus
Surgical procedurex
Administer antibiotics (cefuroxime 1500 mg) at opx
Antiplatelet therapy: aspirin 75 mg for 8 wksx
Patency control of VAPxxxWater column test was performed w/ saline solution at 3 & 6 mos to ensure VAP outlet had not blocked

DOB = date of birth; FU = follow-up.

Imaging Methodology

MR or CT venography was used to verify the connections between the transverse sinus and sigmoid sinus so that drainage from the sagittal sinus would not be impeded if one of the internal jugular veins (IJVs) became obstructed. Only patients who met this requirement were included in the study because in some cases the anatomy can vary. This was a precaution, e.g., if placement of the device in the right jugular caused occlusion, then venous outflow could divert from the sagittal sinus to the left jugular vein and vice versa. MRI or CT was used to determine 1) lack of overdrainage, defined by the absence of subdural hematomas or fluid collections and absence of collapse of the ventricles; and 2) lack of local thrombus formation or endothelial proliferation. CT scans were standard of care at 1 month and MRI or CT scans were performed as part of the study at 6 months. Lung scintigraphy was used to determine the possible presence of lung emboli preoperatively and at 6 months.

Surgical Procedure

A standard ventricular drain was inserted in the right or left frontal horn of the cerebral ventricles via precoronal burr hole and connected to the subcutaneously placed control reservoir and one-way valve. The newly designed protective nitinol frame on the silicone catheter of the investigational device collapses into a standard introducer. The Seldinger technique was then used to insert the guidewire, dilator, and Peel-Away sheath (Cook Medical) into the IJV (Fig. 1) The introducer containing the device was inserted through the Peel-Away sheath and then radiographically guided as far as the junction between the sigmoid sinus and top of the IJV before the nitinol frame was released and expanded in the jugular foramen. The silicone catheter of the device was then connected to the unidirectional fixed pressure valve before being led subcutaneously to the unidirectional valve control reservoir. The correct position of the investigational device was confirmed by a final radiograph (Fig. 1). The device and accessories can also be seen on the CT scan in Fig. 2.

FIG. 1.
FIG. 1.

Step-by-step procedure for the VAP. The patient is draped and prepared in the usual fashion in a supine position with the head turned slightly to the left to expose the right neck region. An ultrasound-guided marking for entry to the IJV (A). A small skin incision was made above the IJV. The platysma muscle was bluntly dissected. Using ultrasound, a needle was inserted into the IJV and a guidewire was introduced via the needle and led up to the jugular foramen under radiographic guidance (B). A dilator (trochard) with a peel-away sheath was placed over the guidewire (C) and pushed into the IJV. The dilator was then removed and the introducer containing the investigational device (the VAP inserted using a guidewire) was led up to the jugular foramen via the peel-away sheath under radiographic guidance (D). While holding the device in place, the introducer was retracted (E); the investigational device will then unfold in the foramen. To prevent backflow, the investigational device and tube were temporally closed off with a clamp. A ventricular drain was inserted in the lateral ventricle in a standard fashion. Before the assembly of the shunt system (control reservoir and unidirectional valve), the VAP was thoroughly flushed with Ringer’s solution. Correct placement of the VAP at the venous sinus in the jugular foramen was confirmed at the end of surgery via radiographic guidance (F).

FIG. 2.
FIG. 2.

A 3D reconstructed CT scan showing the position of the VAP.

Aspirin Use

Antiplatelet therapy (aspirin, 75 mg/day) was administered for 8 weeks after shunt implantation due to the possibility of the distancer provoking an endothelial reaction leading to platelet aggregation when it was released in the jugular foramen. Platelet inhibition using aspirin reduces endothelial dysfunction and platelet aggregation and thereby diminishes thrombus formation.9 Once the endothelium had accommodated the nitinol frame and the inflammatory reaction had ceased, the risk of thrombus formation was considered minimal.

Water Column Test

The water column test was performed at 3 and 6 months postoperatively by penetrating the silicone dome of the control reservoir with a slim cannula (0.6-mm diameter) coupled to a transparent tube containing sterile physiological saline solution. This cannula was inserted percutaneously into the control reservoir. Keeping the tube in a vertical position, the fluid flows into the drain and passes through the device if it is patent. Free in-flow is defined as continuous steady flow of saline solution from an approximately 20-cm height to an approximately 5-cm height. The pressure in the control reservoir reflects the pressure in the ventricles (ICP). The control reservoir has a one-way valve with zero opening pressure, therefore the pressure measured by the water column test is, in this way, the same as that of the ventricles.

Investigational Device and Shunt Accessories

Since the purpose of the investigational device was to support drainage of CSF from the ventricles into the intracranial venous sinus as part of a shunt system, complementary off-the-shelf shunt accessories were required. Both the investigational device and the CE-marked accessories were provided by CSF-Dynamics A/S.

The investigational device is called the venous access port (VAP) and is manufactured from only three components, each with critical functions (Fig. 3): the silicone catheter, resistance tube, and nitinol frame. The resistance tube and nitinol frame are at the distal end of the catheter, which diverts fluid from the complementary valve (see accessories description below). The function of the frame is to support and center the outlet, ensuring that it does not contact the endothelium on the inside of the vein. The function of the polyetheretherketone (PEEK) tube, fitted at the end of the catheter, is to provide built-in flow resistance. The flow resistance in the assembled VS shunt is critical to maintain normal ICP and avoid overdrainage. The resistance tube is proportioned to achieve resistance of 10 mm Hg/ml/min following the Davson equation10,11 (see Discussion below).

FIG. 3.
FIG. 3.

Technical drawing of the VAP showing the nitinol frame, PEEK resistance tube, and silicone catheter.

The accessories comprised a standard ventricular drain, control reservoir with unidirectional valve, and fixed-pressure unidirectional valve. The function of the main unidirectional valve with built-in control reservoir was to allow verification of patency, and the purpose of the secondary unidirectional fixed opening pressure valve was to ensure backflow did not occur. The accessories can be seen assembled with the investigational device in Fig. 4.

FIG. 4.
FIG. 4.

Schematic drawing of the shunt system with the control reservoir, unidirectional drain, ventricular drain, and VAP. © CSF-Dynamics A/S, published with permission.

Results

Twelve patients diagnosed with normal pressure hydrocephalus (NPH) aged between 66 and 82 years were treated with a standard ventricular drain, standard control reservoir with unidirectional valve, standard fixed-pressure unidirectional valve, and the investigational outlet device positioned at the junction of the jugular foramen/sigmoid sinus. Two patients did not reach the endpoints. Patient 4 (Table 2) died from pneumonia just before the 6-month follow-up; the VAP had been patent until at least the 3-month follow-up. Patient 12 (Table 2) was found to experience no clinical effect from the shunt at the 3-month follow-up, and the water column test demonstrated that the device was not patent. Shunt revision was planned; during the reoperation it was observed that the device had not been correctly positioned in the jugular foramen during surgery as intended, but low in the IJV where it was not protected by the fixed structure of the jugular foramen. In the remaining 10 patients, the shunt was patent and working at the 3- and 6-month follow-up evaluations.

TABLE 2.

Summary of the results

Pt No.3-Mo FU: Shunt Flow Test, Water Column Inflow6-Mo FUComments
Shunt Flow Test, Water Column InflowWater Column Level (mm H2O)Lung ScintigraphyVein Occlusion on MRINerve SxsGait Improvement*Dementia Improvement*
1FreeFree50NoNoneNone00
2FreeFree55NoNoneNone11
3FreeFree40NoNoneNone10
4FreeNANANANANANANADied at 5.5 mos, unrelated
5FreeFree40NoNoneNone20
6FreeFree40NoNoneNone11
7FreeFree45NoNoneNone00
8FreeFree50NoNoneNone20
9FreeFree30NoNoneNone21
10FreeFree50NoNoneNone11
11FreeFree50NoNoneNone00
12ClosedNANANANANANANAVAP misplaced in jugular vein

NA = not applicable; Pt = patient; Sxs = symptoms.

Possible scores: −2, −1, 0, 1, 2.

While all adult types of hydrocephalus patients were eligible for enrollment, the study was conducted during the COVID-19 pandemic, when waiting times for MR venograms and lung scintigraphy were extended significantly. It was not possible to coordinate a fast turnaround of these examinations needed for patients with (for example) subarachnoid hemorrhage, which meant that the department could only recruit patients with NPH to conduct the study.

ICP pressure measured in the control reservoir via the water column tests was within normal limits in all 10 remaining patients at 3- and 6-month follow-up evaluations showing free flow through the outlet. No sign of overdrainage was observed on follow-up MRI. No thrombus formation or endothelial proliferation was noted in any of the patients on MR or CT venograms. Lung perfusion scintigraphy showed no signs of lung emboli. The results are summarized in Table 2. Apart from the 2 patients mentioned above who were omitted from these final results, in 10 patients the endpoint was achieved, with the outlet remaining patent for at least 6 months.

The clinical effect on gait disturbance, dementia, and incontinence showed improvement in general and was recorded as the secondary endpoint (Table 2). These data were based on the patients’ and/or relatives’ own observations and the sample size is too small to allow for any comparisons to historical data from the literature.

Discussion

The study was designed to demonstrate that the investigational device can remain patent when placed in the intracranial venous sinus and that it can function effectively for at least 6 months. This criterion is based on the experience from the initial study in 2002 in which more than half of the shunts became blocked at the end of the outlet in the vein (overgrown by endothelium) within approximately 3 months. Because the general survival curve of shunts decreases exponentially, we opted to double the time frame to demonstrate significant improvement. In addition, 6 months is often used in the literature to determine the general survival rate of standard shunts and is reported to be between 30%6 and 50%,5 the latter based on specific data for adults and the elderly.

The initial study on intracranial venous shunting was led by Børgesen at the University Hospital Copenhagen in 1999 using the first generation of the SinuShunt (CSF-Dynamics A/S). This shunt system worked as expected in the initial trials and resulted in immediate relief of hydrocephalus symptoms and did not cause symptoms of overdrainage. The results on the initial 46 patients were reported in 2004.8 Further data collected from the neurosurgical departments participating in the trial (150 total patients) confirmed these observations on the immediate clinical effect of shunting to the intracranial sinus. However, the study at the University Hospital Copenhagen was unable to demonstrate long-term success since after the preliminary clinical results were published, it was found that the majority of outlets had ceased to function after approximately 3 months and had become embedded in endothelium, with the pouch formed obliterating the distal end of the outlet. Explantations revealed an important discovery: there was no evidence of blood clots inside or around the outlet nor was there any sinus obstruction by thrombosis. Similar results of shunting to the sagittal sinus were reported by Baert et al.12 in 2018 in which clinical benefit was also observed but where the devices rapidly became occluded. Likewise, Toma et al.’s13 review of 7 case series comprising 265 VS shunts noted that the clinical effect was satisfactory with no cases of thrombosis or occlusion found.

While the investigational device is, stated simply, a drainage catheter, the design addresses the challenges of ICP control as well as providing a solution to tackle overdrainage that occurs when too much fluid is drawn out of the ventricles (the siphon effect, described below). Despite antisiphon features being added to many shunt designs, overdrainage is still a common issue and causes a miserable quality of life for patients who experience it as well as being the cause of malfunction.

The device tested builds on the concept of the first generation of the SinuShunt, the functionality of which was based on resistance to outflow. The principal design change since the first generation is the introduction of the nitinol frame at the end of the outlet. In the 20 years that passed since the first trial was halted, vascular nitinol stents had become widely used in the transverse sinus for treatment of intracranial hypertension. Since the safety of nitinol had thus been established for long-term use in the vasculature, the decision was made to borrow from stent technology and use a stent-like frame to overcome endothelial encasement of the silicone drain found in the initial 2002 study.

The resistance of the assembled shunt remains critical to the balance of ICP and overdrainage and is set following the Davson equation10,11 ICP = FR × Rout + Pss, in which FR is the formation rate of CSF, Rout is the resistance to CSF outflow (Rout), and Pss is the pressure in the sagittal sinus. Opening pressure of the one-way valve is 5 cm H2O, and the resistance of the entire system is designed and dimensioned to 10 mm Hg/ml/min. The setting of the flow resistance is based on the Rout as measured in healthy patients by Ekstedt14 and by Albeck et al.15 with normal values ranging from 6 to 12 mm Hg/ml/min.

The device is designed to be placed in the jugular foramen to avoid the siphon effect. The siphon effect, or hydrostatic force, is commonly experienced with standard ventriculoperitoneal and ventriculoatrial shunting due to the height difference between ventricles and the shunt outlet and is extremely difficult to resolve mechanically because the force changes in tandem with the constantly changing position of the patient (sitting/standing/lying down). Placing the outlet in the jugular foramen ensures there is almost no height difference regardless of the individual’s physical position.

Different placements have been investigated for the VS shunt outlets in the past,12,16,17 but the jugular foramen is particularly well-suited as an outlet site for several additional reasons. Primarily, it is in close proximity to the intracranial cavity while at the same time offering a fixed placement for a centralizing, supporting frame such as the one designed. The effect of the location on ICP is important: instead of ICP being determined by the shunt itself (e.g., in shunts with adjustable pressure) in combination with a distant drainage site with its own pressure variables (e.g., the peritoneum), the ICP is determined by the pressure in the venous sinus and the built-in flow resistance of the outlet. The jugular foramen is also surrounded by bone, apart from a small part of its anteromedial wall,18,19 and will therefore not collapse; the end of the vein, the jugular bulb, is made of dura mater, a strong fibrous wall. Branches of the vagus and hypoglossal nerves are located in the anteromedial part of the foramen, separated from the vein by a fibrous membrane, a continuation of the dura. The tympanic nerve (Jacobson’s nerve) is also situated in its canal in the medial part of the foramen, however, because all the nerves are covered by bone or a fibrous membrane, they are protected from the slight mechanical force exerted by the expanded frame, thereby avoiding possible side effects such as hoarseness or dry mouth. The mean diameter of the approximately round IJV in the foramen is 9 mm with a standard deviation of 2.5 mm, and the median is 8.5 mm.20 The nitinol frame of the investigational device has an unfolded diameter of 12 mm and is able to adapt to a noncircular form, and will thus be in contact with the whole circumference of the wall and able to stay in position on a long-term basis while keeping the outlet centrally placed within the frame. In addition to the advantages, the insertion procedure developed in the current study is intended to be easy to perform. The outlet device is inserted with an introducer sheath via the IJV in the neck using a standard intravascular technique and standard imaging technology (fluoroscopy).

In pursuit of the ideal shunt, the method of shunting to the intracranial venous sinus merits serious consideration because it offers several advantages over alternative diversion sites. The drainage of CSF is controlled only by the pressure differences between the ICP and the pressure in the sinus, therefore there is no need for antisiphon devices because the siphon effect is eliminated. Overdrainage will not occur from a change of position between the horizontal and vertical posture. When overdrainage is avoided, so are complications of subdural fluid collections or subdural hematomas. Fluctuations of ICP caused by fluctuations of the peritoneal pressure are avoided. The common complications related to the peritoneal drain, e.g., cyst formation, bowel perforation, peritoneal irritation, and drain displacement which will lead to shunt revision are avoided. And long periods of low ICP are avoided. Intracranial venous sinus drainage could also reduce the incidence of normal tension glaucoma; Hamarat et al.21 found that the risk of developing normal tension glaucoma after shunting for NPH was over 25%. It is also important to note that the placement of a device in the jugular foramen will not hinder the Starling resistor effect of the collapse of the IJV in the neck (shown by Holmlund et al.22). The IJV collapse maintains ICP when in the upright position.23 The IJV collapse is still possible with the device located at the point of the jugular foramen as the collapse takes place below the jugular foramen and therefore its regulating effect on ICP is not affected.

One drawback of shunting to the intracranial sinus is that the growth of the cranium in infants and children cannot be compensated through an extended drainage catheter length as it can in ventriculoperitoneal shunting. A device that can accommodate this growth will need to be developed for this group of patients. In summary, the potential exists for mimicking physiological drainage providing the outlet device placed in the intracranial venous sinus does not occlude, and it is possible to manage ICP and imitate the balance between CSF production, reabsorption resistance, and pressure in the receiving compartment by diverting CSF into the same cranial space as normalcy. In so doing, overdrainage due to hydrostatic pressure differences and complications from drains and/or the drainage site common to standard shunts can be avoided.

Conclusions

The current study represents the first attempt to place a specially designed outlet device in the jugular foramen for the purposes of diverting CSF while mimicking physiological principles. The patency of the outlet at 6 months indicates that a shunt outlet can remain in the vein without occlusion by endothelial hyperproliferation or thrombus formation and that the technological improvements made are effective. Shunting to the intracranial sinus with this device can therefore be considered a realistic future possibility for diversion of CSF with relatively few adaptations to existing practices of shunt surgery, but with significant gains by avoiding the siphon effect and lowering shunt failure rates. These findings will be explored in a larger study to further demonstrate longevity and measure clinical benefit.

Acknowledgments

We thank Katrina Gillard of CSF-Dynamics A/S for contributions to the manuscript and proofreading. This study was funded by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement no. 849502.

Disclosures

Dr. Andersen reported nonfinancial support from CSF-Dynamics A/S (travel reimbursement for a conference) during the conduct of the study, grants from the Danish 3R-Center, and nonfinancial support (fundoscopy equipment and travel for a conference) from StatuManu Aps outside the submitted work. Dr. Børgesen has received personal fees from CSF-Dynamics A/S during the conduct of the study, is the inventor of the investigational device, and is Chief Clinical Officer of CSF-Dynamics A/S.

Author Contributions

Conception and design: Munthe, Pedersen, Poulsen, Børgesen. Acquisition of data: Munthe. Analysis and interpretation of data: Munthe, Andersen, Børgesen. Drafting the article: Munthe, Børgesen. Critically revising the article: all authors. Reviewed submitted version of manuscript: Munthe, Poulsen, Andersen, Børgesen. Approved the final version of the manuscript on behalf of all authors: Munthe. Statistical analysis: Munthe, Børgesen. Study supervision: Munthe, Poulsen, Børgesen.

Supplemental Information

Previous Presentations

Results from this study were previously presented as oral presentations at the AANS Annual Meeting in Philadelphia, Pennsylvania, on May 2, 2022; at the Scandinavian Neurosurgical Congress in Bergen, Norway, on May 15, 2022; at the Hydrocephalus Society Conference in Gothenburg, Sweden, on September 10, 2022; and at the European Association of Neurosurgical Societies Congress in Belgrade, Serbia, on October 18, 2022.

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  • 10

    Børgesen SE, Gjerris F. Relationships between intracranial pressure, ventricular size, and resistance to CSF outflow. J Neurosurg. 1987;67(4):535539.

  • 11

    Lalou AD, Levrini V, Garnett M, et al. Validation of Davson’s equation in patients suffering from idiopathic normal pressure hydrocephalus. Acta Neurochir (Wien). 2018;160(5):10971103.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Baert EJ, Dewaele F, Vandersteene J, Hallaert G, Kalala JO, Van Roost D. Treating hydrocephalus with retrograde ventriculosinus shunt: prospective clinical study. World Neurosurg. 2018;118:e34e42.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Toma AK, Tarnaris A, Kitchen ND, Watkins LD. Ventriculosinus shunt. Neurosurg Rev. 2010;33(2):147153.

  • 14

    Ekstedt J. CSF hydrodynamic studies in man. 1. Method of constant pressure CSF infusion. J Neurol Neurosurg Psychiatry. 1977;40(2):105119.

  • 15

    Albeck MJ, Børgesen SE, Gjerris F, Schmidt JF, Sørensen PS. Intracranial pressure and cerebrospinal fluid outflow conductance in healthy subjects. J Neurosurg. 1991;74(4):597600.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    El-Shafei IL, El-Shafei HI. The retrograde ventriculovenous shunts: the El-Shafei retrograde ventriculojugular and ventriculosinus shunts. Pediatr Neurosurg. 2010;46(3):160171.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Wen HL. Ventriculo-superior sagittal sinus shunt for hydrocephalus. Surg Neurol. 1982;17(6):432434.

  • 18

    Das SS, Saluja S, Vasudeva N. Complete morphometric analysis of jugular foramen and its clinical implications. J Craniovertebr Junction Spine. 2016;7(4):257264.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Freitas CAF, Santos LRMD, Santos AN, Amaral Neto ABD, Brandão LG. Anatomical study of jugular foramen in the neck. Rev Bras Otorrinolaringol (Engl Ed). 2020;86(1):4448.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Lv X, Wu Z. Anatomic variations of internal jugular vein, inferior petrosal sinus and its confluence pattern: implications in inferior petrosal sinus catheterization. Interv Neuroradiol. 2015;21(6):769773.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Hamarat Y, Bartusis L, Deimantavicius M, et al. Can the treatment of normal-pressure hydrocephalus induce normal-tension glaucoma? A narrative review of a current knowledge. Medicina (Kaunas). 2021;57(3):234.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Holmlund P, Johansson E, Qvarlander S, et al. Human jugular vein collapse in the upright posture: implications for postural intracranial pressure regulation. Fluids Barriers CNS. 2017;14(1):17.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Qvarlander S, Sundström N, Malm J, Eklund A. Postural effects on intracranial pressure: modeling and clinical evaluation. J Appl Physiol (1985). 2013;115(10):14741480.

    • PubMed
    • Search Google Scholar
    • Export Citation
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  • Expand

Illustration from Alattar and McDowell (pp 1485–1486). DALL-E 2023-02-11 18.52.39. “Hand with transparent skin and android skeleton visible underneath” was generated using DALL-E, a deep learning AI model developed by OpenAI, on February 11, 2023, with the instructional phrase in quotation marks.

  • FIG. 1.

    Step-by-step procedure for the VAP. The patient is draped and prepared in the usual fashion in a supine position with the head turned slightly to the left to expose the right neck region. An ultrasound-guided marking for entry to the IJV (A). A small skin incision was made above the IJV. The platysma muscle was bluntly dissected. Using ultrasound, a needle was inserted into the IJV and a guidewire was introduced via the needle and led up to the jugular foramen under radiographic guidance (B). A dilator (trochard) with a peel-away sheath was placed over the guidewire (C) and pushed into the IJV. The dilator was then removed and the introducer containing the investigational device (the VAP inserted using a guidewire) was led up to the jugular foramen via the peel-away sheath under radiographic guidance (D). While holding the device in place, the introducer was retracted (E); the investigational device will then unfold in the foramen. To prevent backflow, the investigational device and tube were temporally closed off with a clamp. A ventricular drain was inserted in the lateral ventricle in a standard fashion. Before the assembly of the shunt system (control reservoir and unidirectional valve), the VAP was thoroughly flushed with Ringer’s solution. Correct placement of the VAP at the venous sinus in the jugular foramen was confirmed at the end of surgery via radiographic guidance (F).

  • FIG. 2.

    A 3D reconstructed CT scan showing the position of the VAP.

  • FIG. 3.

    Technical drawing of the VAP showing the nitinol frame, PEEK resistance tube, and silicone catheter.

  • FIG. 4.

    Schematic drawing of the shunt system with the control reservoir, unidirectional drain, ventricular drain, and VAP. © CSF-Dynamics A/S, published with permission.

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    Sugerman HJ. Effects of increased intra-abdominal pressure in severe obesity. Surg Clin North Am. 2001;81(5):10631075, vi.

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    McAllister JP II, Williams MA, Walker ML, et al. An update on research priorities in hydrocephalus: overview of the third National Institutes of Health-sponsored symposium "Opportunities for Hydrocephalus Research: Pathways to Better Outcomes.". J Neurosurg. 2015;123(6):14271438.

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    Garegnani L, Franco JVA, Ciapponi A, Garrote V, Vietto V, Portillo Medina SA. Ventriculo-peritoneal shunting devices for hydrocephalus. Cochrane Database Syst Rev. 2020;6(6):CD012726.

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    LeHanka A, Piatt J. Readmission and reoperation for hydrocephalus: a population-based analysis across the spectrum of age. J Neurosurg. 2020;134(3):12101217.

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    Kofoed Månsson P, Johansson S, Ziebell M, Juhler M. Forty years of shunt surgery at Rigshospitalet, Denmark: a retrospective study comparing past and present rates and causes of revision and infection. BMJ Open. 2017;7(1):e013389.

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  • 7

    Landspatientregisteret. Landspatientregisteret: Avanceret udtræk. Accessed March 14, 2023. https://www.esundhed.dk/Emner/Operationer-og-diagnoser/Landspatientregisteret-Avanceret-udtraek

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    Børgesen SE, Pieri A, Cappelen J, Agerlin N, Gjerris F. Shunting to the cranial venous sinus using the SinuShunt. Childs Nerv Syst. 2004;20(6):397404.

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    Hamilos M, Petousis S, Parthenakis F. Interaction between platelets and endothelium: from pathophysiology to new therapeutic options. Cardiovasc Diagn Ther. 2018;8(5):568580.

    • PubMed
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    • Export Citation
  • 10

    Børgesen SE, Gjerris F. Relationships between intracranial pressure, ventricular size, and resistance to CSF outflow. J Neurosurg. 1987;67(4):535539.

  • 11

    Lalou AD, Levrini V, Garnett M, et al. Validation of Davson’s equation in patients suffering from idiopathic normal pressure hydrocephalus. Acta Neurochir (Wien). 2018;160(5):10971103.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Baert EJ, Dewaele F, Vandersteene J, Hallaert G, Kalala JO, Van Roost D. Treating hydrocephalus with retrograde ventriculosinus shunt: prospective clinical study. World Neurosurg. 2018;118:e34e42.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Toma AK, Tarnaris A, Kitchen ND, Watkins LD. Ventriculosinus shunt. Neurosurg Rev. 2010;33(2):147153.

  • 14

    Ekstedt J. CSF hydrodynamic studies in man. 1. Method of constant pressure CSF infusion. J Neurol Neurosurg Psychiatry. 1977;40(2):105119.

  • 15

    Albeck MJ, Børgesen SE, Gjerris F, Schmidt JF, Sørensen PS. Intracranial pressure and cerebrospinal fluid outflow conductance in healthy subjects. J Neurosurg. 1991;74(4):597600.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    El-Shafei IL, El-Shafei HI. The retrograde ventriculovenous shunts: the El-Shafei retrograde ventriculojugular and ventriculosinus shunts. Pediatr Neurosurg. 2010;46(3):160171.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Wen HL. Ventriculo-superior sagittal sinus shunt for hydrocephalus. Surg Neurol. 1982;17(6):432434.

  • 18

    Das SS, Saluja S, Vasudeva N. Complete morphometric analysis of jugular foramen and its clinical implications. J Craniovertebr Junction Spine. 2016;7(4):257264.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Freitas CAF, Santos LRMD, Santos AN, Amaral Neto ABD, Brandão LG. Anatomical study of jugular foramen in the neck. Rev Bras Otorrinolaringol (Engl Ed). 2020;86(1):4448.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Lv X, Wu Z. Anatomic variations of internal jugular vein, inferior petrosal sinus and its confluence pattern: implications in inferior petrosal sinus catheterization. Interv Neuroradiol. 2015;21(6):769773.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Hamarat Y, Bartusis L, Deimantavicius M, et al. Can the treatment of normal-pressure hydrocephalus induce normal-tension glaucoma? A narrative review of a current knowledge. Medicina (Kaunas). 2021;57(3):234.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Holmlund P, Johansson E, Qvarlander S, et al. Human jugular vein collapse in the upright posture: implications for postural intracranial pressure regulation. Fluids Barriers CNS. 2017;14(1):17.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Qvarlander S, Sundström N, Malm J, Eklund A. Postural effects on intracranial pressure: modeling and clinical evaluation. J Appl Physiol (1985). 2013;115(10):14741480.

    • PubMed
    • Search Google Scholar
    • Export Citation

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