WO2025219319A1

WO2025219319A1 - Apparatus for shunting cerebrospinal fluids and method of assembling thereof

Info

Publication number: WO2025219319A1
Application number: PCT/EP2025/060214
Authority: WO
Inventors: Lars Ulrik Nielsen; Svend Erik BØRGESEN; Robert NAUMOVSKI; Tom Hede Markussen
Original assignee: CSF Dynamics AS
Current assignee: CSF Dynamics AS
Priority date: 2024-04-19
Filing date: 2025-04-14
Publication date: 2025-10-23
Anticipated expiration: 2026-10-19
Also published as: WO2025219312A1

Abstract

A cerebrospinal fluid shunt device comprises: a tubular inlet (4) comprising an inlet end (41) configured for insertion into a cerebrospinal fluid containing space of the individual, the inlet end having an inlet opening (411) for receiving cerebrospinal fluid, a tubular outlet (2) comprising an outlet end (21) for insertion into a venous system cavity of the individual, the outlet end comprising an outlet opening (211), the tubular outlet comprises a tubular nozzle member (212), a fixator (213) is attached to the outlet end and configured to secure a location of the outlet end in the venous system cavity by exerting a radial outward force onto a wall of the venous system cavity at a deployment location of the outlet end in the venous system cavity.

Description

APPARATUS FOR SHUNTING CEREBROSPINAL FLUIDS AND METHOD OF ASSEMBLING THEREOF

Technical Field

The present disclosure relates to apparatus and methods for shunting cerebrospinal fluids from a cerebrospinal fluid containing space of an individual to facilitate drainage of cerebrospinal fluids and to relieve, e.g., an elevated intracranial pressure in the individual.

Various methods disclosed herein use a cerebrospinal fluid shunt device comprising a tubular outlet having an outlet end with an outlet opening.

Background

The complication rates associated with shunting cerebrospinal fluid (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 drainage sites, such as adjustable valves or anti-gravitational features, but even recent reviews fail to register the impact of these enhancements on shunt failure rates.

Many current shunting technologies do not address a fundamental issue: The choice of drainage sites (most commonly the peritoneum and atrium) is “unphysiological” and fluctuating and/or arbitrary 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 anti-siphoning 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 re-operations 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%.^4-6

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 apparatus and methods for relieving elevated cerebrospinal pressure in an individual by diverting cerebrospinal fluids from the ventricles to a sinus system cavity or another suitable drainage site.

In subjects suffering from elevated intracranial pressures, such as, e.g., hydrocephalus, drainage of cerebrospinal fluids from the ventricles is impaired, and it is necessary to provide a shunt device to ensure sufficient drainage of cerebrospinal fluids from the ventricles.

When inserting a shunt device into the ventricles to drain cerebrospinal fluids to relieve an elevated intracranial pressure, the shunt device should preferably restore the physiological drainage of cerebrospinal fluids from the ventricles. Excess drainage of cerebrospinal fluids from the ventricles should be avoided.

In view of the above-cited technical challenges there is a need for improved shunt devices and methods aimed at draining excess cerebrospinal fluids from the ventricles without the risk of over-drainage or under-drainage, or for shunt devices or methods that at least can serve as alternatives to existing solutions.

Summary

According to a first aspect, disclosed herein are embodiments of a cerebrospinal fluid shunt device for shunting cerebrospinal fluid from a cerebrospinal fluid containing space and into a venous system cavity of an individual, wherein the cerebrospinal fluid shunt device comprises a tubular inlet, a tubular outlet and a fixator, wherein the tubular inlet comprises an inlet end configured for insertion into a cerebrospinal fluid containing space of the individual, the inlet end having an inlet opening for receiving cerebrospinal fluid, wherein the tubular outlet has an outlet end configured for insertion into a venous system cavity of the individual, the outlet end comprising an outlet opening, wherein the inlet opening is fluidly connected with the outlet opening to allow cerebrospinal fluid to flow from the inlet opening to the outlet opening, wherein the tubular outlet comprises a flexible tubular member and a tubular nozzle member, wherein the flexible tubular member comprises a tubular wall defining an inner lumen having a distal open end, wherein the tubular nozzle member has a proximal portion and a distal portion, the proximal portion extending into the inner lumen of the flexible tubular member and the distal portion extending out of the distal open end of the flexible tubular member, wherein the fixator is configured to secure a location of the outlet end at a deployment location in the venous system cavity, wherein the fixator comprises an annular attachment member configured for attachment of the fixator to the flexible tubular member, and wherein the flexible tubular member and the proximal portion of the tubular nozzle member extend through the annular attachment member.

The tubular nozzle member provides a stable outflow nozzle at the outlet end of the flexible tubular member, which can be held securely and centered by the fixator at the deployment location within the venous system cavity. The provision of the tubular nozzle member whose proximal portion extends into the inner lumen of the flexible tubular member in combination with the annular attachment member, which is axially located along the flexible tubular member such that it surrounds both the flexible tubular member and the proximal portion of the tubular nozzle member inserted into the flexible tubular member, allows the outlet end to be securely assembled from only few parts.

Various embodiments of the tubular outlet can efficiently and securely be assembled with the fixator, even without the need for any glue or bonding material.

In particular, a method is provided for assembling a tubular outlet of a cerebrospinal fluid shunt device for shunting cerebrospinal fluid from a cerebrospinal fluid containing space and into a venous system cavity of an individual. The method comprises: providing a flexible tubular member comprising a tubular wall defining an inner lumen having a distal open end; providing a fixator configured to secure a location of an outlet end of the tubular outlet in the venous system cavity, wherein the fixator comprises an annular attachment member configured for attachment of the fixator to the flexible tubular member, providing a tubular nozzle member having a proximal portion and a distal portion, advancing the flexible tubular member through the annular attachment member, inserting the proximal portion of the tubular nozzle member into the inner lumen of the flexible tubular member with the distal portion extending out of the distal open end of the flexible tubular member, applying an axial force to the flexible tubular member to axially stretch the flexible tubular member, axially displacing the annular attachment member along the stretched flexible tubular member to a position along the flexible tubular member where the flexible tubular member and the inserted proximal portion of the tubular nozzle member extend through the annular attachment member, releasing the applied axial force.

The annular attachment member defines a central hole. In the assembled tubular outlet, the flexible tubular member and the inserted proximal portion of the tubular nozzle member extend through the central hole of the annular attachment member, i.e. the annular attachment member surrounds the flexible tubular member and the inserted proximal portion of the tubular nozzle member. The annular attachment member, the flexible tubular member and the inserted proximal portion of the tubular nozzle member are arranged substantially coaxial.

The radial dimension of the central hole defined by the annular attachment member, the outer diameter of the proximal portion of the tubular nozzle member, and the wall thickness of the tubular wall of the flexible tubular member may be selected such that the annular attachment member and the tubular nozzle member are axially fixated relative to the flexible tubular member when the attachment member surrounds the flexible tubular member and the inserted proximal portion of the tubular nozzle member. During assembly, the applied axial force may be strong enough to cause the wall thickness of the tubular wall to be reduced enough for the annular attachment member to be slidable along the flexible tubular member over the proximal portion of the tubular nozzle member. When the axial force is released again after axially positioning the annular attachment member, the tubular wall returns to its un-stretched wall thickness causing the annular attachment member to be fixated along the flexible tubular member and causing the inserted tubular nozzle member to be retained inside the inner lumen and projecting through the annular member.

It will be appreciated that some of the above steps may be performed in different orders. For example, the proximal portion of the tubular nozzle member may be inserted into the inner lumen of the flexible tubular member before or after the flexible tubular member is advanced through the annular attachment member. Similarly, the flexible tubular member may be advanced through the annular attachment member before the axial force is applied. Alternatively, in particular when the proximal portion of the tubular nozzle member is inserted into the inner lumen of the flexible tubular member before the flexible tubular member is advanced through the annular attachment member, the flexible tubular member may be advanced through the annular attachment member while the axial force is applied.

In some embodiments, the proximal portion comprises two axially spaced apart (i.e. spaced apart along the longitudinal axis of the tubular nozzle member) bulging portions axially separated by an intermediate portion, the intermediate portion having a smaller outer diameter than each of the bulging portions, and wherein the annular attachment member is axially positioned at a position along the flexible tubular member and the proximal portion of the tubular nozzle member between the spaced apart bulging portions of the proximal end inserted into the inner lumen of the flexible tubular member. Accordingly, when assembling the tubular outlet, the annular attachment member may be axially displaced along the stretched flexible tubular member to a position along the flexible tubular member between the spaced apart bulging portions of the proximal end inserted into the inner lumen of the tubular member. When the applied axial force is released when the annular attachment member is thus positioned, the flexible tubular member

The distal portion of the tubular nozzle member may comprise a conical portion having an outer diameter that gradually decreases towards the distal tip, thereby facilitating steady blood flow along the tubular nozzle member and reducing the risk of overgrowth by endothelium tissue and/or the risk of deposit of proteins, biofilm and/or the like on the tip end. When the outer diameter of the tubular nozzle member at the distal tip is small, the risk of the tip being overgrown or contaminated by deposits and the open end being clogged is reduced, in particular when the distal tip also is a rounded tip that provides a smooth outer surface without sharp edges. In some embodiments, the outer diameter of the tubular nozzle member at the distal tip is between 0.8 mm and 2 mm, such as between 1 mm and 1.5 mm. In some embodiments, the opening towards the inner lumen of the tubular nozzle member has a diameter of between 0.2 mm and 0.9 mm, such as between 0.3 mm and 0.5 mm, such as between 0.35 mm and 0.4 mm, thereby ensuring sufficient flow of CSF into the blood stream, in particular when the outflow of CSF from the outlet opening is directed in a retrograde orientation as compared to the direction of the blood stream.

In some embodiments, the transition between the proximal portion and the distal portion is defined by a radially outward projecting edge to which the tubular wall of the flexible tubular member abuts when the proximal portion extends into the inner lumen of the flexible tubular member. The edge may have an outer diameter substantially equal to an outer diameter of the flexible tubular member, thereby providing a flush transition between the outer surfaces of the distal portion of the tubular nozzle member and the flexible tubular member. The outer diameter of the distal portion may gradually decrease from the edge and towards the tip of the tubular nozzle member.

In some embodiments, the distal portion has a rounded distal tip, thereby facilitating steady and smooth blood flow along the tubular nozzle member.

The flexible tubular member may be made from a suitable elastic material, such as silicone. The tubular nozzle member is preferably stiffer than the flexible tubular member. The proximal portion of the tubular nozzle member may have an outer diameter small enough to be inserted into the inner lumen of the flexible tubular member. In some embodiments, the tubular nozzle member may have an outer diameter large enough to be retained inside the flexible tubular member when extending into the inner lumen of the flexible tubular member, at least when the annular attachment member surrounds the proximal portion of the tubular nozzle member. The flexible tubular member may be radially expandable and/or have an elastically deformable tubular wall. The outer diameter of the proximal portion of the tubular nozzle member may, at least at one or more axial locations along the proximal portion, be large enough to radially expand the flexible tubular member slightly and/or otherwise deform the elastic tubular wall of the flexible tubular member. The resulting elastic forces of the flexible tubular member may retain the proximal portion inside the inner lumen, at least when the annular attachment member surrounds the proximal portion of the tubular nozzle member and the flexible tubular member.

Generally, the tubular inlet may be integrally formed with the tubular outlet. Alternatively, the tubular inlet and the tubular outlet may be formed as separate elements connectable directly or indirectly with each other, e.g. via a shunt body as described herein, or otherwise.

In some embodiments, the fixator is configured to secure a location of the outlet end in the venous system cavity by exerting a radial outward force onto a wall of the venous system cavity at a deployment location of the outlet end in the venous system cavity. The fixator is configured to be converted from a compacted state of the fixator into an expanded use state of the fixator to secure the outlet end at the deployment location, wherein the radial force is between about 0.1 Newton and 1.0 Newton in the expanded use state.

The inventors have realized that the radial force from about 0.1 Newton to 1.0 Newton in the expanded use state is strong enough to secure the fixator and, hence, the outlet end at the deployment state and to prevent it from being unintentionally displaced. The radial force from about 0.1 Newton to 1.0 Newton in the expanded use state is also weak enough to reduce or even eliminate the risk that the fixator damages or otherwise impairs the wall of the venous system cavity, in particular the vein wall, or that the fixator damages or otherwise impairs structures, such as bone or nerves, in the proximity of the venous system cavity at the deployment location.

According to a second aspect, the present disclosure provides a method of implanting an embodiment of the cerebrospinal fluid shunt described above and in the following and a method of shunting cerebrospinal fluid from a cerebrospinal fluid containing space of an individual to a foramen jugulare of the individual, using an embodiment of the cerebrospinal fluid shunt described above and in the following.

In various embodiments of the method of implanting a cerebrospinal fluid shunt, the method comprises positioning the cerebrospinal fluid shunt with at least part of an inlet end of the tubular inlet, the inlet end comprising an inlet opening, into a cerebrospinal fluid containing space of the individual, and with at least part of an outlet end of the tubular outlet, the outlet end comprising an outlet opening, at a deployment location at, in particular in, a foramen jugulare of the individual, such that the inlet opening is fluidly connected with the outlet opening so that cerebrospinal fluid is able to flow from the inlet opening to the outlet opening.

In various embodiments, the method of shunting cerebrospinal fluid from a cerebrospinal fluid containing space of an individual to a foramen jugulare of the individual comprises the steps of: i) inserting at least part of the inlet end of the tubular inlet into a cerebrospinal fluid containing space of the individual, ii) inserting at least part of an outlet end of a tubular outlet into the foramen jugulare of the individual, and iii) shunting cerebrospinal fluid from the cerebrospinal fluid containing space of the individual to the foramen jugulare of the individual.

There is also provided a method of inserting the cerebrospinal fluid shunt in a cerebrospinal fluid containing space and in a foramen jugulare of an individual. Various embodiments of said method comprise the steps of a) inserting at least part of the inlet end of the tubular inlet into a cerebrospinal fluid containing space of the individual, b) inserting at least part of the outlet end of the tubular outlet into the foramen jugulare of the individual, and c) operably connecting the inlet opening inserted into the cerebrospinal fluid containing space of the individual with the outlet opening of the outlet end inserted into the foramen jugulare of the individual so that cerebrospinal fluid is able to flow from the inlet opening to the outlet opening.

Embodiments of the methods disclosed herein are useful for treating individuals, including human beings, suffering from elevated intracranial pressure, such as hydrocephalus, including normal pressure hydrocephalus. The cerebrospinal fluid containing space can be a ventricle or a subarachnoid space or another suitable cerebrospinal fluid containing space. The ventricle may be a lateral ventricle.

When at least a part of the outlet end is positioned in the foramen jugulare, the outlet opening may be positioned inside the foramen jugulare or immediately superior or inferior the foramen jugulare.

In some embodiments, a shunt body of the shunt device may operably connect under practical circumstances the inlet end of the tubular inlet, the inlet end comprising the inlet opening inserted into the cerebrospinal fluid containing space of the individual, with the outlet end of a tubular outlet, the outlet end comprising the outlet opening and being inserted into the foramen jugulare of the individual or into another suitable outlet deployment site. The shunt body may be connected at one end to the tubular inlet, and connected at another end to the tubular outlet configured for insertion into the foramen jugulare of the vena jugularis of the individual or into another suitable outlet deployment site.

When practicing the above-captioned methods, an outlet end of the tubular outlet, the outlet end comprising the outlet opening, may initially be inserted into vena jugularis and then guided through the vena jugularis and into the foramen jugulare. The outlet end of the tubular outlet is thus deployed inside the vena jugularis at a position where the vena jugularis passes through the foramen jugulare.

Accordingly, some embodiments of the methods disclosed herein may comprise:

- guiding the outlet end of the tubular outlet, the outlet end comprising the outlet opening, through the vena jugularis towards the foramen jugulare, and

- locating the outlet end of the tubular outlet in a cavity of the foramen jugulare, such as, e.g., the jugular bulb or an upper portion of the vena jugularis.

When located in the foramen jugulare, the outlet end of the tubular outlet, the outlet end comprising the outlet opening, is preferably secured by the fixator attached to the tubular outlet. One way of securing the outlet end of the tubular outlet in the foramen jugulare is by converting the fixator attached to the outlet end of the tubular outlet from a compacted state into an expanded use state. When the fixator attached to the outlet end of the tubular outlet is changed from a compacted state to an expanded use state, the fixator exerts a force, in particular a radially outward force, on the walls of a foramen jugulare cavity, in particular on a cavity wall of the vena jugularis passing through the foramen jugular, and maintains the outlet end of the tubular outlet, the outlet end comprising the outlet opening, at a position in the foramen jugulare radially displaced from and without contacting endothelial tissue. The outlet end with the fixator attached to it may, in practical circumstances, be partly positioned inside the jugular foramen and partly extend superiorly and/or inferiorly out of the foramen jugulare.

Brief description of the Drawings

Embodiments of various aspects of the apparatus and methods for shunting of cerebrospinal fluid disclosed herein will be described in more detail below and with reference to the drawings, in which:

FIGs. 1A-B illustrate a shunt device for draining cerebrospinal fluids in an individual.

FIGs. 2A-B schematically shows the outlet end of a tubular outlet of an embodiment of a shunt device.

FIG.3 schematically shows another embodiment of the outlet end of a tubular outlet of an example of a shunt device.

FIGs. 4A-B illustrate an example of a shunt body of an embodiment of a shunt device.

FIG. 5 illustrates the dural venous sinus system of a human patient.

FIGs. 6A-D illustrate a process for insertion of the outlet end of the tubular outlet into the foramen jugular of an individual.

FIG. 7 illustrates an example of a method of inserting a cerebrospinal fluid shunt in a cerebrospinal fluid containing space and in the vena transversa of an individual.

FIGs. 8A-C illustrate a process of assembling an embodiment of the outlet end of a tubular outlet of an example of a shunt device.

FIG. 9 illustrates an example of a method of extracting an outlet end of a shunt device from a sinus cavity system of an individual. Detailed Disclosure

Embodiments of various aspects of the shunting of cerebrospinal fluid will be described in more detail below. Alternative embodiments substantially identical or essentially similar to the below-disclosed embodiments will be within reach of a skilled person aiming to practice the below-disclosed methods of shunting cerebrospinal fluids in an individual and/or to provide the below-disclosed shunt device.

Shunt devices for use in draining cerebrospinal fluids in an individual

FIGs. 1A-B illustrate a shunt device for draining cerebrospinal fluids in an individual. FIG. 1 A shows the shunt device implanted in a human patient 5, while FIG. 1 B shows an enlarged view of the outlet end of the shunt device positioned in the foramen jugulare.

Generally, a shunt device for use in the methods disclosed herein and/or in other methods comprises a tubular inlet 4 comprising an inlet end 41 with an inlet opening 411 configured for insertion into a cerebrospinal fluid (CSF) containing space of an individual. The shunt device further comprises a tubular outlet 2 having an outlet end 21 for insertion via a penetration point 51 into the vena jugularis 52 and for being guided towards a deployment site in the foramen jugulare 53.

FIGs. 2A-B and FIG. 3 illustrate respective examples of an outlet end 21 of a tubular outlet 2 of a shunt device for draining cerebrospinal fluids in an individual, e.g. of the shunt device of FIGs. 1 A-B. The outlet end 21 has an outlet opening 211 and is configured for insertion in a sinus system cavity, such as vena jugularis, in particular in the foramen jugulare 53 or another suitable deployment position.

Referring to FIG. 2A-B, and with continued reference to FIGs. 1A-B, the above- mentioned tubular elements, i.e. the tubular inlet and the tubular outlet, comprise inner lumens that extend through the respective tubular elements. The inner lumen of the tubular inlet 4 and the inner lumen of the tubular outlet 2 are operably connected so that cerebrospinal fluids can be shunted or drained through the shunt device from the inlet opening 211 inserted into a cerebrospinal fluid containing space to the outlet opening inserted into a sinus system cavity, such as vena jugularis, in particular in the foramen jugulare (“jugular foramen”) and/or bulbus superior venae jugularis (“jugular bulb”) 54. The shunt device comprises a fixator 213 for securing the outlet opening 211 of the shunt device when the outlet opening is inserted into a sinus system cavity and for avoiding contact of the outlet opening with the endothelial wall of the sinus system cavity, such as vena jugularis and/or jugular bulb, and/or bone sections, such as the jugular foramen. The fixator also serves to maintain the outlet end of the tubular outlet at a distance from endothelium tissue and bones, such as at a predetermined and/or essentially fixed distance from endothelium tissue and bones.

The shunt devices disclosed herein comprise a tubular inlet 4 having an inlet end 41 with an inlet opening 411 configured for insertion into a CSF containing space, lin particular into a ventricle of an individual. The shunt devices of such embodiments may further comprise a shunt body 3, and a tubular outlet 2 having an outlet end 21 with an outlet opening 211 , the outlet end being configured for insertion into the vena jugularis at the foramen jugulare, or at another suitable deployment location. The tubular inlet 4 may thus be a ventricular catheter.

In various embodiments, the shunt devices disclosed herein comprise a flow restricting part, in particular a tubular nozzle member as described herein and, optionally, an additional flow restricting part. The flow restricting part is positioned between the inlet opening and the outlet opening. The shunt device may further comprise a one-way valve preventing back-flow of cerebrospinal fluids, i.e. preventing cerebrospinal fluids from flowing from the outlet opening to the inlet opening of the shunt device.

In some embodiments, the shunt device may comprise a fixed or adjustable pressurecontrol and/or flow-control valve for regulating the amount of CSF being drained. A fixed valve may regulate the intracranial pressure based on a predetermined pressure setting. An adjustable valve (sometimes also referred to as a programmable valve) may regulate the intracranial pressure based on a pressure and/or flow setting that can be adjusted by a physician using an external adjustment tool. An adjustable valve may be configured to adjust the opening pressure of the valve and/or to adjust the flow resistance of the adjustable valve. Alternatively, or additionally, the adjustable valve may be adjustable to a closed state, where the adjustable valve remains closed regardless of the pressure. The tubular outlet may also be referred to as a drainage catheter or a sinus catheter and the outlet end with the attached fixator may be referred to as a venous access port (VAP).

The shunt body 3 may comprise a housing and one or two check valves. The housing may be a titanium housing. The housing may accommodate an antechamber. Each of the one or two check valves may be a ball-in-cone check valve, a duckbill valves, and/or an umbrella valve. In case of two check valves both check valves may be of the same type or of different types. The antechamber may be constructed with a silicone dome to enable compression (i.e. , palpation) and penetration with a cannula. One of the ball-in-cone check valves may prevent backflow into the ventricles when the dome is compressed for the purposes of functional performance. The second ball-in-cone check valve may be spring-loaded. The spring may be configured to provide a predetermined opening pressure, e.g. of about 3 ± 1.5 cm H2O (water column), and the ball-in-cone prevents backflow from the outlet end of the shunt device.

The inlet and the outlet of the housing of the shunt body may comprise two barb connectors, one for a ventricular catheter and one for the tubular outlet.

The tubular outlet may comprise, or consist of, a flexible tubular member 22 (which will also be referred to as a catheter tube 22) and a tubular nozzle member 212. A fixator 213 is attached at the outlet end of the flexible tubular member 22. The flexible tubular member 22 may be a silicone catheter tube, e.g. a sulphate impregnated silicone catheter tube. The silicone catheter tube is preferably long enough (e.g. 60 cm long) to allow it to be cut to length during implantation. The silicone catheter tube 22 holds the tubular nozzle member 212, which may be a PEEK (polyether ether ketone) nozzle. The tubular nozzle member provides a stiff outflow at the catheter end which can be held securely and centered within the vein by the fixator. The fixator 213 may be an electropolished nitinol fixator which facilitates a secure fixation in the jugular foramen or at another suitable deployment location.

The flow rate of CSF through the shunt device is governed by the stable differential pressure (DP) between the shunt inlet (in particular the ventricles of the brain) and the shunt outlet, and by the production rate of CSF (about 0,35 ml/min, and relatively constant), which is the same principle as in conventional physiological CSF drainage. However, in various embodiments disclosed herein, the shunt outlet is positioned in the jugular foramen or at another suitable deployment location in the sinus cavity system. This is in contrast to conventional VP or VA valves, which drain to the peritoneum or right atrium of the heart and where the differential pressure is different. The functionality of conventional shunts is also challenged by gravity and as a result these valves often incorporate programmable or other flow regulating features to try to address this. These additional features are unnecessary with embodiments of the shunt device disclosed herein and with embodiments of the methods where the outlet end of the shunt device are positioned in the jugular foramen or a venous sinus cavity.

Shunt body

FIGs. 4A-B illustrate an example of a shunt body of an embodiment of a shunt device. FIG. 4A shows a three-dimensional view of the shunt body, while FIG. 4B shows a cutaway three-dimensional view of the shunt body.

In various embodiments, the shunt body 3 is configured for subcutaneous placement on the calvarium of the patient. In particular, the shunt body is preferably shaped and sized for such placement. To this end, the shunt body may have a generally flat housing 31 having a thickness/height large enough to make it palpable when implanted subcutaneously. The flat housing 31 has a bottom wall 311 that, in use, faces the calvarium, and a top wall 312 of the shunt body housing faces, in use, away from the calvarium. The flat body has a circumference, which may be formed by a circumferential wall 313 extending between the top and bottom walls, or by the top and bottom walls converging towards each other, or otherwise. The shunt body has an inlet connector 32, which is preferably located at the circumference of the flat body, for fluidly connecting the tubular inlet. The shunt body has an outlet connector 33, which is preferably located at the circumference of the flat body, for fluidly connecting the tubular outlet.

In some embodiments, the shunt body comprises flow restricting means 34 aimed at controlling the flow of cerebrospinal fluids through the shunt device in such a way that the flow rate of cerebrospinal fluid through the shunt device is such that the flow of cerebrospinal fluids through the shunt device is similar to the flow of cerebrospinal fluids from the ventricles and into the sagittal sinus in an individual under normal physiological conditions, i.e. conditions at which flow of cerebrospinal fluids and/or intracranial pressure conditions would be deemed physiological to the extent that insertion of a shunt device into a CSF containing space of an individual would not be contemplated or required to increase or modulate a cerebrospinal fluid flow rate or to relieve or modulate an increased intracranial pressure. The flow restriction means may be formed by a reduced diameter conduit or otherwise. In addition, or alternatively to a flow restriction means in the shunt body, the shunt device may include alternative flow restriction means, e.g. a tubular nozzle member at the outlet end as described herein, or otherwise.

The shunt body 3 preferably comprises a check valve 37 aimed at preventing back-flow of cerebrospinal fluids from the outlet end of the outlet to the inlet end of the inlet. The opening pressure of the check valve is preferably from about 2 mm Hg (i.e. 2,7 cm H2O) to less than about 5 mm Hg (i.e. 6,8 cm H2O), and the opening pressure of the check valve is preferably independent of the rate at which cerebrospinal fluids flow through the flow restricting means of the shunt device. In the example of FIGs. 3A-B, the check valve 37 is spring loaded. The spring provides a specific opening pressure (e.g. about 3 ± 1.5 cm H2O), to correlate with the difference between intracranial pressure (ICP) and the pressure in the jugular foramen. In particular, in the illustrated embodiment, the check valve 37 is formed by a valve ball 371 which is biased against a valve seat by a flat spring element 372, e.g. a flat nitinol spring, which may be secured in the housing by a cover 373.

In the example of FIGs. 4A-B, the shunt body 3 comprises a control reservoir 35, formed as an antechamber to the check valve 37. The control reservoir 35 is fluidly connected with the inlet connector 32 and with the outlet connector. The present example includes two check valves 36 and 37. Check valve 36 is located between the outlet connector and the control reservoir while check valve 37 is located between the control reservoir 35 and the outlet connector 33. Both check valves may comprise a valve ball 361 and 371, respectively, such as sapphire balls or otherwise.

The control reservoir 35 is a chamber defined by a bottom wall 311 of the shunt body housing 31 and an opposite soft dome-shaped wall 38 (which may be transparent to allow visual inspection of the control reservoir 35). The dome-shaped wall may be made from silicone rubber or from another suitable material. The dome-shaped wall may be held in place by a titanium ring 381 or otherwise. The control reservoir 35 allows the check valve 37 to be primed during surgery, and for the system to be verified for through-flow after surgery (e.g. through compression or water-column test). The two check valves 36 and 37 prevent backflow from the outlet end and into the ventricles. When the dome is compressed (by the surgeon), the inlet valve closes. When the dome is decompressed (when the surgeon releases pressure), the inlet valve opens and the outlet valve closes.

The housing 31, including the valve seats of valves 36 and 37, the inlet connector 32, the outlet connector 33, and the cover 373 may be made from titanium or from another suitable material. Generally, the materials of the various components should preferably be medical grade, biocompatible and suitable for long-term use.

The various components of the shunt body may be assembled by press-fitting them into each other or otherwise. Press fitting ensures a durable assembly without requiring adhesives, clamps, or other similar elements.

Generally, shunting cerebrospinal fluids from the ventricles to the vena jugularis at the foramen jugulare, with embodiments of the shunt devices disclosed herein reduces the risk of overdrainage of cerebrospinal fluids caused by excessive differences between the pressure in the ventricles, where the inlet opening of the shunt device is located when the tubular inlet of the shunt device has been inserted into the ventricles, and the pressure in the vena jugularis, where the outlet opening of the shunt device is located when the tubular outlet of the shunt device has been inserted into the vena jugularis at the foramen jugulare.

As described above, the shunt body of various embodiments of the shunt device preferably comprises a control reservoir. A control reservoir may have several functions. For example, it is possible to use the control reservoir as a pump. A medical practitioner will be able to ’’palpate” through the skin to control whether the shunt is operational. It is possible in this way to monitor if the shunt device has become blocked at the inlet end or at the outlet end.

By applying a variable and increasing force to the control reservoir, it is also possible to evaluate whether the outlet end of the shunt device has become blocked. In case the control reservoir takes a relatively long time to refill after an increasing pressure has been applied, this would be an indication that the inlet end of the shunt device has become blocked.

The palpating functionality of a control reservoir may also be used to prime the shunt device prior to or during insertion. By applying a pressure to the control reservoir it may be possible to remove undesirable gaseous fluids, including air, from the shunt device. The control reservoir preferably has transparent wall sections so that gaseous fluids may be visibly detected.

The control reservoir may also be used for performing riser tube tests. A medical practitioner may insert a thin needle into the control reservoir and through a silicone dome. The tube is filled with water, and the water enters the needle. The height of the rising water is indicative of the ICP.

The control reservoir may also be used by a medical practitioner to evaluate or modulate for testing purposes the flow rate of cerebrospinal fluids through the shunt.

Tubular outlet / venous access port (VAP)

Again referring to FIGs. 2A-B, an example of an outlet end of the tubular outlet will be described. The outlet end 21 of the present examples with the attached fixator 213 is also called the venous access port (VAP). The VAP of the present examples may be manufactured from only three components, each with distinct and interesting functions: The catheter tube 22 (e.g. silicone cathetertube), the tubular nozzle member 212, and the fixator 213, e.g. formed as a nitinol frame.

The tubular nozzle member 212 and nitinol frame 213 are at the distal end of the catheter tube 22, which discharges fluid from the shunt body of the shunt device. The function of the fixator is to support and center the outlet end with the outlet opening 211 , ensuring that it does not contact the endothelium on the inside of the vein.

The tubular nozzle member 212 may be a polyetheretherketone (PEEK) tubular nozzle member. The tubular nozzle member may be fitted at the end of the catheter tube 22 and serve to provide built-in flow resistance.

Generally, the VAP is operable to divert CSF from the shunt body to the top of the jugular vein at the jugular foramen. The tubular nozzle member 212 may provide a stiff end to the silicone catheter tube 22 and it ensures that CSF is released into the bloodstream in a measured manner while the fixator 213 allows the catheter to be placed in the jugular vein at the point where it passes through the jugular foramen. The fixator 213 will remain where it is placed due to the expansion force of the nitinol. The annular neck 2131 of the fixator secures the tubular nozzle member 212 in the center of the fixator.

FIGs. 2A-B illustrate the outlet end of a tubular outlet of an embodiment of a cerebrospinal fluid shunt device that is particularly efficient to manufacture while providing a secure assembly. FIG. 2A shows the outlet end 21 with the fixator 213 in its fully expanded, unconstrained state, while FIG. 2B shows the outlet end inserted into a delivery catheter 30 and with the fixator 213 in its compacted state. When the outlet end is deployed in the vena jugularis or other venous sinus cavity, the fixator will be in an expanded use state where the fixator is typically only partly expanded and still exerts an outward radial force on the cavity wall of the cavity in which the fixator is deployed and by which the expansion of the fixator is constrained.

The tubular outlet comprises a flexible tubular member in the form of a catheter tube 22. The catheter tube comprises a tubular wall 221 defining an inner lumen 222 having a distal open end 223.

The tubular outlet further comprises a tubular nozzle member 212 having a proximal portion 2123 and a distal portion 2122. The proximal portion extends into the inner lumen of the flexible tubular member and the distal portion extends out of the distal open end of the flexible tubular member. The distal portion has a distal tip 2121 defining the outlet opening 211 of the outlet end. The proximal portion comprises two longitudinally (i.e. axially spaced apart along the longitudinal axis of the tubular nozzle member) spaced apart bulging portions 2124 and 2125, which axially separated by an intermediate portion 2126. The intermediate portion has a smaller outer diameter than each of the bulging portions. In the present embodiments, the bulges of the bulging prortions extend around the entire circumference of the tubular nozzle member. In other embodiments, the bulges may only extend around a part of the circumference. For example, the bulges may be provided as one or more radial protrusions distributed along the circumference. The fixator 213 is configured to secure a location of the outlet end in the venous system cavity as described herein. In the present embodiment, the fixator comprises a nitinol mesh. The fixator comprises an annular attachment member 2131 configured for attachment of the fixator to the flexible tubular member 22. To this end, the flexible tubular member 22, with the proximal end 2123 of the tubular nozzle member 212 inserted into the inner lumen 222 of the flexible tubular member, extends through the annular attachment member 2131, and the annular attachment member is axially positioned at a position along the flexible tubular member between the spaced apart bulging portions 2124 and 2125 of the proximal end inserted into the inner lumen of the flexible tubular member. The fixator comprises radio-opaque markers 2132 arranged at the attachment member and/or radio-opaque markers 2133 arranged at the distal end of the fixator 213, thereby facilitating accurate position of the outlet end during insertion/implantation.

The tubular nozzle member 212 is a stiff, tube-like element with an inner lumen having a small diameter, smaller than the inner lumen of the catheter tube 22. The inner lumen of the tubular nozzle member 213 may be configured to create a significant and well- defined flow resistance that reduces the output flow of CSF, thereby simulating the normal physiological drainage. In one embodiment, the inner diameter is 0.25 mm, and the length of the tubular nozzle member is approximately 20 mm. However, other suitable dimensions may be chosen.

The tubular nozzle member 212 provides a stiff extension of the flexible catheter tube 22, which may be made from silicon or another suitable, flexible material. The stiffness and shape of the tubular nozzle member 212, in combination with the attached fixator 213, ensures that the outlet flow from the outlet opening 211 is held in the middle (or close to middle) of the blood flow - away from the vein wall.

The reduced diameter of the tubular nozzle member 212 compared to the catheter tube 22 also results in an increased flow velocity of the CSF exiting the outlet opening 211. The high speed ensures an efficient mixing of CSF with blood at the distal tip of the tubular nozzle member. This in turn helps to prevent coagulation of the blood, which may otherwise be provoked at certain mixing ratios of CSF and blood (in particular at about 6% of CSF in blood) and could cause undesired blockage of the outlet opening. Besides the mixing dynamics, the small diameter of the inner lumen of the tubular nozzle member ensures that the volume and area of the mixture-zone between CSF and blood and, hence a potential coagulation zone, is minimized. The extent of any potential coagulation occurring inside the inner lumen may thus be reduced, e.g. during an intermittent interruption of the CSF flow due to the pressure in the brain being temporarily lower than the pressure in the vein.

The tubular nozzle member may be manufactured from PEEK. This material has a very low general friction coefficient, and it is resilient against biological material binding to the surface. This property in combination with the small diameter lumen is beneficial in order to avoid permanent blockage. If a small blockage should occur inside or outside the nozzle, the low friction and the low binding properties will ensure that the blockage can be pushed out by the pressure from the CSF.

The outer surface and shape of the tubular nozzle member 212 is shaped and sized to minimize the surface and flow resistance of the blood flow. This includes a conical shape of the distal portion 2122 of the tubular nozzle member, and the round and smooth edges of the tip 211.

FIG. 3 schematically shows another embodiment of the outlet end of a tubular outlet of an example of a shunt device. The outlet end of this embodiment is similar to the embodiment of FIGs. 2A-B, the only difference being the outer shape of the distal portion 2122 of the tubular nozzle member. In the present embodiment, the conical part of the distal portion 2122 has a maximum outer diameter that corresponds to the outer diameter of the flexible tubular member, when the proximal portion of the tubular nozzle member is inserted in the inner lumen of the flexible tubular member, i.e. such that the outer circumferential surface of the flexible tubular member is flush with the outer surface of the conical distal portion, thereby facilitating efficient blood flow along the outlet end and preventing undesired overgrowth with endothelium tissue.

Generally, while other deployment sites of the outlet are possible, the jugular foramen is a particularly suitable placement point for the fixator 213, both because it connects to the dural venous sinus where CSF normally drains and because the foramen jugulare surrounds the vein with a rigid bone structure 56 which provides a solid “tunnel” fixation for the fixator. There is also a negligible difference in elevation between the outlet and the ventricles which avoids hydrostatic pressure differences which otherwise can affect conventional shunts. Furthermore, at the point where the jugular passes through the foramen there is no movement in the vein unlike lower in the internal jugular vein.

The fixator may be configured to be collapsed into an introducer 30 with or without tearaway features so that it can easily be inserted, positioned, and then released in the jugular vein/jugular foramen. This procedure may be monitored under fluoroscopy. The hyper-flexible properties of nitinol, allow it to automatically conform to the oval shape of the jugular foramen once released from the introducer, e.g. from a tear-away introducer or other type of introducer.

Once the device has been placed and connected with the shunt body, CSF will flow into the vein at a rate of approximately 0.35 ml/min against the relatively high flow rate of blood at approximately 350 ml/min in the jugular vein.

Fixator for securing an outlet of a shunt device

In preferred embodiments of the shunt device disclosed herein, the outlet of the shunt device comprises a fixator, e.g. as illustrated in FIGs. 2A-B, and FIG. 3.

The fixator may be attached to the outlet end, in particular at or near the outlet opening, and configured to secure a location of the outlet end in the venous system cavity by exerting a radial outward force onto a wall of the venous system cavity at a deployment location of the outlet end in the venous system cavity, in particular in the vena jugularis where the vena jugularis passes through the foramen jugulare.

The fixator, in its expanded use state, may extend from the tubular outlet radially outwards relative to the outlet opening of the tubular outlet. The fixator, in the expanded use state, may extend radially outward from all or part of the tubular outlet.

The fixator may be attached to the tubular outlet at one or more attachment locations, at least a proximal attachment location of the one or more attachment locations preferably being displaced from the outlet opening by a displacement distance. The fixator, in the expanded use state, may have a longitudinal extent defined between the proximal attachment location and a distal end of the fixator, wherein the longitudinal extent is no smaller, preferably larger, than the displacement distance. The fixator, in the expanded use state, may define a cone shape of increasing radial extent between the proximal attachment location and a distal end of the fixator. The fixator may comprise one or more fixator members, each attached to the outlet end of the tubular outlet and, at least in an operational state of the fixator, extending radially away from the outlet end towards the endothelial wall of the sinus system cavity in which the outlet end is deployed, e.g. the endothelial wall of the vena jugularis.

Each of the one or more fixator members may define or be connected to one or more engagement portions. In some embodiments, more than one, e.g. all, fixator members may be connected to the same engagement portion. The one or more engagement portions may be defined as locations of maximum radial protrusion of the fixator member from the outlet end, when the fixator is in its expanded use state. In some embodiments, the engagement portion may be formed as an engagement member, such as a mesh, e.g. a frusto-conical or cylindrical mesh that is connected to the attachment member via the one or more fixator members. In some embodiments, more than one, e.g. all, fixator members may be connected to the same engagement portion or member. When the fixator is deployed in a sinus system cavity, the one or more engagement portions are configured to engage the endothelial wall of the sinus system cavity and to exert a radial outward force onto the wall of the sinus system cavity. In some embodiments, the one or more engagement portions may comprise one or more hooks or other radial outward projections configured to be pushed by the radial expansion force against the wall of the sinus system cavity at the deployment location, thereby preventing or restricting axial displacement of the fixator from the deployment location along the sinus system cavity.

In some embodiments, each of the one or more fixator members is attached to the outlet end at an attachment location along the outlet end. The attachment location may be axially displaced from the outlet opening. The one or more fixator members may all be attached at the same axial attachment location, e.g. by a single annular attachment member, or at respective axial attachment locations. The fixator members may extend radially and axially from the attachment location, e.g. radially outward and axially forward. Here the forward direction refers to the direction from the attachment location towards the outlet opening. The fixator members may axially extend from the attachment location towards and, optionally, beyond the outlet opening. The fixator may include a single fixator member or a set of more than one, such as two, three, four or even more fixator members. The one or more engagement portions of the single fixator member or of the set of fixator members may be distributed, preferably uniformly distributed, along the entire circumference of the outlet member, thereby causing the fixator to impart radial outward forces along the circumference of the endothelial wall. Each fixator member may be an elongated arm or wire, e.g. a nitinol arm or wire. A small number of radially extending arms reduces the cross-sectional obstruction caused by the deployed fixator.

The fixator may comprise connector members capable of interconnecting one or more fixator members, such as connector members capable of interconnecting two or more, such as at least three fixator members.

The fixator can be in the form of an expandable, resilient mesh comprising, e.g., at least two or three engagement portions defining maximum radial protrusions of the resilient mesh from the outlet, when the fixator is in its expanded use state. The resilient mesh preferably comprises a superelastic and/or hyperelastic material, such as, e.g., nitinol.

By providing a fixator comprising a resilient yet superelastic and/or hyperelastic mesh, a more resilient structure of the fixator is achieved, and this in turn provides more stability and increased ability for spanning cavities of the jugular foramen having irregular shapes.

The superelastic and/or hyperelastic mesh should be sufficiently coarse so that it does not significantly impair the passage of fluids through the sinus system cavity, in particular the vena jugularis at the foramen jugulare, e.g. att the jugular bulb, during use of the shunt device.

The fixator is flexible, preferably superelastic and/or hyperelastic, and when the fixator is in the expanded use state, it extends outwardly from all or part of the tubular outlet.

The fixator in an outwardly expanded use state preferably secures the tubular outlet comprising the outlet end and the outlet opening in the venous system cavity where it is deployed, e.g. in a sinus cavity system or the vena jugularis. When deployed in the foramen jugulare and when in its outwardly expanded use state, the fixator preferably secures the tubular outlet comprising the outlet end and the outlet opening in the foramen jugulare by exerting a force on the boundaries or bone structures defining a foramen jugulare cavity in the individual in which the tubular outlet is located after inserting and guiding through the vena jugularis. The fixator may exert the force via the wall of the vena jugularis in which the outlet end is deployed.

The radial force exerted by the fixator onto the walls of the sinus system cavity it is deployed in, e.g. onto the foramen jugulare cavity, may be a balanced radially orientated spring force. The radial spring force is sufficient to expand the fixator from its compacted state, in particular responsive to being released from an introducer that constrains the fixator to its compacted state. The radial spring force is sufficient to cause the fixator to adopt its expanded use state in which the fixator adapts its shape to the irregular circumferential cavity wall of the sinus system cavity at the deployment location and exerts a radial force onto the cavity wall.

The radial force is sufficient to expand the fixator from a compacted state to a fully expanded state when the fixator is not confined by any outer walls. In some embodiments, in such an unconstrained, fully expanded state, the diameter of the fixator is from about 10 mm to about 15 mm, such as for example 12.5 mm. The radially orientated spring force is also sufficient to secure and maintain the location and orientation of the fixator when deployed in the foramen jugulare and when in its expanded use state. In the expanded use state, the fixator is partly expanded but still constrained by the walls of the vena jugularis and by the walls of the foramen jugulare. The fixator is operable to adapt its shape to the lumen it is deployed in. The foramen jugulare has a noncircular shape. Typically, the foramen jugulare has a cross-sectional wall-to-wall distance of between 6 mm - 7 mm along one direction and a cross- sectional wall-to-wall distance of about 12 mm - 15 mm along another direction. It will be appreciated that the shape and size of the foramen jugulare may vary from individual to individual.

The radial force, in particular the radial spring force, exerted by the fixator in its deployed state on the sinus cavity it is deployed in is balanced and limited in such a way that it does not cause the fixator to penetrate the endothelial wall of the sinus system cavity it is deployed in, e.g. the endothelial wall of the vena jugularis in the foramen jugulare. When the fixator is for deployment in the foramen jugulare, the radial force is selected such that it does not affect the nerves that are located in the foramen jugulare. The radial force, in particular the radial spring force, is preferably from about 0,5 Newton to about 1 ,5 Newton, such as about 0.7 Newton, for example about 0.9 Newton, such as about 1.0 Newton, for example about 1.1 Newton, such as about 1.3 Newton, in the compacted state when the fixator is compacted in an introducer during insertion or retraction. The radial force, in particular the radial spring force, is preferably from about 0.1 Newton to 1.0 Newton in an expanded use state when the fixator is deployed in a sinus system cavity, in particular in the foramen jugulare, such as between 0.1 Newton and 0.8 Newton, such as between 0.1 Newton and 0.5 Newton, such as between 0.2 Newton and 0.5 Newton ,such as about 0.2 Newton, for example about 0.3 Newton, such as about 0.4 Newton.

In the expanded use state, the fixator is typically partly compacted compared to a fully expanded state to which the fixator expands when not constrained in a lumen. In some embodiments, in the unconstrained, fully expanded state, the diameter of the fixator is from about 10 mm to about 15 mm, such as for example about 11 mm, for example about 12 mm, such as about 13 mm, for example about 14 mm. In one embodiment, in the unconstrained, fully expanded state, the diameter of the fixator is 11.7 mm.

In some embodiments, in the expanded use state, i.e. when deployed in a sinus cavity system, such as in the foramen jugulare, the fixator may have a diameter, at least along one transverse direction, of between 3 mm and 9 mm, such as between 4 mm and 8 mm, such as between 5 mm and 7 mm, e.g. about 5 mm, or about 6 mm or about 7 mm. When the fixator is deployed inside a non-circular cavity, e.g. in the foramen jugulare, the fixator may adopt an irregular shape with a non-circular crosssection. The diameter of the fixator in the expanded use state may thus be defined as the diameter of an inscribed circle around the geometric centre of the cross section, i.e. as the length of the shortest line passing through the geometric center of the cross section between two points on the circumference of the fixator. The diameter may be determined at a longitudinal position along the fixator where the fixator has its largest radial extent.

In some embodiments, the radial spring force may be measured by measuring the force required to compact the fixator between two parallel plates to a nominal diameter, the nominal diameter corresponding to the diameter of the fixator when deployed in the sinus cavity system at the intended deployment site, e.g. in the foramen jugulare. Accordingly, in some embodiments, the radial spring force measured as a force required to compact the fixator between two parallel plates arrange parallel to the longitudinal axis of the fixator to a plate-to-plate distance of 6 mm, is preferably from about 0.1 Newton to 1.0 Newton, such as between 0.1 Newton and 0.8 Newton, such as between 0.2 Newton and 0.5 Newton ,such as about 0.2 Newton, for example about 0.3 Newton, such as about 0.4 Newton.

When the fixator is in the outwardly expanded use state and secured in the foramen jugulare, the tubular outlet comprising the outlet end, and the outlet opening is preferably secured in the foramen jugulare essentially in a retrograde orientation with respect to the flow of blood through the vena jugularis, i.e. the flow direction of the CSF exiting the outlet opening is opposite to the flow direction of the blood flow in the vena jugularis.

The fixator, in its outwardly expanded use state, preferably maintains the tubular outlet comprising the outlet end and the outlet opening at least at a predetermined minimum distance from the endothelial wall of the sinus system cavity it is deployed in, e.g. from the endothelial wall of the vena jugularis in the foramen jugulare.

In the expanded use state, the flexible, preferably superelastic and/or hyperelastic, fixator is configured to adopt an irregular shape, such as, e.g., a non-circular shape that reflects the corresponding irregular shape of the foramen jugulare. The superelastic and/or hyperelastic fixator may, e.g., comprise a nitinol frame. It is beneficial that the fixator is configured to adopt an irregular shape that corresponds to the irregular shape of the foramen jugulare cavity in which the fixator is located when in the expanded use state.

By adopting an irregular shape that corresponds well to the irregular shape of the foramen jugulare, the contacting between the fixator and the foramen jugulare cavity into which it is inserted, e.g. the jugular bulb or other part of the vena jugularis, becomes evenly distributed and the flow of blood in the vena jugularis is minimally affected.

The fixator may be provided with one or more than one set of fixator members, and each set of fixator members may be arranged to protrude from the tubular outlet at different and/or predetermined distances from the outlet opening of the outlet. Different sets of fixator members provide an increased stability to the fixator, and each set may have the same or a different number of fixator members.

Foramen jugulare and bulbus superior venae jugularis

Various embodiments of the device and method disclosed herein provide shunting of cerebrospinal fluids to a venous system cavity of an individual, including a human being. The venous system cavity may be a sinus system cavity of the venous sinus system of the individual. In particular, various embodiments of the device and method disclosed herein provide shunting of cerebrospinal fluids to the vena jugularis of an individual, including a human being. In particular, various embodiments of the device and method disclosed herein provide shunting of cerebrospinal fluids to an outlet location inside the upper vena jugularis, where the outlet location is located at a position where the vena jugularis passes through the foramen jugulare of the individual. In particular, the outlet opening may be secured in or otherwise to the foramen jugulare. In some embodiments, at least a portion of the outlet end and/or the fixator may extend into the bulbus superior venae jugularis located immediately above the foramen jugulare.

FIG. 5 illustrates the dural venous sinus system of a human patient. In particular, FIG. 5 illustrates the internal jugular vein (vena jugularis) 52, the jugular bulb 54, the sigmoid sinus 55, the transverse sinus 57, the straight sinus 581 , the superior sagittal sinus 582, and the inferior sagittal sinus 583. For the purpose of the present disclosure, the upper end of the vena jugularis is considered to be part of the venous sinus system, i.e. the term “sinus system cavity” as used herein, is intended to include at least the uppermost part of the vena jugularis, where the vena jugularis extends through the jugular foramen and/or above the part of the vena jugularis that can partly collapse when the individual is in an upright body position (thereby affecting the pressure like a Startling resistor). Other examples of a sinus system cavity include the jugular bulb, the sigmoid sinus and the transverse sinus.

The internal jugular vein, which is also referred to simply as the jugular vein or the vena jugularis throughout this document, is a paired vein that collects blood from the brain and the superficial parts of the face and neck. The internal jugular vein begins in the jugular foramen, at the base of the skull, in particular in the posterior compartment of the foramen jugulare. It is somewhat dilated at its origin, which is called the superior bulb. It runs down the side of the neck in a vertical direction, and at the root of the neck, it unites with the subclavian vein to form the brachiocephalic vein (innominate vein).

The jugular foramen is a large opening located at the posterior end of the petrooccipital suture between the jugular process of the occiput and the petrosal portion of the temporal bone. It serves as a passage for the glossopharyngeal nerve, vagus and accessory nerves, as well as the internal jugular vein.

As can best be seen in FIG. 1 B, at the foramen jugulare 53, in particular at the jugular bulb 54 immediately superior to the foramen jugulare, the vena jugularis 52 is connected to the sigmoid sinus 55 at one end of the sigmoid sinus, and the sigmoid sinus is connected at the other end thereof to the transverse sinus. The sigmoid sinus therefore connects the transverse sinus with the jugular vein.

The vena jugularis passes through the base of the skull through the jugular foramen. The vena jugularis is completely surrounded by bone in the tunnel (foramen jugulare) through the skull, except from a part of the anterior wall where hard fibrous tissue covers the vagus nerve.

The pars venosa (or pars vascularis) is situated in the posterolateral aspect of the jugular foramen and contains the internal jugular vein (IJV), the posterior meningeal branch of the ascending pharyngeal artery, the vagus nerve (cranial nerve X), the auricular branch of the vagus nerve (Arnold’s nerve), and the spinal accessory nerve (cranial nerve XI).

A smaller pars nervosa is located in the anteromedial portion of the jugular foramen and contains the glossopharyngeal nerve, the tympanic branch of the glossopharyngeal nerve (Jacobsen’s nerve), and the inferior petrosal sinus. Both the pars venosa and the smaller pars nervosa contain neural as well as vascular entities and structures.

The walls of the jugular foramen are formed anterolaterally by the petrous bone and posteromedially by the occipital bone. The foramen is directed in an anterior, lateral, and inferior direction. The diameter of the jugular vein in the foramen is typically in the range 7 of from 10 mm. In rare cases, the foramen has been observed to have a diameter below 3 mm. The largest reported size of the vein is 14 x 7 mm. According to morphometric studies, the osseous jugular foramen can be more accurately described as a triangular canal with an endocranial (-14.5 x 7 mm) and an exocranial opening (-9 x 17 mm). It lies about 23 mm medial to the apex of the mastoid tip, 15 mm medial to the tympanomastoid suture, and 5 mm above the intracranial orifice of the hypoglossal canal.

The walls of the venous sinus are tightly connected to the bone-surface (periosf). The walls cannot be penetrated in this area. The tympanic nerve (Jacobson’s nerve) passes in a canal in the anteromedial part of the jugular fossa. It is contained in its own canal, in 20% fully enclosed in bone, else covered by dura mater.

A branch of the vagus nerve (cranial nerve X) passes through the anterior-medial part of the jugular foramen. A continuation of the dura separates - as a fibrous membrane - the nerve from the jugular vein.

The jugular vein in the foramen jugulare cannot be penetrated or even pushed outwards by a fixator described herein when such a structure, for example in the form, e.g., of an expandable, resilient and super- and/or hyperelastic mesh, is inserted into and expanded into a use state in the foramen jugulare. The walls of the foramen jugulare cannot be penetrated, except from the antero-medial fibrous wall, and in such case only by sharp instruments. Hence, a fixator comprising, e.g., an expandable, resilient and super- and/or hyperelastic mesh, may contact, but not penetrate, the walls of the vena jugularis inside the foramen jugulare when the outlet end of a shunt device according to various embodiments disclosed herein is inserted into the vena jugularis inside the foramen jugulare and expanded into an expanded use state.

Immediately below the jugular foramen, the vena jugularis may be surrounded by cartilage of other stiff tissue. Accordingly, a deployment position of the outlet end immediately below the jugular foramen may also be suitable. Generally, the outlet end may be located inside the top of the vena jugularis, such as the top 3 - 4 cm of the vena jugularis. Such a deployment position and, in particular, a deployment position immediately below the jugular foramen where the vena jugularis is surrounded by stiff tissue, may be regarded as a deployment position at the jugular foramen. A deployment position where at least a portion of the fixator is located inside the jugular foramen may be preferred, as the vena jugularis may have a relatively large diameter below the skull. Generally, a deployment position where the outlet opening and/or at least a portion of the fixator is/are located inside the jugular foramen, may be considered a deployment position in the jugular foramen. In some situations, a part of the fixator may be located inside the jugular foramen while another portion of the fixator may be located immediately above and/or below the jugular foramen. It is generally preferred that the fixator is located at a position along the vena jugularis high enough to avoid the pulsating of the vena jugularis. It will be appreciated that there are two jugular veins and two jugular foramen, a left one and a right one. A deployment position in both is possible. However, in most situations a position in the right jugular foramen may be preferred, as the right jugular foramen is often larger.

The sigmoid sinus has an s-shaped curve along the internal wall of the occipital bone and continues upward in the transverse sinus.

The roof of the sinus, inside the skull, above the bony tunnel, is part of the dura mater, a strong surface of fibrous tissue that is only permeable by a sharp instrument. It is not possible to penetrate the wall with a guidewire or an introducer sheath.

The jugular foramen, including the portion of the vena jugularis immediately below the jugular foramen, where the vena jugularis is surrounded by stiff tissue, offers an optimal site for the placement of a venous access port according to various embodiments disclosed herein. The cavities of the jugular foramen are not collapsible, their forms remain independent of external forces and venous pressure, and the walls can only be perforated by sharp instruments.

Once inserted into the foramen jugulare, a fixator, such as, e.g., a nitinol frame may be expanded to a predetermined size. This expansion will exert a certain pressure on the surroundings, including wall sections of the foramen jugulare.

The expansion-force of a fixator, e.g., a nitinol fixator, placed in the jugular vein inside the jugular foramen, must be sufficient to keep the fixator in place. However, the wall of the vein is attached to bone except for the antero-medial part, where the nerves are situated. The nerves are separated from the vein, as mentioned above, by a sheath of dura, and in some cases by an osseous crista. The flexible geometry of the hyperelastic materials from which the fixator may be manufactured will ensure that the pressure exerted by the expanded fixator is essentially evenly distributed over and around the internal area of the jugular vein in the foramen jugulare.

The internal wall of the foramen jugulare is covered by endothelium. Endothelium is a layer of active cells, and in the arterial system, the cells react quickly when exposed to foreign objects or when the inner wall is penetrated or scarred by instruments.

Arterial intravascular stents become overgrown or embedded by this layer of cells. This is probably also the case in the venous system. Experiences gained from clinical trials involving replacement of drains in the transverse sinus indicate that drains became encapsulated at the internal wall of the vein. However, stents placed in the transverse sinus, e.g., in a treatment of a narrowed sinus that results in intracranial hypertension, remain patent for years.

Despite being both structurally rigid and of an irregular shape, the present inventor has surprisingly found that it is advantageous to locate and secure an outlet end of a tubular outlet of a sinus system catheter of a shunt device within the irregularly shaped cavities of the foramen jugulare.

Using the irregularly shaped cavities of the foramen jugulare for the insertion into the sinus system of an outlet end of a tubular outlet makes it possible for a medical practitioner to monitor and control the process of inserting the shunt device.

An outlet end of a tubular outlet of a shunt device according to various embodiments disclosed herein is inserted into the vena jugularis by known surgical procedures, and the outlet end of the tubular outlet is actively guided upwards through the vena jugularis to the foramen jugulare in a retrograde orientation, i.e. against the direction of the flow of blood through the vena jugularis.

The tubular outlet of the shunt device preferably comprises a fixator which is in a compacted state during insertion or retraction from the vena jugularis, including into the foramen jugulare, and in an expanded use state after having been inserted into the vena jugularis and located in an irregularly shaped cavity of the foramen jugulare. When cerebrospinal fluids are drained from the ventricles to the vena jugularis at or inside the foramen jugulare, the fixator is expanded into and essentially spans and exerts a radial force onto irregularly shaped cavities of the foramen jugulare.

The fixator is preferably made from a superelastic material or an alloy that is sufficiently flexible to adopt the shape of the irregular cavities of the foramen jugulare. Nitinol is an example of a superelastic material that may be used for manufacturing the fixator.

Methods of shunting cerebrospinal fluids to the foramen jugulare

The brain and spinal cord are encased in the cranium and vertebral column inside a thin membrane known as the meninges. The space within the meninges includes, among others, the ventricles, and cerebrospinal fluids are produced in the chorioid plexus of the ventricles at a rate of 0.3 to 0.4 ml/min under normal conditions.

The cerebrospinal fluids flow through the ventricles, aqueduct and basal cisterns over the cerebral surface to the arachnoid villi, and the cerebrospinal fluids are absorbed from the arachnoid villi into the sagittal sinus. The sagittal sinus is connected to the transverse sinus and the sigmoid sinus. Cerebrospinal fluids enter the vena jugularis from the sigmoid sinus via the foramen jugulare.

In one embodiment there is provided a method of shunting cerebrospinal fluid from the ventricles to the foramen jugulare of an individual suffering from elevated intracranial pressure. Shunt devices capable of being used in this method comprise a tubular inlet having an inlet end with an inlet opening configured for insertion into the ventricles of an individual, a shunt body, and a tubular outlet having an outlet end with an outlet opening configured for insertion into the vena jugularis at the foramen jugulare.

The shunt device diverts CSF from the ventricles of the brain to the jugular foramen, at the point where the sigmoid sinus meets the internal jugular vein. Various embodiments of this method are based on the principle that there is a positive and physiological differential pressure (DP) between the shunt inlet (ventricles of the brain) to the shunt outlet (the jugular foramen) that drives CSF to flow into the systemic blood circulation.

The principle of operation of the shunt device may be based on a spring-loaded ball-in- cone valve and a flow restricting element. The shunt device may be a passive system which avoids hydrostatic pressure differences usually found when shunting from the ventricles of the brain to the peritoneum or right atrium of the heart.

In various embodiments, the method comprises the steps of: a) inserting at least a part of the inlet end of the tubular inlet, the inlet end comprising the inlet opening, into the ventricles or a subarachnoid space of an individual, b) inserting at least a part of the outlet end of the tubular outlet, the outlet end comprising the outlet opening, and a fixator in a compacted state into the vena jugularis of the individual, c) guiding the outlet end of the tubular outlet and the fixator in a compacted state through the vena jugularis towards the foramen jugulare, d) locating the outlet end of the tubular outlet, the outlet end comprising the outlet opening, and the fixator in a compacted state in a cavity of the foramen jugulare essentially in a retrograde orientation, and e) changing the state of fixator from the compacted state to an expanded use state, wherein the fixator in the expanded use state exerts a force on foramen jugulare cavity wall sections, thereby securing the tubular outlet comprising the outlet opening in a predetermined position away from the wall sections in the foramen jugulare cavity.

When methods of shunting cerebrospinal fluid from a cerebrospinal fluid containing space of an individual to the foramen jugulare of the individual comprise the steps of i) inserting at least part of an inlet end of a tubular inlet, the inlet end comprising an inlet opening, into a cerebrospinal fluid containing space of the individual, ii) inserting at least part of an outlet end of a tubular outlet, the outlet end comprising an outlet opening, into the foramen jugulare of the individual, and iii) shunting cerebrospinal fluid from the cerebrospinal fluid containing space of the individual to the foramen jugulare, e.g. including the jugular bulb, of the individual, the individual typically suffers from elevated intracranial pressure, such as, e.g., hydrocephalus, including normal pressure hydrocephalus, and it is thus necessary to shunt cerebrospinal fluids from a ventricle or a subarachnoid space of the individual, including a human being, to the sinus system cavity, including the vena jugularis at the foramen jugulare.

In one embodiment, there is provided a method of inserting a cerebrospinal fluid shunt device in a cerebrospinal fluid containing space and in the foramen jugulare of an individual. The method comprises the steps of a) inserting at least part of an inlet end of a tubular inlet, the inlet end comprising an inlet opening, into a cerebrospinal fluid containing space of the individual, b) inserting at least part of an outlet end of a tubular outlet, the outlet end comprising an outlet opening, into the foramen jugulare of the individual, and c) operably connecting the inlet opening inserted into the cerebrospinal fluid containing space of the individual with the outlet opening inserted into the foramen jugulare of the individual so that cerebrospinal fluid is able to flow from the inlet opening to the outlet opening.

The outlet end of the tubular outlet comprising the outlet opening is initially inserted into the vena jugularis and guided through the vena jugularis and into the foramen jugulare and secured in the foramen jugulare by a fixator comprised by, or attached to, the tubular outlet. The fixator securing the tubular outlet comprising the outlet end and the outlet opening in the foramen jugulare is converted from a compacted state into an expanded use state to secure the tubular outlet comprising the outlet end and the outlet opening in the foramen jugulare.

The fixator is flexible, preferably superelastic and/or hyperelastic, and the fixator in the expanded use state extends outwardly from all or part of the tubular outlet. The fixator in the outwardly expanded use state secures the tubular outlet comprising the outlet end and the outlet opening in the foramen jugulare by applying or exerting a force on the boundaries or bone structures defining a foramen jugulare cavity, including the upper vena jugularis or jugular bulb, in which the tubular outlet is located after having been inserted into and guided through the vena jugularis.

The fixator in the outwardly expanded use state secures the tubular outlet comprising the outlet end and the outlet opening in the foramen jugulare essentially in a retrograde orientation with respect to the flow of blood through the vena jugularis, and the fixator maintains the tubular outlet comprising the outlet end and the outlet opening at least in a predetermined minimum distance from the endothelial wall of the vena jugularis in the foramen jugulare.

In one embodiment, a method of inserting a cerebrospinal fluid shunt in a cerebrospinal fluid containing space and in foramen jugulare of an individual comprises the steps of a) inserting at least part of an inlet end of a tubular inlet, the inlet end comprising an inlet opening, into a cerebrospinal fluid containing space of the individual, b) inserting at least part of an outlet end of a tubular outlet, the outlet end comprising an outlet opening, into a foramen jugulare of the individual, and c) operably connecting the inlet opening inserted into the cerebrospinal fluid containing space of the individual with the outlet opening inserted into the foramen jugulare of the individual so that cerebrospinal fluid is able to flow from the inlet opening to the outlet opening, wherein the inlet opening inserted into the cerebrospinal fluid containing space of the individual and the outlet opening inserted into the foramen jugulare of the individual are operably connected by a shunt body connected at one end to the tubular inlet having an inlet end with an inlet opening configured for insertion into the ventricles of an individual, and connected at another end of the shunt body to the tubular outlet having an outlet end with an outlet opening configured for insertion into the vena jugularis at the foramen jugulare of the individual, d) guiding the tubular outlet comprising the outlet end and the outlet opening through the vena jugularis towards the foramen jugulare, e) locating the tubular outlet comprising the outlet end and the outlet opening in a cavity of the foramen jugulare, and f) changing the state of the fixator from a compacted state to an expanded use state, wherein the fixator in the expanded use state applies or exerts a force on a foramen jugulare cavity and maintains the tubular outlet comprising the outlet end and the outlet opening in an essentially fixed position in the foramen jugulare away from and with a minimum distance to endothelial tissue of the vena jugularis.

The insertion of the shunt device disclosed herein may be performed as follows: A ventricular catheter may be inserted into a cerebral ventricle, e.g. the right or left frontal horn of the cerebral ventricles, via pre-coronal burr hole, and connected to the subcutaneously placed shunt body including the control reservoir and one-way valve. The outlet end of the tubular outlet of the shunt device, including the fixator, may be collapsed into a suitable introducer, e.g. a standard introducer, and inserted into the jugular vein at a penetration point at the patient’s neck. To this end, the Seidinger technique may be used to insert the introducer (e.g. using a guidewire, dilator, and peel-away sheath) into the vena jugularis.

The introducer containing the device may be inserted through a peel-away sheath and then radiographically guided as far as the junction between the sigmoid sinus and top of the vena jugularis before the fixator (e.g. a nitinol frame/mesh) is released and expanded in the jugular foramen. The silicone catheter of the tubular outlet may then be connected to a unidirectional fixed pressure valve before being led subcutaneously to the shunt body. The correct position of the outlet end may be confirmed by a final radiograph. The device and accessories can also be observed in a CT scan.

FIGs. 6A-D illustrate a process for insertion of the outlet end of the tubular outlet (VAP) into the foramen jugular of a patient.

Generally, the outlet end of the tubular outlet may be inserted at an access location into the vena jugularis. The outlet end of the tubular outlet inserted into the vena jugularis may then be guided in a cranial direction through the vena jugularis to the deployment location at the foramen jugulare, e.g. to the junction between the sigmoid sinus and the top of the vena jugularis. The outlet end may be secured at the deployment location by a fixator attached to the tubular outlet.

The insertion of the outlet end (VAP) may be performed using the Seidinger technique, the same standard vascular access technique which is used for placing the distal drainage catheters of conventional VA shunts. The difference between the two placement methods is that, in VA catheter placement, the distal drainage catheter is guided downwards into the atrium of the heart of the patient (about 20 cm from the insertion point) whereas, with the shunt device disclosed herein, the outlet end is guided upwards to the jugular foramen (about 10 cm from the insertion point). As with VA catheter placement, the placement of the VAP may be monitored through fluoroscopy.

FIG. 6A illustrates the tip of a peel-away sheath 80 being guided through the jugular vein 52 up to the jugular foramen just below the jugular bulb 54.

FIG. 6B illustrates that, when the tip of the tear-away sheath 80 has been advanced to, and is located in, the jugular foramen, the tear-away sheath 80 is retracted, and the fixator 213 expands, e.g. due to the spring-force of the nitinol material.

FIG. 6C illustrates the deployed outlet end 21 after the introducer 80 has been further retracted. The fixator 213 has adjusted to the geometry of the jugular foramen (normally oval shaped).

FIG. 6D shows a peroperative x-ray with the outlet end put in place. The surgeon can monitor the positioning of the tear-away sheath and VAP using fluoroscopy. In FIG. 6E, the VAP has just been released, and the introducer is being retracted. The left arrow indicates the tubular nozzle member of the VAP, while the right arrow indicates tip of the retracted introducer sheath.

Methods of shunting cerebrospinal fluids via the vena transversa

According to some embodiments, when using an embodiment of the shunt device disclosed herein, the vena transversa or sigmoid sinus may serve as an alternative drainage site when shunting CSF from a CSF containing space, such as from the ventricles. To this end, the inlet end of the tubular inlet may be inserted into the CSF containing space, e.g. into a ventricle of the patient, as described herein.

The outlet end 21 of the tubular outlet 2 may be inserted into the vena transversa 57, via a burr hole 515 at the back of the cranium and via a penetration point of the sinus transversus. The outlet end 21 with the fixator 213 may then be advanced to, and deployed in the vena transversa 57 or the sigmoid sinus 55. In this embodiment, the outlet end 21 is oriented in an antegrade orientation, i.e. such that the outlet flow from the outlet end is along the flow direction of the blood flow through the vena transversa or the sigmoid sinus. The CSF flow discharged from the outlet then follows the blood flow through one of the internal jugular veins 52.

When the outlet end includes a fixator 213 as described herein, the risk of clogging the outlet opening by overgrowth of endothelium tissue is reduced.

In one embodiment, a method of inserting a cerebrospinal fluid shunt in a cerebrospinal fluid containing space and in the vena transversa of an individual comprises the steps of a) inserting at least part of an inlet end of a tubular inlet, the inlet end comprising an inlet opening, into a cerebrospinal fluid containing space of the individual, b) inserting at least part of an outlet end of a tubular outlet, the outlet end comprising an outlet opening, into the vena transversa, preferably via a burr hole in the vicinity of the vena transversa of the individual, and c) operably connecting the inlet opening inserted into the cerebrospinal fluid containing space of the individual with the outlet opening inserted into the vena transversa of the individual so that cerebrospinal fluid is able to flow from the inlet opening to the outlet opening, d) guiding the outlet end and the outlet opening through the vena transversa towards a deployment site in the vena transversa or sigmoid sinus, e) locating the outlet end and the outlet opening at the deployment site, and f) changing the state of the fixator from a compacted state to an expanded use state, wherein the fixator in the expanded use state applies or exerts a force on a wall of the vena transversa or sigmoid sinus and maintains the outlet end and the outlet opening in an essentially fixed position in the vena transversa or sigmoid sinus and with a minimum distance to endothelial tissue of the vena transversa or sigmoid sinus. The inlet opening inserted into the cerebrospinal fluid containing space of the individual and the outlet opening inserted into the vena transversa of the individual are operably connected by a shunt body connected at one end to the tubular inlet having an inlet end with an inlet opening configured for insertion into the ventricles of an individual, and connected at another end of the shunt body to the tubular outlet having an outlet end with an outlet opening configured for insertion into the vena transversa of the individual.

FIGs. 8A-C illustrate a process of assembling an embodiment of the outlet end of a tubular outlet of an example of a shunt device, e.g. the outlet end of FIGs. 2A-B or FIG. 3. The assembly comprises the tubular outlet and a fixator 213. The tubular outlet comprises a flexible tubular member 22 and a tubular nozzle member 212, e.g. as described in connection with FIGs. 2A-B or FIG. 3 above, or otherwise. Accordingly, the assembly process comprises the assembly of the following three parts: the flexible tubular member 22, the tubular nozzle member 212, and the fixator 213.

These three parts may be assembled using an assembly rig (not shown). The assembly process utilizes the elastic properties of the material from which the flexible tubular member is made, e.g. silicone. The flexible tubular member 22 is stretchable by applying an axial force to the flexible tubular member, which reduces the diameter of the tube, and also the thickness of the tube wall. The thinner diameter and wall thickness make it possible to slide the three components together. After they are assembled, the stretching is released, and the silicon tube expands. When the silicone tube is expanded, the three components are fixated and cannot be pulled apart under normal use conditions. The spring-load-properties of the silicone material assure a proper fixation.

In particular, the flexible tubular member 22 may initially be advanced through the annular attachment member 2131, i.e. though the central opening defined by the annular attachment member, such that the flexible tubular member 22 extends through the annular attachment member. The proximal portion of the tubular nozzle member 212 may be advanced into the inner lumen of the flexible tubular member 22 through the distal open end of the inner lumen, such that the distal portion of the tubular nozzle member axially projects out of the distal open end. The resulting part assembly is illustrated in FIG. 8A. It will be appreciated that the order of the two previous steps may be reversed, i.e. the proximal portion of the tubular nozzle member may be inserted into the inner lumen before advancing the flexible tubular member though the annular attachment member. In particular, when employing this alternative order of assembly steps, the tubular member may be advanced through the annular attachment member with the proximal end of the flexible tubular member leading.

An axial force may then be applied to the flexible tubular member 22 to axially stretch the flexible tubular member, as illustrated in FIG. 8B. This may e.g. be done by suspending opposite ends of the flexible tubular member in an assembly rig such that the opposite ends can be pulled axially apart from each other so as to stretch the flexible tubular member. The axial stretching causes the thickness of the tubular walls of the flexible tubular member to be reduced, which in turn causes the total diameter of the flexible tubular member with the stiff tubular nozzle member inserted in it to be reduced, in particular at the locations of the bulging portions 2124 and 2125. The annular attachment member 2131 is sized large enough that it can snuggly slide past at least one of the bulging portions 2124 and 2125 when the flexible tubular member is stretched axially, and small enough that it cannot slide past the bulging portions 2124 and 2125 when no axial force is applied to the flexible tubular member.

Accordingly, when the flexible tubular member is axially stretched, as illustrated in FIG. 8B, the fixator may be axially slid along the flexible tubular member until the annular attachment member is positioned between the spaced apart bulging portions of the proximal end that is inserted into the inner lumen of the flexible tubular member.

When the applied axial force is released, the annular member is fixated between the bulging portions, as illustrated in FIG. 80.

This assembly process avoids the need for any glue/adhesive or mechanical fixation elements, for example a screw or a clip. This in turn avoids the risk of chemical release of glue/adhesive of the implanted outlet end or the unintentional detachment of small mechanical elements before or during use.

Methods of extracting an outlet end of a shunt device from a sinus cavity system

There may be situations when the outlet end of the shunt device disclosed herein may need to be extracted again after having been implanted to a deployment location in the sinus system cavity. In some situations, only the outlet end is to be removed while, in other situations both the outlet end and the inlet end, or even the entire shunt device are to be removed.

Various embodiments of the shunt device disclosed herein allow for an easy extraction of the outlet end. Generally, the extraction of a previously implanted outlet end from its deployment location may be performed by performing the steps of the insertion method, e.g. the method described in connection with FIG. 5A-D above, in reverse order.

FIG. 9 illustrates an example of a method of extracting an outlet end of a shunt device from a sinus cavity system of an individual, in particular an outlet end as described in connection with FIGs. 2A-B or FIG. 3.

The removal procedure may utilize a suitable extraction sheath 90. The extraction sheath may be sized and shaped to be inserted into the sinus system cavity where the outlet end is deployed, e.g. into the vena jugularis, and the extraction sheath may have an inner lumen large enough to accommodate the outlet end, including the fixator in its compacted state. The extraction sheath may be advanced along the sinus system cavity with the flexible tubular catheter 22 of the outlet end penetrating through the inner lumen of the extraction sheath 90. When the distal open end 901 of the extraction sheath reaches the attachment member 2131 at which the fixator 213 is attached to the flexible tubular catheter 22 via flexible arms 2134, further advancement of the extractor sheath, e.g. while applying a suitable pull force to the flexible tubular catheter, releases the fixator from the surrounding endothelium tissue and forces the expanded fixator into its compacted state so that the flexible tubular member with the fixator can be withdrawn inside the extractor sheath 90.

If the fixator has become overgrown by endothelium tissue, as illustrated in FIG. 9, it may be necessary to release or free away the fixator from the wall of the sinus cavity. To this end an extractor sheath 90 may have a distal open end 901 that is configured to aid loosening of the fixator 213 from the cavity wall, e.g. when the outer portion of the fixator has become overgrown by endothelium tissue. To this end, the open end 901 may be slanted and/or include a metal tip, e.g. a multi-sided, threaded, corrugated or otherwise irregularly shaped or textured edge that aids releasing of the fixator from endothelium tissue when the extractor sheath is rotated around its own longitudinal axis. To this end, the extractor sheath may be advanced as an inner sheath inside an outer support sheath. The rotation of the extractor sheath around its longitudinal axis may be performed manually or by means of a mechanical dilator where the extractor sheath is mounted on a pistol that mechanically rotates the sheath.

Examples of suitable extractor sheaths include the SteadySheath® by Cook Medical or the Evolution ® RL rotational TLE system by Cook Medical that includes an outer sheath and an inner extractor sheath with a multi-sided metal tip. The inner sheath has a handle trigger-driven rotational tip at the end. This inner sheath is mounted on a pistol that mechanically rotates the inner sheath.

In some embodiments, the extractor sheath may be used in combination with a snare.

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Claims

Patent claims

1. A cerebrospinal fluid shunt device for shunting cerebrospinal fluid from a cerebrospinal fluid containing space and into a venous system cavity of an individual, wherein the cerebrospinal fluid shunt device comprises a tubular inlet, a tubular outlet and a fixator, wherein the tubular inlet comprises an inlet end configured for insertion into a cerebrospinal fluid containing space of the individual, the inlet end having an inlet opening for receiving cerebrospinal fluid, wherein the tubular outlet has an outlet end with an outlet opening, the outlet end being configured for insertion into a venous system cavity of the individual, wherein the inlet opening is fluidly connected with the outlet opening to allow cerebrospinal fluid to flow from the inlet opening to the outlet opening, wherein the tubular outlet comprises a flexible tubular member and a tubular nozzle member, wherein the flexible tubular member comprises a tubular wall defining an inner lumen having a distal open end, wherein the tubular nozzle member has a proximal portion and a distal portion, the proximal portion extending into the inner lumen of the flexible tubular member and the distal portion extending out of the distal open end of the flexible tubular member, wherein the fixator is configured to secure a location of the outlet end at a deployment location in the venous system cavity, wherein the fixator comprises an annular attachment member configured for attachment of the fixator to the flexible tubular member, and wherein the flexible tubular member and the proximal portion of the tubular nozzle member extend through the annular attachment member.

2. The cerebrospinal fluid shunt device according to claim 1, wherein the proximal portion comprises two axially spaced apart bulging portions axially separated by an intermediate portion, the intermediate portion having a smaller outer diameter than each of the bulging portions, and wherein the annular attachment member is axially positioned at a position along the flexible tubular member and the proximal portion of the tubular nozzle member between the spaced apart bulging portions of the proximal end inserted into the inner lumen of the flexible tubular member.

3. The cerebrospinal fluid shunt device according to claim 1 or 2, wherein the distal portion has a distal tip, in particular a rounded distal tip, the distal tip defining the outlet opening of the outlet end.

4. The cerebrospinal fluid shunt device according to claim 2 or 3, wherein the distal portion of the tubular nozzle member comprises a conical portion having a gradually decreasing outer diameter, decreasing towards the distal tip.

5. The cerebrospinal fluid shunt device according to any one of the preceding claims, wherein the distal portion has an increased-diameter portion having an outer diameter substantially equal to an outer diameter of the flexible tubular member.

6. The cerebrospinal fluid shunt device according to claim 5, wherein the increased- diameter portion has a proximal end defining an abutment surface for abutment to a distal end of the tubular wall the flexible tubular member when the proximal portion of the tubular nozzle member extends into the inner lumen of the flexible tubular member.

7. The cerebrospinal fluid shunt device according to any one of the preceding claims, wherein the annular attachment member comprises one or more radio-opaque markers.

8. The cerebrospinal fluid shunt device according to any one of the preceding claims, wherein the fixator is configured to be converted from a compacted state of the fixator into an expanded use state of the fixator to secure the outlet end at the deployment location.

9. The cerebrospinal fluid shunt device according to claim 8, wherein the fixator, in the expanded use state, extends from the outlet end radially outwards relative to the outlet opening of the outlet end.

10. The cerebrospinal fluid shunt device according to any one of claims 8 through 9, wherein the fixator, in the expanded use state, extends radially outward from all or part of the outlet end.

11. The cerebrospinal fluid shunt device according to any one of claims 8 through 10, wherein the fixator, in the expanded use state, defines a cone shape of increasing radial extent between the annual attachment member and a distal end of the fixator.

12. The cerebrospinal fluid shunt device according to any one of claims 8 through 11 , wherein the fixator comprises one or more fixator members, each fixator member being attached to the annular attachment member, and each fixator member being configured, in the expanded use state, to extend radially outward from the annular attachment member and longitudinally from the annular attachment member towards the outlet opening.

13. The cerebrospinal fluid shunt device according to any one of claims 8 through 12, wherein the fixator is configured, in the expanded use state, to maintain the outlet opening at least in a predetermined minimum distance from the endothelial wall of the venous system cavity.

14. The cerebrospinal fluid shunt device according to any one of the preceding claims, wherein the fixator is configured to secure a location of the outlet end in the venous system cavity by exerting a radial outward force onto a wall of the venous system cavity at the deployment location of the outlet end in the venous system cavity.

15. The cerebrospinal fluid shunt device according to claim 14, when dependent on any one of claims 8 through 13, wherein the radial force is from about 0.1 Newton to 1.0. Newton in the expanded use state.

16. The cerebrospinal fluid shunt device according to claim 14 or 15, wherein the radial force is large enough to keep the fixator in place.

17. The cerebrospinal fluid shunt device according to any one of claims 14 through 16, wherein the radial force is and essentially evenly distributed along a circumference of the fixator.

18. The cerebrospinal fluid shunt device according to any one of claims 14 through 17, wherein the radial force is a spring force.

19. The cerebrospinal fluid shunt device according to any one of claims 14 through 18, wherein the radial force is small enough to prevent the fixator to penetrate the endothelial wall of the venous system at the deployment location.

20. The cerebrospinal fluid shunt device according to any one of claims 14 through 19, wherein the fixator is configured to secure the outlet end and the outlet opening at the foramen jugulare by exerting a radial outward force on the boundaries or bone structures defining the foramen jugulare in the individual.

21. The cerebrospinal fluid shunt device according to any one of the preceding claims, wherein the fixator is configured to secure the outlet end inside a foramen jugulare of the individual.

22. The cerebrospinal fluid shunt device according to any one of the preceding claims, wherein the fixator is configured to secure the outlet end at the foramen jugulare with the outlet opening oriented in a retrograde orientation with respect to the flow of blood through the vena jugularis.

23. The cerebrospinal fluid shunt device according to any one of the preceding claims, wherein the fixator is configured to secure the outlet opening at the foramen jugulare by exerting a radial outward force on the wall of the vena jugularis.

24. The cerebrospinal fluid shunt device according to any one of the preceding claims, wherein the fixator is flexible, preferably hyperelastic and/or superelastic.

25. The cerebrospinal fluid shunt device according to any one of the preceding claims, wherein the flexible tubular member is a silicone catheter.

26. The cerebrospinal fluid shunt device according to any one of the preceding claims, wherein the tubular nozzle member is made from polyether ether ketone.

27. The cerebrospinal fluid shunt device according to any one of the preceding claims, wherein the tubular nozzle member has a stiffness larger than a stiffness of the flexible tubular member.

28. The cerebrospinal fluid shunt device according to any one of the preceding claims, wherein the fixator is attached to the outlet end at or near the outlet opening.

29. The cerebrospinal fluid shunt device of any of the preceding claims, wherein the annular attachment member is axially positioned displaced from the outlet opening by a displacement distance and wherein the fixator, in the expanded use state, has a longitudinal extent defined between the annular attachment member and a distal end of the fixator, wherein the longitudinal extent is no smaller, preferably larger, than the displacement distance.

30. A method of assembling a tubular outlet of a cerebrospinal fluid shunt device for shunting cerebrospinal fluid from a cerebrospinal fluid containing space and into a venous system cavity of an individual. The method comprises:

- providing a flexible tubular member comprising a tubular wall defining an inner lumen having a distal open end;

- providing a fixator configured to secure a location of an outlet end of the tubular outlet in the venous system cavity, wherein the fixator comprises an annular attachment member configured for attachment of the fixator to the flexible tubular member,

- providing a tubular nozzle member having a proximal portion and a distal portion,

- advancing the flexible tubular member through the annular attachment member,

- inserting the proximal portion of the tubular nozzle member into the inner lumen of the flexible tubular member with the distal portion extending out of the distal open end of the flexible tubular member,

- applying an axial force to the flexible tubular member to axially stretch the flexible tubular member,

- axially displacing the annular attachment member along the stretched flexible tubular member to a position along the flexible tubular member where the flexible tubular member and the inserted proximal portion of the tubular nozzle member extend through the annular attachment member,

- releasing the applied axial force.

31. The method according to claim 30, wherein the cerebrospinal fluid shunt device is a cerebrospinal fluid shunt device according to any one of claims 1 through 29.

32. A method of implanting the cerebrospinal fluid shunt of any one of claims 1 through 29, the method comprising positioning the cerebrospinal fluid shunt with at least part of the inlet end of the tubular inlet into a cerebrospinal fluid containing space of the individual, and with at least part of the outlet end of the tubular outlet at a deployment location at a foramen jugulare of the individual, such that the inlet opening is fluidly connected with the outlet opening so that cerebrospinal fluid is able to flow from the inlet opening to the outlet opening.

33. The method according to claim 32, wherein positioning the cerebrospinal fluid shunt comprises: a) inserting at least part of the inlet end into the cerebrospinal fluid containing space of the individual, b) inserting at least part of the outlet end into the foramen jugulare of the individual, and c) operably connecting the inlet opening inserted into the cerebrospinal fluid containing space of the individual with the outlet opening inserted into the foramen jugulare of the individual so that cerebrospinal fluid is able to flow from the inlet opening to the outlet opening.

34. The method of claim 32 or 33, wherein the individual suffers from elevated intracranial pressure.

35. The method of any of claims 32 to 34, wherein the individual suffers from hydrocephalus.

36. The method of claim 35, wherein the hydrocephalus is normal pressure hydrocephalus.

37. The method of any of claims 32 to 36, wherein the cerebrospinal fluid containing space is a cerebral ventricle.

38. The method of claim 37, wherein the cerebral ventricle is a lateral ventricle.

39. The method of any of claims 32 to 38, wherein the cerebrospinal fluid containing space is a subarachnoid space.

40. The method of any of claims 32 through 39, wherein the inlet end is inserted into the cerebrospinal fluid containing space through a burr hole.

41. The method of any of claims 32 to 40, wherein the individual is a human being.

42. The method of any of claims 32 to 41 , wherein the outlet end is positioned in the vena jugularis at a position where the vena jugularis passes through the foramen jugulare.

43. The method of any of claims 32 to 42, wherein the outlet end of the tubular outlet is inserted at an access location into the vena jugularis.

44. The method of claim 43, wherein the outlet end inserted into the vena jugularis is guided in a cranial direction through the vena jugularis to the deployment location at the foramen jugulare.

45. The method of claim 44, wherein the outlet end inserted into the vena jugularis is guided to the junction between the sigmoid sinus and the top of the vena jugularis.

46. The method of any one of claims 32 to 45, wherein the outlet end is secured at the deployment location by the fixator attached to the tubular outlet.

47. The method of claim 46, wherein the outlet end is secured by the fixator inside the foramen jugulare.

48. The method of any of claims 46 to 47, wherein the fixator is converted from a compacted state of the fixator into an expanded use state of the fixator to secure the outlet end at the deployment location.

49. The method of claim 48, wherein the fixator in the expanded use state extends radially outwardly from all or part of the tubular outlet.

50. The method of any of claims 48 to 49, wherein the fixator in the expanded use state secures the outlet end at the foramen jugulare with the outlet opening oriented in a retrograde orientation with respect to the flow of blood through the vena jugularis.

51. The method of any of claims 46 to 50, wherein the fixator in the expanded use state extends from the tubular outlet radially outwards relative to the outlet opening of the tubular outlet.

52. The method of any of claims 46 to 51 , wherein the fixator, in the expanded use state, secures the outlet end and the outlet opening at the foramen jugulare by exerting a radial outward force on the wall of the vena jugularis.

53. The method of any of claims 46 to 52, wherein the fixator, in the expanded use state, secures the outlet end and the outlet opening at the foramen jugulare by exerting a radial outward force on the boundaries or bone structures defining the foramen jugulare in the individual.

54. The method of any of claims 52 to 53, wherein the radial force is large enough to keep the fixator in place.

55. The method of any of claims 52 to 54, wherein the radial force is and essentially evenly distributed along a circumference of the fixator.

56. The method of any of claims 52 to 55, wherein the radial force is from about 0.1 Newton to 1.0 Newton in the expanded use state.

57. The method of any of claims 46 to 56, wherein the fixator in the expanded use state maintains the outlet opening at least at a predetermined minimum distance from the endothelial wall of the vena jugularis at the foramen jugulare.

58. The method of any of claims 32 to 57, wherein the inlet opening inserted into the cerebrospinal fluid containing space of the individual and the outlet opening inserted into the foramen jugulare of the individual are operably connected by a shunt body, the shunt body being connected at one end of the shunt body to the tubular inlet, and connected at another end of the shunt body to the tubular outlet.

59. The method of claim 58, comprising placing the shunt body subcutaneously.

60. The method of any of claims 58 to 59, wherein the connection between the shunt body and the tubular outlet is placed subcutaneously.

61. A method of inserting the cerebrospinal fluid shunt defined in any one of claims 1 through 29 in a cerebrospinal fluid containing space and in a foramen jugulare of an individual, the method comprising the step of positioning the cerebrospinal fluid shunt with at least part of the inlet end of the tubular inlet in a cerebrospinal fluid containing space of the individual, and with at least at least part of an outlet end of the tubular outlet in the foramen jugulare of the individual, such that the inlet opening is fluidly connected with the outlet opening so that cerebrospinal fluid is able to flow from the inlet opening to the outlet opening.

62. A method of shunting cerebrospinal fluid from a cerebrospinal fluid containing space of an individual to a foramen jugulare of the individual, said method comprising the steps of i) providing a cerebrospinal fluid shunt as defined in any one of claims 1 through 29, ii) inserting at least part of the inlet end of the tubular inlet into a cerebrospinal fluid containing space of the individual, iii) inserting at least part of the outlet end of the tubular outlet into the foramen jugulare of the individual, and iv) shunting cerebrospinal fluid from the cerebrospinal fluid containing space of the individual to the foramen jugulare of the individual.

63. A method of inserting the cerebrospinal fluid shunt as defined in any one of claims

1 through 29 in a cerebrospinal fluid containing space and in a foramen jugulare of an individual, said method comprising the steps of a) inserting at least part of the inlet end of the tubular inlet into a cerebrospinal fluid containing space of the individual, b) inserting at least part of the outlet end of the tubular outlet into a foramen jugulare of the individual, and c) operably connecting the inlet opening inserted into the cerebrospinal fluid containing space of the individual with the outlet opening inserted into the foramen jugulare of the individual so that cerebrospinal fluid is able to flow from the inlet opening to the outlet opening.

64. The method according to claim 63, wherein the method, in particular the inserting at least part of the outlet end, comprises the further steps of d) guiding the outlet end of the tubular outlet, the outlet end comprising the outlet opening, through the vena jugularis towards the foramen jugulare, and e) locating the tubular outlet end in a cavity of the foramen jugulare.

65. A method of shunting cerebrospinal fluid from a cerebral ventricle of an individual to the vena transversa or the sigmoid sinus of the individual, said method comprising the steps of i) providing a cerebrospinal fluid shunt as defined in any one of claims 1 through 29, ii) inserting at least part of the inlet end of the tubular inlet into a cerebral ventrical of the individual, iii) inserting at least part of the outlet end of the tubular outlet into the vena transversa of the individual, iv) converting the fixator from a compacted state into an expanded use state when the at least part of the outlet end is positioned at a deployment site inside the vena transversa or the sigmoid sinus, and v) shunting cerebrospinal fluid from the cerebral ventricle of the individual to the vena transversa or the sigmoid sinus of the individual.