port

Abstract

A device for providing fluid access to a mammalian central nervous system includes a fluid port to allow fluid access, a housing including a bottom surface that engages the exterior of the body and the skull, and a fluid tube connected to the fluid port and extending below the housing. In various aspects, no portion of the housing extends below the bottom surface. The fluid tube is curved to run along a groove in the skull. The bottom surface includes teeth. A septum seals the fluid port and a cap engages the exterior of the body to compress the septum. The device includes a guide member and a connector having a needle for fluidly connecting with the guide member through the fluid port. The connector engages the guide member and the needle assumes a predetermined position when the connector and the guide member are engaged. Also provided is a method of implanting the device.

Description

[Technical field]

[0001] The present invention relates to medical devices for providing fluid access for the delivery or removal of fluids from within the body, and in particular to devices for providing fluid access to the central nervous system of a mammal. [Background technology]

[0002] Direct delivery of therapeutic agents to the central nervous system (CNS) has been explored for many years with the aim of bypassing the blood-brain barrier (BBB) ​​and minimizing the risk of off-target and systemic side effects of therapeutic agents.

[0003] Direct drug delivery to the CNS dates back to 1885, when the first lumbar puncture was performed to administer cocaine for anesthesia (Corning). Direct introduction of therapeutic agents into the cerebrospinal fluid (CSF) via intraventricular or intrathecal injections or infusions has continued to evolve, including the use of implantable pumps for chronic infusions. These methods of administration are used to treat a variety of conditions and disorders, including pain, spasticity, leptomeningeal carcinomatosis, and microbial infections. Experimentally, administration has also been investigated for the treatment of neurodegenerative disorders, including Parkinson's disease, Alzheimer's disease, Huntington's disease, spinal muscular atrophy, and lysosomal storage disorders.

[0004] Therapeutic agents have also been infused directly into targeted regions of the brain parenchyma for the treatment of neurodegenerative diseases, lysosomal storage diseases, and brain tumors. This can be achieved using a method called convection-enhanced delivery (CED), first described by Bobo in 1994. Here, a therapeutic infusate is delivered at a carefully controlled flow rate through a thin cannula placed in the brain target region such that a pressure gradient is created at the port of the cannula, delivering the infusate into the tissue. The infusate carries the drug by bulk flow, displacing extracellular fluid and achieving a uniform drug concentration. CED facilitates precise anatomical targeting and delivery of therapeutic concentrations through clinically relevant regions of brain tissue or tumors.

[0005] With such an approach, the BBB can act to keep the drug in the brain, reducing systemic side effects. Many neurological disorders treatable by infusion into the CSF or directly into the brain parenchyma require repeated administration over months to years. To avoid patients having to repeatedly place cannulas for each treatment, the cannula can be left in place and connected to an implantable infusion pump. However, the use of implantable pumps is limited because many treatments can require complex infusion therapy, a requirement that cannot be met by currently available programmable pumps. As one pump is required per cannula, intraparenchymal drug delivery using CED may require four or more implantable pumps, which are difficult for patients to handle due to their relatively bulky nature. The biggest contraindication to the use of implantable pumps is that many drugs deteriorate when stored at body temperature in the pump reservoir. In addition, percutaneous filling of the reservoir poses the risk of cumulative infection and, in some cases, repeated subcutaneous inoculations can induce immune responses to protein therapies. Summary of the Invention [Problem to be solved by the invention]

[0006] An alternative to the provision of an implantable pump for intermittent infusion of therapeutic agents into the CNS is to provide an implantable, septum-sealed reservoir connected to a percutaneously accessible cannula, an example of which is described in EP 1 426 074.

[0007] The disadvantage of such devices for repeated injections into the CNS is the need to penetrate the skin to access the reservoir, which entails a cumulative risk of infection or induction of an immune response to the treatment. Prolonged retention of the percutaneous needle in the subcutaneous reservoir during injection increases these risks, as well as the risk of needle displacement. Moreover, if multiple cannulas need to be placed, an equal number of reservoirs must be implanted, which increases the risk proportionately.

[0008] To this end, various attempts have been made to provide improved devices.

[0009] WO 2007 / 104961 describes a subcutaneously implantable septum-sealed fluid connector with multiple lumens for connection to a cannula. The cannula can be connected to an infusion pump by cutting it to the connector when required and attaching it to a male connector with multiple needles, each of which is connected to an infusion line and pump. The drawback of this system is that the patient must undergo multiple surgical procedures to open and close wounds to access the connector, with the associated inconvenience and discomfort, as well as an increased risk of infection.

[0010] WO 2008 / 062173 describes a percutaneous access device for neurological applications that allows repeated infusion of therapeutic agents into the CNS by CED, thus avoiding the risks associated with repeated surgery and multiple needle sticks into the skin. The device comprises at least one intracranial catheter connected to at least one port housed within a device body, the device body having an extracorporeal surface and a subcutaneous surface. The lumen of the port is accessible from the extracorporeal surface through a seal, and the device is stabilized with a perforated subcutaneous flange to promote biointegration with the subcutaneous tissue. A drawback of this device is that the tissue must integrate with the surface of the device to create a tight seal at the tissue-device interface and prevent infection of the subcutaneous tissue and, therefore, the brain. Such integration is highly unlikely due to the inherent mobility of the skin and device movement within soft tissue. As such, such devices can become sterilized and infected, posing significant risks to the patient.

[0011] US Patent No. 8,827,987 describes a percutaneous bone anchoring device for drug delivery to the CNS. The device includes one or more ports for supplying fluids to one or more cannulas implanted in the brain, accessible from the external surface through a septum seal. The device is inserted into a complementary recess formed in the bone and is held by gripping features on the inner surface of the recess. A number of problems arise when deploying such a device.

[0012] First, creating recesses in the bone to complement the contours of the device requires precise machining of the bone with guided instruments to facilitate an effective interference fit to secure the device. This requires image-guided surgery and the use of a stereo guide or robot to guide instruments to cut the skull to a known depth so as not to penetrate the brain. Also, the need to place and fix jigs in the skull can increase the size of the incision required to implant the device. This adds complexity to implantation, increases operative time, and exposes patients to the risk of infection and surgical complications.

[0013] Second, the skull is thin, especially in children, e.g., 2 mm thick, and in such circumstances there is insufficient engagement with the inner surface of the bone recess to hold the device. Penetrating the entire thickness of the skull would create a direct pathway from the external surface through the skin and bone to the meninges surrounding the brain, creating a risk of infection from meningitis or epidural abscess unless a hermetic seal is formed at the device-bone interface during implantation. Also, implanting the subcutaneous portion of the device through thin bone would compress brain tissue.

[0014] Third, U.S. Patent No. 8,827,987 teaches the use of an impactor or other tool to bring the device into intimate contact with a bone recess and provide a friction fit, simplifying surgical implantation and providing a more reliable attachment of the device to the subject than can be achieved using adhesives, screws, etc. However, the opposite may also be true, as abnormally high stresses concentrated in the bone by impaction can cause pressure necrosis, which can result in the implant loosening and failing.

[0015] WO 97 / 49438 describes a percutaneous fluid transfer device that includes a plate that can be fixed to the skull using bone screws. WO 99 / 34754 also describes a percutaneous fluid transfer device that can be screwed to bone.

[0016] In view of the shortcomings of the prior art devices discussed above, a need remains for improved devices that provide fluid access to the central nervous system of a mammal. [Means for solving the problem]

[0017] According to a first aspect of the present invention there is provided an apparatus for providing fluid access to a central nervous system of a mammal, the apparatus comprising: a housing having a fluid port allowing delivery or removal of fluid from the central nervous system, an exterior portion allowing access to the fluid port, and a bottom surface configured to engage an outermost surface of a skull; and a fluid tube connected to the fluid port and extending below the housing through the bottom surface, wherein no part of the housing extends below the bottom surface, and wherein the fluid tube is configured to bend to run along a groove formed in the outermost surface of the skull.

[0018] By positioning the device such that no portion of the housing extends below the lowest surface that engages the skull, it is unnecessary to cut a precisely sized recess in the skull to accommodate the device. This significantly reduces the time required to implant the device and eliminates the need for additional jigs or guides to screw into the skull as with prior art devices. This reduces the risks to the patient from increased surgical time and wound size. Additionally, by eliminating the need for a precise fit between the device and the skull recess, the risk of infection, pressure necrosis, and other risks associated with prior art devices is also reduced.

[0019] Optionally, when the bottom surface of the housing engages the outermost surface of the skull, no portion of the device penetrates an inner surface of the skull. By avoiding breaching the inner surface of the skull, the risk of infection of the patient's brain can be significantly reduced.

[0020] Optionally, the bottom surface is configured to engage and be attached to the outermost surface of the skull using a plurality of screws that inhibit relative movement of the device and skull and provide a fixed connection to the skull, thereby reducing the risk of marsupialization around the device.

[0021] Optionally, the fluid tube is configured to bend at a point below the bottom surface, allowing the fluid tube to run internally along a channel away from the area protected by the cover of the device itself, reducing exposure of the fluid tube to the outside environment and reducing the risk of infection where the tube enters the skull.

[0022] According to a further aspect of the present invention, there is provided an apparatus for providing fluid access to a central nervous system of a mammal, comprising: a housing having a fluid port allowing delivery or removal of fluid from the central nervous system, an exterior portion allowing access to the fluid port, and a bottom surface configured to engage an outermost surface of a skull; and a fluid tube connected to the fluid port and extending from the housing, the bottom surface of the housing having a plurality of teeth for engaging the outermost surface of the skull.

[0023] The teeth on the bottom surface that engages the skull reduce the risk of relative movement of the device and the skull, which reduces the risk of marsupialization around the device. The teeth also help displace the cement used to seal the device to the skull, helping to better fill gaps between the device and the skull surface that can increase the risk of infection.

[0024] Optionally, the plurality of teeth are distributed across the bottom surface. The plurality of teeth are distributed across at least 50% of the area of ​​the bottom surface. Distributing the teeth across the entire surface ensures uniform engagement of the appliances and further reduces the risk of relative movement.

[0025] According to a further aspect of the present invention, there is provided an apparatus for providing fluid access to a central nervous system of a mammal, the apparatus comprising: a fluid port allowing delivery or removal of fluid from the central nervous system; a housing having an exterior portion allowing access to the fluid port; a fluid tube connected to the fluid port and extending from the housing; a septum sealing the fluid port; and a cap configured to engage the exterior portion of the housing and compress the septum when the cap is attached.

[0026] The cap is adapted to protect the septum from mechanical damage and the effects of ultraviolet light, which can degrade materials such as silicone used in the septum. The cap also serves to keep the septum clean when the fluid port is not in use. The cap prevents dirt, infectious material, grease, hair, skin and other debris from adhering to the septum, which may enter the brain through the fluid port during use of the device. By providing a cap that compresses the septum when not in use, the fluid port can be effectively sealed with a thinner septum than in prior art devices. When the cap is removed to allow the septum to be pierced with a needle to transfer fluid, the relatively thin and uncompressed septum is less likely to be punctured by the passage of the needle. Additionally, the shear forces exerted on the septum by the passage of the needle are significantly reduced, reducing the formation of wear debris and reducing degradation of the septum that may compromise its sealing effectiveness. Wear debris is undesirable because it can block fluid tubing or be carried to the central nervous system, causing inflammation.

[0027] Optionally, the cap is configured to compress the septum by applying a force perpendicular to the plane of the septum, meaning that the fluid port can be effectively sealed without applying radial forces which can make needle insertion difficult and likely lead to coring of the septum.

[0028] Optionally, the cap is adapted to engage the external body surface using a mechanical connection that allows for secure and reversible attachment of the cap.

[0029] Optionally, the mechanical connection comprises a first connection structure on the cap and a second connection structure on the exterior body, the cap configured to engage the exterior body by engagement of the first connection structure with the second connection structure. Engaging opposing structures on both the cap and the housing provides a more secure engagement of the cap and the housing allowing for a more consistent application of compressive forces.

[0030] Optionally, the mechanical connection is configured to apply a predetermined compressive force to the septum when the cap is engaged with the exterior body, ensuring that a predetermined force is applied that is sufficient to compress the septum and seal the port, but not so great as to damage the septum or other parts of the device.

[0031] The cap is configured to provide a seal around the septum, which further ensures a clean surface of the septum and reduces the risk of introducing dirt, debris, or pathogens into the CNS through the fluid port.

[0032] Optionally, the device further comprises a connector cap configured to engage the exterior of the housing, the connector cap comprising a needle configured to fluidly connect with the fluid tube via the fluid port, the connector cap being a convenient way of connecting the device to a reservoir or other external source of fluid to be administered to the central nervous system.

[0033] Optionally, the connector cap is adapted to engage the external body surface using a mechanical connection that allows for secure and reversible attachment of the cap.

[0034] Optionally, the mechanical connection comprises a first connection structure on the connector cap and a second connection structure on the exterior body, the connector cap configured to engage the exterior body by engagement of the first connection structure with the second connection structure. Engaging opposing structures on both the cap and the housing can provide a more secure engagement between the cap and the housing, allowing for a more consistent application of compressive forces.

[0035] Optionally, the device comprises a septum sealing the fluid port, and the connector cap is configured to compress the septum by exerting a force perpendicular to the plane of the septum when the connector cap is engaged with the exterior of the housing, meaning that the septum can provide an effective seal around the needle without exerting radial forces which may complicate needle insertion and likely lead to coring of the septum.

[0036] Optionally, the mechanical connection is configured such that when the connector cap engages the exterior body, the needle is advanced a predetermined distance through the septum, such that the connector cap is configured to advance the needle a sufficient distance to ensure a reliable fluid connection between the needle and the fluid port of the device without risking damage to any component due to the needle being advanced too far.

[0037] Optionally, the connector cap further comprises a second fluid tube in fluid communication with the needle and extending from a side of the connector cap opposite the needle, and a plurality of grooves configured to hold the second fluid tube, The second fluid tube allows the connector cap to be connected to a reservoir or syringe pump for use in administering a therapeutic agent, and the grooves in the connector cap allow the fluid tube to be held in a convenient location during use of the device, reducing the risk of mis-dosing or damage to components during administration of fluid.

[0038] According to a further aspect of the present invention, there is provided an apparatus for providing fluid access to a central nervous system of a mammal, comprising: a fluid port enabling delivery or removal of fluid from the central nervous system; a housing having an exterior allowing access to the fluid port; a guide member; one or more fluid tubes connected to the fluid port and extending from the housing; and a connector configured to engage with the guide member, the connector comprising one or more needles configured to fluidly connect with each of the fluid tubes via the fluid port, the connector and guide member configured such that when the connector engages the guide member, each of the needles assumes a predetermined position relative to each of the fluid tubes.

[0039] The use of the connector and guide member greatly simplifies operation of the device by eliminating the need for the user to visually align the needle with the fluid port. This is particularly advantageous when multiple fluid ports and needles are provided for delivering different treatments, as the risk of delivering a treatment through the wrong fluid port is greatly reduced. The guide member ensures that the needle always passes through the fluid port in the same position. This reduces wear on the seal and extends the life of the device, especially when a septum is used to seal the port.

[0040] Optionally, the device comprises a septum sealing the fluid port, and the connector and guide member are configured such that when the connector engages the guide member, each of the needles is advanced a predetermined distance through the septum, thereby ensuring that the needles advance sufficiently to penetrate the septum and reach the fluid port, but without risking damage to other components of the device such as the needles or fluid tubing.

[0041] Optionally, the guide member comprises a plurality of guide posts, and the connector comprises a cam configured to engage the guide posts, the cam and the guide posts configured such that rotation of the cam advances the needle a predetermined distance to a predetermined location. Using the guide post and cam arrangement, an appropriate level of force can be applied in a controlled manner to advance the needle through the septum. By utilizing the mechanical advantage provided by the cam, the cam and guide member provide a mechanical advantage to the user, reducing the force that must be applied to the device to advance the needle. This increases the reliability of the fluid connection to the fluid port while also reducing the likelihood of damage to the device during use. Additionally, the guide posts can be designed with a large aspect ratio of length to diameter, which reduces the angular misalignment that occurs when mating the connector. The use of multiple small diameter guide posts provides more accurate guiding over a shorter distance than prior art designs that use relatively short, wide cylinders mated to a recess in the skull. This allows for the use of a thinner connector, which reduces the likelihood of the device being bumped and damaged during clinical use.

[0042] Optionally, the cam and guide post are further configured to reversibly lock the needle in place once the needle has advanced a predetermined distance. Removably locking the needle significantly reduces the likelihood of needle movement during use of the device and further enhances the reliability of the fluid connection to the fluid port.

[0043] Optionally, the guide member is removably attached to the exterior of the housing using a mechanical connection. A removable guide member reduces the size of the device when not in use and improves user convenience. Also, different guide members can be provided for different device and connector configurations.

[0044] Optionally, the mechanical connection includes a first connecting structure on the guide member and a second connecting structure on the external body, the guide member being removably attached to the external body by engagement of the first connecting structure with the second connecting structure. Engaging opposing structures on both the cap and the housing can provide a more secure engagement between the cap and the housing, allowing for a more consistent application of compressive forces.

[0045] Optionally, the mechanical connections comprise one or more of threads, snap-fit ​​connections, interference fit connections, and grub screws that provide sufficient retention while being small and easy to use enough to be suitable for use within the device.

[0046] Optionally, a surface of the housing configured to contact tissue of the mammal comprises at least one of a texture and a coating configured to promote tissue integration by the device, thereby reducing the risk of bacterial infiltration that may cause inflammation and infection.

[0047] Optionally, the housing of the device is formed from titanium and / or polyetheretherketone. Titanium has high strength and a relatively low density, as well as being biocompatible, making it a suitable material for medical implants. PEEK is also biocompatible and lightweight.

[0048] Optionally, the device further comprises a septum sealing the fluid port, the septum being a pre-pierced or split septum, which allows a needle to penetrate the septum and reduces the risk of debris being generated when the needle pierces the septum, thereby reducing the possibility of unintended introduction of foreign material into the central nervous system.

[0049] Optionally, the housing includes one or more protrusions configured to compress the septum, thereby allowing the fluid port to be effectively sealed with a thinner septum than prior art devices by compressing the septum using structure on the housing in a manner similar to that described above with respect to the cap.

[0050] According to a further aspect of the present invention there is provided a kit for implanting a device for providing fluid access to the central nervous system of the mammal, comprising any of the devices described above and a quantity of acrylic cement.

[0051] Acrylic cement is particularly suitable for fixing devices to the skull because it can fill any gaps or irregularities around the device and any incisions made in the skull to fix the device. This prevents the introduction of foreign material or contaminants that could cause infection or inflammation. However, acrylic cement suitable for medical use is typically provided in relatively large quantities and hardens rapidly. Providing a predetermined amount of cement as part of a kit with the device ensures that the appropriate amount of cement is available when implanting the device and reduces waste of unused cement.

[0052] Optionally, the acrylic cement includes an antimicrobial agent, which further reduces the risk of infection after installation of the device.

[0053] According to a further aspect of the present invention there is provided a method of implanting a device for providing fluid access to a central nervous system of a mammal comprising forming a groove in an outermost surface of the mammal's skull, the groove extending from an implantation site towards a cannula providing a fluid connection to the central nervous system of the mammal, the groove not penetrating an inner surface of the skull, connecting a fluid tube of the device to the cannula, filling the groove with acrylic cement, inserting the fluid tube into the groove and engaging a bottom surface of the device with the outermost surface of the skull at the implantation site.

[0054] Forming a groove and inserting a fluid tube into the groove provides a method of implanting a device that can be performed quickly and requires less precision than existing methods of implanting similar devices, which require guide tools and jigs to create a recess in the skull shaped to match the profile of the device to be inserted. This means that both surgical invasiveness and operative time are reduced, and procedural risks to the patient are greatly reduced. Filling the groove with acrylic cement holds the tube within the groove and fills any voids around the tube and device to prevent infection.

[0055] Optionally, the method further comprises removing an area of ​​scalp from the implantation site large enough to accommodate an external portion of the housing of the device, removing a portion of the scalp allows the skin to fit around the device and facilitates integration of the device.

[0056] Optionally, the method further comprises removing subcutaneous fat and hair follicles in a predetermined area around the implantation site. Removing the relatively mobile subcutaneous fat between the dermis and periosteum of the skin causes their fusion, and when the combined layers come into contact with the surface of the device, the mobility of the dermis layer is reduced, facilitating the integration of the device. This reduces the risk of suturing and infection, and also makes the skin and periosteum immediately above the subcutaneous portion of the device more level with the surrounding skin. [Brief description of the drawings]

[0057] Embodiments of the invention will now be described, by way of non-limiting examples, with reference to the accompanying drawings, in which: [Figure 1] FIG. 1 is a cross-sectional view of a device having a single fluid port. [Diagram 2] FIG. 1 is an exploded view of a device having multiple fluid ports. [Diagram 3] FIG. 2 is a cross-sectional view of the single fluid port device of FIG. 1 when fixed to the skull. [Figure 4] FIG. 4 is an exploded view of the device having a single fluid port of FIGS. 1 and 3. [Diagram 5]FIG. 13 is an exploded view showing a connector for a device having a single fluid port. [Figure 6] 3 is an exploded view of a connector and guide member of the device having multiple fluid ports and fluid tubes shown in FIG. 2. [Figure 7] FIG. 13 is a perspective view showing attachment of a guide member to a housing of a device having multiple fluid ports. [Figure 8] 13 is a perspective view showing the attachment of a connector to a housing of a device having multiple fluid ports using a guide member. FIG. [Figure 9] 1A-1D are cross-sectional and top views of a device having two fluid ports for use in intrathecal delivery when engaged with a cap. [Figure 10] 10A-10C are various exploded views of the two fluid port device of FIG. 9. [Figure 11] 10A and 10B are cross-sectional and top views of the device of FIG. 9 when engaged with a guide member and connector. [Figure 12] FIG. 10 is an exploded view showing the connector and guide member of the device having two fluid ports and fluid tubes of FIG. [Figure 13] FIG. 13 is a perspective view showing the attachment of a connector to a housing of a device having two fluid ports using a guide member. [Figure 14] FIG. 1 illustrates the placement of the device when used for intrathecal delivery of a therapeutic agent. [Figure 15] FIG. 1 illustrates the use of the device in intrathecal delivery of a therapeutic agent. [Figure 16] FIG. 9 is a diagram showing a kit including the guide member and connector of FIGS. 6 to 8. [Figure 17] 1 is a flow chart of a method of implanting a device to provide fluid access. [Figure 18] 1A-1D illustrate several steps of a method of implanting a device to provide fluid access. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0058] FIG. 1 illustrates a device 10 for providing fluid access to the central nervous system (CNS) of a mammal. The device 10 provides a percutaneous fluid transfer device that provides repeated access for the removal or delivery of fluids to the CNS. As discussed above, the fluid access provided by such a device 10 may be used for the treatment or diagnosis of neurological disorders. The device 10 is particularly suited for use in delivering therapeutic agents to the CNS directly into the brain parenchyma using methods of convection-enhanced delivery (CED) or by injection into the cerebrospinal fluid (CSF).

[0059] The device 10 comprises a fluid port 12 allowing for the delivery or removal of fluid from the central nervous system, a housing 14 including an exterior portion 16 allowing access to the fluid port 12, and a fluid tube 20 connected to the fluid port 12. The housing 14 may further include a bottom surface 18 configured to engage the outermost surface of a mammalian skull. In the context of the device 10, the direction "down" or "below" refers to the direction toward the interior of the skull when the device 10 engages the outermost surface of the skull. This direction may also be referred to as the distal direction, i.e., the direction such that the bottom surface 18 is at the distal end of the housing 14.

[0060] After implantation of the device, fluid port 12 is connected to an implanted cannula or catheter via fluid tubing 20. The implanted cannula is typically placed within the CSF (intracerebroventricular or intrathecal) and allows for infusion of fluids into the CNS using device 10 via fluid port 12 and fluid tubing 20. Fluid port 12 can be connected to an extracorporeal infusion line, which can be connected to a reservoir or other suitable source or drain of fluid, such as a syringe pump.

[0061] As shown in FIG. 2, the device 10 may include multiple fluid tubes 20, where each fluid tube 20 is independently accessible via a fluid port 12. After implantation, each fluid tube 20 is connected to a corresponding implanted cannula or catheter. This allows for fluid access to different regions of the CNS, or for the infusion of multiple different fluids. Alternatively, the fluid tubes 20 may provide fluids directly to the CNS, rather than being fluidly connected to the CNS via a catheter. The fluid ports 12 may include one or more filters for filtering fluids passing through the fluid ports 12. For example, the filters may include a bacterial filter and / or a gas filter to prevent the introduction of bacteria or gases into the CNS.

[0062] Multiple fluid tubes 20 can be used to deliver different therapeutic agents to different regions of the brain, or the same therapeutic agent to multiple regions. The embodiment shown in Figure 2 is particularly suited for this type of application, and has four small diameter fluid tubes 20.

[0063] Multiple fluid tubes 20 can also be used for intrathecal administration, for example, by draining and / or circulating the CSF. Circulation of the CSF can be used to make the concentration of therapeutic agent in the CSF more uniform when administered to the CSF, or to filter or replace the CSF in the treatment of diseases such as meningitis. For example, as shown in FIG. 15, a first fluid tube 20 can be connected to a first catheter 80 inserted into a cerebral vena cava or ventricle for infusion of therapeutic agent, and a second fluid tube 20 can be connected to a lumbar catheter 82 inserted into the spinal column for drainage of the CSF. This allows mixing of the therapeutic agent with the CSF and closed circulation of the CSF-therapeutic agent mixture, ensuring uniform distribution of the therapeutic agent throughout the CNS, and / or filtering cellular debris from the CSF. Other applications include injecting therapeutic agent both above and below an obstruction in the CSF, and / or delivering multiple agents simultaneously. Such an arrangement can also allow for continuous and / or intermittent infusion into the CSF, and sampling of the CSF, as well as ambulatory infusion. This reduces discomfort and the potential for complications such as infection compared to existing methods such as lumbar puncture or intraventricular injection.

[0064] Advantages of the percutaneous septum sealing devices described herein for providing fluid access to the CNS include the ability to deliver therapeutic agents or inert fluids directly to the brain or spinal parenchyma and / or to the cerebrospinal fluid, either continuously or intermittently, for periods of hours, days, weeks, months, or years without the need for repeated surgical procedures. The devices also facilitate the intermittent removal of CSF or fluid from the CNS parenchyma, including fluid from tumors, developmental or infected cysts, without the need for repeated invasive procedures.

[0065] CNS disorders that may be treated with therapeutic agents delivered through the device include, but are not limited to, neurodegenerative diseases, movement disorders, enzyme deficiency states, neuroinflammatory diseases, CNS infections, acquired neurological injuries, epilepsy, cancer, subarachnoid hemorrhage, and cerebral vasospasm.

[0066] Neurodegenerative diseases include dementia, Lewy body disease, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS), multiple system atrophy, spinal muscular atrophy, Friedreich's ataxia, Huntington's disease, Parkinson's disease, Parkinson's disease plus syndrome, and corticobasal degeneration. Enzyme deficiencies include lysosomal storage diseases, Tay-Sachs disease, Sandhoff disease, neuronal ceroid lipofuscinosis, Niemann-Pick disease type C, Hunter syndrome, Hurler disease, and Gaucher disease. Neuroinflammatory diseases include multiple sclerosis and prion diseases. CNS infections include meningitis, encephalitis, and brain abscess. Acquired neurological injuries include stroke, traumatic brain injury, and spinal cord injury. Cancers include leptomeningocarcinosis or brain tumors. Brain tumors may be characterized by the presence of primary or secondary brain tumors. Primary brain tumors may be astrocytomas, such as glioblastoma multiforme (GBM), or diffuse intrinsic cavernous gliomas (DIPGs).

[0067] By way of example, therapeutic agents include, but are not limited to, neurotrophins, histone deacetylase inhibitors, gene therapy, enzymes, immunotherapy, siRNA, antisense oligonucleotides, chemotherapy, Auger electron emitting agents, immunotoxins, molecular targeted therapy, monoclonal antibodies, oncolytic viruses, viral vectors, chemotherapeutic agents, nanoparticles such as gold and iron nanoparticles, antispasmodics, thrombolytic agents, and botulinum toxin.

[0068] The therapeutic agent can be administered in the form of a pharmaceutical composition, which may contain any pharma- ceutically acceptable carrier, adjuvant, or vehicle. Pharmaceutically acceptable carriers, adjuvants, and vehicles that can be used in pharmaceutical compositions include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins such as human serum albumin, buffer substances such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinylpyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, polyethylene-polyoxypropylene block polymers, and polyethylene glycol.

[0069] The therapeutic agent may be administered in an inert diluent, such as artificial CSF, which may be injected directly into the subarachnoid space or ventricles as a substitute for endogenously produced CSF, into the brain parenchyma before and / or after injection of the therapeutic agent, or co-injected with a therapeutic agent delivered through a separate cannula.

[0070] The use of a device to intermittently inject therapeutics directly into targeted regions of the brain parenchyma through a permanently implanted thin cannula has advantages in the treatment of neurological disorders. The blood-brain barrier prevents many therapeutics from reaching therapeutic targets in the CNS when delivered to the systemic circulation, and the treatment of many CNS disorders requires that treatment be restricted to specific brain regions to limit potential side effects. Direct infusion of therapeutics into the brain parenchyma using convection-enhanced delivery (CED) techniques allows for homogeneous and precise administration of selected therapeutic doses and achieves long tissue exposure times, as the blood-brain barrier acts to retain the therapeutic in the brain. CED has a long biological half-life in the CNS, allowing infusions to be repeated at intervals of days, weeks, or months to maintain therapeutic efficacy. The device facilitates intermittent infusion without repeated potentially risky surgery. The device also allows for dosage adjustments depending on the patient's response and side effects, which may not be feasible with one-off gene therapy, for example. Examples of potential uses of the device for intermittent infusion into the brain parenchyma include:

[0071] 1. Neurotrophins such as glial cell line derived neurotrophic factor (GDNF) and brain dopamine neurotrophic factor (CDNF) are infused intermittently into the putamen via two or four cannulas to achieve neurological recovery in Parkinson's disease. A phase II study in which 42 Parkinson's disease patients were infused with GDNF into the putamen monthly over 18 months, and 17 CDNF patients were treated with a similar regimen via a percutaneous port, demonstrated that this treatment is safe and effective (Whone A. et al, Brain, Volume 142, Issue 3, 1 March 2019).

[0072] 2. To treat Huntington's disease, antisense oligonucleotides (ASOs) targeting huntingtin protein RNA (HTT RNA) are intermittently infused. This is accomplished by cannulae placed in the putamen and caudate nucleus. This method of treating Huntington's disease appears to be more effective at achieving therapeutic concentrations of ASOs in the caudate and tegmental nucleus, the structures most affected in Huntington's disease, than delivery to the CSF, which has been used previously.

[0073] 3. HDACis, hepatocellular carcinoma deacetylase inhibitors, have been shown to be neuroprotective in models of neurodegenerative diseases such as Parkinson's disease, Huntington's disease, Alzheimer's disease, spinal muscular atrophy, and amyotrophic lateral sclerosis (ALS). HDACs act ubiquitously, but the majority do not cross the blood-brain barrier. With the use of this device, intermittent infusion of HDACis to relevant CNS targets can be achieved.

[0074] 4. Treatment of epilepsy and movement disorders by injecting botulinum toxin directly into targeted areas of the brain parenchyma has been described (US Patent Application Publication No. 20080160121). Injection of botulinum toxin into the brain parenchyma reversibly inhibits the release of neurotransmitters such as acetylcholine, norepinephrine, and glutamate, suppressing symptoms for 2 to 6 months. Intermittent injection of botulinum toxin into epileptogenic tissues, such as the medial temporal lobe in patients with drug-resistant temporal lobe epilepsy, via the device is considered to be effective as a long-term treatment. Use of the device, which intermittently injects botulinum toxin into functional targets in the brain to create reversible damage, is effective in controlling movement disorders such as dystonia, dyskinesia, and Parkinson's disease, and injection into the globus pallidus and ventral intermediate nucleus of the thalamus (VIM) is effective in controlling tremors. In addition, the device can be used to intermittently inject botulinum toxin into the anterior cingulate cortex to induce reversible functional damage and control chronic pain. Similarly, reversible functional damage caused by intermittent injection of botulinum toxin can be used to treat major psychiatric disorders, including depression by targeting the subpyramidal cortex and ventral putamen / ventral striatum, and obsessive-compulsive disorder by targeting the ventral putamen / ventral striatum.

[0075] 5. Repeated administration of drugs to the same target area by CED without the need for further surgery. This is particularly important in the treatment of malignant brain tumors, because repeated exposure to chemotherapy is essential to ensure that cells are adequately exposed to the drug. Monthly infusions of a combination of HDACi, sodium valproate, and carboplatin into the cerebral cortex via a percutaneous septum-sealed port have been shown to be safe and effective in pediatric patients with diffuse intrinsic pontine glioma (Szychot E. et al, Int.J of Clinical Oncology,2021). Similarly, monthly infusions of carboplatin into the brain parenchyma via a percutaneous septum-sealed port have been shown to effectively suppress recurrent glioblastoma (Barua NU,et al.Drug Delivery2016).

[0076] Examples of uses of the device, which provides fluid access to the cerebrospinal fluid (CSF) to deliver therapeutic agents to the CNS, include the following:

[0077] 1. Treatment of meningeal carcinomatosis. This is a complication of cancer in which the cancer spreads from the original tumor site to the meninges that surround the brain and spinal cord. 18.1 million people are diagnosed with cancer each year, and while cancer survival rates are improving, the number of patients with meningeal carcinomatosis is increasing. Meningeal carcinomatosis occurs in 5-8% of solid cancers (including: 40% of breast cancer patients, 20% of lung cancer patients, and 10% of melanoma patients). It occurs in 5-15% of hematologic tumors and 10-32% of primary CNS tumors. It is usually fatal within 3-6 months. Current treatment options for meningeal carcinomatosis include delivery of chemotherapy via lumbar puncture or intraventricular infusion via an Ommaya reservoir. For example, for leukemia patients, methotrexate 15 mg per day for 5 days every 2 weeks or cytarabine 30 mg per day for 3 days. However, intrathecal therapy by lumbar puncture has many problems. It is painful (general anesthesia is required in children) and difficult to perform. The procedure is traumatic and carries the risk of infection. Without effective circulation of CSF within the spinal cord, drug concentrations will be inhomogeneous, potentially resulting in local drug toxicity due to localized high concentrations at the injection site or underdosing in areas distant from the injection site. Complications include seizures, arachnoiditis, motor and sensory disorders, headache, nausea, vomiting, and necrotizing leukoencephalopathy. CSF blockage above the injection site can result in untreated areas, limiting the volume of infusate. Intraventricular infusion into an Ommaya reservoir has similar problems, as well as a high incidence (approximately 10%) of infection and / or catheter misplacement. The use of percutaneous septum-sealing devices to deliver chemotherapy agents to the CSF for the treatment of meningeal carcinomatosis facilitates painless, sterile, repeated access to CSF ​​and continuous outpatient infusion with a portable infusion pump. This allows for the maintenance of therapeutic agent concentrations in the CSF over an extended period of time. When using a dual catheter device, one catheter can deliver a chemotherapy agent to the cisterna magna or ventricular region, for example, and then intermittently withdraw CSF through a second catheter in the lumbar membrane to determine therapeutic agent concentrations in the CSF. A device with dual catheters, one implanted in the cisterna magna or ventricle and the second in the lumbar membrane, can be used to deliver therapeutic agents while infusing artificial CSF through the former and draining CSF through the latter.This allows for an even distribution of therapeutic agents throughout the CSF space and removes tumor debris within the CSF. The described dual catheter system can also be used to deliver chemotherapy above and below tumors that block CSF pathways.

[0078] 2.Provide fluid access to the CSF through two or more catheters, infusing artificial CSF through one catheter and withdrawing CSF through a second catheter to flush blood and pathogens from the CSF. Such an approach is effective in treating subarachnoid hemorrhage because it removes blood products from the CSF that can cause cerebral vasospasm and stroke. This may include the simultaneous infusion of thrombolytic agents to hasten removal of blood clots. The device can also be used to infuse anticonvulsants, such as nimodipine, into the CSF to suppress cerebral vasospasm. In some cases of meningitis, the device can also be used to infuse artificial CSF through one catheter and drain infected CSF through a second catheter. It also provides a means to deliver antibiotics and antivirals to the CSF and maintain tightly controlled concentrations that can be periodically sampled and monitored via a second catheter in the CSF space.

[0079] 3. Injection of antisense oligonucleotides into the CSF. Such injections have shown efficacy in experimental models of Alzheimer's disease, frontotemporal dementia, Huntington's disease, amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy (SMA). Treatment of SMA by intermittent injection into the CSF via lumbar puncture has been approved for clinical use. The transcutaneous septum sealing device described herein provides an alternative means of administration with the advantages of the approach described herein.

[0080] The device 10 of FIG. 1 or FIG. 2 may include a seal that seals the fluid port 12. The seal may include a valve. The valve may be actuated or open when connected to a corresponding interconnecting member. For example, the valve may be a mechanical valve, requiring the valve to be physically actuated to allow fluid flow. The valve may be self-sealing, such that it automatically closes upon removal of the connecting member. Alternatively, the valve may be a pressure sensitive valve that is actuated to open when fluid flows and close when fluid flow stops. The pressure sensitive valve may consist of a split seal or a split septum.

[0081] In Figs. 1 and 2, the seal is a septum 22 that seals the fluid port 12. The septum 22 can be accessed by a hollow needle 24 or a blunt hollow cannula. In the latter case, the septum 22 is preferably a pre-pierced septum or a split septum. The septum 22 may be formed from medical grade silicone. If the device 10 includes multiple fluid tubes 20, the septum 22 may seal one of the fluid tubes 20 or may seal multiple fluid tubes 20. The diameter of the septum 22 may be 1-10 mm, preferably 2-5 mm, for example 3 mm. The thickness of the septum is 0.5-5 mm, preferably 1-3 mm, for example 1.5 mm. However, the septum 22 is not limited thereto and any suitable dimensions may be used depending on the configuration of the device 10. The housing 14 may further include a retaining member 23, such as a press-fit ring, for retaining the septum in a desired position within the housing. The retaining member 23 may be made of plastic (eg, polyetheretherketone) or metal (eg, titanium).

[0082] The housing 14 is preferably formed from a plastic (such as polyetheretherketone) or a metal (such as titanium), both of which are strong, lightweight, and biocompatible. The housing 14 can be formed by any suitable manufacturing method, such as molding, casting, milling, etc. The housing 14 is preferably formed by 3D printing. The housing 14 includes a molded portion 26 therein to which the other components of the device 10 (such as the fluid tube 20) are attached. The molded portion 26 can be formed from a plastic, such as polyetheretherketone (PEEK) or carbotan. The molded portion 26 may include alignment features, such as recesses 27 (see FIG. 2), which cooperate with corresponding alignment features 29 in the housing 14 to ensure that the molded portion is correctly oriented when the device 10 is assembled.

[0083] The housing 14 may include one or more protrusions 25 configured to compress the septum 22. Optionally, the protrusions 25 are provided by moldings 26. The protrusions 25 may be configured to create a localized compression in the septum 22. The protrusions 25 may be configured to create a localized compression at the entrance of the fluid port 12. The protrusions 25 may compress the septum 22 around a region of the septum 22 where the needle 24 advances through the septum 22. For example, if the septum 22 is a pre-pierced or split septum, the region may include a perforation or a break in the septum 22. The protrusions 25 may compress the septum 22 from a side of the septum 22 facing the interior of the housing 14. The protrusions 25 may take the form of an annular ridge around a region where the needle 24 advances through the septum 22.

[0084] Fluid from the needle 24 may be delivered at a pressure higher than normal intracranial pressure during injection in order to force it into the CNS. As a result, the septum 22 may not normally provide sufficient sealing force around the needle to prevent leakage of fluid. The protrusion 25 acts as a valve seat compressing the septum 22 around the area where the needle 24 penetrates the septum. Compression of the septum 22 ensures a fluid-tight seal that prevents leakage of fluid when the device 10 is used to administer or remove fluid. If the device 10 includes multiple fluid tubes 20 that are intended to be accessed using separate needles 24, a protrusion 25 may be provided around each area of ​​the septum 22 through which the needle 24 is advanced. In this case, compression of the septum 22 also prevents cross-leakage or contamination between the multiple fluid tubes 20.

[0085] Needles 24 may include hubs 21 that are configured to engage the proximal (outer) surface of septum 22 and compress septum 22 when needles 24 are advanced into position. If needles 24 include hubs 21, projections 25 preferably have a shape and size corresponding to hub 21 such that the area of ​​septum 22 compressed by projections 25 is similar and opposed to the hub of each needle 24. This helps to create a seal around needle 24 during fluid transfer.

[0086] The external body portion 16 provides access to the fluid port 12. Typically, the fluid port 12 is accessed from the proximal end of the external body portion 16. The external body portion 16 has a cylindrical shape and can pass through an opening in the skin. The external body portion 16 may have a diameter of 1 to 10 mm, preferably 2 to 6 mm, and more preferably about 4 mm. The external body portion 16 may have a height of about 1 to 15 mm, preferably 2 to 10 mm, and more preferably 6 mm. However, the external body portion 16 is not limited thereto, and any suitable dimensions may be used depending on the configuration of the device 10.

[0087] In addition to the external body 16, the device 10 may include a subcutaneous portion 17 having a larger diameter than the external body 16 and disposed at the distal end of the housing 14. In FIG. 1, the subcutaneous portion 17 is disc-shaped and typically has a thickness of 0.5-3 mm, preferably about 1 mm, but may generally have any suitable shape. A bottom surface 18 may be provided by the subcutaneous portion 17.

[0088] Surfaces of the housing 14 that are configured to contact mammalian tissue may be provided with at least one of a texture and a coating configured to promote tissue integration, including bone integration of the bottom surface 18 with the skull, and integration of other surfaces of the housing 14 with soft tissue. It may be particularly advantageous to provide textures and / or coatings on surfaces of the housing 14 other than the surface of the external body 16, such as surfaces configured to be located under the skin after implantation and / or surfaces configured to contact soft tissue. This preferably includes the surface of the subcutaneous layer 17. Suitable textures and coatings include microporous surfaces, 3D printed textured surfaces, plasma sprayed titanium coatings, and / or hydroxyapatite coatings. Tissue integration may seal the tissue-device interface and prevent bacterial ingress, thereby reducing the likelihood of persistent or recurrent inflammation and / or infection in the soft tissue surrounding the device 10, which may cause significant pathology.

[0089] One or more fluid tubes 20 are connected to the fluid port 12 and preferably extend from below the housing 14 through the bottom surface 18. The fluid tubes 20 are preferably made of a flexible material to allow for easy placement during implantation. Examples of suitable materials for the fluid tubes 20 include polyurethanes with low protein binding, such as carbotan, or PEEK. The outer diameter of the fluid tubes 20 is between 0.2 and 3 mm, with about 1 mm or about 1.5 mm being preferred. The inner diameter of the fluid tubes 20 is between 0.1 and 1 mm, with about 0.2 mm or about 0.7 mm being preferred. Different dimensions may be preferred depending on the application.

[0090] In some situations, the device 10 may be used to administer a therapeutic agent to one or more regions of the brain, for example, by CED. In this situation, a smaller diameter for the fluid tube 20 is desirable. The smaller the diameter, the more fluid tubes 20 can be included in the same device 10 and fit into the groove 32. Also, minimizing the dead volume of the fluid tube 20 reduces the waste of therapeutic agent during each administration due to unused agent remaining in the fluid tube 20. In such applications, the outer diameter of the fluid tube 20 is 0.5-2 mm, preferably about 1 mm. In such applications, the inner diameter of the fluid tube 20 is 0.1-0.5 mm, preferably about 0.2 mm.

[0091] In some circumstances, the device 10 may be used to drain and / or circulate CSF. In this situation, it is preferable for the fluid tube 20 to have a larger diameter so that the CSF can be circulated and / or drained at an appropriate rate. In such applications, the outer diameter of the fluid tube 20 is 0.5-3 mm, preferably 0.6-2.5 mm, and more preferably about 1 mm. In such applications, the inner diameter of the fluid tube 20 is 0.3-1 mm, preferably 0.5-0.7 mm. For example, the inner diameter is at least 0.4 mm, optionally at least 0.5 mm, and more preferably at least 0.6 mm. The inner diameter of the fluid tube 20 may be large enough to allow the free flow of at least 10 ml of CSF per hour.

[0092] FIG. 3 shows the device 10 implanted. The bottom surface 18 engages with the outermost surface 30 of the skull. Thus, the device 10 is secured or attached to the outermost surface 30 of the skull. In FIG. 3, the device 10 is configured such that the bottom surface 18 engages and is attached to the outermost surface 30 of the skull using a number of screws 28. The screws 28 secure the device 10 to the outermost surface 30 through two or more holes in the subcutaneous region 17. The screws 28 in FIG. 3 are 2 mm in diameter, however, any suitable diameter screw may be used, for example, a screw 28 having a diameter of 1-3 mm, depending on the requirements of the device 10. Optionally, the bottom surface 18 may be configured to engage and be attached to the outermost surface 30 of the skull using other means, for example, an adhesive.

[0093] Optionally, as shown in FIGS. 1-3, no portion of the housing 14 extends below the bottom surface 18. Thus, only the tips of the screws and fluid tubes 20 extend below the bottom surface 18 of the housing 14, all the way to the outermost surface 30 of the skull. This configuration has the advantage over prior art devices that the skull does not need to be precisely machined to create a precisely shaped hole to accommodate the device. This is typically done using a skull mounting fixture with a series of specialized cutting tools, using stereotactic or robotic guidance. Mounting the device on the surface of the skull greatly simplifies the implantation method and reduces the time of surgery, thereby reducing costs and the associated risks to the patient from prolonged anesthesia and infection. Additionally, the device 10 can be placed in areas of the skull where the bone is thin, which is not possible with prior art devices that require a recess of a specific depth to be machined into the skull. Similarly, the device can be placed in the skulls of children and babies, whose skulls are very thin.

[0094] As shown in FIG. 3, the fluid tube 20 can be configured to bend to run along a groove 32 formed in the outermost surface 30 of the skull. Preferably, the fluid tube 20 is bent at approximately 90 degrees. The groove 32 can extend from the implantation site where the device 10 is implanted and from below the bottom surface 18. The fluid tube 20 extends through the bottom surface 18 below the housing 14 and into the groove 32. By running in a bend within the groove 32, the fluid tube 20 can exit from below the device 10 and connect to a corresponding implanted cannula or catheter. The fluid tube 20 is preferably configured to bend at a point below the bottom surface 18, e.g., the fluid tube 20 enters the groove 32 at a point below the bottom surface 18. This can further protect the fluid tube 20 and its entry point into the groove 32, further reducing the risk of infection. The groove 32 is preferably filled with bone cement (e.g., acrylic cement) before the fluid tube 20 is placed therein. The cement seals and holds the portion of the fluid tube 20 proximal to the device 10 in the desired position within the groove 32. Filling the groove 32 with bone cement also restores the integrity of the outermost surface 30 of the skull and reduces the risk of infection.

[0095] Advantageously, by housing the bends in the fluid tubes 20 in grooves 32 formed in the outermost surface 30 of the skull, rather than within the device 10 itself, the size of the device 10 can be significantly reduced both above and below the skull surface. This is advantageous where the skull is thin. For example, a child's skull is typically 2mm thick, and a bulky device that extends below the skull surface as disclosed in the prior art would risk compressing the brain.

[0096] It is possible that the inner surface (inner table) of the skull may be breached when forming the groove 32. In this case, the fluid tube 20 may be partially below the inner surface of the skull even though no portion of the housing 14 is below the lowermost surface 18 of the device 10. However, it is preferred that no portion of the device 10 extends through the inner surface of the skull when the lowermost surface 18 of the housing 14 is engaged with the outermost surface 30 of the skull. This reduces the chance of irritation or infection to the brain.

[0097] Furthermore, configuring the fluid tube 20 to run along the groove 32 in a curved manner means that the fluid tube 20 is fixed within the groove for a distance beneath the skin away from the housing 14. This reduces movement of the fluid tube 20 that may disturb the skin around the device 10 and prevent the skin from sealing around the device 10. This significantly reduces the risk of infection or marsupialization around the device 10. This is particularly true in comparison to some known devices in which the tube extends subcutaneously from the housing over the surface of the skull. To reinforce this advantage, optionally, no portion of the fluid tube 20 extends outside the housing 14 (i.e., does not exit the housing 14 past the outer surface of the housing 14) except through the lowermost surface 18. As a result, the device 10 is configured such that no portion of the fluid tube 20 extends outside the housing 14 (i.e., does not exit the housing 14 past the outer surface of the housing 14) above the outermost surface 30 of the skull when the device 10 engages the outermost surface 30 of the skull.

[0098] As shown in FIGS. 1 and 3, the bottom surface 18 of the housing 14 may include a plurality of teeth 34 for engaging the outermost surface 30 of the skull. The teeth 34 grip the outermost surface 30 of the skull and provide increased stability to the device 10. The inventors have recognized that the relative fixation of the device 10 and the skin greatly enhances integration of the device 10 with the dermis of the skin. The integration and relative fixation of the dermis reduces the risk of marsupialization around the device 10, which in turn greatly reduces the risk of complications such as infection. Additionally, the teeth 34 accommodate irregularities in the outermost surface 30, greatly reducing the shearing effect on the screws 28 or any attachment means used to engage the bottom surface 18 of the housing 14 with the outermost surface 30 of the skull. The feature that no portion of housing 14 extends below bottom surface 18, combined with fixation of device 10 to the skull surface, for example by screws 28 passing through subcutaneous tissue 17, provides stability for device 10 even in thin skulls.

[0099] The teeth 34 constitute a roughening of the lowermost surface 18 of the housing 14. There may be two or more teeth 34. Preferably, the plurality of teeth 34 are distributed over the lowermost surface 18, for example distributed over at least 50%, preferably at least 70%, more preferably at least 80% of the area of ​​the lowermost surface 18. The plurality of teeth may be comprised of a large number of small teeth 34. The teeth 34 may be sharpened to facilitate engagement with the outermost surface 30 of the skull. The teeth 34 may have a height (i.e., an extension distance extending from the lowermost surface 18) of less than 3 mm, preferably less than 1 mm. The teeth 34 are driven into and penetrate the outermost surface 30 of the skull when the bone fixation screw 28 is tightened, thereby fixing the device 10 to the outermost surface 30 in a desired position. In addition to improving the immediate stability of the device 10, the penetration of the outermost surface 30 by the teeth 34 promotes bone integration for long-term stability.

[0100] The device may be engaged to the skull via a layer of acrylic cement, which acts to fill any gaps between the teeth 34, typically between the bottom surface 18 and the outermost surface 30 of the skull, and may also provide an adhesive effect. When used in this manner, the acrylic cement may also provide a sealing effect.

[0101] 4 shows an exploded view of an embodiment of device 10 including septum 22 sealing fluid port 12 and further including cap 36. Cap 36 is configured to engage exterior portion 16 of housing 14 and compress septum 22 when installed on the device.

[0102] In general, septum sealing devices may be configured to apply a high compressive pressure to the septum so that it seals adequately when the needle is removed. This high compressive pressure is applied by the housing of the device radially in the plane of the septum (i.e., perpendicular to the direction in which the needle is being inserted through the septum). That is, the septum is forced tightly against the diameter of the needle being forced through it, ensuring a seal around the needle. However, such high compressive pressure within the septum may impede the radial displacement of the hollow needle as it passes through the septum, which may result in the hollow needle scraping away the septum material and blocking the needle and / or port. Thus, the high compressive force (which is useful in itself to ensure the sealing effect of the septum) may lead to damage to the septum as it interacts with the needle. Furthermore, when a hollow needle is inserted through the septum into a port, the compressive force on the septum material at the entrance to the septum-sealed port increases significantly. As a result, the septum material is forced into the port. Fragments of the septum material may shear off and obstruct fluid flow through the port. The shear forces on the compressed septum material with repeated needle passes can produce wear debris that can eventually obstruct flow through the port or be carried to the CNS, causing localized inflammation. Degradation of the compressed septum from repeated needle passes also reduces its effectiveness as a fluid and hermetic seal, posing risks to the patient and shortening the lifespan of the device.

[0103] To address these issues with septum sealing devices, the present device 10 can include a cap 36 configured to engage the exterior 16 of the housing 14 and compress the septum 22 when the cap 36 is installed. The cap 36 is configured to compress the septum 22 by exerting a force perpendicular to the plane of the septum 22, i.e., parallel to the direction in which a needle is intended to be inserted through the septum 22. In this way, the device 10 uses the protective cap 36 to exert a compressive force on the septum 22, rather than exclusively compressing the septum 22 when it is installed in the device 10 (e.g., using only radial compression). This means that the septum 22 can be made thinner and more flexible while still maintaining an effective seal (preventing fluid leakage and air ingress) when the cap 36 is installed. The septum 22 can be subjected to tension and / or compression only from the cap 36. That is, when the cap 36 is not engaged with the device 10, the septum 22 is not subjected to significant compression and / or tension forces. This in turn reduces the likelihood of coring or shear fragmentation of the septum 22, while still providing an airtight seal of the septum 22 and fluid port 12 when the device 10 is not in use.

[0104] This configuration may allow a relatively large diameter needle, e.g., 1 mm diameter, to pass through the septum 22 while reducing the likelihood of perforating the septum 22. This configuration may also allow for the use of smaller, more delicate needles than the prior art because less force is required to advance the needle through the septum 22, potentially allowing for a smaller device 10 and the use of more needles 24 per single device 10. When installed, the cap 36 also serves to protect the septum 22 from external trauma and UV damage.

[0105] The cap 36 may include one or more protrusions 33 (not visible in FIG. 4), e.g., annular ridges. The protrusions 33 may be configured to compress the septum 22, e.g., by creating a localized compression on the septum 22. The protrusions 33 may be configured to create a localized compression at the entrance to the fluid port 12. The protrusions 33 may compress the septum 22 around a region of the septum 22 where the needle 24 advances through the septum 22. For example, if the septum 22 is a pre-pierced or split septum, the region may include a perforation or break in the septum 22. The protrusions 33 may compress the septum 22 from a side of the septum 22 that faces the exterior of the housing 14. In the case where the device 10 comprises a plurality of fluid tubes 20 connected to the fluid ports 12, the device 10 may comprise a plurality of protrusions 33 configured to individually seal each fluid tube 20 and prevent cross-leakage of fluid between the fluid tubes 20. The protrusions 33 may be provided by removable components of the cap 36, such as the disks 38 in the embodiment of FIG. 4. In the case where the housing 14 comprises protrusions 25 configured to compress the septum 22 as described above, the protrusions 25 of the housing 14 and the protrusions 33 of the cap 36 may have matching shapes and / or sizes to compress and interact with the septum 22 between the two sets of protrusions 25, 33. The removable components may be manufactured from metal or plastics such as polytetrafluoroethylene (PTFE). This configuration may simplify manufacturing by allowing only the removable components to need to be changed for different configurations of the device 10 having different shapes and / or numbers of fluid tubes 20. The septum contacting surfaces in the cap 36 may be antimicrobial, for example by impregnation with silver.

[0106] The cap 36 may be configured to provide a seal around the septum 22, for example, by sealing around the septum. The cap 36 may include a seal member 19 (not visible in FIG. 4, but visible in FIG. 9) for providing a (preferably air-tight) seal between the cap 36 and the exterior body portion 16 of the housing 14. The seal member 19 may be a compliant silicone or polyurethane ring attached to the underside of the cap 36. The seal member 19 may be configured to engage a proximal surface of the exterior body portion 16 of the housing 14. When the cap 36 is engaged to the exterior body portion 16, the seal member 19 is compressed between the exterior body portion 16 of the housing 14 and the cap 36 to form a (preferably air-tight) seal around the septum 22. The seal around the septum 22 seals (preferably air-tight) the area or volume around the septum 22, thereby preventing access of fluids or gases to the septum 22 from outside the device 10. This further helps ensure surface cleanliness of septum 22, reducing the risk of dirt, debris, or pathogens being introduced into the CNS via fluid port 12. As with the septum contacting surface in cap 36, sealing member 19 may have antimicrobial properties, for example via silver impregnation.

[0107] When the device 10 is used to deliver or extract fluids to or from the CNS, the cap 36 is removed. Preferably, the septum 22 is washed with a disinfectant solution and the needle 36 is inserted through the septum 22 and into communication with the fluid port 12 to transfer the fluid. During this transient exchange while the cap 36 is removed, the septum 22 only needs to exert sufficient pressure to maintain a fluid-air seal to counter the intracranial pressure. Since intracranial pressure is typically between 7-15 mmHg and can rise up to 25 mmHg, a relatively thin and flexible septum 22 is sufficient to maintain an airtight seal. Depending on the desired application, the septum 22 can be chosen to be sufficiently flexible to allow a small amount of fluid to leak from the fluid port 12 while the septum 22 is exposed without the cap 36 or needle 24 in place. This can be advantageous as a small outward flow of liquid further reduces the possibility of unwanted material passing through the fluid port 12 to the CNS.

[0108] The cap 36 may be configured to engage the external body 16 with a mechanical connection. The mechanical connection may comprise one or more of a thread, a snap-fit ​​connection, an interference-fit connection, and a grub screw. If a thread is used, the thread may be a single entry thread or a multiple entry thread. In FIG. 4, the mechanical connection comprises a dual thread 40. An example of a suitable thread is a Spiralock thread provided by Spiralock Corp. The mechanical connection may be tamper-evident, for example, requiring a special or proprietary tool to install and remove the cap 36. The mechanical connection may comprise a first connection structure on the cap 36 and a second connection structure on the external body 16. The cap 36 may be configured to engage the external body 16 by engagement of the first and second connection structures. In the embodiment of FIG. 4, the second connection structure is provided by a male dual thread 40. The first connection structure is provided by a corresponding female thread on the cap 36.

[0109] The mechanical connection can be configured such that a predetermined compressive force is applied to the septum 22 when the cap 36 is engaged with the exterior body 16. The predetermined force can be sufficient to compress the septum 22 to create an airtight seal, but not so great as to risk damaging the septum 22.

[0110] The mechanical connection can be configured to provide an indication when the mechanical connection is exerting a predetermined force, i.e., when the mechanical connection is fully engaged with the external body 16. This can use visual markings or tactile feedback when the mechanical connection reaches a predetermined position. Additionally or alternatively, the mechanical connection can be configured such that it is not possible to exert more than a predetermined force, for example, by providing a physical limit to how tightly the mechanical connection can be engaged.

[0111] The mechanical connection may be configured to reversibly secure the cap 36, preferably in a position where a predetermined force is applied. This may prevent the cap 36 from loosening while the device 10 is not in use and may ensure consistent application of the predetermined force. The reversible locking may also contribute to providing tactile feedback when the cap 36 is fully engaged with the external body 16, as described above. Combined with the tamper-resistant feature, the reversible locking may also reduce the risk of patient tampering with the cap 36 and / or the device 10.

[0112] The cap 36 may include a tool-engaging structure that allows a tool to engage the cap 36 to tighten or loosen the cap 36. In FIG. 4, the tool-engaging structure includes radial grooves 42 into which a specialized screwdriver head can be secured. The specialized nature of the tool-engaging structure may contribute to the tamper-resistant properties and mechanical connection of the cap 36. The tool-engaging structure also allows for the use of tools, which provides the advantage of easier handling of small components of the device 10 and reduces direct contact between the user and components of the device 10, reducing the risk of bacterial contamination.

[0113] FIG. 5 illustrates an embodiment in which the device 10 includes a connector cap 44 configured to engage the exterior part 16 of the housing 14. The connector cap 44 may include a needle 24 configured to fluidly connect with the fluid tube 20 via the fluid port 12. The needle 24 is a hollow needle through which fluid can pass. The connector cap 44 has a similar shape and size as the cap 36. This may be convenient in some circumstances, but is not required. Preferably, when the exterior part 16 and / or the connector cap 44 are substantially cylindrical, the needle 24 is coaxially positioned within the connector cap 44. This aids in correct positioning of the needle 24, as it reduces constraints on the angular position of the connector cap 44 relative to the exterior part 16.

[0114] The connector cap 44 may be configured to engage the external body 16 with a mechanical connection. The mechanical connection may comprise one or more of threads, a snap-fit ​​connection, an interference-fit connection, and a grub screw. If threads are used, the threads may be single entry or multiple entry threads. The mechanical connection may be tamper-proof, as described above for the cap 36. The mechanical connection may comprise a first connection structure on the connector cap 44 and a second connection structure on the external body 16. The connector cap 44 may be configured to engage the external body 16 by engagement of the first and second connection structures. In the embodiment of FIG. 5, the second connection structure is provided by a male double thread 40. The first connection structure is provided by a corresponding female thread 41 of the connector cap 44.

[0115] The mechanical connection may be configured to advance the needle 24 a predetermined distance through the septum 22 upon engagement of the connector cap 44 with the exterior body 16. The predetermined distance may be large enough to allow the needle 24 to fluidly connect with the fluid tube 20 via the fluid port 12, but not so large as to risk damage to the fluid port 12, the fluid tube 20, or the needle 24 by forcing these components together in an unintended manner.

[0116] The mechanical connection can be configured to provide an indication when the needle 24 has been advanced a predetermined distance, i.e., when the mechanical connection is fully engaged with the external body 16. This can use visual markings or tactile feedback when the mechanical connection reaches a predetermined position. Additionally or alternatively, the mechanical connection can be configured to prevent the needle 24 from being advanced beyond a predetermined distance, for example, by providing a physical limit on the distance the needle 24 can be advanced.

[0117] The mechanical connection may preferably be configured to reversibly lock the connector cap 44 in place once the needle 24 has advanced a predetermined distance through the septum 22. The reversible locking may also serve to provide tactile feedback when the connector cap 44 is fully engaged with the exterior body 16. The reversible locking may be achieved using a lockable screw or the like.

[0118] The connector cap 44 may be configured to compress the septum 22 when the connector cap 44 engages the exterior body part 16 of the housing 14. The connector cap 44 may compress the septum 22 by applying a force in a direction perpendicular to the plane of the septum 22, i.e., parallel to the direction in which the needle 24 of the connector cap 44 is inserted through the septum 22, in a manner similar to that described for the cap 36 above. To accomplish this, the connector cap 44 may include one or more protrusions configured to compress the septum 22 around the needle 24 once the needle 24 has advanced a predetermined distance. The protrusions may be in the form of an annular ridge around the needle 24. The protrusions may be configured to compress the septum 22 by creating a localized compression on the septum 22. The protrusions may be configured to provide a localized compression at the entrance of the fluid port 12. The protrusions may compress the septum 22 around a region of the septum 22 where the needle 24 advances through the septum 22. For example, if the septum 22 is a pre-pierced or split septum, the region may include a perforation or a break in the septum 22. The protrusion may compress the septum 22 from the side of the septum 22 that faces the exterior of the housing 14.

[0119] Fluid from the needle 24 may be delivered at a pressure higher than normal intracranial pressure during injection in order to force it into the CNS. As a result, the septum 22 may not normally provide sufficient sealing force around the needle to prevent leakage of fluid. This may occur particularly when a relatively thin and flexible septum 22 is used in the device 10 intended for use with the cap 36. Providing protrusions on the connector cap 44 to compress the septum 22 around the needle 24 means that when fluid is introduced through the second fluid tube 46 and the needle 24, the fluid will not leak to the atmosphere. When the housing 14 includes protrusions 25 configured to compress the septum 22 around the area where the needle 24 advances through the septum 22, the protrusions 25 of the housing 14 and the protrusions of the connector cap 44 may have matching shapes and / or sizes such that there is interaction between the two sets of protrusions to further compress the septum 22.

[0120] Connector cap 44 may include tool engagement structure that allows a tool to engage connector cap 44 to tighten or loosen connector cap 44, substantially as described for cap 36. In Figure 5, the tool engagement structure includes radial grooves 42 into which a specialized screwdriver head can be secured.

[0121] 5, connector cap 44 may further include a second fluid tube 46 in fluid communication with needle 24 and extending from the opposite side of connector cap 44 from needle 24. Second fluid tube 46 provides an extracorporeal extension tube for connecting device 10, via fluid port 12 and fluid tube 20, to a source of fluid supply (or drainage) to (or from) the CNS.

[0122] The connector cap 44 may further include a plurality of grooves 42 configured to hold the second fluid tube 46, as shown in the inset of FIG. 5. The plurality of grooves 42 preferably comprises four grooves, more preferably six grooves. The second fluid tube 46 is preferably flexible (similar to the fluid tube 20), and the grooves 42 may be configured to hold the second fluid tube 46 by press-fitting the second fluid tube 46 into one of the grooves 42. The grooves 42 may be substantially horizontal. The grooves 42 allow the second fluid tube 46 to enter the connector cap 44 substantially vertically from the bottom, but to exit the connector cap 44 laterally. The configuration of the connector cap 44 and the grooves 42 allows the second fluid tube 46 to bend at a controlled radius to prevent tangling of the second fluid tube 46, and allows the second fluid tube 46 to be held along a desired radial trajectory for connection to a fluid source (or drain source). This configuration provides a compact, low profile means for connecting to a pump, such as an ambulatory pump for chronic drug administration. In the example of Figure 5, groove 42 also functions as a tool engagement structure, as described above in connection with cap 36.

[0123] The device 10 with the connector cap 44 may be provided as part of a kit for managing the introduction or removal of fluids with a dedicated driver for facilitating engagement of the connector cap 44 with the external body 16. If the connector cap 44 includes grooves 42, the dedicated driver preferably has teeth at radial positions corresponding to the grooves 42 of the connector cap 44. The dedicated driver is preferably hollow and includes one less tooth than the number of grooves 42 of the connector cap 44. This allows the dedicated driver to engage the connector cap 44 when secured in place in the groove without interfering with the second fluid tube 46. This is because the second fluid tube 46 can extend radially through the opening provided by the missing teeth of the driver. The dedicated driver also provides the advantage of easier handling of the small components of the device 10, reducing direct contact between the user and the components of the device 10, reducing the risk of bacterial contamination. In practice, the connector cap 44 may be supplied separately from other parts of the device 10, such as the housing, in a kit including, for example, the connector cap 44 and the driver 60. Providing the connector cap 44 separately may be appropriate, for example, if the connector cap 44 is supplied as a sterile consumable item intended for single use only for injection or removal of fluid.

[0124] The connector cap 44 and the connector cap 44 with a single needle 24 centrally disposed coaxially with the external body cavity 16 are best suited when the device 10 has a single fluid tube 20. When multiple fluid tubes 20 are present within the device 10, a connector 50 and separate guide member 48 may be provided, as shown in Figure 6. However, the use of the guide member 48 and connector 50 is not limited to use when multiple fluid tubes 20 are present, and may also be used with a device 10 having only a single fluid tube 20.

[0125] 6 illustrates an embodiment of device 10 including a guide member 48 and a connector 50 configured to engage with guide member 48. Guide member 48 and / or connector 50 may be made from a plastic (such as PEEK) or a metal such as titanium.

[0126] The connector 50 may include one or more needles 24 configured to fluidly connect with the respective fluid tubes 20 via the fluid ports 12. In FIG. 6, the connector 50 includes four needles 24 and the device 10 includes four fluid tubes 20 (not shown in FIG. 6 but located inside the external body 16). Similar to the connector cap 44 described above, the connector 50 may include one or more second fluid tubes 46 in fluid communication with each of the needles 24, thereby allowing the needles 24 to be connected to a source (or drain) of fluid. For example, the connector 50 shown in FIG. 6 includes four second fluid tubes 46, one in fluid communication with each of the four needles 24.

[0127] If the device 10 includes a septum 22 sealing the fluid port 12, the connector 50 and guide member 48 can be configured such that upon engagement of the connector 50 and guide member 48, each of the needles 24 is advanced a predetermined distance through the septum 22. The predetermined distance may be large enough to allow the needles 24 to fluidly connect with the fluid tube 20 via the fluid port 12, but not so large as to risk damaging the fluid port 12, the fluid tube 20, or the needles 24 by forcing these components together in an unintended manner.

[0128] The connector 50 may engage with the guide member 48 via one or more of the following mechanical connections: a screw, a snap-fit ​​connection, an interference fit connection, and a grub screw. If a screw is used, the screw may be a single entry screw or a multiple entry screw. The mechanical connection may be configured to provide an indication when the needle 24 has advanced a predetermined distance, i.e., when the mechanical connection is fully engaged with the external body 16. This may use visual markings or tactile feedback when the mechanical connection reaches a predetermined position. Optionally or alternatively, the mechanical connection may be configured such that the needle 24 cannot advance beyond a predetermined distance, for example, by providing a physical limit on the distance the needle 24 can advance. The mechanical connection may be configured to reversibly lock the connector 50 in a position where the needle 24 has advanced a predetermined distance through the septum 22. The reversible locking also contributes to providing tactile feedback when the connector 50 is fully engaged with the guide member 48.

[0129] The connector 50 may include one or more protrusions for compressing the septum 22 around the needle 24 once the needle has advanced a predetermined distance. The protrusions may be in the form of annular ridges around each needle 24. Fluid from the needle 24 may be delivered at a pressure higher than normal intracranial pressure during injection to force the fluid into the CNS. As a result, the septum 22 may not normally provide a sufficient sealing force around the needle to prevent leakage of the fluid. This may be especially true when a relatively thin and flexible septum 22 is used in the device 10 intended for use with the cap 36. Providing protrusions on the connector 50 to compress the septum 22 around the needle 24 means that when fluid is introduced through the second fluid tube 46 and the needle 24, there is no leakage to the atmosphere or cross contamination of the fluid between the needle 24 and the fluid tube 20.

[0130] The guide member 48 may be integrally formed with the exterior body portion 16 of the housing 14. Alternatively, as shown in FIG. 6, the guide member 48 may be removably attached to the exterior body portion 16 of the housing 14, for example, using a mechanical connection. The mechanical connection may comprise one or more of a thread, a snap-fit ​​connection, an interference-fit connection, and a grub screw. If a thread is used, the thread may be a single entry thread or a multi-entry thread. For example, in FIG. 6, the mechanical connection comprises a grub screw 52 on the guide member 48 configured to engage an outer surface of the exterior body portion 16. The mechanical connection may comprise a first connection structure on the guide member 48 and a second connection structure on the exterior body portion 16, such that engagement of the first and second connection structures removably attaches the guide member 48 to the exterior body portion 16. In FIG. 6, the mechanical connection comprises a first and second connection structure in addition to the grub screw 52. The second connection structure may be provided by three hemispherical protrusions 56 on the external body 16, and the first connection structure may be provided by two conical recesses (not visible in FIG. 6) on the underside of the guide member 48 and one conical recess on the distal end of the grub screw 52. Tightening of the grub screw drives all three conical recesses of the guide member 48 and the grub screw 52 onto the three protrusions 56 on the external body 16 in a unique and repeatable orientation.

[0131] When connector 50 includes multiple needles 24 and device 10 includes multiple fluid tubes 20, the axis of connector 50 must be properly aligned with the axis of housing 14 to ensure that each needle 24 makes the correct fluid connection with a corresponding fluid tube 20 via fluid port 12. This is necessary to ensure that the correct fluid is delivered to (or removed from) the correct region of the CNS. To accomplish this, connector 50 and guide member 48 are configured such that, upon engagement of connector 50 and guide member 48, each of needles 24 assumes a predetermined position relative to a respective one of the fluid tubes 20.

[0132] The guide member 48 can take a variety of forms to achieve the correct relative alignment. For example, the guide member 48 can include a plurality of guide posts 58. The connector 50 can then be configured to engage with the guide posts 58. The use of the guide posts 58 reduces angular deviations that occur when engaging the connector 50, as compared to prior art designs in which a relatively short, wide cylinder is engaged into a recess in the skull. This is especially true when the guide posts 58 are designed with a large aspect ratio of length to diameter. The length to diameter ratio of the guide posts 58 can be at least 2:1, and preferably at least 3:1.

[0133] In Figure 6, connector 50 includes a cam 54 configured to engage a guide post 58 (two guide posts 58 in the case of Figure 6) present on guide member 48. Cam 54 and guide posts 58 are configured such that rotation of cam 54 advances needle 24 a predetermined distance to a predetermined position. This process is shown in further detail in Figures 7 and 8.

[0134] In FIG. 7, the guide member 48 is attached to the external body 16 by engagement of the first and second connecting structures and tightening of the grub screw 52 with a driver 60. The connector 50 can then be engaged to the guide member 48. In FIG. 8, the connector 50 is in the process of being engaged to the guide member 48. The cam 54 engages the guide post 58 and as the cam 54 rotates, an inclined surface in the cam 54 interacts with a corresponding structure on the end of the guide post 58, thereby fully engaging the connector 50 with the guide member 48 and advancing the needle 24 longitudinally a predetermined distance. Rotation of the cam 54 relative to the remainder of the connector 50 can be accomplished manually by a user grasping the cam 54 or with a tool or actuator. The cam 54 and the guide post 58 may be further configured to reversibly lock the needle 24 in position once the needle 24 has advanced the predetermined distance.

[0135] After fluid transfer, the connector 50 can be removed from the guide member 48 by rotating the cam 54 to release the lock and withdrawing the needle 24 through the septum 22. During this operation, any protrusions that may be present on the connector 50 will first disengage from the septum 22 as the cam 54 is released, reducing the compressive force on the septum 22. The needle 24 can then be removed with less shear force on the septum 22, reducing wear on the septum 22.

[0136] If guide member 48 is removably attached to the extracorporeal portion 16, it is similarly important that guide member 48 be properly aligned with the extracorporeal portion 16 to ensure that needle 24 of connector 50 fluidly connects with the correct one of the fluid tubes 20. Thus, the mechanical connections used to attach guide member 48 to the extracorporeal portion 16 can be configured such that guide member 48 assumes a predetermined position relative to the extracorporeal portion 16 upon attachment of guide member 48 to the extracorporeal portion 16.

[0137] The device 10 including the guide member 48 and the connector 50 may be provided as part of a kit 62 for administration of fluid input or removal as shown in FIG. 16. The kit 62 may further include a driver 60 for facilitating engagement of the connector 50 with the guide member 48 and / or attachment of the guide member 48 to the exterior body 16. The kit 62 may further include an extension line 64 that may be connected to the second fluid line 46 to facilitate connection to a fluid source or drainage source located further away from the patient. In practice, the guide member 48 and the connector 50 may be supplied separately from other components of the device 10, such as the housing 14. Providing the guide member 48 and the connector 50 separately may be suitable, for example, when the connector 50 is supplied as a sterile consumable intended for a single use for fluid input or removal.

[0138] 9-13 show another embodiment of the device 10 with the cap 36, which may include two fluid tubes 20. This embodiment may include two fluid tubes 20 with larger diameters and may be particularly suitable for intrathecal delivery of therapeutic agents. The embodiment shown in FIGS. 9-13 is substantially similar to the embodiment described above, but the shape of the outer body 16 and the cap 36 is different and not cylindrical. In this embodiment, the outer body 16 may be composed of a substantially flat straight portion and a curved U-shaped portion. When viewed from above, the straight edges appear straight and the curved edges appear curved. The non-circular shape allows for proper rotational positioning of the engagement cap 36 or guide member 48 when engaging with the outer body. The features of the above-described embodiments may be combined or used with the embodiment of FIGS. 9-13 as appropriate.

[0139] In Figure 9, protrusions 33 of cap 36 are visible. Because the embodiments of Figures 9-13 include multiple fluid tubes 20, cap 36 may include multiple protrusions 33 configured to individually seal each fluid tube 20 and prevent cross-leakage of fluid between the fluid tubes 20.

[0140] In the embodiment of FIG. 9, the mechanical connection by which the cap 36 engages the external body 16 may include a grub screw 52 in the cap 36 and first and second connection structures. The first connection structure may be provided by a hemispherical protrusion 56 on the cap 36. The second connection structure may be provided by a recess 31 provided on the outer surface of the external body 16. The hemispherical protrusion 56 and the grub screw 52 may be configured to engage the recess 31 to secure the cap 36 to the external body 16. The hemispherical shape of the protrusion 56 may be advantageous in that it allows the protrusion 56 to act as a fulcrum to rotate the cap 36 to the closed position. This is also facilitated by having two or more first connection structures (in this case, two hemispherical protrusions 56) located in a first plane and two or more corresponding second connection structures (in this case, two recesses 31) located in a second plane.

[0141] FIG. 10 is an exploded view of the device 10 with the cap 36 at various levels of disassembly. The fluid port 12 may include a funnel 70 attached to the proximal end of each fluid tube 20 to help guide the needle 24 into fluid connection with the respective fluid tube 20. The funnel 70 may be attached to the respective fluid tube 20 via a bayonet fitting, although in general any suitable fluid-tight fitting may be used. After the funnel 70 is attached to the fluid tube 20, the funnel portion 70 with the attached fluid tube 20 may be press-fit into channels in the housing 14. The channels may be provided by profiled holes in the housing 14. If the housing 14 includes a molded portion 26, the channels may be provided at least in part by the molded portion 26.

[0142] The passageway and funnel 70 may be configured such that when the funnel 70 is fully seated within the passageway, the rim of the funnel 70 protrudes above the inner planar surface of the exterior 16 of the housing 14 that contains the septum 22. The protruding rim may then provide a protrusion 25 in the housing 14 that may act as a valve seat for the septum 22 around where the needle 24 penetrates the septum 22. This configuration has the advantage of not requiring a separate component within the housing 14 to provide the protrusion 25 that needs to be integrated into or sealed to the housing 14, thereby reducing manufacturing complexity.

[0143] In the process of pressing each of the funnels 70 into the passages of the housing 14, each fluid tube 20 is compressed between the bayonet fitting of the funnels 70 within the bore of the fluid tube 20 and the walls of the passage. This further secures the fluid tube 20 to the housing 14 and forms a seal (preferably effective to seal against fluids and gases, preferably an airtight seal) between the outer surface of the fluid tube 20 and the inner surface of the housing 14. The funnels 70 and corresponding passages thereby provide the projections 25, sealing the outer surface of the fluid tube 20 to the inner surface of the housing 14 and providing a simple, combined solution for securing the fluid tube 20 in place within the housing 14.

[0144] Figure 11 is a cross-sectional view and a top view of the device with guide member 48 and connector 50 engaged with exterior body part 16 of housing 14. In this view, protrusions 55 of connector 50 are shown compressing septum 22. Figure 12 is an exploded perspective view of device 10 with guide member 48 and connector 50, similar to Figure 6. Figure 13 shows engagement of guide member 48 and connector 50, similar to Figures 7 and 8.

[0145] FIG. 14 shows the positional relationship of the device 10 of FIGS. 9-13 once implanted and connected to a first catheter 80 and a lumbar catheter 82.

[0146] The device 10 may be provided as part of a kit for implanting the device 10 to provide fluid access to the central nervous system of a mammal, the kit including the device 10 according to any of the preferred embodiments described above and a quantity of acrylic cement.

[0147] As described above, the fluid tube 20 can be configured to run along a groove 32 formed in the outermost surface 30 of the skull. Once the fluid tube 20 is positioned within the groove 32, the groove is preferably filled with acrylic cement. However, acrylic cement is typically supplied for orthopedic surgery in quantities much larger than necessary to fill the groove 32. This can result in significant waste of acrylic cement due to the limited time of use of the acrylic cement after opening. Thus, by supplying a kit consisting of the device 10 and an appropriate amount of acrylic cement to fill the groove, waste of acrylic cement and associated costs can be significantly reduced. The kit also makes the surgery to implant the device 10 quicker and more convenient since the appropriate amount of acrylic cement can be easily obtained. This eliminates the need to open a large package of acrylic cement and measure out the appropriate amount during surgery. Since the time of use of the acrylic cement is relatively short, it is necessary to measure the acrylic cement during surgery since the cement cannot be pre-measured before surgery. Preferably, the acrylic cement includes an antibacterial agent. This reduces the possibility of infection after implantation of the device 10.

[0148] The acrylic cement may be included with the device 10 in a kit as shown in FIG. 16 that also includes other components of the device 10, such as the guide member 48 and the connector 50. The kit may further include the cap 36. The kit may also include a tool such as a driver 60 for reversibly securing the guide member 48 or the cap 26 to the exterior 16 of the housing 14 of the device 10. The kit may further include a tool such as a spatula suitable for spreading the acrylic cement and removing excess cement. The kit may further include fittings used to connect the fluid tube 20 to a catheter or cannula for delivery or removal of fluids from the CNS. Such fittings may include bayonet-type fittings. The fittings may be marked with unique identifiers (e.g., numbers or color bands) to distinguish them from one another and ensure that the correct fluid tube 20 is connected to the correct catheter or cannula.

[0149] A method of assembling the device 10 may be provided as follows. The method may include inserting the proximal end of the fluid tube 20 into the housing 14 through the bottom surface 18. As described in relation to FIG. 10, if the device 10 includes one or more funnels, the method may include fitting the funnels 70 to the respective fluid tubes 20, for example by fitting a bayonet fitting of the funnels 70 inside the fluid tubes 20 to form an interference fit. The method may further include fitting the funnels 70 into the respective passages in the housing 14. Preferably, the fitting of the funnels 70 into the passages is performed such that the walls of each fluid tube 20 are compressed between the funnels 70 and the passages. This forms a strong permanent connection. Fitting the funnels 70 into the passages may include pressing the funnels 70 into the passages.

[0150] If the device 10 includes a shaped portion 26, the method may include the step of mating the shaped portion 26 to the exterior body portion 16 of the housing 14. If the shaped portion 26 provides a passageway for the funnel 70, the shaped portion 26 may be mated to the exterior body portion 16 before or after mating the funnel 70 to the passageway.

[0151] The method may include fitting the septum 22 to the exterior 16 of the housing 14. This step may be performed before or after fitting the shaped portion 26 to the exterior 16, depending on the design of the housing 14. For example, in the device 10 of FIG. 4, the septum 22 is fitted to the housing 14 at the same time as or before the shaped portion 26. However, in the device of FIG. 10, the septum 22 may be attached after the shaped portion 26, if present. The method may include inserting a retaining member 23 into the housing 14 after the septum 22 and shaped portion 26 are fitted. Insertion of the retaining member 23 may compress the septum 22 around the edge of the septum 22.

[0152] A method for implanting a device for providing fluid access to the central nervous system of a mammal can be used to implant any of the devices 10 described above. Figure 17 shows a flow chart of the method, and Figure 18 visually illustrates several steps of the method. The device 10 is implanted at an implantation site in the skull. Preferably, the implantation site is post-auricular on the temporal bone or on the parietal bone. The method for implanting the device 10 is typically performed with the patient under anesthesia.

[0153] The method includes, at step S10, removing an area of ​​scalp at an implantation site large enough to accommodate the external part 16 of the housing 14 of the device 10. This is shown in FIG. 18a. After cleaning the skin at the selected implantation site with an antiseptic solution, the area of ​​scalp is removed. A punch hole may be formed, for example, by drilling through the scalp to the skull surface using a skin biopsy punch sized to accommodate the external part 16 of the device 10. If the external part 16 is substantially cylindrical, the skin biopsy punch may be a punch of a similar diameter to the external part 16, for example 2-7 mm in diameter, preferably 4 mm or 5 mm. The sharp cylindrical end of the punch marks the surface of the skull.

[0154] The method includes, in step S20, removing subcutaneous fat and hair follicles in a predetermined area around the implantation site. This is shown in FIG. 18b. This can be accomplished by inserting an ultrasonic aspirator through the punch hole. The predetermined area may comprise a substantially circular area having a radius of 0.5-2 cm, preferably about 1 cm from the center of the scalp removal area (i.e., punch hole). Removing subcutaneous fat and hair follicles is not essential, but is advantageous in reducing scalp mobility at the interface between the skin and the device 10. This promotes tissue adhesion and integration with the device 10.

[0155] The method includes, at step S30, forming a groove 32 in the outermost surface of the mammal's skull. The groove 32 may be formed by making a rostrocaudal incision in the scalp centered on the excised area of ​​the scalp. The scalp and periosteum are then retracted. Alternatively, a C-shaped incision with a radius of 1-3 cm, preferably about 2 cm, is made centered on the excised area of ​​the scalp and the scalp along with the periosteum is retracted. A radial groove 32 is then made in the skull from the center of the removed area of ​​the scalp. The groove can be formed with a 1-4 mm burr, preferably a 2 mm or 3 mm burr. The groove is made deep enough to accommodate one or more fluid tubes 20 of the device 10 below the outermost surface of the skull. The groove 32 extends from the implantation site toward a cannula that provides a fluid connection to the mammal's central nervous system. The groove 32 does not necessarily extend to the cannula. Preferably, the groove extends at least 5 mm, preferably at least 10 mm, toward the cannula to accommodate the fluid tube 20 that connects to the implanted cannula. The groove 32 does not penetrate the inner surface of the skull. The groove does not require a precisely defined shape or path and can be made by eye using hand-held tools. The tool can be equipped with a depth limiter to fix the depth of the groove, but otherwise the surgeon is free to determine the path of the groove.

[0156] The method includes connecting the fluid tube 20 of the device 10 to the cannula in step S40. Optionally, there may be multiple cannulas and the device 10 may include multiple fluid tubes 20 connected to each cannula respectively. This step is shown in FIG. 18c. If the device 10 includes a funnel as described in relation to FIG. 10, the method may include attaching the funnel 70 to the fluid tube 20 and / or attaching the funnel 70 to the passage in the housing 14. This step should be performed before the device is attached to the outermost surface 30 of the skull. It may be preferable to perform this step before the step S40 of connecting the fluid tube 20 to the cannula, as it is easier to attach the funnel 70 to the fluid tube 20 before connecting the fluid tube 20 to the cannula. Attaching the funnel 70 to the fluid tube 20 and / or attaching the funnel 70 to the passage in the housing 14 is preferably performed before implantation as part of the assembly of the device 10, as described above, but may also be performed during implantation in some circumstances.

[0157] The method includes, at step S50, filling the grooves 32 with acrylic cement. The grooves 32 are preferably slightly overfilled so that there is enough cement to fill any voids or gaps that may lead to infection.

[0158] The method includes inserting the fluid tube 20 (or multiple fluid tubes 20, if present) into the groove 32 in step S60. Step S60 of inserting the fluid tube 20 includes bending the fluid tube 20, for example a 90 degree bend, to run along the groove 32. The fluid tube is applied directly into the groove filled with cement, which may be squeezed out of the groove during insertion. The acrylic cement secures the fluid tube 20 and fills the intracranial space around the fluid tube 20 to prevent infection. Excess cement is removed from the skull surface and flush with the skull surface above the groove 32.

[0159] Optionally, step S60 of inserting fluid tube 20 into groove 32 may be performed after step S70 of attaching device 10. If desired, step S50 of filling groove 32 with acrylic cement may be performed after step S60 of inserting fluid tube 20 into groove 32 and / or step S70 of attaching device 10. However, this is not preferred because filling groove 32 with cement after inserting fluid tube 20 therein increases the likelihood of leaving voids around fluid tube 20 that may harbor infection.

[0160] As the fluid tube 20 is inserted into the groove 32, it displaces a portion of the uncured acrylic cement, forcing the cement under the bottom surface 18 of the device 10, for example, after or during installation S70 of the device 10. The compression forces the cement into any gaps in the skull surface and into the space between the bottom surface 18 of the housing 14 and the outermost surface 30 of the skull. This helps secure the device 10 to the skull and provides an airtight seal at the interface between the device 10 and the skull. This also ensures that the cement fills any spaces or voids around the bottom surface 18 of the device 10 and the fluid tube 20, so that no voids remain that could lead to infection.

[0161] The method includes, in step S70, engaging the bottom surface of the device 10 with the outermost surface 30 of the skull at the implantation site to attach the device to the skull. This is shown in FIG. 18d. Engaging the bottom surface of the device 10 may include attaching one or more screws 28 to the skull. Engaging the bottom surface 18 of the device 10 may also include, for example, using a hollow cylinder located on the exterior 16 of the housing 14 to press the bottom surface 18 into the outermost surface 30 of the skull and engage the subcutaneous tissue 17. This is particularly advantageous when the bottom surface 18 of the device 10 includes a plurality of teeth 34. Pressing the bottom surface 18 into the outermost surface of the skull in this manner presses the teeth 34 into the outermost surface 30, improving the engagement of the device 10 with the skull. In this step, acrylic cement may also be used at the interface between the bottom surface 18 of the housing and the outermost surface 30 of the skull. This further enhances adhesion and sealing.

[0162] The method includes step S80 of closing the wound created in step S30 forming the groove 32. This is shown in FIG. 18e). If a C-shaped flap with a central punch hole is created in step S30, the extracorporeal portion 16 of the device 10 is pushed into the flap hole as the flap is folded back before closing the periosteum and scalp with sutures. If a linear incision was made in step S30 centered around the scalp removal area, the periosteum and scalp are closed on either side of the punch hole.

Claims

1. 1. A device for providing fluid access to the central nervous system of a mammal, comprising: a fluid port that allows for the delivery or removal of fluid from the central nervous system; a housing having an exterior portion configured to pass through an opening in the mammal's skin to allow access to the fluid port and a lowermost surface configured to engage an outermost surface of a skull; a fluid tube connected to the fluid port and extending below the housing through the bottom surface; no portion of the housing extends below the lowermost surface; The device, wherein the fluid tube is configured to bend to run along a groove formed in the outermost surface of the skull.

2. 10. The device of claim 1, wherein when the lowermost surface of the housing engages the outermost surface of the skull, no portion of the device penetrates the inner surface of the skull.

3. An apparatus as described in claim 1 that satisfies at least one of the following a) and b): a) the lowermost surface is configured to engage and be attached to the outermost surface of the skull using a plurality of screws; b) the lowermost surface of the housing includes a plurality of teeth for engaging the outermost surface of the skull;

4. The device of claim 1 , wherein the fluid tube is configured to bend at a point below the lowermost surface.

5. 1. A device for providing fluid access to the central nervous system of a mammal, comprising: a fluid port that allows for the delivery or removal of fluid from the central nervous system; a housing having an exterior portion configured to pass through an opening in the mammal's skin to allow access to the fluid port and a lowermost surface configured to engage an outermost surface of a skull; a fluid tube connected to the fluid port and extending from the housing; The device wherein the lowermost surface of the housing comprises a plurality of teeth for engaging the outermost surface of the skull.

6. 6. The device of claim 5, wherein the plurality of teeth are distributed across the bottom surface, optionally across at least 50% of the area of ​​the bottom surface.

7. 10. The device of claim 1 or 5, further comprising a septum sealing the fluid port, and a cap configured to engage the exterior of the housing and compress the septum when the cap is attached.

8. 1. A device for providing fluid access to the central nervous system of a mammal, comprising: a fluid port that allows for the delivery or removal of fluid from the central nervous system; a housing having an exterior configured to pass through an opening in the mammal's skin and allow access to the fluid port; a fluid tube connected to the fluid port and extending from the housing; a septum sealing the fluid port; a cap configured to engage the exterior portion of the housing and compress the septum when the cap is attached; An apparatus comprising:

9. 9. The device of claim 8, wherein the cap is configured to compress the septum by applying a force perpendicular to the plane of the septum.

10. 9. The device of claim 8, wherein the cap is configured to engage the external body surface using a mechanical connection, and optionally the device satisfies at least one of the following: a) a) to c) a) the mechanical connection portion comprises a first connection structure on the cap and a second connection structure on the external body portion, the cap being configured to engage with the external body portion by engagement of the first connection structure with the second connection structure; b) the mechanical connection is configured to apply a predetermined compressive force to the septum when the cap is engaged with the extracorporeal body; c) said mechanical connection comprises one or more of a screw, a snap-fit ​​connection, an interference-fit connection, and a grub screw;

11. The device of claim 8 , wherein the cap is configured to provide a seal around the septum.

12. 9. The device of claim 1, further comprising a connector cap configured to engage with the exterior of the housing, the connector cap comprising a needle configured to fluidly connect with the fluid tube via the fluid port.

13. 13. The device of claim 12, wherein the connector cap is configured to engage the external body part using a mechanical connection, and optionally the device satisfies at least one of the following: a) a) to c) a) the mechanical connection portion comprises a first connection structure on the connector cap and a second connection structure on the external body part, the connector cap being configured to engage with the external body part by engagement of the first connection structure with the second connection structure; b) the device comprises a septum sealing the fluid port, and the mechanical connection is configured such that when the connector cap engages the exterior body, the needle advances a predetermined distance through the septum; c) said mechanical connection comprises one or more of a screw, a snap-fit ​​connection, an interference-fit connection, and a grub screw;

14. 13. The device of claim 12, wherein the device comprises a septum sealing the fluid port, and the connector cap is configured to compress the septum by applying a force perpendicular to the plane of the septum when the connector cap is engaged with the exterior of the housing.

15. The connector cap further comprises: a second fluid tube in fluid communication with the needle and extending from a side of the connector cap opposite the needle; and a plurality of grooves configured to hold the second fluid tube.

16. the fluid tube comprises one or more fluid tubes; the device further includes a guide member and a connector configured to engage the guide member, the connector comprising one or more needles configured to fluidly connect with respective ones of the fluid tubes via the fluid ports; 10. The device of claim 1 or 5, wherein the connector and the guide member are configured such that when the connector engages the guide member, each of the needles assumes a predetermined position relative to a respective one of the fluid tubes.

17. 1. A device for providing fluid access to the central nervous system of a mammal, comprising: a fluid port that allows for the delivery or removal of fluid from the central nervous system; a housing having an exterior configured to pass through an opening in the mammal's skin and allow access to the fluid port; A guide member; one or more fluid tubes connected to the fluid ports and extending from the housing; a connector configured to engage the guide member; the connector comprises one or more needles configured to fluidly connect with each of the fluid tubes via the fluid ports; The connector and the guide member are configured such that when the connector engages the guide member, each of the needles assumes a predetermined position relative to a respective one of the fluid tubes.

18. the device includes a septum sealing the fluid port; 18. The device of claim 17, wherein the connector and the guide member are configured such that when the connector engages the guide member, each of the needles advances a predetermined distance through the septum.

19. The guide member includes a plurality of guide posts, the connector includes a cam configured to engage the guide post; 20. The device of claim 18, wherein the cam and guide post are configured such that rotation of the cam advances the needle a predetermined distance to a predetermined position, and optionally, the cam and guide post are further configured to reversibly lock the needle in position once the needle has advanced the predetermined distance.

20. 18. The device of claim 17, wherein the guide member is removably attached to the external body portion of the housing using a mechanical connection, and optionally the device satisfies at least one of the following: a) and b). a) the mechanical connection includes a first connection structure on the guide member and a second connection structure on the external body surface, and the guide member is removably attached to the external body surface by engagement of the first connection structure with the second connection structure; b) said mechanical connection comprises one or more of a screw, a snap-fit ​​connection, an interference-fit connection, and a grub screw;

21. An apparatus described in any one of claims 1, 5, 8, and 17, which satisfies at least one of the following a) and b). a) a surface of the housing configured to contact tissue of the mammal comprises at least one of a texture and a coating configured to promote tissue integration. b) the housing of the device is made of titanium and / or polyetheretherketone;

22. 18. The device according to claim 1, further comprising a septum that seals the fluid port, and that satisfies at least one of the following a) and b): a) The septum is a pre-pierced septum or a split septum. b) the housing includes one or more protrusions configured to compress the septum;

23. 1. A kit for implanting a device for providing fluid access to the central nervous system of a mammal, comprising: The device according to any one of claims 1, 5, 8 and 17; and a predetermined amount of acrylic cement, optionally wherein the acrylic cement includes an antimicrobial agent.

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