NEUROLOGICAL APPARATUS

[0001] This is a Continuation of application Ser. No. 12/310,207 filed Feb. 17, 2009, which in turn is a U.S. National Phase of PCT/GB2007/003169 filed Aug. 20, 2007, which claims the benefit of British Patent Application No. 0616411.5 filed Aug. 18, 2006. The disclosures of the prior applications are hereby incorporated by reference herein in their entirety.

[0002] The present invention relates to apparatus for use in neurosurgery, for positioning neurosurgical apparatus. In particular, it relates to a guide element for insertion into the brain for guiding tubular instruments such as catheters and guide tubes.

[0003] The blood-brain barrier represents a considerable hurdle to the delivery of therapeutic agents to the nervous system. The term therapeutic agents includes substances which have a therapeutic effect, such as pharmaceutic compounds, genetic materials, biologics (i.e. preparations synthesised from living organisms such as stem cells). The development of techniques to bypass this barrier could revolutionise the management of Parkinson's, Huntingdon's and Alzheimer's disease as well as Glioblastoma Multiforme. Novel agents that could potentially suppress or even reverse the underlying pathological processes of these conditions have been developed. However, the limitations of these therapeutic agents lie in their inability to cross the blood-brain barrier and consequently their failure to reach the necessary structures within the brain when delivered by conventional methods (e.g. oral or intravenously).

[0004] Convection-enhanced delivery (CED) allows the delivery of a therapeutic agent directly to the central nervous system, without the requirement of the therapeutic agent crossing the blood brain barrier. CED utilises fine intracranial catheters and low infusion rates to impart drugs directly into the brain extracellular space. In contrast to direct intraparenchymal injection, encapsulated cells and biodegradable polymers, CED does not depend on diffusion. The use of a carefully designed cannula with a precisely controlled infusion rate leads to the development of a pressure gradient, along which a therapeutic agent passes directly into the extracellular space. Consequently, it is possible to achieve controlled, homogeneous distribution even for relatively large molecules, over large volumes of the brain and spinal cord.

[0005] International patent application WO 03/077764 discloses the implantation of a catheter in a human or non-human brain for intraparenchymal drug delivery. A drug may thus be pumped intermittently or continuously through the catheter to the desired brain target.

[0006] WO 03/077764 further discloses a stereoguide used for the longitudinal guidance of instruments towards a target with the brain which defines an axis along which the instruments are inserted. The stereoguide is carried by a stereotactic frame which is securely attached to the skull of the patient. The stereoguide can be adjusted on the stereotactic frame in order to be positioned very accurately to direct a surgical instrument to the desired position. A guide wire may be used to rigidify tubular instruments inserted into the brain or guide tubular instruments, such as catheters for delivery of therapeutic agents or guide tubes which are inserted into the brain and through which other instruments may be passed.

[0007] A first aspect of the present invention provides a guide element for insertion into the brain to guide implantable instruments, wherein the guide element comprises an elongate part, the elongate part having a composition of at least 80% tungsten carbide.

[0008] Preferably the elongate part has a diameter of less than 1 mm.

[0009] More preferably the elongate part has a diameter of less than 0.6 mm. Even more preferably, the elongate part has a diameter of less than or equal to 0.4 mm.

[0010] The elongate part may include between 5-20% cobalt or nickel. More preferably, the elongate part includes about 5% cobalt or nickel.

[0011] The guide element may further comprise a coating surrounding the elongate part. The coating may comprise a different material than the elongate part. The coating may comprise a bio compatible material. The coating may comprise a plastics material. The coating may be one of polyimide, peek optima or technical polyurethane. Preferably the material of the coating is more resilient than the material of the guide element core.

[0012] Preferably the guide element is a guide wire or guide rod.

[0013] A second aspect of the present invention provides a guide element for insertion into the brain to guide implantable instruments, wherein the guide element comprises an elongate part, the elongate part comprising a material which fails rather than bends under force.

[0014] A third aspect of the present invention provides a guide element for insertion into the brain to guide implantable instruments, wherein the guide element comprises an elongate part, the elongate part comprising a non ductile material.

[0022] FIGS. 1-3 illustrate a guide tube, inner tube and catheter respectively according to the present invention.

[0023] The guide tube 10 is shown in FIG. 1 and comprises a length of tube 12 with a hub 14 at one end. In this example it is made from a polyurethane plastic such as carbothane 55 DB20. However, it may be made from any material which is biocompatible and sufficiently rigid at room temperature to maintain its central aperture. In this example, the tube 12 has an outer diameter of 0.6 mm and an inner diameter of 0.5 mm.

[0024] The guide tube is inserted into the brain through an aperture (e.g. burr hole) in the skull created by the surgeon. Once the length of tubing is inserted into the brain, the hub can be attached to the patient's skull, for example by bonding into a burr hole in the skull using an acrylic cement. A wire may be used to guide the guide tube into place, as disclosed in WO03/07784. Before insertion, the guide tube is cut to a length short of the target. The distal end of the guide tube will typically fall several millimetres short of the target.

[0025] The hub of the guide tube is preferably domed and has a cut out slit 16 which links the central aperture of the tube to a side of the hub.

[0026] The inner tube 18 is illustrated in FIG. 2 and comprises two connected lengths of tubing, the distil tubing 20, which in this example has an outer diameter of 0.42 mm and an inner diameter of 0.2 mm and proximal tubing 22 which has a larger diameter. A stop element 24 links the proximal and distil tubing. The distal and proximal lengths of tubing are typically made of a polyurethane plastic, such as carbothane 85AB20, although other material could also be used. The stop element 24 is in this case also constructed using polyurethane plastic, such as carbothane 72 DB20. Again other suitable materials may be used.

[0027] The stop element 24 has a central body 26 which is generally cylindrical and a pair of diametrically opposed wings 28,30 each containing a countersunk hole 32,34 whereby the stop element may be screwed to the outer surface of the skull of the patient. The inner tube with distal and proximal lengths of tubing and stop element is described in more detail in WO03/077785.

[0028] The stop element has two roles. Firstly, when the inner tube is inserted into the guide tube, the stop element abuts against the hub of the guide tube, thereby forming a stop and defining the length of the distil tubing which extends from the tubing of the guide tube. Secondly, the wings of the stop element are used to fix the inner tube to the skull of the patient.

[0029] The role of fixing the inner tube to the skull of the patient may be accomplished by alternative means. For example, a pair of wings may be provided on the proximal tubing, for example by overmoulding onto the tubing. These wings may be provided with apertures to receive screws which when screwed into the skull fix the wings and proximal tubing in place. This arrangement allows one wing to be folded onto the other, so that a single screw is inserted through both apertures of the wings. This arrangement has the advantage that it causes some clamping of the catheter within the proximal tubing.

[0030] The catheter 36 is illustrated in FIG. 3 and comprises a fine length of tubing 38 and is typically made from fused silica. Alternative materials may be used which are inert and have low viral binding properties. The fused silica typically has an outer diameter of 0.2 mm and an inner diameter of 0.1 mm. The catheter is provided at one end with a barb 40 which acts as a stop. This may be directly moulded onto the catheter and may be made from a polyurethane plastic such as carbothane.

[0031] The barb 40 has a stepped cylindrical profile with a central aperture. A region of greatest diameter 41 has straight sides which form a stop against which the end of the proximal tubing abuts when the catheter is inserted into the inner tubing. On either side of the region of greatest diameter is a cylindrical portion 43 with a waisted 45 portion of decreased diameter. In use, tubing is pushed over the cylindrical portion until it abuts the region of greatest diameter 41. As the tubing passes over the waisted portion 45 it deforms to form a seal. As the catheter 36 is inserted into the inner tubing 18, the end of the proximal tubing 22 is pushed over one of the cylindrical portions 43. Connector tubing (not shown) which connects the catheter to a pump may be attached to the other cylindrical portion of the barb in the same manner.

[0032] In order to perform neurosurgery, the surgeon needs, in the first instance, to understand the patient's neuroanatomy and hence identify the position of the desired target. This is normally achieved by fixing a stereotactic reference frame to the patient's head, elements of which can be seen on diagnostic images, and from which measurements can be made. The stereotactic frame then acts as a platform from which an instrument is guided to a desired target using a stereoguide that is set to the measured co-ordinates. Once an instrument is guided to the desired target treatment can begin. This is described in more detail in WO03/077784.

[0033] The stereoguide is used to first insert a guide element into the brain towards the target. The guide tube is inserted into the brain by threading it over the guide element using the secured stereoguide and fixed in place as described above. The guide element is then removed, leaving the guide tube in place. FIGS. 4A and 4B illustrate the assembled guide tube 10, inner tubing 18 and catheter 36. FIG. 4A is the assembly outside the skull and FIG. 4B is the assembly with the catheter inserted into the brain 42. FIG. 4B illustrates the hub 14 of the guide tube 10 fixed in place in a hole in the skull 44 by bone cement 46. The inner tube is inserted into the guide tube by inserting the distil tubing 20 into the guide tube 10 until the stop element 24 abuts the hub 14 of the guide tube. The stop element 24 thus acts as a stop to control the amount the length of the inner tubing which is inserted into the brain. The catheter 36 is inserted into the inner tube and is pushed through until its barb abuts the end of the proximal tubing 22 of the inner tubing.

[0034] Once the guide tube, inner tube and catheter are all inserted, the proximal tubing containing the catheter extending out of the skull from the hub of the guide tube are bent through 90 degrees so that the stop element lies flat against the skull, as illustrated in FIG. 4B. This is then fixed in position using screws 48 passing through the countersunk holes. The cut out slit 16 in the hub 14 of the guide tube allows this 90 degree bend. Further clamping may be provided by additional fixing means on the inner tube (such as wings over moulded on the inner tube) through which screws may be attached to the skull.

[0035] The length of guide tube, inner tube and catheter are arranged so that the inner tube extends into the brain further than the guide tube (e.g. 10 mm) and the catheter extends into the brain further than the inner tube (e.g. 10 mm)

[0036] With the guide tube, inner tube and catheter all in place, the catheter can be connected to a pump (not shown) via connector tubing which connects to the barb of the catheter.

[0037] WO03/077784 discloses a method of inserting fine instruments such as catheters and electrodes into the brain. A small diameter tungsten guidewire of 0.6 mm diameter is inserted into a fine tube and fixed within it, with the wire projecting from its end. The fine tube and wire are lowered together to the target in the brain using a stereoguide. The fine tube is then removed and the guide tube is threaded onto the wire and inserted into the brain. Once the guide tube is installed the guide wire is removed.

[0038] In practice, the guidewire may be inserted without the use of the fine tube.

[0039] FIG. 5 illustrates a guide wire 52 inserted into the brain using a stereoguide 50. The stereoguide is carried by a stereotactic frame (not shown) which is securely attached to the skull 54 of the patient. FIG. 5 shows a guide wire 52 inserted though guide elements 54,56 and clamps 58 of the stereoguide, through an aperture 60 in the skull 54 and into the brain. A guide tube 10 is shown threaded onto the guide wire, ready to be inserted into the brain. A stereoguide suitable for insertion of the guide wire into the brain is disclosed in WO03/077784.

[0040] For insertion of very fine catheters, a guide wire of very small diameter is required, for example 0.2 mm.

[0041] When the guide wire is inserted into the brain, it must penetrate the pia mater which is the delicate innermost layer of the meninges, the membranes surrounding the brain and spinal cord. The thin, mesh-like pia mater closely envelops the entire surface of the brain, running down into the fissures of the cortex. It joins with the ependyma which lines the ventricles to form choroid plexuses that produce cerebrospinal fluid.

[0042] Tungsten wire has the disadvantage that at these small diameters it can bend. This bending can cause the tip of the guide element to reach the wrong target in the brain, resulting in the subsequent guide tube and catheter being installed incorrectly.

[0043] In the present invention a guide element (e.g. a guide wire or guide rod) is made from a material, such as tungsten carbide, which is a stiff and brittle material.

[0044] Tungsten carbide has a different failure mode to tungsten. As tungsten is a non ductile material, it will fail rather than bend under force. This is unlike tungsten which will yield and deform under force. Thus a guide element (e.g. guide wire or guide element) made from a material which fails rather than bends under force and/or comprises a non ductile material, such as tungsten carbide, will not bend and the tip is inserted at the correct position.

[0045] The guide element comprises an elongate part, for example made of tungsten carbide. The tungsten carbide may include a percentage of other elements, for example cobalt. The addition of cobalt has the function of improving binding properties and is typically added in a range of 5-20% by weight. A suitable composition of the tungsten carbide guidewire is 95% WC and 5% Co, although other compositions may be used. An alternative additive is nickel, which also improves binding properties. Nickel also has the effect of increasing corrosion resistance and increasing biocompatibility. As before, nickel may be added in the range of 5-20% by weight.

[0046] An example of the dimensions of the tungsten carbide elongate part of the guide element is a diameter of 0.36 mm. The elongate part of the tungsten carbide guide element preferably has a diameter of less than 1 mm, although preferably a diameter of less than 0.6 mm and even more preferably a diameter of less than or equal to 0.4 mm.

[0047] When the guide element is inserted into the brain, it passes through the relatively tough pia mater (for approximately 5 mm) and then a much softer region of brain. Any breakage of the tungsten carbide will thus occur in the first 5 mm, during which the broken guide element can easily be removed.

[0048] The elongate part of the guide element may be coated with a material which will hold it together if it breaks. The coating comprises a biocompatible material which is more resilient than the tungsten carbide core. It may comprise a biocompatible plastics material, for example polyimide, peek optima or technical polyurethane. A suitable coating could be applied by over moulding. The thickness of the coating is chosen to effectively hold broken pieces of the guide element together whilst limiting the increase in diameter of the guide element. The coating thickness will typically be in the range of 0.1 to 0.25 mm

[0049] The guide element may comprise, for example a guide wire or guide rod.

[0050] The guide element may be made from materials other than tungsten carbide which fail rather than bend under force and/or which are non ductile.