Cranial prosthesis

Abstract

The present invention relates to cranial prostheses and their use in therapy. More specifically, it relates to a cranial prosthesis comprising a plate with holes, the holes including a plurality of holes substantially equidistant from a central location. One such cranial prosthesis comprises a curved plate with holes (1), the holes including four holes (2) substantially equidistant from a central location. The plate further comprises a further hole at the central location (3), removable screw / suture fixation tabs (4) for attaching the cranial prosthesis to the skull via screws / sutures, removable fixation means consisting of a flap (6) for fixing the electrodes when closed, and a recess (7) in the form of a channel suitable for the escape of an extension lead wire, the recess having at least one exit point (15) for connecting the individual electrodes to the main lead wire. A removable protective cap (5) can be placed over the removable fixation means when closed.

Description

[Technical field]

[0001] The present disclosure relates to a cranial prosthesis, more particularly, to a cranial prosthesis comprising a plate with holes and recesses suitable for lead wire escape, the holes including a plurality of holes substantially equidistant from a central point. [Background technology]

[0002] Electrotherapy involves the use of electrical energy in therapy and can be applied to a variety of treatments, including the use of electrical devices such as deep brain stimulators (DBS) for neurological disorders such as Parkinson's disease. Electrotherapy can be used as a physical therapy for muscle stimulation, pain management, wound healing, and can also be used to treat psychiatric conditions such as anxiety, insomnia, depression, hyperarousal, and obsessive-compulsive disorder.

[0003] Electrical therapy has also proven to be an effective treatment for glioblastoma multiforme (GBM), the most common type of primary brain tumor in adults. A Phase III multicenter clinical trial has shown that electrotherapy, when used in addition to surgery (e.g., surgical resection), chemotherapy, and radiation therapy, can extend overall patient survival up to 21 months (Stupp et al., JAMA, 2017, 318(23):2306-16, doi:10.1001 / jama.2017.18718.). This is achieved by delivering an alternating sinusoidal electric field of a predetermined frequency (50-300 kHz) to the head. At these frequencies, the electric fields have been shown to interfere with mitosis in cancer cells, thereby slowing the growth of recurrent tumors and prolonging patient survival (Kirson et al., PNAS, 2007, 104(24):10152-7, doi:10.1073 / pnas.0702916104). Summary of the Invention [Problem to be solved by the invention]

[0004] Currently, there is only one electrotherapy device in clinical use for cancer treatment. In this device, a therapeutic electric field is delivered to the patient's head by a transducer array attached to the scalp. These transducers are connected to an external battery and stimulator pack that the patient must carry around, with a recommended daily treatment time of 18 hours per day. However, there are several problems with this external stimulation approach. First, the electric field generated within the brain (where the tumour resection margins are located) is exponentially weaker than the electric field at the skin surface where the electric field is generated, limiting the therapeutic effect. With this in mind, to ensure the generation of an electric field of sufficient effective strength at the treatment site, large and heavy batteries are used, resulting in a very cumbersome device that affects the independence and mobility of the patient. Furthermore, the scalp-mounted transducers are very visible, taking about 50 minutes to attach to the head every morning, and requiring the patient to shave their head every two days. This has a significant impact on the patient's quality of life, as continuous placement of the transducers on the scalp can cause severe skin irritation and associated pain due to the large currents flowing through the skin. These effects on patients' quality of life result in only a small proportion of patients following the recommended daily dosing times (Toms et.al.,Journal of Neuro-Oncology,2019,141(2):467-473,doi:10.1007 / sll060-018-03057-z). There is a clear correlation between the number of hours that GBM patients receive daily electrotherapy and their overall survival. Patient compliance issues directly limit the efficacy of treatment, as data strongly suggest that continuous (24 hours / day) treatment achieves the greatest overall survival.

[0005] Many challenges of existing treatments can be overcome by delivering electric fields from within the tumor or tumor resection cavity. This would allow for higher field strengths, which should improve patient outcomes. Furthermore, this approach would eliminate the issue of painful skin irritation experienced with the existing devices listed above (e.g., no sensation from within brain tissue). This would allow for continuous electrical treatment, potentially greatly improving patient outcomes. Delivery of electric fields from within the tumor or tumor resection cavity also has advantages for the ancillary devices required to deliver the charge. By applying the electric field in a focused manner, exponentially lower voltages would be required to generate the same field strength than existing devices. Using lower voltages would allow for the use of smaller batteries (longer life) and allow for smaller and more implantable devices. Fully implanting the device would overcome several quality of life issues. Nothing would be visible from the outside of the body, nothing would be cumbersome to carry around, and in the case of brain tumors, no need to shave the head.

[0006] Deep brain stimulation (DBS) is a neurosurgical procedure that involves the placement of a medical device called a neurostimulator, which sends electrical impulses to a predetermined target in the brain through implanted electrodes. Typically, DBS treatment is performed by a single implanted electrode, which may have multiple active sites along its axis. DBS is used to treat movement disorders such as Parkinson's disease, essential tremor, and dystonia. These electrodes can be partially implanted into the patient's brain through a cranial hole formed in the patient's skull. The cranial hole is usually formed using a drill fitted with a special drill bit. The electrodes are connected to a charge delivery device through leads, which are implanted through the cranial hole and secured in place through a cranial hole cover. Various such systems have been disclosed. For example, US Patent US2019308025A1 describes a cranial implant for securing a device in a cranial hole. US Patent US2019282802A1 describes a kit and method for securing a cranial hole plug for a stimulation system. US Patent Publication US2014257325A1 describes a concave cranial cavity cover and a method for using the same. US Patent Publication US2013304216A1 describes a cranial cavity cover and a method for using the same. However, all of these systems describe devices for a single electrode.

[0007] JingLe Jiang et al. (J.Neurosci.Methods 2017 Feb 1,277:21-29) described a testbed to optimize electrodes embedded in the skull or artificial skull replacement components used after injury. They theorized that chronic brain recordings would be beneficial to monitor brain health and seizure progression after injury or surgery, and that embedding electrodes directly into these artificial skull replacement components would be a novel, low-risk way to perform chronic brain monitoring in these patients. The device by JingLe Jiang et al. is not used or suitable to support optimal placement of electrodes embedded within brain tissue.

[0008] When treating brain tumors, cancer cells can be located at any point in three-dimensional space within the tumor or tumor resection margins, and can be targeted to localized tissue regions (<1 cm2) that are the target of deep brain stimulation techniques. 3 ) much larger size (10cm 3 A total tissue volume of about 1000 mm can be covered. To ensure effective treatment of all cancer cells within a tumor or tumor margin, it is necessary to generate an electric field in a relatively large tissue volume such that the minimum electric field strength at any spatial point in the 3D volume of the tumor margin is sufficient to prevent mitosis of the cancer cells. This can be defined as the clinically effective electric field. Since the electric field strength decreases exponentially with increasing distance from the stimulation electrode, the generation of a large volume of clinically effective electric field can be better achieved by using multiple electrodes implanted on spatially separated tracks. By implanting these multiple electrodes along the circumference or periphery of the tumor or tumor margin, it is possible to reduce the maximum distance between any point in 3D space within the tumor or tumor margin and the nearest implanted electrode. This increases the minimum electric field strength in the total volume within the tumor or tumor margin. This reduces the required input voltage and the energy required to generate a clinically effective electric field, which in turn extends the battery life and reduces the overall size of the stimulation device. This allows for complete implantation of the medical device, which in turn can improve the quality of life of the patient without affecting the therapeutic effect.

[0009] In addition to ensuring that the electric field strength is a clinically effective electric field, it is also advantageous for the electric field to be as close to uniform as possible. Here, a uniform electric field is defined as an electric field in which the electric field strength of any point in the electric field is independent of the position of the point in 3D space. A uniform electric field further reduces the energy required to generate a clinically effective electric field by reducing the area of ​​the electric field that is overstimulated beyond the clinically effective electric field strength. The uniformity of the electric field generated by multiple implanted electrodes can be increased by implanting multiple electrodes substantially equidistant from a central location. The uniformity of the electric field generated by multiple implanted electrodes can be further increased by implanting an electrode at a central location. The uniformity of the electric field can be further increased by implanting one or more multiple electrodes substantially equidistant from a central location (e.g., a concentric arrangement with an optional electrode at a central location).

[0010] WO 2017 / 039762 describes a low-profile intracranial device for use in surgery, particularly cranioplasty, craniomaxillofacial surgery, and neurosurgery, but does not anticipate multi-electrode electrotherapy or the associated problems addressed by the cranial prosthesis of the present application. US 2010 / 0280585 describes a method and device for fixing electrodes, particularly surgery, and in particular a method and device for fixing at least one electrode, for example at least one deep brain stimulator (DBS) electrode, to an anatomical structure. However, it does not anticipate or address the problems associated with multi-electrode electrotherapy addressed by the cranial prosthesis of the present application.

[0011] Although electrotherapy with multiple electrodes implanted in the brain offers many advantages over existing electrotherapy, a device is needed to secure the electrodes to the skull in order to safely implant the electrodes and hold them securely in place during surgery. The device is economically compatible with the charge delivery device and can accommodate and preferably organize the leads connecting the multiple implanted electrodes to the charge delivery device, since loose leads pose a risk of skin erosion and wound breakdown after the device is surgically implanted. In addition, correct placement helps protect the leads from induced currents during MRI scans. The device must be able to fix these leads in place while reducing irregular protrusions. Surgical ease of use is also important, since the device is implanted as part of a complex surgical procedure. The more difficult it is for the surgeon to implant, the longer the surgery will take. Longer surgery times mean more danger for the patient and more cost for the hospital system. This application describes a novel cranial prosthesis suitable for use in electrotherapy to treat brain tumors and metastases. [Means for solving the problem]

[0012] The present specification describes, in part, a cranial prosthesis comprising a plate with holes and recesses suitable for escaping lead wires, the holes including a plurality of holes substantially equidistant from a central location.

[0013] This specification also describes, in part, manufacturing processes for cranial prostheses, which include injection molding, machining, casting or 3D printing.

[0014] This specification also describes, in part, a cranial prosthesis for use in electrical therapy.

[0015] Many embodiments of the present invention are detailed throughout the specification and will be apparent to those of skill in the art, and the present invention should not be construed as being limited to any of the described embodiments.

[0016] "A" means "at least one." In any embodiment, when "a" is used to refer to a given material or element, "a" may mean one.

[0017] "Comprising" means that a given material or element can include other materials or elements. In any embodiment where "comprising" is described, the given material or element can form at least 10% w / w, at least 20% w / w, at least 30% w / w, or at least 40% w / w of that material or element. In any embodiment where "comprising" is mentioned, "comprising" can also mean "consisting" (or "consists of") or "consisting essentially of" (or "consists essentially of") the given material or element.

[0018] "Consisting" or "consists of" means that a given material or element is made up entirely of that material or element. In any embodiment where "consisting" or "consists of" is mentioned, the given material or element may be made up of 100% w / w material or element.

[0019] "Consisting essentially" or "consists essentially of" means that a given material or element consists almost entirely of that material or element. In any embodiment where "consisting essentially" or "consists essentially of" is referred to, the given material or element can be made up of at least 50% w / w, at least 60% w / w, at least 70% w / w, at least 80% w / w, at least 90% w / w, at least 95% w / w, or at least 99% w / w of that material or element.

[0020] By "substantially" it is meant more than 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 99%.

[0021] In any embodiment where "comprising" is mentioned, "comprising" can also mean "consisting" (or "consists of") or "consisting essentially of" (or "consists essentially of") the specified materials or elements.

[0022] In any embodiment where "is" or "may be" is used to define a material or element, "is" or "may be" can mean that the material or element "consists of" or "consists essentially of" that material or element.

[0023] The claims are embodiments.

[0024] The embodiments may be combined.

[0025] (Cranial Prosthesis) Here, the cranial prosthesis comprises a plate with holes, specifically a plate with holes and recesses suitable for the escape of lead wires, the holes including a plurality of holes substantially equidistant from a central point. The cranial prosthesis typically replaces a portion of the patient's original skull that is removed during surgery. Ideally, the cranial prosthesis includes an outward facing surface that is designed to avoid pressure points on the overlying skin.

[0026] In one embodiment, the cranial prosthesis comprises one or more materials, such as metals (e.g., titanium and its alloys), stainless steel, and cobalt-chromium-molybdenum alloys, polymers (e.g., polyetheretherketone, polyethylene, polypropylene, acrylonitrile, butadiene styrene, polysiloxanes, polyamides, and polysulfones), ceramics (e.g., zirconia, alumina, and silicate glasses), and composites of the above materials.

[0027] In one embodiment, the cranial prosthesis may include a carbon material, for example a graphene-based material.

[0028] In one embodiment, the cranial prosthesis may include metallic cranial prostheses, such as cranial prostheses made from titanium and its alloys, stainless steel, and cobalt-chromium-molybdenum alloys.

[0029] In one embodiment, the cranial prosthesis may include a polymeric cranial prosthesis, for example, a cranial prosthesis made from polyetheretherketone, polyethylene, polypropylene, acrylonitrile, butadiene styrene, polysiloxane, polyamide, and polysulfone.

[0030] In one embodiment, the cranial prosthesis may include a polymeric cranial prosthesis.

[0031] In one embodiment, the cranial prosthesis may include a polyetheretherketone cranial prosthesis.

[0032] In one embodiment, the cranial prosthesis may include a polyethylene cranial prosthesis.

[0033] In one embodiment, the cranial prosthesis may include a polypropylene cranial prosthesis.

[0034] In one embodiment, the cranial prosthesis may include an acrylonitrile cranial prosthesis.

[0035] In one embodiment, the cranial prosthesis may include a styrene butadiene cranial prosthesis.

[0036] In one embodiment, the cranial prosthesis may include a polysiloxane cranial prosthesis.

[0037] In one embodiment, the cranial prosthesis may include a polyamide cranial prosthesis.

[0038] In one embodiment, the cranial prosthesis may include a polysulfone cranial prosthesis.

[0039] In one embodiment, the cranial prosthesis may include ceramics, such as zirconia, alumina, and silicate glass cranial prostheses.

[0040] In one embodiment, the cranial prosthesis may include a curved hole plate.

[0041] In one embodiment, the cranial prosthesis comprises a curved hole plate shaped to restore the original contour of the skull.

[0042] In one embodiment, the cranial prosthesis comprises a curved hole plate having a shape substantially similar to the removed skull fragment.

[0043] In one embodiment, the cranial prosthesis may comprise a uniformly curved hole plate, where the curvature is evenly distributed.

[0044] In one embodiment, the cranial prosthesis may comprise a non-uniformly curved hole plate, where the curvature is non-uniformly distributed.

[0045] In one embodiment, the cranial prosthesis may comprise a curved hole plate having an asymmetric curvature, where the radius of curvature in one direction is not equal to the radius of curvature in a direction perpendicular to that direction.

[0046] In one embodiment, the cranial prosthesis can include a curved hole plate with an asymmetric curvature similar to that of a portion of the skull. The cranial prosthesis can be manufactured in a variety of asymmetric shapes to allow the surgeon to select the shape that most closely resembles the portion of the skull that was surgically removed.

[0047] In one embodiment, the cranial prosthesis can be custom manufactured for each patient. Custom manufacturing can be accomplished, for example, using the patient's own computed tomography (CT) scan. When the cranial prosthesis is custom manufactured, the replacement parts can more closely replicate the natural skull and fit more smoothly with the intact skull.

[0048] In one embodiment, the cranial prosthesis has a substantially circular shape.

[0049] In one embodiment, the cranial prosthesis has a substantially circular shape with an average diameter between 1 cm and 15 cm.

[0050] In one embodiment, the cranial prosthesis has a substantially circular shape with an average diameter between 3 cm and 12 cm.

[0051] In one embodiment, the cranial prosthesis has a circular shape.

[0052] In one embodiment, the cranial prosthesis has a circular shape with an average diameter of 1 cm to 15 cm.

[0053] In one embodiment, the cranial prosthesis has a circular shape with an average diameter of 3 cm to 12 cm.

[0054] In one embodiment, the cranial prosthesis has a circular shape with an average diameter of 6 cm to 12 cm.

[0055] In one embodiment, the cranial prosthesis has a circular shape with an average diameter of 8 cm to 10 cm.

[0056] In one embodiment, the cranial prosthesis has a thickness of less than 1 cm.

[0057] In one embodiment, the cranial prosthesis has a thickness of less than 0.9 cm.

[0058] In one embodiment, the cranial prosthesis has a thickness of less than 0.8 cm.

[0059] In one embodiment, the cranial prosthesis has a thickness of less than 0.7 cm.

[0060] In one embodiment, the cranial prosthesis has a thickness of less than 0.6 cm.

[0061] In one embodiment, the cranial prosthesis has a thickness of less than 0.5 cm.

[0062] In one embodiment, the cranial prosthesis has a thickness of 0.5 to 0.8 cm.

[0063] (Recess suitable for lead wire escape) The cranial prosthesis includes a recess suitable for the escape of the lead wire. In one embodiment, the cranial prosthesis can comprise a plate with holes, the holes including a plurality of holes substantially equidistant from a central location, the plate with holes including further recesses. These further recesses may be in the body of the plate and included on the outwardly facing surface of the plate. In one embodiment, the recesses are channels suitable for the escape of the extension lead wires connecting the individual electrodes to the main lead. In one embodiment, the plate with holes includes further recesses, the further recesses are channels suitable for the escape of the extension lead wires connecting the individual electrodes to the main lead. The extension lead wires may be connected to the electrodes or may be part of the electrodes themselves. The main lead wire is a lead wire that can be connected to a charge delivery device. When the extension lead wires are arranged to escape, the possibility of them becoming dislodged during use is reduced.

[0064] In one embodiment, the recesses suitable for lead escape include a series of interconnecting channels.

[0065] In one embodiment, the recess suitable for lead escape is a recessed channel around the periphery.

[0066] In one embodiment, the recess suitable for lead escape includes a series of interconnecting channels and a recessed channel around the periphery.

[0067] In one embodiment, the recess suitable for lead escape comprises a peripherally recessed channel at least 1 mm away from the outer edge of the cranial prosthesis.

[0068] In one embodiment, the recess suitable for lead escape comprises a peripherally recessed channel at least 2 mm away from the outer edge of the cranial prosthesis.

[0069] In one embodiment, the recess suitable for lead escape comprises a peripherally recessed channel at least 3 mm away from the outer edge of the cranial prosthesis.

[0070] In one embodiment, the recess suitable for lead escape comprises a series of interconnecting channels with at least one exit point, which may be a further recess on the periphery of the cranial prosthesis, allowing an extension lead to be connected (or formed) to the main lead.

[0071] In one embodiment, the recess suitable for lead escape comprises a recessed channel around its periphery having at least one exit point. In one embodiment, the at least one exit point is between 1 and 10 exit points. In one embodiment, the at least one exit point is between 4 and 10 exit points. In one embodiment, the at least one exit point is two exit points. In one embodiment, the at least one exit point is four exit points. In one embodiment, the at least one exit point is eight exit points.

[0072] In one embodiment, the recess suitable for lead escape comprises a series of interconnected channels with multiple exit points, which allow adaptive positioning of the primary lead to be determined during surgery, in one embodiment, only one of the exit points is utilized for connection to the primary lead.

[0073] In one embodiment, the recess for lead escape comprises a recessed channel around its periphery having multiple exit points.

[0074] In one embodiment, the recess suitable for lead escape comprises a recessed channel of varying width around its periphery. The varying width allows for narrower sections of the channel to secure the lead in place and act as pinch points. These varying widths can be achieved by gradual undulations or by one or more protrusions within the channel.

[0075] (hole) Here, the cranial prosthesis comprises a plate with holes and recesses suitable for escaping lead wires, the holes including a plurality of holes substantially equidistant from a central point.

[0076] In one embodiment, a plurality of holes refers to at least two holes.

[0077] In one embodiment, a plurality of holes refers to at least three holes.

[0078] In one embodiment, a plurality of holes refers to at least four holes.

[0079] In one embodiment, a plurality of holes refers to at least five holes.

[0080] In one embodiment, multiple holes refers to two holes.

[0081] In one embodiment, the plurality of holes refers to three holes.

[0082] In one embodiment, the plurality of holes refers to four holes.

[0083] In one embodiment, the plurality of holes refers to five holes.

[0084] In one embodiment, the hole refers to a substantially circular hole.

[0085] In one embodiment, the holes refer to circular holes.

[0086] In one embodiment, the holes refer to slits.

[0087] In one embodiment, the hole refers to a cross-shaped hole.

[0088] In one embodiment, there may be multiple holes substantially equidistant from a central location (eg, in a concentric arrangement).

[0089] (center location) Here, the cranial prosthesis comprises a plate with holes and recesses suitable for the escape of lead wires, the holes including a plurality of holes substantially equidistant from a central location, the central location being relative to the holes and not necessarily being at the center of the plate with holes, although it may be so.

[0090] In one embodiment, substantially equidistant from the center point means that the closest point of each hole is the same distance from the center point to within ±20%.

[0091] In one embodiment, substantially equidistant from the center point means that the midpoint of each hole is the same distance from the center point to within ±20%.

[0092] In one embodiment, substantially equidistant from the center point means that the closest point of each hole is the same distance from the center point, within ±10%.

[0093] In one embodiment, substantially equidistant from the center point means that the midpoint of each hole is the same distance from the center point to within ±10%.

[0094] In one embodiment, substantially equidistant from the center point means that the closest point of each hole is the same distance from the center point, within ±5%.

[0095] In one embodiment, substantially equidistant from the center point means that the midpoint of each hole is the same distance from the center point to within ±5%.

[0096] In one embodiment there is an additional hole at the central location. In a further embodiment the hole at the central location has a different shape than the other holes.

[0097] (Fixing means) In one embodiment, the cranial prosthesis further comprises fixing means for fixing the electrodes in position within the holes. This is particularly useful when the holes in the plate are larger than the electrodes. In the open state, the fixing means allow for flexible positioning of the electrodes. In the closed state, the fixing means can be used to clamp the electrodes and fix their position. These fixing means can be integral parts of the cranial prosthesis or can be separate parts that can be attached to the cranial prosthesis.

[0098] In one embodiment, the securing means may include a locking component insert, for example, which tightens when locked.

[0099] In one embodiment, the fastening means may include a ball and socket fastener.

[0100] In one embodiment, the securing means may include a threaded locking component.

[0101] In one embodiment, the securing means may include one or more slidable locking components.

[0102] In one embodiment, the securing means may include a flap that secures the electrode when closed. The flap may be attached to the hole plate via a hinge.

[0103] In one embodiment, the fastening means may include a clip that clamps the electrode.

[0104] In one embodiment, the fastening means may include a bayonet fitting.

[0105] In one embodiment, the fastening means comprises one or more materials, such as metals (e.g., titanium and its alloys), stainless steel, and cobalt-chromium-molybdenum alloys, polymers (e.g., polyetheretherketone, polyethylene, polypropylene, acrylonitrile, butadiene styrene, polysiloxanes, polyamides, and polysulfones), ceramics (e.g., zirconia, alumina, and silicate glasses), and composites of the above materials.

[0106] In one embodiment, the fastening means may comprise a carbon material, for example a graphene-based material.

[0107] In one embodiment, the fastening means may include metals, such as titanium and its alloys, stainless steel, and cobalt-chromium-molybdenum alloys.

[0108] In one embodiment, the fastening means may include a polymer, for example, polyetheretherketone, polyethylene, polypropylene, acrylonitrile, butadiene styrene, polysiloxane, polyamide, and polysulfone.

[0109] In one embodiment, the fastening means may include ceramics, such as zirconia, alumina, and silicate glasses.

[0110] (Protective cap) In one embodiment, protective caps can be placed over the holes in the plate. These caps protect the electrodes and extension leads and help hold the electrodes in place. The caps can be placed directly over the holes or, if additional fixation means are used, they can be placed over the additional fixation means.

[0111] In one embodiment, the protective cap includes a low profile protective cap.

[0112] In one embodiment, the protective cap comprises a press-fit protective cap.

[0113] In one embodiment, the protective cap comprises a plastic protective cap.

[0114] In one embodiment, the protective cap comprises a polysiloxane protective cap.

[0115] In one embodiment, the protective cap comprises a polyetheretherketone protective cap.

[0116] In one embodiment, the protective cap comprises a friction-fit protective cap.

[0117] In one embodiment, the protective cap comprises a snap-on protective cap.

[0118] In one embodiment, the protective cap includes a threaded fitting.

[0119] In one embodiment, the protective cap includes a bayonet fitting.

[0120] In one embodiment, the protective cap includes an electrical connect and integrates an extension lead that connects the implantable electrode to the main lead.

[0121] (Fixing means) In one embodiment, the cranial prosthesis can be fixed in place within the cranial window.

[0122] In one embodiment, an adhesive is used to secure the cranial prosthesis.

[0123] In one embodiment, the cranial prosthesis includes means for attaching the cranial prosthesis via screws, such as screw fixation tabs, which are either integrated into the cranial prosthesis or fixed to the cranial prosthesis. Suitable screws include titanium screws.

[0124] In one embodiment, the cranial prosthesis includes means for attaching the cranial prosthesis via fixation tabs that allow for placement of appropriate screws or sutures passing through them.

[0125] Alternatively, a series of fixation holes can be introduced along the periphery of the cranial prosthesis, allowing the attachment of fixation plates, for example titanium bone plates, or allowing the placement of sutures.

[0126] (process) The described cranial prostheses can be manufactured by a variety of techniques, including injection molding, machining (e.g., computer numerical control machining), casting or 3D printing (e.g., fused deposition modeling, stereolithography, selective laser sintering).

[0127] In one embodiment, there is provided a process for manufacturing the cranial prostheses described herein that includes injection molding.

[0128] In one embodiment, a process for manufacturing a cranial prosthesis as described herein is provided that includes machining (eg, computer numerically controlled machining).

[0129] In one embodiment, a process for manufacturing a cranial prosthesis as described herein is provided that includes casting.

[0130] In one embodiment, a process for manufacturing the cranial prostheses described herein is provided that includes 3D printing (e.g., fused deposition modeling, stereolithography, selective laser sintering).

[0131] (Use of cranial prostheses) The cranial prostheses described herein can be used intraoperatively in electrotherapy, including the following procedures:

[0132] 1. Incise the scalp and fold back the skin flap. 2. Open a cranial window large enough to accommodate the prosthesis and remove the bone. 3. Place the prosthesis over the cranial window and secure it in place. 4. Insert the electrodes. 5. Secure the electrodes in place. 6. Cut the electrodes to the appropriate length. 7. Attach the extension leads to the electrodes. 8. Optionally, attach and secure protective caps to electrodes. 9. Organize the wiring in the channel so it is not noticeable and secure it in place. 10. Replace the flap and suture it. 11. Connect the main leads to the charge delivery device.

[0133] Alternatively, the cranial prostheses described herein can be used intraoperatively in electrotherapy, including the following procedures:

[0134] 1. The scalp is incised and the skin flap is retracted. 2. Open a cranial window large enough to accommodate the prosthesis and remove the bone. 3. Place the prosthesis over the cranial window and secure it in place. 4. Insert the electrodes. 5. Secure the electrodes in place. 6. Optionally cut the electrodes to the appropriate length. 7. Optionally attach extension leads to the electrodes if not already integrated into the electrodes or protective caps. 8. Optionally, attach protective caps to the electrodes to secure them or make electrical contact. 9. Organize the wiring in the channel so it is not noticeable and secure it in place. 10. Replace the flap and suture it. 11. Connect the main leads to the charge delivery device.

[0135] (Electrotherapy) In one embodiment, an electrical therapy device is provided that includes a cranial prosthesis comprising a plate with holes and recesses suitable for escaping lead wires, the holes including a plurality of holes that are substantially equidistant from a central location.

[0136] In one embodiment, a multi-electrode electrotherapy device is provided that includes a cranial prosthesis comprising a plate with holes and recesses suitable for escaping lead wires, the holes including a plurality of holes that are substantially equidistant from a central location.

[0137] In one embodiment, an electrotherapy is provided that includes a cranial prosthesis as described herein. In one embodiment, electrotherapy refers to multi-electrode electrotherapy. Electrotherapy is the use of electrical energy as a treatment.

[0138] In one embodiment, there is provided the use of electrotherapy comprising the cranial prosthesis described herein for the treatment of:

[0139] Brain tumors (including grade I, II, III, or IV glioma), pilocytic astrocytoma, subependymal giant cell astrocytoma, diffuse astrocytoma, oligodendroglioma, oligodendroglioma NOS, anaplastic astrocytoma, undifferentiated astrocytoma differentiated oligodendroglioma, undifferentiated oligodendroglioma NOS, glioblastoma, giant cell glioblastoma, glioblastoma multiforme, subependymal giant cell astrocytoma, follicular astrocytoma, pleomorphic xanthoastrocytoma, glioma, oligoastrocytoma, Meningiomas (including grade I, II, or III meningiomas and other neoplasms involving the meninges (e.g., hemangiopericytoma)), childhood brain tumors (including ependymoma, medulloblastoma, atypical teratoid / rhabdomyosarcoma (AT / RT), choroid plexus papilloma, choroid plexus carcinoma, intracranial teratomas, and embryonal tumors with multilayered rosettes (ETMR)), pineal region tumors (e.g., pineoblastoma), pituitary region tumors (e.g., pituitary adenoma, craniopharyngioma, chordoma), Brain metastases (e.g., from lung cancer, breast cancer, genitourinary cancer, osteosarcoma, and melanoma), Stimulation of neural tissue to treat or alleviate symptoms of neurological conditions (e.g., promoting neurological recovery after stroke / traumatic brain injury); Recording brain activity for diagnostic purposes or to enable brain-computer interface communication; Deep brain stimulation (e.g., for the treatment of movement disorders (e.g., Parkinson's disease, essential tremor, dystonia), and psychiatric symptoms (e.g., anxiety, insomnia, depression, hyperarousal, obsessive-compulsive disorder)); Pain management, or Wound healing.

[0140] In one embodiment, there is provided the use of electrotherapy comprising the cranial prosthesis described herein for the treatment of diffuse midline glioma.

[0141] In one embodiment, there is provided the use of electrotherapy comprising the cranial prosthesis described herein for stimulation of seizure onset zones for the treatment or palliation of symptoms of drug-resistant epilepsy.

[0142] In one embodiment, there is provided the use of electrical therapy with a cranial prosthesis as described herein for adjuvant therapy.

[0143] In one embodiment, there is provided the use of electrotherapy comprising the cranial prosthesis described herein for the treatment of brain tumors.

[0144] In one embodiment, there is provided the use of electrotherapy comprising the cranial prosthesis described herein for the treatment of grade I, II, III, or IV gliomas.

[0145] In one embodiment, there is provided the use of electrotherapy comprising the cranial prosthesis described herein for the treatment of grade I glioma.

[0146] In one embodiment, there is provided the use of electrotherapy comprising the cranial prosthesis described herein for the treatment of pilocytic astrocytoma.

[0147] In one embodiment, there is provided the use of electrotherapy comprising the cranial prosthesis described herein for the treatment of grade II glioma.

[0148] In one embodiment, there is provided the use of electrotherapy comprising the cranial prosthesis described herein for the treatment of diffuse astrocytoma or oligodendroglioma.

[0149] In one embodiment, there is provided the use of electrotherapy comprising the cranial prosthesis described herein for the treatment of grade III glioma.

[0150] In one embodiment, there is provided the use of electrotherapy comprising the cranial prosthesis described herein for the treatment of anaplastic astrocytoma or anaplastic oligodendroglioma.

[0151] In one embodiment, there is provided the use of electrotherapy comprising the cranial prosthesis described herein for the treatment of grade IV glioma.

[0152] In one embodiment, there is provided the use of electrical therapy comprising the cranial prosthesis described herein for the treatment of giant cell glioblastoma or glioblastoma multiforme.

[0153] In one embodiment, there is provided the use of electrical therapy comprising the cranial prosthesis described herein for the treatment of glioblastoma multiforme.

[0154] In one embodiment, there is provided the use of electrotherapy comprising the cranial prosthesis described herein for the treatment of brain tumors following surgical resection.

[0155] In one embodiment, there is provided the use of electrotherapy with the cranial prosthesis described herein for the treatment of grade I, II, III, or IV gliomas following surgical resection.

[0156] In one embodiment, there is provided the use of electrotherapy comprising the cranial prosthesis described herein for the treatment of grade I glioma following surgical resection.

[0157] In one embodiment, there is provided the use of electrotherapy including the cranial prosthesis described herein for the treatment of pilocytic astrocytoma following surgical resection.

[0158] In one embodiment, there is provided the use of electrotherapy comprising the cranial prosthesis described herein for the treatment of grade II glioma following surgical resection.

[0159] In one embodiment, there is provided the use of electrotherapy with the cranial prosthesis described herein for the treatment of diffuse astrocytoma or oligodendroglioma following surgical resection.

[0160] In one embodiment, there is provided the use of electrotherapy comprising the cranial prosthesis described herein for the treatment of grade III glioma following surgical resection.

[0161] In one embodiment, there is provided the use of electrical therapy including the cranial prosthesis described herein for the treatment of anaplastic astrocytoma or anaplastic oligodendroglioma following surgical resection.

[0162] In one embodiment, there is provided the use of electrotherapy comprising the cranial prosthesis described herein for the treatment of grade IV glioma following surgical resection.

[0163] In one embodiment, there is provided the use of electrotherapy comprising the cranial prosthesis described herein for the treatment of diffuse midline glioma.

[0164] In one embodiment, there is provided the use of electrical therapy involving the cranial prosthesis described herein for the treatment of brain metastases.

[0165] In one embodiment there is provided the use of electrotherapy including the cranial prostheses described herein for the treatment or palliation of drug-resistant epilepsy.

[0166] In one embodiment, there is provided the use of electrical therapy including the cranial prosthesis described herein for the treatment of giant cell glioblastoma or glioblastoma multiforme following surgical resection.

[0167] In one embodiment, there is provided the use of electrical therapy including the cranial prosthesis described herein for the treatment of glioblastoma multiforme following surgical resection.

[0168] (use) In one embodiment, a cranial prosthesis for use in electrotherapy is provided, the cranial prosthesis comprising a plate with holes, the holes including a plurality of holes substantially equidistant from a central location.

[0169] In one embodiment, a cranial prosthesis for use in multi-electrode electrotherapy is provided, the cranial prosthesis comprising a plate with holes, the holes including a plurality of holes substantially equidistant from a central location.

[0170] In one embodiment, a cranial prosthesis for use in electrotherapy is provided, the cranial prosthesis comprising a plate with holes and recesses suitable for escaping lead wires, the holes including a plurality of holes substantially equidistant from a central location.

[0171] In one embodiment, a cranial prosthesis for use in multi-electrode electrotherapy is provided, the cranial prosthesis comprising a plate with holes and recesses suitable for escaping lead wires, the holes including a plurality of holes substantially equidistant from a central location.

[0172] In one embodiment, there is provided a cranial prosthesis as described herein for use in electrotherapy, which in one embodiment refers to multi-electrode electrotherapy.

[0173] Electrotherapy is the use of electrical energy as a treatment.

[0174] In one embodiment, there is provided a cranial prosthesis as described herein for use in the following electrotherapy treatments:

[0175] Brain tumors (including grade I, II, III, or IV glioma), pilocytic astrocytoma, subependymal giant cell astrocytoma, diffuse astrocytoma, oligodendroglioma, oligodendroglioma NOS, anaplastic astrocytoma, undifferentiated astrocytoma differentiated oligodendroglioma, undifferentiated oligodendroglioma NOS, glioblastoma, giant cell glioblastoma, glioblastoma multiforme, subependymal giant cell astrocytoma, follicular astrocytoma, pleomorphic xanthoastrocytoma, glioma, oligoastrocytoma, Meningiomas (including grade I, II, or III meningiomas and other neoplasms involving the meninges (e.g., hemangiopericytoma)), childhood brain tumors (including ependymoma, medulloblastoma, atypical teratoid / rhabdomyosarcoma (AT / RT), choroid plexus papilloma, choroid plexus carcinoma, intracranial teratomas, and embryonal tumors with multilayered rosettes (ETMR)), pineal region tumors (e.g., pineoblastoma), pituitary region tumors (e.g., pituitary adenoma, craniopharyngioma, chordoma), Brain metastases (e.g., from lung cancer, breast cancer, genitourinary cancer, osteosarcoma, and melanoma), Stimulation of neural tissue to treat or alleviate symptoms of neurological conditions (e.g., promoting neurological recovery after stroke / traumatic brain injury); Recording brain activity for diagnostic purposes or to enable brain-computer interface communication; Deep brain stimulation (e.g., for the treatment of movement disorders (e.g., Parkinson's disease, essential tremor, dystonia), and psychiatric symptoms (e.g., anxiety, insomnia, depression, hyperarousal, obsessive-compulsive disorder)); Pain management, or Wound healing.

[0176] In one embodiment, there is provided a cranial prosthesis as described herein for use in electrotherapy treatment of diffuse midline glioma.

[0177] In one embodiment there is provided a cranial prosthesis as described herein for use in the electrotherapy treatment of drug-resistant epilepsy or the symptomatic palliation of drug-resistant epilepsy.

[0178] In one embodiment there is provided a cranial prosthesis as described herein for use in adjuvant therapy.

[0179] In one embodiment, there is provided a cranial prosthesis as described herein for use in electrotherapy treatment of brain tumors.

[0180] In one embodiment there is provided a cranial prosthesis as described herein for use in the electrotherapy treatment of grade I, II, III or IV gliomas.

[0181] In one embodiment, there is provided a cranial prosthesis as described herein for use in the electrotherapy treatment of grade I glioma.

[0182] In one embodiment there is provided a cranial prosthesis as described herein for use in the electrotherapy treatment of pilocytic astrocytoma.

[0183] In one embodiment, there is provided a cranial prosthesis as described herein for use in electrotherapy treatment of grade II glioma.

[0184] In one embodiment there is provided a cranial prosthesis as described herein for use in the electrotherapy treatment of diffuse astrocytoma or oligodendroglioma.

[0185] In one embodiment there is provided a cranial prosthesis as described herein for use in the electrotherapy treatment of grade III glioma.

[0186] In one embodiment there is provided a cranial prosthesis as described herein for use in the electrotherapy treatment of anaplastic astrocytoma or anaplastic oligodendroglioma.

[0187] In one embodiment, there is provided a cranial prosthesis as described herein for use in electrotherapy treatment of grade IV glioma.

[0188] In one embodiment, there is provided a cranial prosthesis as described herein for use in electrotherapy treatment of diffuse midline glioma.

[0189] In one embodiment, there is provided a cranial prosthesis as described herein for use in electrotherapy treatment of brain metastases.

[0190] In one embodiment there is provided a cranial prosthesis as described herein for use in electrotherapy treatment of drug-resistant epilepsy or symptom relief from drug-resistant epilepsy.

[0191] In one embodiment there is provided a cranial prosthesis as described herein for use in electrotherapy treatment of giant cell glioblastoma or glioblastoma multiforme.

[0192] In one embodiment, there is provided a cranial prosthesis as described herein for use in electrotherapy treatment of glioblastoma multiforme.

[0193] In one embodiment, there is provided a cranial prosthesis as described herein for use in electrotherapy treatment of a brain tumor following surgical resection.

[0194] In one embodiment, there is provided a cranial prosthesis as described herein for use in electrotherapy treatment of grade I, II, III, or IV gliomas following surgical resection.

[0195] In one embodiment, there is provided a cranial prosthesis as described herein for use in electrotherapy treatment of grade I glioma following surgical resection.

[0196] In one embodiment, there is provided a cranial prosthesis as described herein for use in electrotherapy treatment of pilocytic astrocytoma following surgical resection.

[0197] In one embodiment, there is provided a cranial prosthesis as described herein for use in electrotherapy treatment of grade II glioma following surgical resection.

[0198] In one embodiment, there is provided a cranial prosthesis as described herein for use in electrotherapy treatment of diffuse astrocytoma or oligodendroglioma following surgical resection.

[0199] In one embodiment, there is provided a cranial prosthesis as described herein for use in electrotherapy treatment of grade III glioma following surgical resection.

[0200] In one embodiment, there is provided a cranial prosthesis as described herein for use in electrotherapy treatment of anaplastic astrocytoma or anaplastic oligodendroglioma following surgical resection.

[0201] In one embodiment, there is provided a cranial prosthesis as described herein for use in electrotherapy treatment of grade IV glioma following surgical resection.

[0202] In one embodiment, there is provided a cranial prosthesis as described herein for use in electrotherapy treatment of giant cell glioblastoma or glioblastoma multiforme following surgical resection.

[0203] In one embodiment, there is provided a cranial prosthesis as described herein for use in electrotherapy treatment of glioblastoma multiforme following surgical resection.

[0204] (Treatment method) According to a further embodiment there is provided a cranial prosthesis as defined herein for use in a method of treatment of the human or animal body by therapy.

[0205] According to a further embodiment there is provided a cranial prosthesis as defined herein for use in a method of electrotherapy of the human or animal body by therapy.

[0206] According to a further feature of the present embodiment, there is provided a method of electrotherapy in a warm-blooded animal, such as a human, comprising administering electrotherapy to said animal comprising a cranial prosthesis as defined herein.

[0207] According to a further feature of the present embodiment, there is provided a method for treating:

[0208] Brain tumors (including grade I, II, III, or IV glioma), pilocytic astrocytoma, subependymal giant cell astrocytoma, diffuse astrocytoma, oligodendroglioma, oligodendroglioma NOS, anaplastic astrocytoma, undifferentiated astrocytoma differentiated oligodendroglioma, undifferentiated oligodendroglioma NOS, glioblastoma, giant cell glioblastoma, glioblastoma multiforme, subependymal giant cell astrocytoma, folliculoid astrocytoma, pleomorphic xanthoastrocytoma, glioma, oligoastrocytoma, Meningiomas (including grade I, II, or III meningiomas and other neoplasms involving the meninges (e.g., hemangiopericytoma)), childhood brain tumors (including ependymoma, medulloblastoma, atypical teratoid / rhabdomyosarcoma (AT / RT), choroid plexus papilloma, choroid plexus carcinoma, intracranial teratomas, and embryonal tumors with multilayered rosettes (ETMR)), pineal region tumors (e.g., pineoblastoma), pituitary region tumors (e.g., pituitary adenoma, craniopharyngioma, chordoma), Brain metastases (e.g., from lung cancer, breast cancer, genitourinary cancer, osteosarcoma, and melanoma), Stimulation of neural tissue to treat or alleviate symptoms of neurological conditions (e.g., promoting neurological recovery after stroke / traumatic brain injury); Recording brain activity for diagnostic purposes or to enable brain-computer interface communication; Deep brain stimulation (e.g., for the treatment of movement disorders (e.g., Parkinson's disease, essential tremor, dystonia), and psychiatric symptoms (e.g., anxiety, insomnia, depression, hyperarousal, obsessive-compulsive disorder)); Pain management, or Wound healing.

[0209] In a warm-blooded animal, such as a human, it comprises administering to said animal electrical therapy involving a cranial prosthesis as defined herein.

[0210] According to a further feature of the present embodiment there is provided a method of treating diffuse midline glioma in a warm-blooded animal such as a human, the method comprising administering to said animal an electrical therapy comprising a cranial prosthesis as defined herein.

[0211] According to a further feature of the present embodiment there is provided a method of treating or alleviating symptoms from drug resistant epilepsy in a warm-blooded animal such as a human, the method comprising administering to said animal an electrical therapy comprising a cranial prosthesis as defined herein.

[0212] According to a further feature of the present embodiment there is provided a method of treating a brain tumour in a warm-blooded animal such as a human, the method comprising administering to said animal an electrical therapy comprising a cranial prosthesis as defined herein.

[0213] According to a further feature of this embodiment, there is provided a method of treating grade I, II, III, or IV glioma in a warm-blooded animal, such as a human, comprising administering to said animal an electrical therapy comprising a cranial prosthesis as defined herein.

[0214] According to a further feature of the present embodiment there is provided a method for the treatment of grade I glioma in a warm-blooded animal such as a human, the method comprising administering to said animal an electrical therapy comprising a cranial prosthesis as defined herein.

[0215] According to a further feature of the present embodiment there is provided a method of treating pilocytic astrocytoma in a warm-blooded animal such as a human, the method comprising administering to said animal electrical therapy involving a cranial prosthesis as defined herein.

[0216] According to a further feature of the present embodiment there is provided a method of treating grade II glioma in a warm-blooded animal such as a human, the method comprising administering to said animal an electrical therapy comprising a cranial prosthesis as defined herein.

[0217] According to a further feature of the present embodiment there is provided a method of treating astrocytoma or oligodendroglioma in a warm-blooded animal such as a human, the method comprising administering to said animal an electrical therapy comprising a cranial prosthesis as defined herein.

[0218] According to a further feature of the present embodiment there is provided a method of treating grade III glioma in a warm-blooded animal such as a human, the method comprising administering to said animal an electrical therapy comprising a cranial prosthesis as defined herein.

[0219] According to a further feature of the present embodiment there is provided a method of treating anaplastic astrocytoma or anaplastic oligodendroglioma in a warm-blooded animal such as a human, the method comprising administering to said animal electrical therapy involving a cranial prosthesis as defined herein.

[0220] According to a further feature of the present embodiment there is provided a method of treating grade IV glioma in a warm-blooded animal such as a human, the method comprising administering to said animal an electrical therapy comprising a cranial prosthesis as defined herein.

[0221] According to a further feature of the present embodiment there is provided a method of treating diffuse midline glioma in a warm-blooded animal such as a human, the method comprising administering to said animal an electrical therapy comprising a cranial prosthesis as defined herein.

[0222] According to a further feature of the present embodiment there is provided a method of treating brain metastases in a warm-blooded animal such as a human, the method comprising administering to said animal an electrical therapy comprising a cranial prosthesis as defined herein.

[0223] According to a further feature of the present embodiment there is provided a method of providing treatment or palliation of drug-resistant epilepsy in a warm-blooded animal such as a human, the method comprising administering to said animal an electrical therapy comprising a cranial prosthesis as defined herein.

[0224] According to a further feature of the present embodiment there is provided a method of treating giant cell glioblastoma or glioblastoma multiforme in a warm-blooded animal such as a human, the method comprising administering to said animal an electrical therapy comprising a cranial prosthesis as defined herein.

[0225] According to a further feature of the present embodiment, there is provided a method of treating glioblastoma multiforme in a warm-blooded animal such as a human, the method comprising administering to said animal an electrical therapy comprising a cranial prosthesis as defined herein.

[0226] According to a further feature of the present embodiment, there is provided a method of treating a brain tumour following surgical resection in a warm-blooded animal such as a human, the method comprising administering to said animal an electrical therapy comprising a cranial prosthesis as defined herein.

[0227] According to a further feature of the present embodiment, there is provided a method of treating grade I, II, III or IV glioma following surgical resection in a warm-blooded animal such as a human, the method comprising administering to said animal an electrical therapy comprising a cranial prosthesis as defined herein.

[0228] According to a further feature of the present embodiment there is provided a method for the treatment of grade I glioma following surgical resection in a warm-blooded animal such as a human, the method comprising administering to said animal an electrical therapy comprising a cranial prosthesis as defined herein.

[0229] According to a further feature of the present embodiment, there is provided a method of treating pilocytic astrocytoma following surgical resection in a warm-blooded animal such as a human, the method comprising administering to said animal electrical therapy involving a cranial prosthesis as defined herein.

[0230] According to a further feature of the present embodiment there is provided a method for the treatment of grade II glioma following surgical resection in a warm-blooded animal such as a human, the method comprising administering to said animal an electrical therapy comprising a cranial prosthesis as defined herein.

[0231] According to a further feature of the present embodiment, there is provided a method of treating diffuse astrocytoma or oligodendroglioma following surgical resection in a warm-blooded animal such as a human, the method comprising administering to said animal electrical therapy involving a cranial prosthesis as defined herein.

[0232] According to a further feature of the present embodiment there is provided a method for the treatment of grade III glioma following surgical resection in a warm-blooded animal such as a human, the method comprising administering to said animal an electrical therapy comprising a cranial prosthesis as defined herein.

[0233] According to a further feature of the present embodiment, there is provided a method of treating anaplastic astrocytoma or anaplastic oligodendroglioma following surgical resection in a warm-blooded animal such as a human, the method comprising administering to said animal electrical therapy involving a cranial prosthesis as defined herein.

[0234] According to a further feature of the present embodiment there is provided a method for the treatment of grade IV glioma following surgical resection in a warm-blooded animal such as a human, the method comprising administering to said animal an electrical therapy comprising a cranial prosthesis as defined herein.

[0235] According to a further feature of the present embodiment, there is provided a method of treating diffuse midline glioma following surgical resection in a warm-blooded animal such as a human, the method comprising administering to said animal an electrical therapy comprising a cranial prosthesis as defined herein.

[0236] According to a further feature of the present embodiment, there is provided a method of treating brain metastases following surgical resection in a warm-blooded animal such as a human, the method comprising administering to said animal electrical therapy involving a cranial prosthesis as defined herein.

[0237] According to a further feature of the present embodiment there is provided a method of providing treatment or palliation of drug-resistant epilepsy in a warm-blooded animal such as a human, the method comprising administering to said animal an electrical therapy comprising a cranial prosthesis as defined herein.

[0238] According to a further feature of the present embodiment, there is provided a method of treating giant cell glioblastoma or glioblastoma multiforme following surgical resection in a warm-blooded animal such as a human, the method comprising administering to said animal an electrical therapy comprising a cranial prosthesis as defined herein.

[0239] According to a further feature of the present embodiment, there is provided a method of treating glioblastoma multiforme following surgical resection in a warm-blooded animal such as a human, the method comprising administering to said animal an electrical therapy comprising a cranial prosthesis as defined herein.

[0240] (kit) In one embodiment, 1. A cranial prosthesis as described herein; and 2. One or more electrodes; 3. A charge delivery device; A kit is provided comprising:

[0241] In one embodiment, 1. A cranial prosthesis as described herein; and 2. One or more electrodes; A kit is provided comprising:

[0242] In one embodiment, 1. A cranial prosthesis as described herein; and 2. A charge delivery device; A kit is provided comprising: [Brief description of the drawings]

[0243] [Figure 1A] FIG. 1 shows a plan view of a cranial prosthesis comprising a hole plate (1), the hole including four holes (2) that are substantially equidistant from a central point. [Figure 1B] FIG. 1 shows a plan view of a cranial prosthesis comprising a plate with holes (1), including four holes (2) substantially equidistant from a central point, with at least one exit point (15), further comprising a recess suitable for the escape of the lead wires (7) and a protrusion into the channel (14). [Figure 2A] This is a top view of a cranial prosthesis comprising a hole plate (1) including four holes (2) substantially equidistant from a central location, the plate also having a further hole at the central location (3) and incorporating screw fixation tabs (4) for attaching the cranial prosthesis to the skull via screws. [Figure 2B] A top view of a cranial prosthesis with a hole plate (1) including four holes (2) substantially equidistant from a central point, the plate also showing a further hole at a central point (3) and at least one exit point (15), with a recess suitable for the escape of the lead wires (7), a protrusion into the channel (14) and an integrated screw hole (13). [Figure 3A]A side exploded view of a cranial prosthesis with a curved hole plate (1), which includes four holes (2) substantially equidistant from a central point. The plate also includes a further hole at the central point (3), removable screw fixing tabs (4) for attaching the cranial prosthesis to the skull via screws, removable fixing means consisting of a flap (6) that fixes the electrodes when closed, and a recess (7) in the form of a channel suitable for the escape of the lead wires (7), which have at least one exit point (15) and connect the individual electrodes to the main lead wire. A removable protective cap (5) can be placed over the removable fixing means when closed. The cranial prosthesis is shown. [Figure 3B] A side exploded view of a cranial prosthesis with a curved hole plate (1), which includes four holes (2) substantially equidistant from a central point. The plate also includes a further hole at the central point (3), removable screw fixing tabs (4) and screw holes (13) for attaching the cranial prosthesis to the skull via screws or sutures, removable fixing means consisting of a flap (6) that fixes the electrodes when closed, and a recess (7) in the form of a channel suitable for the escape of the leads (7), which have at least one exit point (15) and connect the individual electrodes to the main lead and a protrusion into the channel (14) that serves to fix the leads in place. A removable protective cap (5) is shown in the cranial prosthesis, which can be placed over the removable fixing means when closed. [Figure 4A] A diagram showing the cranial prosthesis in situ, comprising a curved holed plate (1), removable screw fixing tabs (4) for attaching the cranial prosthesis to the skull (9) via screws (10), removable fixing means consisting of a flap (6) that fixes the electrodes (8) when closed, and a recess (7) in the form of a channel suitable for the escape of extension leads, the recess (7) having at least one exit point (15) and connecting the individual electrodes to the main lead. [Figure 4B]A diagram showing the cranial prosthesis in its biological position, comprising a curved holed plate (1), removable screw fixing tabs (4) and screw holes (13) for attaching the cranial prosthesis to the skull (9) via screws (10), removable fixing means consisting of a flap (6) that fixes the electrodes (8) when closed, and a recess (7) in the form of a channel suitable for the escape of extension leads, having at least one exit point (15), connecting the individual electrodes to the main lead and protrusions into the channel (14) that serve to fix the leads in place. [Figure 5A] The cranial prosthesis in position comprises a curved holed plate (1), removable screw fixing tabs (4) for attaching the cranial prosthesis to the skull (9) via screws (10), and removable fixation means consisting of a flap (6) that fixes the electrodes (8) when closed. The electrodes are connected to extension leads (11), which connect the individual electrodes to the main lead (12) via one of the exit points (15). A removable protective cap (5) can be placed over the removable fixation means when closed. [Figure 5B] The cranial prosthesis in position comprises a curved hole plate (1) with removable screw fixing tabs (4) and screw holes (13) for attaching the cranial prosthesis to the skull (9) via screws (10) or sutures. The electrodes are connected to extension leads (11) placed in recesses in the form of channels (7) and connect the individual electrodes to the main lead (12) via one of the exit points (15). Protrusions into the channels (14) help to fix the leads in place and removable protective caps (5) are placed over the electrodes. [Figure 6]The cranial prosthesis in position without a protective cap, comprising a curved holed plate (1), removable screw fixing tabs (4) and screw holes (13) for attaching the cranial prosthesis to the skull (9) via screws (10), and removable fixing means consisting of a flap (6) that fixes the electrodes (16) when closed. The electrodes are connected to extension leads (11) placed in recesses in the form of channels (7) that connect the individual electrodes to the main lead (12) via one of the exit points (15). A protrusion into the channel (14) serves to fix the lead in place. [Figure 7] 5B, side and top views of a cranial prosthesis with a curved hole plate. The curved hole plate includes an asymmetric curvature, where the radius of curvature in one direction is not equal to the radius of curvature in the direction perpendicular to said direction. For example, the asymmetric curvature is similar to the cross-section of the skull. The cranial prosthesis can be manufactured in a variety of asymmetric shapes, allowing the surgeon to select the shape that most closely resembles the part of the skull removed in surgery. The cranial prosthesis includes a curved multi-hole plate (1), a removable protective cap (5), a recess (7) in the form of a channel suitable for the escape of the extension leads that connect the individual electrodes to the main lead (12) through one of the exit points (15), a screw hole (13) for attaching the cranial prosthesis to the skull, and a protrusion into the channel (14) that serves to fix the lead in place. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0244] According to a first aspect of the present disclosure, there is provided a cranial prosthesis comprising a plate with holes, the holes including a plurality of holes substantially equidistant from a central location.

[0245] According to a second aspect of the present disclosure, there is provided a cranial prosthesis according to the first aspect, wherein the holes include a plurality of at least four holes substantially equidistant from a central point.

[0246] According to a third aspect of the present disclosure there is provided a cranial prosthesis according to the first or second aspect, comprising an additional hole in a central location.

[0247] According to a fourth aspect of the present disclosure, there is provided a cranial prosthesis according to any one of the first to third aspects, comprising a curved hole plate.

[0248] According to a fifth aspect of the present disclosure, there is provided a cranial prosthesis according to any one of the first to fourth aspects, comprising a recess suitable for allowing a lead wire to escape.

[0249] According to a sixth aspect of the present disclosure, there is provided a cranial prosthesis according to any one of the first to fifth aspects, having a substantially circular shape.

[0250] According to a seventh aspect of the present disclosure, there is provided a cranial prosthesis according to any one of the first to sixth aspects, comprising fixing means for fixing the electrodes in position within the holes.

[0251] According to an eighth aspect of the present disclosure, there is provided a cranial prosthesis according to any one of the first to seventh aspects, comprising a protective cap for placement over the hole and helping to hold the electrode in place.

[0252] According to a ninth aspect of the present disclosure, there is provided a cranial prosthesis according to any one of the first to eighth aspects, comprising means for attaching the cranial prosthesis to the skull via screws.

[0253] According to a tenth aspect of the present disclosure there is provided a cranial prosthesis according to any one of the first to ninth aspects, the cranial prosthesis being made of metal, polymer and / or ceramic.

[0254] According to an eleventh aspect of the present disclosure, there is provided a method of manufacturing a cranial prosthesis according to any one of the first to tenth aspects, comprising injection moulding, machining, casting or 3D printing.

[0255] According to a twelfth aspect of the present disclosure, there is provided a cranial prosthesis according to any one of the first to tenth aspects for use in electrotherapy.

[0256] According to a thirteenth aspect of the present disclosure, Brain tumors (including grade I, II, III, or IV glioma), pilocytic astrocytoma, subependymal giant cell astrocytoma, diffuse astrocytoma, oligodendroglioma, oligodendroglioma NOS, anaplastic astrocytoma, undifferentiated astrocytoma differentiated oligodendroglioma, undifferentiated oligodendroglioma NOS, glioblastoma, giant cell glioblastoma, glioblastoma multiforme, subependymal giant cell astrocytoma, folliculoid astrocytoma, pleomorphic xanthoastrocytoma, glioma, oligoastrocytoma, Meningiomas (including grade I, II, or III meningiomas and other neoplasms involving the meninges (e.g., hemangiopericytoma)), childhood brain tumors (including ependymoma, medulloblastoma, atypical teratoid / rhabdomyosarcoma (AT / RT), choroid plexus papilloma, choroid plexus carcinoma, intracranial teratomas, and embryonal tumors with multilayered rosettes (ETMR)), pineal region tumors (e.g., pineoblastoma), pituitary region tumors (e.g., pituitary adenoma, craniopharyngioma, chordoma), Brain metastases (e.g., from lung cancer, breast cancer, genitourinary cancer, osteosarcoma, and melanoma), Stimulation of neural tissue to treat or alleviate symptoms of neurological conditions (e.g., promoting neurological recovery after stroke / traumatic brain injury); Recording brain activity for diagnostic purposes or to enable brain-computer interface communication; Deep brain stimulation (e.g., for the treatment of movement disorders (e.g., Parkinson's disease, essential tremor, dystonia), and psychiatric symptoms (e.g., anxiety, insomnia, depression, hyperarousal, obsessive-compulsive disorder)); Pain management, or wound healing, The present invention provides a cranial prosthesis according to any one of the first to tenth aspects for use in electrotherapy treatment of a patient.

[0257] According to a fourteenth aspect of the present disclosure there is provided a cranial prosthesis according to any one of the first to tenth aspects for use in electrotherapy treatment of a brain tumour.

[0258] According to a fifteenth aspect of the present disclosure there is provided a method of treating glioblastoma multiforme in a warm-blooded animal such as a human, comprising administering to said animal an electrical therapy comprising a cranial prosthesis according to any one of the first to tenth aspects.

[0259] According to a sixteenth aspect of the present disclosure, 1. A cranial prosthesis according to any one of the first to tenth aspects, 2. One or more electrodes; 3. A charge delivery device; A kit comprising:

Claims

1. The plate has a hole and a recess suitable for escaping the lead wire. the holes include a plurality of holes substantially equidistant from a central location; Cranial prosthesis.

2. The holes include four holes that are substantially equidistant from a central location.

2. The cranial prosthesis of claim 1.

3. Including an additional hole in the center portion, 3. A cranial prosthesis according to claim 1 or 2.

4. With a curved hole plate, A cranial prosthesis according to any one of claims 1 to 3.

5. the recess suitable for the escape of the lead wires is constituted by a series of interconnecting channels and a recessed channel around the periphery; A cranial prosthesis according to any one of claims 1 to 4.

6. the recess adapted for lead escape includes a recessed channel around its periphery having multiple exit points; A cranial prosthesis according to any one of claims 1 to 5.

7. having a substantially circular shape; A cranial prosthesis according to any one of claims 1 to 6.

8. a fixing means for fixing the electrode in position within the bore; A cranial prosthesis according to any one of claims 1 to 7.

9. with a protective cap placed over the hole to help hold the electrode in place; A cranial prosthesis according to any one of claims 1 to 8.

10. means for attaching the cranial prosthesis to the skull via screws or sutures; A cranial prosthesis according to any one of claims 1 to 9.

11. A cranial prosthesis made of metal, polymer, and / or ceramics. A cranial prosthesis according to any one of claims 1 to 10.

12. A method for producing the cranial prosthesis according to any one of claims 1 to 11, comprising the steps of: Including injection molding, machining, casting or 3D printing; method.

13. The cranial prosthesis according to any one of claims 1 to 11, one or more electrodes; a charge delivery device; and Including the kit.

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