# Patent

## Title
Implantable neurostimulator with integral hermetic electronic enclosure, circuit substrate, monolithic feed-through, lead assembly and anchoring mechanism

## Abstract

An implantable medical device is provided for the suppression or prevention of pain, movement disorders, epilepsy, cerebrovascular diseases, autoimmune diseases, sleep disorders, autonomic disorders, abnormal metabolic states, disorders of the muscular system, and neuropsychiatric disorders in a patient. The implantable medical device can be a neurostimulator configured to be implanted on or near a cranial nerve to treat headache or other neurological disorders. One aspect of the implantable medical device is that it includes an electronics enclosure, a substrate integral to the electronics enclosure, and a monolithic feed-through integral to the electronics enclosure and the substrate. In some embodiments, the implantable medical device can include a fixation apparatus for attaching the device to a patient.

## Background
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a continuation of U.S. application Ser. No. 12/765,712, filed Apr. 22, 2010, now U.S. Pat. No. 8,494,641, which application claims the benefit under 35 U.S.C. 119 of U.S. Provisional Application No. 61/171,749, filed Apr. 22, 2009, and U.S. Provisional Application No. 61/177,895, filed May 13, 2009. These applications are herein incorporated by reference in their entirety.


FIELD OF THE INVENTION
The invention relates generally to a stimulating apparatus used to deliver electrical stimulation to a peripheral, central or autonomic neural structure. More specifically, the current invention relates to a neurostimulator apparatus designed to deliver electrical stimulation to the sphenopalatine ganglion (SPG) to treat primary headaches, such as migraines, cluster headaches and/or many other neurological disorders, such as atypical facial pain and/or trigeminal neuralgias.
BACKGROUND OF THE INVENTION
Electrical stimulation of peripheral, central and autonomic neural structures have shown increased interest due to the potential benefits it may provide to individuals suffering from many neurological and behavioral diseases. Many of these therapies today are not well accepted or are considered last in the therapeutic options due to the invasive nature of the therapy even though the efficacy may be quite good. This has created a need for less invasive therapies that are directed toward patient and physician clinical needs.
Primary headaches are one of the most debilitating ailments that afflict millions of individuals worldwide. The specific pathophysiology of headaches is unknown. Known sources of headache pain consist of trauma, vascular, autoimmune, degenerative, infectious, drug and medication-induced, inflammatory, neoplastic, metabolic-endocrine, iatrogenic, musculoskeletal and myofacial causes. Also, even though the possible underlying cause of the headache pain is identified and treated, the headache pain may persist.
Currently, the sphenopalatine (pterygopalatine) ganglion (SPG) is a target of manipulation in clinical medicine to treat headaches. The SPG is a large extra cranial parasympathetic ganglion. It consists of parasympathetic neurons that innervate (in part) the middle cerebral and anterior cerebral blood vessels, the facial blood vessels, and the lacrimal glands. A ganglion is a mass of nervous tissue found in some peripheral and autonomic nerves. Ganglia are located on the roots of the spinal nerves and on the roots of the trigeminal nerve. Ganglia are also located on the facial, glossopharyngeal, vagus and vestibulochoclear nerves. The SPG is a complex neural ganglion with multiple connections, including autonomic, sensory and motor. The maxillary branch of the trigeminal nerve and the nerve of the pterygoid canal, also known as the vidian nerve, which is formed by the greater and deep petrosal nerves send neural projections to the SPG. The fine branches from the maxillary nerve (pterygopalatine nerves) form the sensory component of the SPG, and these fibers pass through the SPG and do not synapse. The greater petrosal nerve carries the preganglionic parasympathetic axons from the superior salivary nucleus, which is located in the Pons, to the SPG. These fibers synapse onto the postganglionic neurons within the SPG. The deep petrosal nerve connects the superior cervical sympathetic ganglion to the SPG and carries postganglionic sympathetic axons that again pass through the SPG without any synapses.
The sphenopalatine ganglion (SPG), also called the pterygopalatine ganglion, is located within the pterygopalatine fossa. The pterygopalatine fossa (PPF) is bounded anteriorly by the maxilla, posteriorly by the medial plate of the pterygoid process and greater wing of the sphenoid process, medially by the palatine bone, and superiorly by the body of the sphenoid process. Its lateral border is the pterygomaxillary fissure (PMF), which opens to the infratemporal fossa.
Treatment of the SPG is mostly performed in attempted treatments of severe headaches, such as cluster headaches or chronic migraines. Various clinical approaches have been used for over 100 years to modulate the function of the SPG to treat headaches. These procedures vary from least invasive (e.g., transnasal anesthetic blocks) to much more invasive (e.g., surgical ganglionectomy) as well as procedures such as surgical anesthetic injections, ablations, gamma knife and cryogenic surgery. Most of these procedures have very good short term efficacy outcomes (days to months), however these results are usually temporary and the headache pain returns. A chronically implanted neurostimulator apparatus designed to deliver electrical stimulation to the SPG may provide much better long term efficacy in these patients. This application details the design of a neurostimulator for this purpose.
SUMMARY OF THE INVENTION
In some embodiments, an implantable medical device configured for delivery of electrical stimulation to the Sphenopalatine Ganglion (SPG) is provided, comprising an electronics enclosure, a substrate integral to the electronics enclosure, and a monolithic feed-through integral to the electronics enclosure and the substrate.
In some embodiments, the device further comprises a fixation apparatus integral to the electronics enclosure. The fixation apparatus can comprise at least one preformed hole configured to accept a bone screw. In some embodiments, the fixation apparatus is malleable and configured to be formed around the zygomaticomaxillary buttress.
In some embodiments, the electronics enclosure comprises an ASIC, an inductive coil, and a diode array.
In some embodiments, the implantable medical device is sized and configured for implantation into the pterygopalatine fossa. In other embodiments, the implantable medical device is sized and configured for implantation on the posterior maxilla.
In one embodiment, the device further comprises a stimulation lead coupled to the electronics enclosure. The stimulation lead can be constructed to an angle off an axis of the electronics enclosure. In some embodiments, the angle is approximately 0 to 60 degrees. In other embodiments, the angle is approximately 30 degrees.
In one embodiment, the implantable medical device is configured to lay flat against the posterior maxilla, and the stimulation lead is angled so as to maintain contact with the posterior maxilla as it extends to the pterygopalatine fossa.
In another embodiment, the stimulation lead is sized and configured to pass through a lateral opening of the pterygopalatine fossa. In some embodiments, a diameter of the stimulation lead is approximately 2-12 mm.
In one embodiment, the device can further comprise at least one electrode disposed on the stimulation lead. The device can further comprise at least one electrode wire coupling the at least one electrode to the electronics enclosure.
In some embodiments, the device further comprises a platinum/iridium tubing configured to connect the at least one electrode wire to the monolithic feed-through. In some embodiments, the platinum/iridium tubing comprises at least one witness hole.
In another embodiment, the device comprises a thin-film flex circuit configured to connect the at least one electrode wire to the monolithic feed-through. In another embodiment, a protrusion feature is disposed on the monolithic feed-through.
Some embodiments of the device further comprise an inductive coil configured to receive power and communication from an external controller at a depth of approximately 1-3 cm.
In some embodiments, the electronics enclosure comprises an ASIC printed on the electronics enclosure. Another embodiment further comprises at least one annular ring coupled to the electronics enclosure and configured to receive exposed ends of the monolithic feed-through.
Another embodiment of the device further comprises a stiffening mechanism configured to increase the linear stiffness of the stimulation lead. In some embodiments, the stiffening mechanism comprises a malleable wire. In other embodiments, the stiffening mechanism comprises a coiled wire. In yet another embodiment, the stiffening mechanism comprises a tapered supporting wire.
An implantable stimulator configured for delivery of electrical stimulation to a nerve is provided, comprising a housing, an electronics enclosure disposed on or in the housing, and a stimulation lead coupled to the electronics enclosure, the stimulation lead including a malleable wire configured give the stimulation lead rigidity to penetrate tissue and malleability to conform to a target anatomy.
In some embodiments, the stimulator comprises an attachment plate coupled to the housing, the attachment plate configured to accept a bone screw for attachment to bone.



BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a lateral view the neurostimulator in communication with the anatomy;
FIG. 2 is an isometric view of the neurostimulator;
FIGS. 3a-3b are top and side section views of the neurostimulator;
FIG. 4 is a transparent view illustrating the electrode wire interconnects;
FIG. 5 is a transparent view illustrating an electrode flex circuit interconnect;
FIG. 6 is an isometric view of a feed-through interconnect embodiment;
FIG. 7 is an exploded view of the neurostimulator's electronics enclosure;
FIG. 8 is an exploded view of an electronics enclosure embodiment;
FIG. 9 is an isometric view of the electronics enclosure embodiment;
FIG. 10 is a top down view of the neurostimulator's electronics and enclosure;
FIG. 11 is an isometric view of a feed-through interconnect embodiment;
FIG. 12 illustrates embodiments of the lead cross-sections;
FIG. 13 illustrates axial cross-sectional insets of lead embodiments;
FIG. 14 is an isometric view of an embodiment of a bendable lead;
FIG. 15 is an isometric view of an embodiment of a bendable lead;
FIG. 16 is an isometric view of an embodiment of a bendable lead.



DETAILED DESCRIPTION OF THE INVENTION
Referring to FIG. 1, a neurostimulator 100 is shown within the intended anatomy for the treatment of primary headaches and other neurological disorders. The neurostimulator of this embodiment comprises of a stimulator body 200a, an integral stimulation lead 200b, and an integral fixation apparatus 200c. The neurostimulator 100 can be implanted such that the stimulator body 200b is positioned medial to the zygoma 205 on the posterior maxilla 206 within the buccal fat pad of the cheek, and the integral fixation apparatus 200c is anchored to the zygomaticomaxillary buttress 203, such as by using standard craniomaxillofacial bone screws, for example. The integral stimulation lead 200c can be placed within the pterygopalatine fossa 202, or more specifically, in very close proximity to the sphenopalatine ganglion 204.
FIG. 2 illustrates one embodiment of an implantable neurostimulator 200. In this embodiment, the neurostimulator 200 comprises of a stimulator body 200a, an integral stimulation lead 200b, which includes one or more stimulating electrodes 201, and an integral fixation apparatus 200c. The neurostimulator 200 of this embodiment can be an inductively powered device having the necessary micro-electronics to store programmable stimulation parameters, deliver electrical stimulation per the programmed parameters and to allow bi-directional telemetry to enable communication with an external controller. An external transmitter (not shown) provides powers to and communications with the implanted neurostimulator.
The neurostimulator's micro-electronics can be housed in the stimulator body 200a, a hettnetic enclosure that protects the micro-electronics from fluid ingress when implanted within the body. The stimulator body can further include an electronics enclosure, a micro-electronics assembly, a monolithic feed-through assembly, and a lead interconnect assembly, and the stimulator body can be molded with a protective outer layer. In some embodiments the dimensions of the stimulator body are 8 mm wide, 4 mm thick, and 14 mm long.
The neurostimulator is sized and configured to be implanted on the posterior maxilla, so the neurostimulator thickness is limited by the available free space between the posterior maxilla and the coronoid process of the mandible. The average distance between the posterior maxilla and the coronoid process, measured from 79 patients using computed tomography, was 13±3 mm with a range of 6-24 mm (unpublished work). Thus, in some embodiments the thickness of the neurostimulator can range from 1 to 10 mm. The width and length of the neurostimulator are also limited by the surrounding anatomy, but in some embodiments the width and length are such that the neurostimulator maintains physical contact with the posterior maxilla. Thus, the neurostimulation width can range from 1-20 mm, and the length can range from 1-25 mm.
Electrical stimulation can be carried from the micro-electronics to one or more of the stimulating electrodes 201 through the stimulation lead 200b. The stimulation lead can be connected to the stimulator body through a series of feed-through assemblies. In the embodiment of FIG. 2, the stimulator body 200a and a portion of the stimulating lead 200b are shown with a biocompatible outer layer 202, created using a reaction injection molding (RIM) process, to protect the feed-through assemblies, provide strain relief to the stimulation lead and create an isodiametric neurostimulator. The neurostimulator is isodiametric because the size is maintained or decreases from the most proximal portion of the stimulator body to the most distal portion of the stimulating lead. In addition, the configuration of the outer layer does not contain any sharp corners or edges. This allows the neurostimulator to be implanted and explanted without grabbing or tearing of surrounding tissue. In some embodiments, the outer protective layer is created from biocompatible urethane and silicone co-polymer. The protective layer can be up to 1 mm thick, however in some embodiments the protective layer can be 0.1 to 2 mm thick. In other embodiments, different encapsulations methods and materials may be used, including but not limited to, potting, injection molding, casting, conformal coating, or adhering a compliant, semi-compliant, or rigid silicone rubber, epoxy, thermo-set or thermoplastic polymers or combination of any of the described methods and materials around the electronic assembly, lead interconnect, and lead assembly.
Also referring to FIG. 2, the integral fixation apparatus 200c can include a biocompatible mini-plate with one or more preformed holes extending off the body of the neurostimulator. The preformed holes can be designed to accept a standard bone screw. For example, the preformed holes can be approximately 1.9 mm in diameter and be sized to accept a standard bone screw with a diameter between 1.5-1.8 mm. The preformed holes can also be designed with a ninety-degree chamfer that allows the head of the standard bone screw to recess into the mini-plate and reside flush with the outboard face of mini-plate. In one embodiment the mini-plate is made from titanium (grade 2), which provides both good mechanical fatigue resistance and good flexibility. However, in other embodiments, the mini-plate can be made from other materials such as: commercially pure titanium such as grades 1, 3, or 4 and alloys such as grade 5 or 23; stainless steels such as 304 or 316; other biocompatible metals; and biocompatible plastics such as PEEK, nylon, or polypropylene.
Additionally, as shown in FIG. 2 the one or more preformed holes are set in a linear configuration off the proximal end of the stimulator body to increase the flexibility of the mini-plate. In the intended target anatomy, the mini-plate can be anchored to the thick dense bone of the zygomatic process of the maxilla, generally referred to the zygomaticomaxillary buttress. When the stimulator body is positioned on the posterior maxilla, the mini-plate must be formed around the buttress without adversely moving or dislodging the stimulator body and the stimulation lead. Thus, the mini-plate must be malleable so that it can be formed around the buttress as well as resistant to flex fatigue from repeat bending. In one embodiment, in which the mini-plate is made from titanium (grade 2), the center-to-center distance between each of the preformed holes can be 6 mm, and the width of the beam between each preformed hole can be 1.3 mm. In this embodiment, the mini-plate provides the proper amount of malleability and flex resistance needed to form the mini-plate around the buttress and to allow for long term reliability for the chronic implantable neurostimulator. Also, the second moment of area across the mini-plate is designed to be constant, which facilitates uniform bending and typically creates a larger more uniform arch. The larger arch that is formed from bending of the mini-plate helps to resist stress concentrations and promotes matching of the surface of the mini-plate to the underlying anatomical bone features. In other embodiments, the center-to-center distance between each of the preformed holes can be between 3-10 mm and the width of the beam between each preformed hole can be 0.5 to 3 mm.
Additionally, in another embodiment, the arrangement of the preformed holes on the mini-plate can be configured into a Y configuration (a single mini-plate extending off the stimulator body with two tails extending out like a Y), a T configuration (a single mini-plate formed into a T), an L configuration (a single mini-plate formed into an L) or an X configuration (a single mini-plate formed into a X, with one leg of the X attached to the stimulator body). In any of these configurations, each of the mini-plates can contain one or more preformed holes and include the same features described above. In additional embodiments, the neurostimulator can include one or more mini-plates projecting off the stimulator body, including but not limited to a mini-plate extending off the opposing end of the stimulator body from the stimulating lead, and one or more mini-plates extending off the two other adjacent sides of the neurostimulator.
FIG. 2 also illustrates the stimulating lead 200b of neurostimulator 200. In this embodiment, the stimulating lead comprises of one or more stimulation electrodes 201 and a corresponding number of connecting lead wires for each of the stimulating electrodes. Each connecting lead wire connects to a feed-through on the stimulating body. The connecting wires provide a conduit to deliver electrical stimulation pulses between the micro-electronics and the stimulating electrodes. In one embodiment, the stimulation lead projects from the distal face of the stimulator body constructed to an angle of 30 degrees off the stimulator axis. In this embodiment, the inboard planer side of the neurostimulator body is configured to lay flat against and in interment communication with the posterior maxilla, which also coincides with the stimulator surface from which the integral fixation apparatus 200c extends. The angle of the stimulating lead projecting off the stimulator body allows the lead to maintain contact with the posterior maxilla as it courses from the stimulator body to the pterygopalatine fossa and reduces any stress on the stimulating lead by reducing the lead curvature. In some embodiments, the degree of the angle between the stimulator body and stimulating lead can range from between approximately 0 to 60 degrees. In yet other embodiments the stimulating lead may contain multiple compound angles with the neurostimulator, the angles may be on or off axis with the stimulator body.
In the embodiment of FIG. 2, the stimulating lead includes seven cylindrical stimulating electrodes 201 that can be configured to provide either cathodic or anodic stimulation. In this embodiment the stimulating lead comprises at least 5 stimulating cathodic electrodes, or working electrodes. The working electrodes are configured to be implanted in very close proximity to the SPG within the pterygopalatine fossa and to be used for delivering the stimulation pulses from the micro-electronics. In some embodiments, the two most proximal electrodes to the stimulator body 200a can be electronically coupled to create a larger reference or return electrode. This reference electrode can be configured as an anode and positioned on the stimulating lead such that it is the farthest electrode from the SPG.
The length and spacing of the electrodes are configured to optimize stimulation of the SPG. The average height and width of the SPG has been found to be 3.28 mm, range 2-6 mm and 1.76 mm, range 1-3 mm respectively. In some embodiments, the spacing distance between any two adjacent stimulation electrodes is no greater than 1.0 mm and each electrode is 1.5 mm in length. The electrode length and the spacing assures that at least one electrode maintains communication with the SPG. In other embodiments the electrode spacing can range from 0.3-4 mm, and the length of each electrode can range from 0.4 to 4 mm. In one embodiment, the stimulating lead and hence each electrode, is 1 mm in diameter. The diameter of the stimulating lead can be designed such that the lead passes through the lateral opening the pterygopalatine fossa, called the pterygopalatine fissure, which has been reported to be between 2-12 mm wide. In other embodiment, the diameter of the lead can range from 0.5 to 3 mm. Each stimulation electrode has a thickness of 0.1 mm; a minimum thickness of 0.05 mm is needed prevent damage during manufacturing and implantation. The stimulation electrodes can be made from 90/10 platinum/iridium alloy. However, in other embodiments the stimulation electrodes can be made from other biocompatible metallic alloys, including but not limited to platinum, platinum alloys, palladium, palladium alloys, titanium, titanium alloys, various stainless steels, or any other conductive biocompatible metals and biocompatible non-metals such as but not limited to carbon.
FIG. 3a is an elevated view and FIG. 3b is a sectioned side view of neurostimulator 300, and illustrates the integral design of the neurostimulator. In FIG. 3a, the neurostimulator 300 includes stimulator body 300a, integral stimulating lead 300b, which includes one or more stimulation electrodes 301, and integral fixation apparatus 300c. FIG. 3b shows a sectioned side view of the neurostimulator through the line A-A in FIG. 3a. In this embodiment, the sectioned side view shows the hermetic electronics enclosure within the stimulator body 300a, integral stimulation lead 300b, electrode wire interconnect assembly 305 and the electrode connection wires 303. Also shown in FIG. 3b is the protective (insulation) outer layer 304, which encapsulates the stimulator body and the proximal portion of the stimulation lead. The protective layer also covers the proximal portion of the stimulation lead to provide additional strain relief at the junction between the lead and the stimulator body. This layer is formed by reaction injection molding (RIM) with a biocompatible urethane and silicone co-polymer. Other encapsulations methods and materials may include potting, injection molding, casting, conformal coating, or adhering a compliant, semi-compliant, or rigid silicone rubber, epoxy, thermo set or thermoplastic polymers or combination of any of the described methods and materials around the electronic assembly, lead interconnect, and lead assembly.
FIG. 4 shows an enlarged detail view of the encapsulated hermetic electronics enclosure 411, feed through assembly and interconnect assembly. The feed-through wires 410 projecting from the upper surface of the hermetic electronic enclosure 411 can be bonded to the enclosure. In some embodiments, the feed-through wires are brazed onto the enclosure using gold braze 412. In other embodiments the feed-through wires can be adhered using a glass frit to the enclosure or otherwise molded or bonded to the enclosure. The feed-through wires can be served upward and then down along the enclosure toward the stimulation lead and connected to the electrode wires 414. In some embodiments, a platinum/iridium tube 413 is used to connect the electrode wires to the feed-through wires. The proximal segment of the platinum/iridium tubing can be crimped onto the feed-through wires and the distal end of the tubing can be crimped to the electrode wires 414. The platinum/iridium tubing includes at least two witness holes 416. These witness holes allow the operator to verify that the wires are appropriately placed prior to applying the crimp. In other embodiments the platinum/iridium tubing can be resistance welded; laser welded, brazed, or otherwise secured using epoxy or other conductive adhesives to the feed-through and electrode wires.
FIG. 4 also shows the outer protective encapsulation layer (in transparency). In one embodiment, the outer protective layer is a copolymer; a blend of biocompatible urethane and silicone co-polymer uniquely compounded to provide superior adhesion to the substrate while providing a tissue friendly interface. The protective layer can be molded over the stimulator body and a portion of the stimulating lead using a reaction injection molding (RIM) process. The material can be stable, biocompatible, resistant to oxidation and have increased mechanical properties compared to other polyurethanes and silicones. The protective layer is designed to provide electrical isolation between exposed conductors as well as a primary biocompatible interface between the tissue and the implanted device. The use of this material to surround the electrode wire interconnect assembly to the feed-through assembly provides stability and electrical insulation to each interconnection. The material can also be molded onto a proximal portion of the stimulation lead to act as a strain relief.
FIG. 5 illustrates an alternative embodiment of an electrode wire to feed-through interconnect system similar to the embodiment described above, except that each electrode is connected to the feed-through assembly using an organic thin-film flex circuit 520. The flex circuit can comprise of a polyamide film with printed trace lines made of a conductive material such as gold. In one embodiment, the flex circuit contains at least six trace lines printed on the polyamide film with each trace line corresponding to one electrode. In another embodiment, the polyamide film is expanded near the interconnect assembly, such that the printed trace lines are equally spaced with the feed-through assembly wires. Then each trace line on the polyamide film is extended off the film like a comb with individual fingers, each finger representing on printed trace line. Each trace can then be crimped onto the feed-through assembly wires as described above. The polyamide film can be narrowed once it enters into the stimulating lead assembly. In one embodiment, the narrowed film is no wider than 0.5 mm, such that the film is smaller than the diameter of the lead assembly (e.g., 1.0 mm). In one embodiment, the polyamide film that comprises the flex circuit is 0.1 mm thick, however in other embodiments the flex circuit can be approximately 0.05 to 0.5 mm thick. In other embodiments, the flex circuit can take on the shape needed to facilitate the interconnection between the stimulation electrodes and the feed-through assembly.
In one embodiment, as shown in FIG. 6, the electronics enclosure 610 and integral feed-through wires 611 are shown and include an additional protrusion feature 612 in the feed-through assemblies. The protrusion feature is used to increase the surface distance between each of the monolithic feed-through wires and provide a larger surface area for increased adhesion of the copolymer. Once the outer protective layer is molded onto the electronics enclosure it provides stability and protects the electrical connections between the feed-through wires and the electrode wires. If fluid ingress occurs, coupled with the copolymer delaminating, the increased surface distance (i.e., the electrical path) between electrodes will help prevent electrical shorting. In one embodiment, the protrusion features extend above the surface of the electronics enclosure by approximately 0.25 mm. In other embodiments, the protrusions can extend between 0.1 to 0.5 mm above the enclosure. Also shown in FIG. 6, is a staggered configuration of the feed-through assemblies. Due to size constraints on the electronic enclosure, the feed-through assemblies may not be able to be arranged in a linear fashion without unintended electrical shorting between two adjacent feed-through assemblies. By staggering the feed-through assemblies, an increased number of feed-through wires can be used and the distance between adjacent feed-through assemblies could be increased, reducing the risk of electrical shorting.
FIG. 7 is an isometric exploded view of a hermetic electronics enclosure of a neurostimulator. In this embodiment, the hermetic enclosure comprises a substrate and monolithic feed-through 721, a bezel 723 and a lid 724. The hermetic enclosure houses the micro-electronic assembly, an inductive coil 726 and a ferrite core 727. In one embodiment, the substrate is manufactured from stabilized zirconium oxide and the feed-through wires are gold brazed into place and are manufactured from platinum-iridium (80/20). In other embodiments, the substrate and integral monolithic feed-through assembly 721 can be manufactured from one of many ceramic materials, including, but not limited to aluminum oxide, transparent polycrystalline aluminum oxide, stabilized zirconium oxide, aluminum nitride, and silicon nitride. The substrate and monolithic feed-through assembly can be produced using a variety of manufacturing methods including but not limited to post sintering machining, green form pressing and sintering, and injection molding and sintering.
In one embodiment, the bezel 723 and the lid 724 can be manufactured using a high resistance, biocompatible metal such as commercially pure or alloyed titanium. In other embodiments, the bezel can be made out of but not limited to other materials including corrosion resistant stainless steels, refractory's such as aluminum oxide, transparent polycrystalline aluminum oxide, stabilized zirconium oxide, aluminum nitride, and silicon nitride or glass fit.
In one embodiment, the bezel 723 is brazed at the location to the mating edge of the ceramic substrate and monolithic feed-through assembly using pure gold braze. This braze provides a gas tight seal between the bezel and the ceramic substrate of the electronics enclosure. The bezel also exhibits recessed self-alignment nesting features suitable to receive and accommodate the lid 724, which is welded to the bezel providing another gas tight seal at location between the bezel and the lid. The bezel is brazed on the ceramic substrate prior to populating the electrodes within the substrate. By doing so, the titanium lid can be welded onto the titanium bezel after the electronics assembly has been populated within the substrate. The welding between the bezel and the lid can be a low temperature process, which does not affect the electronics within the enclosure. However, if the bezel is not used, the lid would need to be brazed onto the substrate, which is a high temperature process. The high temperature process would adversely affect the electronics. The gold braze between the substrate and the bezel can be done prior to populating the electronics within the substrate allowing a lower temperature weld to be done between the lid and the bezel after populating the electronics.
Referring to FIG. 7, the electronics enclosure can house a micro-electronics assembly, an inductive coil 726 and a ferrite core 727. In this embodiment the inductive coil is connected and bonded into the electronics enclosure and used to inductively receive power and provide bi-directional communication with an external controller (not shown). The inductive coil can be configured such that when implanted within the neurostimulator at a depth of 1-3 cm, the inductive coil can still receive power and communicate with the external controller. The inductive coil can be part of an RC (resistor-capacitor) circuit designed to resonate between 120 and 130 kHz. In one embodiment, the inductive coil resonates via 2.7 to 3.3 nF capacitor. The coil can be 200 turns of 41 gauge bondable solid core magnetic wire and wound into a rectangular orientation, 11.47 mm long by 5.47 mm wide, for example. In one embodiment, the thickness of the coil is 1.5 mm. In other embodiments, the coil is configured such that it includes a step on the inner surface. This step allows for the coil to sit flat on a specific surface of the ceramic substrate and clear the protrusions of the feed-through wires on another portion of the inside surface of the ceramic substrate. The step in the coil can increase the number of turns that can be allowed to fit into the electronics enclosure. The increased number of turns allows for greater distance in which the coil can be externally powered, thus allowing for a greater distance over which bi-directional communication can occur. Additionally, in other embodiments, the length, width and thickness of the coil can be adjusted to fit into the electronics enclosure and configured such to optimize the power transfer and communication distances. The ferrite core can be bonded into the top side of the inductive coil and used to align the magnetic flux to optimize energy transfer. The micro-electronics, inductive coil and ferrite core are all contained within the electronics enclosure and hermetically sealed using a titanium lid.
The hermetic electronics enclosure also supports an integral fixation apparatus 728. The fixation apparatus as described above can be fixed to the enclosure, and in one embodiment the fixation apparatus is laser welded to the enclosure. In other embodiment the fixation apparatus can be bonded using standard biocompatible adhesives, or otherwise mechanical attached, e.g., swage or press fit to the hermetic enclosure. Additionally, the fixation apparatus includes an additional routing feature 729 located on the distal side of the stimulator body. In one embodiment, the routing feature is made from the same titanium as the fixation mini-plate and is configured to curve around the electrode wires as they pass from the stimulating lead to the stimulator body. The electrode wires are guided through the routing feature on the fixation apparatus, where they can be organized and crimped to the feed-through wires on the electronics enclosure.
In an alternative embodiment, as illustrated in FIG. 8, an isometric exploded view of the hermetic electronics enclosure 810 including the integral fixation apparatus which includes the bezel 811 and a lid 812 is shown without the stimulation lead assembly and protective outer layer. In this embodiment, the fixation apparatus is integral to the bezel. The integral bezel and fixation apparatus are then brazed onto the ceramic electronics enclosure.
In this embodiment, the braze bezel 811 also exhibits a recessed self-alignment nesting features suitable to receive and accommodate the lid 812 which can be welded to the braze bezel providing a gas tight seal between the braze bezel and the lid, as shown in FIG. 8.
FIG. 9 illustrates one embodiment of a three-dimensional micro-electronics assembly. In this embodiment the micro-electronics assembly comprises of an Application Specific Integrated Circuit (ASIC) 730, a diode array 731, a diode array interposer 732, an ASIC interposer, and discrete components including but not limited to a resonating capacitor 734 and a smoothing capacitor. In one embodiment, the diode array is soldered or conductive adhesive bonded onto an organic or ceramic interposer. The diode interposer provides a conductive patterned electrical circuit between the arranged diodes. In one embodiment, the diode interposer is then adhesive bonded to the upper surface of the ASIC. The diode array rectifies the alternating current coming from the RC circuit which is then used to power the ASIC.
As shown in FIG. 9, the AISC with the bonded diode array interposer can be adhesive bonded onto a second organic or ceramic interposer. In one embodiment the ASIC is wire-boned using gold ball bonding or wedge bonding between exposed circuit pads on the interposer and exposed pads on the ASIC. The ASIC interposer provides a patterned electrical circuit between discrete components and the ASIC including but not limited to a resonating capacitor and smoothing capacitors. The discrete components are soldered or conductive adhesive bonded to the ASIC interposer. In one embodiment, the micro-electronic assembly, including the ASIC 730, diode array 731, diode array interposer 732, ASIC interposer, resonating capacitor 734 and smoothing capacitor, is bonded or adhered to the lower surface of the brazed hermetic ceramic electronics enclosure, or alternatively, is printed directly into the brazed hermetic ceramic electronics enclosure.
In one embodiment, as shown in FIG. 9, the ASIC interposer contains one or more apertures 736, which are metalized annular rings, to receive the exposed ends of the conductive feed-through pins. The electrical connection between the ASIC interposer and the feed-through wire is done using conductive epoxy. In other embodiments the electrical connections between the ASIC interposer and the feed-through wires can be done using traditional wire-bonding techniques, or soldering the metalized annular rings around the aperture to the feed-through pins.
In other embodiments, as illustrated in FIG. 10, the ASIC interposer described above is metalized directly onto the inner bottom surface of the ceramic substrate. The metalized patterned electrical circuit is metalized using thick film, or a sputtered metal deposition to impose the circuit pattern on the substrate, in which to affix electronic components. Metalizing the substrate facilitates communication between the assembled components and the outside environment at the location where the metalized substrate interfaces with the monolithic feed-through using wires brazed into the enclosure. In one embodiment, the metalized thick film or sputter is a few angstroms thick, and more specifically a 2000 angstrom thick layer of platinum and gold is laid directly on the ceramic substrate to create the patterned electrical circuit.
In other embodiments, as illustrated in FIG. 11, the position of the monolithic feed-through assemblies 911 on the ceramic substrate 910 can protrude through the distal wall of the ceramic substrate. In this embodiment, the substrate can be manufactured from stabilized zirconium oxide and the feed-through pins can be gold brazed into place and can be manufactured from platinum-iridium (80/20). In various other embodiments the integral substrate and monolithic feed-through assembly may be manufactured from one of many ceramic materials, including, but not limited to aluminum oxide, transparent polycrystalline aluminum oxide, aluminum nitride, and silicon nitride. Also the electronics enclosure, integral substrate and monolithic feed-through assembly can be produced using a variety of manufacturing methods including but not limited to post sintering machining, green form pressing and sintering, and injection molding and sintering. The pins may also be manufactured from platinum or other platinum alloys, palladium, titanium, or stainless steel.
FIG. 12 illustrates a side view of one embodiment of the neurostimulator 1200, which can comprise of a stimulator body 1200a, a stimulation lead 1200b, which contains one or more stimulation electrodes 1201, and an integral fixation apparatus 1200c. FIG. 12 also shows two embodiments of the cross-section through the diameter of the stimulation lead 1200b. In one embodiment, the cross-section view AA in FIG. 12, the electrode wires or conductors 1202 that are electrically connected to the feed-through assemblies on the electronic enclosure for each electrode are discrete, independently insulated conductor wires serviced within individual lumens 1203 in the integral stimulation lead 1200b. In one embodiment the stimulation lead is manufactured using a multi-lumen extruded copolymer. The copolymer used in the extruded multi-lumen lead is very similar to the copolymer used in the outer protective (insulating) layer that covers the stimulator body and a portion of the stimulation lead. In this embodiment, the copolymer used has an increased hardness compared to the outer protective layer copolymer. In one embodiment, the conductive electrode wires can be made of stranded platinum-iridium (90/10) wire with a diameter of 0.1 mm. In other embodiments the conductive wire can be made from but not limited to stranded or finely bundled cable assemblies or in alternate embodiments a solid wire. The conductive electrode wires can be manufactured from but not limited to platinum, platinum-iridium alloy, MP35N or a variation of MP35N including a DFT, drawn and filled tubing, stainless steel, gold, or other biocompatible conductor materials. The center lumen in the cross-section can includes a malleable wire segment made from platinum-iridium (90/10) with a diameter up to 0.4 mm. The malleable wire segment in the center lumen, in one embodiment, can be made from but not limited to platinum, platinum-iridium alloy, MP35N or a variation of MP35N including a DFT. The additional of the malleable wire or other stiffening mechanism to the center lumen, in one embodiment, provides the stimulation lead assembly with added mechanical properties, such as, increasing the linear stiffness of the lead and providing increased flex fatigue properties to the entire lead assembly. The increase in the linear stiffness of the stimulation lead is needed to ease the implantation of the neurostimulator. For example, the stimulation lead having a malleable wire can be configured to have the rigidity to penetrate and dissect through blunt tissue, but remain malleable enough to be bent into a shape to conform to the target anatomy.
In one embodiment, the neurostimulator is configured to be implanted within the pterygopalatine fossa, a deep structure located behind the base of the nose, and just anterior the skull base. As described in U.S. Patent Application No. 61/145,122 to Papay, which is incorporated herein by reference, the intended implantation of the neurostimulation into the pterygopalatine fossa is through a trans-oral approach using a custom implantation tool to aid in the placement of the neurostimulator. An increased linear stiffness of the stimulation lead will greatly add to the ease of the implantation. Additionally, as referenced the Papay application, the intended implant location of the stimulator body is on the posterior maxilla with the stimulation lead extending to the pterygopalatine fossa along the posterior maxilla. In this location, the stimulator body and the stimulator lead will be subject to compressive forces due to the motion of the surrounding anatomy from movements of the lower jaw. Thus increasing the flex fatigue resistance of the stimulation lead will increase the life time of the chronically implanted neurostimulator.
Referring still to FIG. 12, in other embodiments, the center lumen of the stimulation lead may not be used to support a wire segment. In one embodiment, a supporting wire 1202 may be floating within the lumen or directly contacting the stimulation lead over-molding encapsulation, as shown in the cross-sectional view AA “ALT” on the right in FIG. 12. This view is in reference to the thin film flex circuit embodiment described above. In this embodiment, the flex circuit 1205 is suspended within the encapsulation of the stimulation lead. Also as discussed above the flex circuit contains one or more printed conductive traces 1206 that electrically connect each electrode to the feed-through assembly on the electronics enclosure.
FIG. 13 shows additional alternate embodiment of a neurostimulator in side view. FIGS. 13a, b, and c also show three sectional details of the neurostimulator illustrating alternative embodiments that include methods to facilitate mechanical manipulation and resistance to fatigue in-vivo. FIG. 13a shows one embodiment in which a coiled wire 1301 may be added to the proximal portion of the stimulation lead as it mates with the stimulator body. In this embodiment the coiled wire can be manufactured from a straight or partially coiled wire made of a highly malleable biocompatible alloy such as palladium, platinum, or annealed platinum. In this embodiment the coiled wire is configured such that the stimulation lead has optimal resistance to fatigue in vivo. To optimize the flex resistance of the inserted coil within the stimulation lead the following parameters can be adjusted; the diameter of the wire, the outer diameter of the coil, pitch of the coil, and the number of turns in the coil. In one embodiment, the coil was manufactured using a palladium wire with a diameter of 0.25 mm, and manufactured into a coil with 5 turns, a coil pitch of 1.0 mm, and an outer diameter 1.0 mm. The coil is then suspended within the over-mold material 1302 of the lead as described above. In this embodiment the electrode wires 1303 that electrically connect the electrodes to the feed-through interconnects transverse through the center of the coiled wire segment.
In alternate embodiments, as shown in FIG. 13c, the supporting wire 1304 can be straight and be manufactured from more rigid materials such as titanium, stainless steel, or nitinol. In other embodiment, a combination between the more rigid straight section of the wire and a coiled wire can be employed. In this embodiment the coiled/straight material can be manufactured using the one wire or using discrete wires for each segment of the supporting wire. In this embodiment, the supporting wire can be manufactured from highly malleable biocompatible alloy such as palladium, platinum, or annealed platinum allow or from more rigid materials such as annealed titanium, stainless steel, nitinol, or any combination thereof.
In yet another alternative embodiment, as shown in FIG. 13b, a tapered supporting wire 1305 can be used. In this embodiment, a tapered wire with a heaver diametric cross-section proximally and tapering to a finer cross-section distally is used to provide support to the stimulation lead. In one embodiment, the tapered wire may be manufactured from either highly malleable biocompatible alloy such as palladium, platinum, or annealed platinum allow. In alternate embodiments the wire can be manufactured from more rigid materials such as annealed titanium, stainless steel, or nitinol. In one embodiment, the tapered supporting wire can start at a diameter of 0.5 mm and taper to a diameter 0.1 mm at the distal portion of the wire. In other embodiments, the tapered wire can start with a diameter between 0.5 to 0.8 mm and taper to a diameter of 0.4 to 0.05 mm. The tapered support wire can provide increased mechanical stability and improved flex resistance at the junction between the stimulation lead and the stimulator body, as well as provide increased bending at the distal tip of the stimulation lead over a straight non-tapered supporting wire.
FIGS. 14, 15 and 16 illustrate the ability of the integral stimulation lead, in one or more embodiments to be bent and/or shaped into any direction and the ability to retain the directional manipulation made to the stimulation lead during implant. FIGS. 14 and 15 depict the ability of the distal stimulation lead to be bent in any direction to accommodate the needed implantation of the neurostimulator. FIG. 16 depicts the ability of the entire stimulation lead to be manipulated into any angle compared to the stimulator body and retain that position during implantation.
It will be appreciated by persons skilled in the art that the present invention is not limited to what has been particularly shown and described. Rather, the scope of the present invention includes both combinations and sub-combinations of the various features described, as well as variations and modifications thereof that are not in the prior art, which would occur to persons skilled in the art upon reading the foregoing description.

## Claims

1. An implantable medical device configured for delivery of electrical stimulation to the Sphenopalatine Ganglion (SPG), comprising:
an electronics enclosure;
a substrate housed in the electronics enclosure;
a monolithic feed-through coupled to the electronics enclosure and the substrate;
a stimulation lead having at least one electrode coupled to the electronics enclosure with at least one electrode wire; and
a platinum/iridium tubing having at least one witness hole, the platinum/iridium tubing being configured to connect the at least one electrode wire to the monolithic feed-through.

2. The implantable medical device of claim 1 further comprising a fixation apparatus attached to the electronics enclosure.

3. The implantable medical device of claim 2 wherein the fixation apparatus comprises at least one preformed hole configured to accept a bone screw.

4. The implantable medical device of claim 2 wherein the fixation apparatus is malleable and configured to be formed around the zygomaticomaxillary buttress.

5. The implantable medical device of claim 1 wherein the electronics enclosure comprises an ASIC, an inductive coil, and a diode array.

6. The implantable medical device of claim 1 wherein the implantable medical device is sized and configured for implantation into the pterygopalatine fossa.

7. The implantable medical device of claim 1 wherein the implantable medical device is sized and configured for implantation on the posterior maxilla.

8. The implantable medical device of claim 1 wherein the stimulation lead is constructed to an angle off an axis of the electronics enclosure.

9. The implantable medical device of claim 8 wherein the angle is approximately 0 to 60 degrees.

10. The implantable medical device of claim 8 wherein the angle is approximately 30 degrees.

11. The implantable medical device of claim 8 wherein the implantable medical device is configured to lay flat against the posterior maxilla, and the stimulation lead is angled so as to maintain contact with the posterior maxilla as it extends to the pterygopalatine fossa.

12. The implantable medical device of claim 8 wherein the stimulation lead is sized and configured to pass through a lateral opening of the pterygopalatine fossa.

13. The implantable medical device of claim 12 wherein a diameter of the stimulation lead is approximately 2-12 mm.

14. The implantable medical device of claim 1 further comprising a thin-film flex circuit configured to connect the at least one electrode wire to the monolithic feed-through.

15. The implantable medical device of claim 1 further comprising a protrusion feature disposed on the monolithic feed-through.

16. The implantable medical device of claim 1 further comprising an inductive coil configured to receive power and communication from an external controller at a depth of approximately 1-3 cm.

17. The implantable medical device of claim 1 wherein the electronics enclosure comprises an ASIC printed on the electronics enclosure.

18. The implantable medical device of claim 17 further comprising at least one annular ring coupled to the electronics enclosure and configured to receive exposed ends of the monolithic feed-through.

19. The implantable medical device of claim 1 further comprising a stiffening mechanism configured to increase the linear stiffness of the stimulation lead.

20. The implantable medical device of claim 19 wherein the stiffening mechanism comprises a malleable wire.

21. The implantable medical device of claim 19 wherein the stiffening mechanism comprises a coiled wire.

22. The implantable medical device of claim 19 wherein the stiffening mechanism comprises a tapered supporting wire.