Systems, implant units, and methods for treating headaches and facial pain

Abstract

Disclosed herein is a neurostimulation system for treating headaches, the system comprising an implant unit configured for implantation within a subject's body, an external unit configured for a location outside the subject's body, and a charging and programming unit, the external unit comprising a processor, a power source, and a primary transmission unit in electrical communication with the power source and the processor, the implant unit comprising at least one electrical conductor, at least one pair of modulating electrodes attached to the at least one electrical conductor, and a secondary transmission unit in electrical communication with the at least one electrical conductor, the processor configured to establish a coupling between the primary transmission unit and the secondary transmission unit and transmit power from the power source to the implant unit via the coupling. Such a method may be beneficial, for example, in pain management, where propagation of pain signals is undesirable.

Description

[Technical field]

[0001] (Technical field) The disclosed subject matter described hereinafter refers to systems and methods for electrical neurostimulation. Further, reference is made to the use of the methods for electrical neurostimulation in the treatment of headaches and facial pain. [Background technology]

[0002] (background) Neuromodulation, i.e., electrical stimulation of nerves, presents an opportunity to treat many physiological conditions and disorders by interacting with the body's own natural neural processes. Neurostimulation involves the inhibition (e.g., blocking), modulation, modification, regulation, or therapeutic alteration of electrical or chemical activity in the central, peripheral, or autonomic nervous systems.

[0003] By modulating the activity of the nervous system, for example through stimulation of nerves or blocking of nerve signals, several different goals can be achieved. Motor neurons can be stimulated at the appropriate time to cause muscle contraction. Sensory neurons can be blocked, for example to relieve pain, or stimulated, for example to provide a signal to a subject. In other examples, modulation of the autonomic nervous system can be used to regulate various involuntary physiological parameters, such as heart rate and blood pressure. Neuromodulation can provide opportunities to treat several diseases or physiological conditions, some examples of which are described in detail below.

[0004] For purposes of this disclosure, the terms "stimulation" and "modulation" are used synonymously unless otherwise specified.

[0005] Typically, a neurostimulator delivers therapy in the form of electrical pulses and includes two or more electrodes in close proximity to a target location, such as a specific nerve or segment thereof. The electrical stimulation is adjustable through various parameters, such as electrode polarity, voltage or current amplitude, pulse frequency, pulse width, electrode configuration and selection, and others, to define the electrical stimulation therapy to be delivered to a user in need of therapy. Such parameters may be preprogrammed or programmable to produce the desired stimulation and results desired from the stimulation therapy.

[0006] Among the conditions in which neurostimulation may be applied is the occurrence of migraine headaches. Conventional treatment typically involves the use of painkillers of various strengths. However, due to nerve involvement in pain sensation, methods and devices targeting neurostimulation may provide a different solution. Pain sensations in the head are transmitted to the brain via afferent or sensory nerve cells. Such nerve cells may include the greater occipital nerve, the lesser occipital nerve, the third occipital nerve, and the trigeminal nerve. When a subject suffers from headaches and facial pain, such as during a migraine, inhibition of these nerves may serve to reduce or eliminate pain sensations.

[0007] Neurostimulation may also be an effective solution for other conditions, such as cluster headaches, or even sleep-disordered breathing and high blood pressure. The foregoing are only a few examples of conditions for which neuromodulation may be beneficial; however, the embodiments of the invention described hereinafter are not necessarily limited to treating only the conditions described above.

[0008] (Prior Art) Known implantable systems for neuromodulation are usually composed of three parts: a lead, a rechargeable or non-rechargeable implantable pulse generator, and an extension for connecting the pulse generator and the lead. These extensions are required for the delivery of electrical stimulation to the occipital nerve, since the pulse generator is implanted in the abdomen or flank. However, this technology has some disadvantages. For example, it leads to insufficient coverage of the pain area in some patients. In addition, the implantation of such a large device requires a long and invasive surgical procedure. Another disadvantage arises from the fact that the excessive need for tunnel creation and extension leads to possible infection, dislocation, lead breakage and erosion risks. Finally, a non-rechargeable implantable pulse generator creates a need for revision, which results in a higher revision rate and higher costs. Summary of the Invention [Means for solving the problem]

[0009] (Summary of the subject matter disclosed) One of the objectives of the present disclosure is to respond to the disadvantages of the prior art and provide an improved system for electrical nerve stimulation. In particular, a system should be provided that allows for a simple and time-efficient implantation procedure, improves results with new techniques and implant techniques, and avoids the burdens of existing techniques.

[0010] According to one aspect of the present disclosure, a neurostimulation system for treating headaches and facial pain is provided, the system comprising: an implant unit configured for implantation within a subject's body; and an external unit configured for a location external to the subject's body, the external unit comprising a processor, a power source, and a primary transmission unit in electrical communication with the power source and the processor, the implant unit comprising at least one conductor, at least one pair of modulating electrodes attached to the at least one conductor, and a secondary transmission unit in electrical communication with the at least one conductor and its electronics, the processor of the external unit configured to establish a coupling between the primary transmission unit and the secondary transmission unit and transmit power from the power source to the implant unit via the coupling.

[0011] The implant unit may preferably comprise only basic circuitry to perform the desired neurostimulation task. Advantageously, this leads to the implant unit not requiring its own energy or power reservoir embedded in its housing. Instead, power supply may be achieved, for example, between the external unit and the implant unit by direct RF transmission (i.e., BLE - Bluetooth Low Energy) or via an inductive transcutaneous radio frequency link (RF) between the physician programmer and the implant unit. According to further embodiments, the implant unit may comprise one or more of the following enclosed in a sealed housing: a secondary transmission unit or antenna for receiving and / or transmitting one or more signals from an external primary transmission unit, an AC / DC converter, a CPU or memory (e.g., an ultra-low power microcontroller), at least one current source, a stimulation lead with at least one modulating electrode, a programmable stimulation profile look-up table, a bootloader embedded software, an analog multiplexer for configuring the modulating electrode connected to a voltage or current source.

[0012] Among the preferred functions of the presented implant unit may be the following: performing neurostimulation therapy according to a stimulation profile stored in a look-up table; periodically performing diagnostics of both the patient and the implant unit thereon; and transmitting data or updates regarding the status of the patient and / or the implant unit to the external unit when an inductive transmission channel between the implant unit and the outside is established.

[0013] Preferably, the external unit is rectangular, circular, or oval and may be mounted on an external carrier. In an even more preferred embodiment, the external unit is ergonomically designed to fit behind the ear of the subject. The external unit may further comprise a housing, which may contain a processor, a primary transmission unit, and a power source. Examples of the external unit include a patch, a button, an earpiece, or other receptacle. In one embodiment, for example, the housing of the external unit may comprise a flexible material so that the external unit may be configured to conform to a desired location. According to an embodiment, the external unit may be encapsulated within the housing and further comprise one or more of the following: a primary transmission unit or antenna for receiving and / or transmitting one or more guided signals from the internal secondary transmission unit, a DC / AC converter, a power source, a CPU or memory (e.g., a microcontroller), a bi-color LED (e.g., for emitting red and / or green light), a vibrator module for providing feedback to the patient when the primary and secondary antennas are aligned with each other, a demodulator for receiving implant unit status and alerts and warnings transmitted from the implant unit, and a push button.

[0014] Among the preferred functions of the external unit may be the following: providing power to supply the implant unit via inductive coupling; recharging a battery located in the external unit when placed on the charging unit; receiving data from the implant unit when an inductive transmission channel between the implant unit and the outside is established and transferring said data to the charging unit; powering a bicolor LED, etc.

[0015] In a preferred embodiment, the primary transmission unit may be a coil antenna. The coil may be made of any suitable conductive material and may be configured to include any suitable arrangement of conductive coils (diameter, number of coils, coil layout, etc.). A coil suitable for use as a primary transmission unit may have a diameter of about 0.5 cm to 10 cm and may be circular, rectangular, or elliptical. In some embodiments, the coil antenna may have a diameter of about 0.5 cm to 2.5 cm. A coil antenna suitable for use as a primary transmission unit may have any number of windings. Additionally, a coil antenna suitable for use as a primary transmission unit may have a wire diameter of about 0.1 mm to 2 mm. According to another embodiment, the transmission unit may be a printed circuit board antenna, or it may be printed directly onto the housing of the external unit.

[0016] The external carrier may be configured for attachment to the skin of the subject. For example, the carrier may be a flexible skin patch configured for adhesion to the skin of the subject, for example, through adhesive or mechanical means. It is also possible to attach the external unit to the skin of the subject via magnetic forces, where the external carrier comprises a magnetic dipole, with a separate opposing dipole located directly beneath the skin of the subject. In this case, the opposing dipole may preferably be part of the implant unit. Further means of attachment may include hook-and-loop based systems (e.g., Velcro®) or ear strap based systems, which would not require any skin adhesive patch. The external carrier may be flexible or rigid, or may have flexible and rigid portions. The external carrier and / or housing of the external unit may further be constructed from any suitable material. In particular, the external carrier or housing may include a flexible material, such that the external unit may be configured to conform to a desired location. Materials of the flexible substrate may include, but are not limited to, plastics, silicones, woven natural fibers, and other suitable polymers, copolymers, and combinations thereof. According to a preferred embodiment of the present invention, the design of the external carrier may allow the skin to "breathe", for example, by being at least partially air permeable. Furthermore, the external carrier may be made of a soft material. Any part of the external unit may be flexible or rigid, depending on the requirements of a particular application. The external unit may be configured to be affixed to the subject. For example, for a subject suffering from headaches and facial pain, the external unit may be attached behind the subject's ear at the level of the mastoid process. A suitable location for the external unit may be determined by communication between the external unit and the implant unit. In addition, the external unit may generate a signal that provides feedback to the subject regarding the optimal position of the external unit. The optimal position may be determined, for example, based on feedback from the implantable unit to the external unit.Once the desired position is detected, a vibrator module located in the external unit may provide a vibration signal indicating correct alignment of the internal and external units.

[0017] Additionally, the carrier may include a connector for selectively or removably connecting the housing, the connector extending or protruding from the external carrier to be received by a recess in the housing. Alternatively, the housing may include a connector to be received by a recess in the external carrier. Preferably, the external carrier will be a mechanically flexible rectangular or circular patch that will conform for placement within the curved area behind the subject's ear.

[0018] According to an additional embodiment, the system may further comprise a physician external unit and a physician programming unit. The physician external unit may be, for example, a normal external unit in the sense of the present disclosure with specialized software installed thereon, the specialized software being specialized for use by a physician. The physician programming unit may be an external computing unit, for example, a PC or a similar handheld or portable device such as a tablet or smartphone. Together, the physician external unit and the physician programming unit may be configured to prepare therapy templates and store configurations with specific names. Furthermore, the physician programming unit may serve for secure identification of the implant unit and establish secure pairing between the implant unit and the physician external unit. Further functions of the physician external unit and physician programming unit may include verifying patient history log files stored within the implant unit, preparing / loading therapies and performing test stimulation sequences during a patient visit, programming the tested therapies during a patient visit, receiving status reports from the implant unit during a patient visit (e.g., electrode impedance, alerts or warnings, history log files, etc.), providing a user friendly interface for visualizing the therapy prior to programming (e.g., showing electrode configuration, current amplitude, pulse duration, on / off cycles, etc.) It is understood that data transfer between the physician external unit and the implant unit may occur in real time.

[0019] The modulating electrode may further be configured to induce a unidirectional and / or bidirectional electric field when supplied with a modulating signal. For this purpose, the modulating electrode may be made of a conductive and biocompatible material such as stainless steel, gold, platinum, iridium, platinum-iridium, platinum-gold, conductive polymers, etc. In particular, the electrode may be configured to facilitate a substantially unidirectional and / or bidirectional electric field sufficient to modulate the occipital nerve when supplied with a modulating signal. Furthermore, the modulating electrode may include an anode and cathode electrode pair, which may be spaced apart by an approximate distance of about 0.2 mm to 20 mm. Other configurations, such as tripolar electrodes (e.g., +-+), may be used as well. Furthermore, a monopolar electrode system may be used, with the housing of the implantable unit comprising a (large) indifferent electrode. The implant may also comprise an electronic component, such as a switch matrix for selecting the configuration.

[0020] The external unit may be configured to communicate with the implant unit. The circuitry of the external unit may be configured to generate an electrical primary signal on the primary transmission unit, which may, for example, induce an electrical secondary signal on the secondary transmission unit in the implant unit. However, in certain embodiments, it may be advantageous to provide a temporary or sustained DC (direct current) field-induced signal at the modulation electrode (e.g., to generate a unidirectional electric field for neural modulation). In addition, a combination of AC and DC signals may be implemented in the system of the present disclosure. To convert the AC secondary signal on the secondary transmission unit to a DC field-induced signal, the implant unit may include a signal modification device, for example, a demodulator or an AC / DC converter. The AC / DC converter may include any suitable converter known to those skilled in the art. For example, in some embodiments, the AC / DC converter may include rectifier circuit components, including, for example, diodes and appropriate capacitors and resistors. In alternative embodiments, the implant unit may include an AC / AC converter or no converter to provide an AC field-induced signal at the modulation electrode.

[0021] As described above, the secondary signal may be configured to generate an electric field between the modulation electrodes. In some cases, the magnitude, orientation, energy density, and / or duration of the generated electric field resulting from the secondary signal on the secondary transmission unit may cause sufficient current flow to modulate one or more nerves in the vicinity of the electrodes. In such cases, the secondary signal may be referred to as a modulation signal and the associated primary signal may be referred to as a modulation control signal. In other cases, the magnitude and / or duration of the electric field-induced signal may generate an electric field that does not result in neural modulation. In such cases, the electric field-induced signal may be referred to as a sub-modulation signal.

[0022] In some cases, the magnitude and / or duration of the generated electric field resulting from the electric field induced signal may be sufficient to modulate one or more nerves in the vicinity of the modulating electrode. In such cases, the electric field induced signal may be referred to as a modulating signal. In other cases, the magnitude and / or duration of the electric field induced signal may generate an electric field that does not result in neural modulation. In such cases, the electric field induced signal may be referred to as a sub-modulating signal. Various types of electric field induced signals may constitute a modulating signal. For example, in some embodiments, the modulating signal may include a medium amplitude and a medium duration, while in other embodiments, the modulating signal may include a higher amplitude and a shorter duration. Various amplitudes and / or durations of the electric field induced signal across the electrode may result in a modulating signal, and whether the electric field induced signal rises to the level of a modulating signal may depend on many factors (e.g., distance from the particular nerve to be stimulated, whether the nerve is branched, orientation of the induced electric field relative to the nerve, type of tissue present between the electrode and the nerve, etc.).

[0023] According to another embodiment, the power source may be permanently or removably coupled to a location within the external unit. The power source may further include any suitable source of power configured to be in electrical communication with the processor. For example, the power source may include a rechargeable and / or replaceable battery, such as a paper battery, a thin film battery, or other type of battery. In some embodiments, the power source may include a generally flat flexible battery. The power source may provide power for the system, and in particular for stimulation. In many embodiments, the size of the external unit should be as small as possible, so the total size of the external unit will be determined by the size of the power source, e.g., the battery. Preferably, the power source is less than 500 mm. 2 Has an area less than or equal to.

[0024] According to a preferred embodiment, the system includes a charging unit configured to charge the power source of the external unit. For example, it can be intended to recharge the power source of the external unit during the day. The charging unit may comprise one or more of the following: a wire connector (e.g., a USB type connector) for power supply, a transmission unit or antenna for establishing an inductive link for recharging the external unit, a CPU or memory (e.g., a microcontroller), a local area network or Internet interface (e.g., a Wi-Fi interface) configured for connection to a web server, at least one LED, a 4G module configured for transferring information to the web server.

[0025] Among the preferred functions of the external unit may be the following: recharging the external unit's rechargeable battery; displaying the external unit's battery status on a display or similar user interface; driving one or more LEDs signaling the charging process; driving an LED signaling receipt of an alert; and transmitting data stored on the external unit and transmitted by the implant unit to a web server using a local area network or Internet interface (e.g., a Wi-Fi interface).

[0026] The implant unit's circuitry, i.e., modulation electrodes, electronics, antenna, and connecting wires, may comprise conductive and / or biocompatible materials such as gold, platinum, iridium, platinum-iridium, platinum-gold, conductive polymers, etc. Preferably, the implant unit is manufactured substantially in one piece using only one material (e.g., silicone) except for the electronic components (i.e., electrodes, wires, transmission unit, insulators, etc.). Alternatively, a biological glue may be used to join the stimulation bridge and transmission unit together.

[0027] According to another preferred embodiment, it is also possible that the conductor comprises a flexible carrier, and the secondary transmission unit and the at least one conductor are each connected to the flexible carrier, which is sized and configured for implantation under the skin. In that case, the conductor with the modulation electrode may also be referred to as a stimulation bridge. The secondary transmission unit may be mounted on the flexible carrier or otherwise integrated therewith. Furthermore, the secondary transmission unit may include a coil antenna. Such a coil antenna may be made of any suitable conductive material and may be configured to include any suitable arrangement of conductive coils (diameter, number of coils, coil layout, etc.). A coil antenna suitable for use as a secondary transmission unit may have a diameter of about 0.5 cm to 5 cm, and may be circular, rectangular, or elliptical. A coil antenna suitable for use as a secondary transmission unit may have any number of windings. Furthermore, a coil antenna suitable for use as a secondary transmission unit may have a wire diameter of about 0.1 mm to 2 mm. According to another embodiment, the transmission unit may be a printed circuit board antenna.

[0028] In some embodiments, the flexible carrier of the implant is comprised of a flexible biocompatible and / or insulating material. Such materials may include, for example, silicone, phenyltrimethoxysilane (PTMS), polymethylmethacrylate (PMMA), Parylene C, polyimide, liquid polyimide, laminated polyimide, black epoxy, polyetheretherketone (PEEK), liquid crystal polymer (LCP), Kapton, etc. In addition to the above, the implant may be encapsulated within at least one layer of a biocompatible material, which may include a ceramic material, a thermoplastic material such as ULTEM, or other compatible material.

[0029] Since the implant unit does not include a power source (e.g., in the form of a battery), it can be kept small. It can therefore be implanted through a short, minimally invasive procedure. In particular, the system according to the present disclosure may be implanted in a one-day hospital stay that should not last more than 30 minutes. The flexible carrier may also be fabricated with a thickness suitable for implantation under the patient's skin. For example, the implant unit may have a thickness of less than 4 mm, in particular less than about 2 mm. In a preferred embodiment, the implant is configured for implantation through a 3 cm incision in the subject's skin at the level of the mastoid process.

[0030] In addition to the above, the modulation electrodes may be located alongside at least one of the conductors. The conductors may comprise the modulation electrodes, preferably configured for implantation in the vicinity of one or more nerves to be modulated such that the electrodes are spaced apart from one another along the longitudinal direction of some of the nerves. It may be beneficial if one of the modulation electrodes is located at one of the ends of the conductors. For example, the modulation electrodes may be spaced apart by a distance of about 1 mm to 20 mm or 5 mm to 10 mm. In a preferred embodiment, the at least one conductor may comprise eight modulation electrodes ("octopole conductors") evenly spaced apart along the conductor. The electrodes may be further configured to facilitate an electric field in response to an applied electrical signal, the electric field including field lines extending longitudinally of the nerve to be modulated.

[0031] The at least one conductor and the modulation electrode may form a stimulation bridge. The stimulation bridge according to this embodiment has an elongated shape. Preferably, the length of the stimulation bridge is at least 20 times the width or diameter of the stimulation bridge. According to a further preferred embodiment, the length of the stimulation bridge is at least 50 times the width or diameter of the stimulation bridge. For example, the conductor may have a diameter of 1-3 mm and a length of up to 100 mm. Once implanted, the at least one stimulation bridge may be located in the subject's body in such a way that it is directed towards a point about 1-1.5 cm above the inion of the subject. Preferably, the at least one stimulation bridge comprises a modulation electrode at the end of the conductor, which has a maximum distance from the secondary transmission unit. The stimulation bridge may be configured for implantation in such a way that the at least one modulation electrode is located along the conductor in close proximity to the secondary transmission unit, which may be mounted on a flexible carrier. The secondary transmission unit may then be located in the vicinity of the C2 vertebra, as this is the junction of the trigeminal cervical complex and the dorsal root ganglion of C2. The precise location of the secondary transmission unit of the implant unit also determines the position of the external unit when attached to the subject's skin.

[0032] With a stimulation bridge as described herein, precise innervation or stimulation of a single nerve is possible, as opposed to only being able to stimulate a larger nerve area, and obviously the latter is still possible in addition to single nerve stimulation with a stimulation bridge as described.

[0033] Preferably, the conductors of the stimulation bridge are elliptical, rectangular or spherical when viewed in transverse cross section, and the electrodes are placed only on the side of the conductors facing the nerve to be stimulated. In this way, the stimulation signal can be focused in a much more precise manner, which in turn is more energy efficient. A stimulation bridge that has an elliptical or spherical shape when viewed in cross section has the added advantage that, once implanted, its rounded "edges" can lead to greater comfort for the subject or patient.

[0034] According to a preferred embodiment, the lead or stimulation bridge may be configured for bilateral or unilateral stimulation, with unilateral stimulation comprising short lead and bilateral stimulation comprising long lead. For example, short lead (unilateral stimulation) may be intended to be shorter than or about 10 cm long, while long lead (bilateral stimulation) may be intended to be longer than 10 cm. A stimulation bridge configured for bilateral stimulation may comprise, for example, a total of 16 electrodes (i.e., two distinct sections each comprising 8 modulation electrodes).

[0035] Moreover, bilateral stimulation requires two incisions, one small (3 cm) incision at the level of the mastoid process and a second one 1-1.5 cm above the inion for implantation of the stimulation bridge. However, according to a preferred embodiment, only one channel would be required for both forms of stimulation (unilateral and bilateral). By using a stimulation bridge with leads longer than 10 cm, i.e. configured for bilateral stimulation, it is possible to stimulate a larger nerve area of ​​the subject using only small incisions. Thus, the medical procedure of implanting the implant unit can be kept relatively short and still allow for highly efficient nerve stimulation.

[0036] The processor may comprise programmable electronics and be configured to cause the transmission of a modulated signal from the primary transmission unit to a secondary transmission unit of an implant unit implanted under the skin of the subject, i.e. under the subcutaneous tissue. The processor may further be configured to adjust one or more characteristics of the modulated signal and generate a sub-modulated control signal adapted to cause a current in at least the modulated electrode below the neuromodulation threshold of the occipital nerve when received by the secondary transmission unit of the implant unit, and to generate a modulated signal adapted to cause a current in the modulated electrode above the neuromodulation threshold of the occipital nerve when received by the secondary transmission unit of the implant unit. In this way, the external unit can generate a magnetic field by radio frequency, which in turn generates a stimulation of the occipital nerve field through the modulated electrode of the implant unit. Thus, there is no longer a need for having an implant pulse generator (IPG) implanted deep in the muscle, or for making loops, making excessive tunneling, or adding extensions up to the IPG, which may take a lot of time during a separate implantation procedure. Preferably, the distance between the external unit and the (implanted) implant unit is less than 5 cm, in particular less than 1 cm.

[0037] According to an embodiment, the processor may be programmable to cause transmission of a modulated signal from the primary transmission unit to the secondary transmission unit of the implant unit based on distinct pre-programmed modulation protocols (including one or more "modes"). For example, a "night mode" protocol may be provided, the protocol including: -reducing the voltage or current amplitude of the modulated signal within a specified range or percentage; adding off periods to the duty cycle; - Switch to "Burst Mode" instead of "Tonic Mode" Includes. Burst stimulation typically delivers groups of pulses at a higher frequency and at a much lower amplitude than tonic stimulation and is considered undetectable by the patient and therefore evident throughout the night. In this manner, effective stimulation can be maintained during the patient's sleep without being interrupted or otherwise uncomfortable.

[0038] The at least one processor may include any electrical circuit that may be configured to perform a logical operation on at least one input variable. The at least one processor may therefore include one or more integrated circuits, microchips, microcontrollers, and microprocessors, digital signal processors (DSPs), field programmable gate arrays (FPGAs).

[0039] According to a further embodiment, the external unit may comprise a storage unit in electrical communication with the processor, configured to store stimulation data. Such data may comprise any form of physiological parameters of the subject, e.g., feedback of the subject and stimulation parameters. In this way, the processor may perform predictive stimulation control based on patient feedback, i.e., based on stored physiological parameters.

[0040] Additionally, the external unit may include an energy harvesting unit configured to derive energy from an external source. The external source may be solar power, thermal power (e.g., in the form of the subject's body heat), kinetic energy (due to the subject's movement), or the like. The energy harvesting unit may further be connected to a power source of the external unit, thereby recharging the power source.

[0041] As part of the preferred embodiment, the implant unit may comprise tines or spikes for fixation of at least one conductor to the tissue of the subject. In this way, dislocation of the implant unit from the tissue, which would otherwise occur due to neck movement of the subject, can be avoided. The tines may be arranged on the flexible carrier and / or on at least one conductor of the implant unit and may preferably be made of a biocompatible material. According to another embodiment, the fixation of the main body of the implant unit may comprise a mesh. It is also possible that RX markers are placed along the conductors to verify correct placement during the surgical procedure, by the use of a RX machine and a screen for visualization of the conductors and the RX markers.

[0042] Furthermore, to optimize communication between the external unit and the internal unit, it is possible that the implant unit is configured for implantation in a substantially hairless area of ​​the head. Modulation of the occipital nerves, such as the greater occipital nerve, the lesser occipital nerve, and the third occipital nerve, and the secondary trigemino-cervical complex is possible through the stimulation bridge, which would be useful for treating headaches and facial pain, such as those from migraine. It may be intended not to stimulate deep brain structures and the spinal cord. Neurostimulation may instead be focused on chronic migraine (CM) and chronic cluster headache (CCH), which are not responsive to pharmacological treatment. There is still an unmet medical need for these patients, especially for CCH.

[0043] The system may further comprise a remote control device configured for adjusting the nerve stimulation. The remote control device allows the subject to self-regulate the electrical stimulation of individual nerves. This is particularly useful for patients suffering from chronic migraine and chronic cluster headache (CCH), who require continuous stimulation. In an embodiment, the remote control device may be in the form of a dedicated software ("app") to be installed on a computer or any suitable handheld device (e.g., on a mobile phone or tablet).

[0044] The coupling between the secondary transmission unit of the implant unit and the primary transmission unit of the external unit can comprise capacitive coupling, inductive coupling, ultrasonic, optical, and / or radio frequency coupling. In particular, such coupling of the primary and secondary transmission units may include any interaction between the primary and secondary transmission units that causes a signal on the secondary transmission unit in response to a signal applied to the primary transmission unit, each signal may comprise power and / or data. In some embodiments, the coupling between the primary and secondary transmission units may include capacitive coupling, inductive coupling, radio frequency coupling, etc., and any combination thereof. As a result of the coupling between the primary and secondary transmission units, when a primary signal is present on the primary transmission unit, a secondary signal may arise on the secondary transmission unit. Such coupling may include inductive / magnetic coupling, RF coupling / transmission, capacitive coupling, or any other mechanism by which a secondary signal may be generated on the secondary transmission unit in response to a primary signal generated on the primary transmission unit.

[0045] According to another embodiment, the implant unit may comprise a processor in addition to the processor configured by the external unit. The processor of the implant unit may therefore be referred to as an internal processor. When implemented, the internal processor may comprise at least one software program installed thereon. The internal processor may therefore be configured to perform and diagnose the stimulation therapy and to send alerts and warnings (A and W) to the external unit if the implant unit encounters a problem.

[0046] As a preferred embodiment, the system for treating headaches and facial pain may comprise an external unit, which is attached to an external carrier that is attached to the patient's skin. This "patient-external unit" may establish a transmission link with an implant unit that is implanted under the subject's skin via its primary transmission unit. Furthermore, the external unit may provide power to the implant unit via induction. The implant unit may then be configured to communicate with the external unit via wireless transmission and may further comprise a boot loader that starts a software program installed on the internal processor of the implant unit. Finally, the implant unit may be configured to perform and diagnose the stimulation therapy and to send alerts and warnings (A and W) to the external unit in case the implant unit encounters a problem. The system may further comprise a charging unit for charging the "patient-external unit" via inductive coupling. However, the charging unit may further be configured to collect the A and W data stored on the external unit and transmitted from the implant unit to the external unit. Furthermore, the charging unit may comprise a charger LED, which may be turned on or off, and an emergency LED. For example, the charger LED may be turned on as long as the external unit is being charged by the charging unit. Similarly, the emergency LED may be turned on when the charging unit receives A and W data from the external unit. Additionally, the charging unit may connect to a web server and upload log files and A and W reports (if present).

[0047] In addition, the preferred system may include a physician programming unit connectable to the external unit. When the external unit is connected to the physician programming unit, it may also be referred to as the "physician external unit." The "physician external unit" may be the same device as the "patient external unit," or it may be a different external device used only by the physician. The physician programming unit may be an external computing unit, for example, a PC or a similar handheld or portable device such as a tablet or smartphone. Together, the physician external unit and the physician programming unit may be configured to prepare therapy templates and store configurations with specific names. Additionally, the physician programming unit may aid in secure identification of the implant unit and establish secure pairing between the implant unit and the physician external unit. The physician programming unit and further functions of the physician programming unit may include verifying patient history log files stored within the implant unit, preparing / loading therapies and performing test stimulation sequences during a patient visit, programming the tested therapy during a patient visit, receiving status reports from the implant unit during a patient visit (e.g., alerts or warnings, history log files, etc.), and providing a user-friendly interface for visualizing the therapy prior to programming (e.g., showing electrode configuration, current amplitude, pulse duration, on / off period, etc.).

[0048] According to another aspect of the present disclosure, an implant unit for use in a neurostimulation system according to any of the preceding claims is presented, the implant unit configured for implantation in the subject's body through an incision in the subject's skin, the implant unit further configured for implantation in the subject's body through a tunnel in the subject's fatty tissue leading from the incision. Preferably, the incision is 0.5-3.5 cm in length. Further, the implant unit may be configured for implantation in a tunnel in the subject's fatty tissue or subcutaneous tissue, the tunnel leading from the incision toward a location 2-3 cm above the inion encompassing the occipital area.

[0049] According to yet another aspect of the present disclosure, a method for electrical stimulation of neuromuscular tissue using a neurostimulation system is described herein, the method including transmitting stimulation parameters from an external unit to an implant unit, generating an electrical stimulation pattern with the external unit, the electrical stimulation pattern comprising at least one modulated signal, delivering the electrical stimulation pattern to an implant unit located within a subject's body, and adjusting the electrical stimulation pattern, the adjusting the electrical stimulation pattern comprising modifying an electrode configuration to increase or decrease a voltage, a current amplitude, a pulse frequency, and / or a pulse width of the electrical stimulation pattern. Such a method may be beneficial, for example, in pain management, where propagation of pain signals is undesirable. Preferably, the method may include one or more stochastic elements to reduce habituation in a patient or subject. For example, the stimulation parameters may comprise stochastic behavior within a defined range, such that the voltage, the current amplitude, the pulse frequency, and / or the pulse width of the electrical stimulation pattern may vary in a stochastic manner. Furthermore, the electrodes in the electrode configuration may stochastically innervate different nerve areas at different times, thereby generating random stimulation patterns.

[0050] The method may further include receiving an alternating current (AC) signal at a secondary transmission unit of the implant unit, the implant unit generating a voltage signal in response to the AC signal. The method may further include applying the voltage signal to at least one pair of modulation electrodes configured for implantation in proximity to the nerve to be modulated. [Brief description of the drawings]

[0051] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate several embodiments of the disclosed subject matter.

[0052] [Figure 1] FIG. 1 depicts a schematic rear view of a subject with a system for unilateral nerve stimulation comprising an implant unit and an external unit, according to an exemplary embodiment of the present disclosure.

[0053] [Diagram 2] FIG. 2 depicts a schematic rear view of a subject with a system for bilateral nerve stimulation comprising an implant unit and an external unit, according to an exemplary embodiment of the present disclosure.

[0054] [Diagram 3] FIG. 3 depicts a schematic diagram of an exemplary embodiment of an implant unit with a unilateral modulated electrode configuration.

[0055] [Figure 4] FIG. 4 depicts a schematic diagram of an exemplary embodiment of an implant unit comprising a bilateral modulating electrode configuration.

[0056] [Diagram 5] FIG. 5 depicts a flowchart of a system for treating headaches and facial pain, according to an exemplary embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0057] DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS FIG. 1 depicts a schematic rear view of a subject with a system 100 for unilateral nerve stimulation, the system comprising an implant unit 300 and an external unit 200 according to an exemplary embodiment of the present disclosure. The external unit 200 is configured for a location external to the subject 700 or patient. The external unit 200 as shown in FIG. 1 is not attached to the subject. However, it may in fact be configured to be affixed to the subject 700. For example, for a subject suffering from headaches, the external unit 200 may be attached near the mastoid process, approximately at the level of the C2 vertebra. A suitable location for the external unit 200 may be determined by communication between the external unit 200 and the implant unit 300 implanted within the subject. The external unit 200 may comprise an external carrier 240 configured for attachment to the skin of the subject 700. For example, the carrier 240 may be a flexible skin patch configured for adhesion to the skin of the subject 700, for example, through adhesive or mechanical means. It is also possible to attach the external unit 200 to the skin of the subject 700 via magnetic forces, with the external carrier 240 comprising magnetic poles, with separate opposing poles located directly beneath the skin of the subject 700. Further means of attachment can include hook-and-loop based systems (e.g., Velcro®). The external carrier 240 can be flexible or rigid, or can have flexible and rigid portions. The external carrier 240 and / or the housing 250 of the external unit 200 can be constructed from any suitable material. In particular, the external unit or the housing 250 can include a flexible material, such that the external unit can be configured to conform to a desired location. Flexible substrate materials can include, but are not limited to, plastics, silicones, woven natural fibers, and other suitable polymers, copolymers, and combinations thereof. Any portion of the external unit can be flexible or rigid, depending on the requirements of a particular application.

[0058] The external unit 200 may also be configured to be affixed to an alternative location proximate the subject. For example, in one embodiment, the external unit 200 may be configured to be fixedly or removably attached to a strap or band that may be configured to fit around a portion of the subject's body. Alternatively, or in addition, the external unit 200 may be configured to remain at a desired location outside the subject's body without being attached to that location.

[0059] The external unit 200 may include a housing 250. The housing 250 may include any suitable container configured to hold a component, such as the primary transmission unit 230 or the processor 210. Additionally, although the external unit 200 is illustrated diagrammatically in FIG. 1, the housing 250 may be any suitable size and / or shape, and may be rigid or flexible.

[0060] The primary transmission unit 230 may be in the form of a coil antenna having a diameter of about 0.5 cm to 5 cm, and may preferably be circular or elliptical. A coil antenna suitable for use as a primary transmission unit may have any number of windings. Further, a coil antenna suitable for use as a primary transmission unit may have a wire diameter of about 0.1 mm to 2 mm.

[0061] As discussed above, the external unit 200 may be configured to adhere to a desired location. Thus, in some embodiments, at least one side of the housing 250 or the external carrier 240 may include an adhesive material. The adhesive material may include a biocompatible material and may allow a subject to attach the external unit 200 to a desired location and remove the external unit 200 upon completion of use. The adhesive may be configured for single or multiple use of the external unit 200. Suitable adhesive materials may include, but are not limited to, biocompatible glues, glues, elastomers, thermoplastics, and emulsions.

[0062] Additionally, the external unit 200 may be associated with a power source 220. The power source 220 may be removably coupleable to the external unit 200 at a location external to the external unit. Alternatively, the power source 220 may be permanently coupled to the external unit 200. If the power source 220 is permanently coupled to the external unit 200, it is contemplated that the power source 220 is rechargeable. The power source 220 may further include any suitable source of power configured to be in electrical communication with the processor. In one embodiment, for example, the power source 220 may include a battery 221.

[0063] The system of FIG. 1 further discloses an implant unit 300 comprising a stimulation bridge 350, the stimulation bridge 350 including a lead 310, a secondary transmission unit 330, and a pair of modulation electrodes 320. The lead 310 in FIG. 1 is approximately 10 cm long and comprises eight pairs of modulation electrodes 320 ("octopole lead") evenly spaced along the lead 310. Furthermore, the implant unit 300 is battery-free, allowing the implant unit 300 to be in the form of the stimulation bridge 350 shown in FIG. 1. The implant unit 300 is thus suitable for use in the neurostimulation system 100 as disclosed herein, as it is configured for implantation within the body of a subject 700 through an incision 600 in the skin of the subject 700, the incision being 0.5-3.5 cm long. Further, the implant unit 100 may be configured for implantation within a tunnel 610 within the tissue of the subject, the tunnel 610 leading from the incision 600 toward a location near the inion 710 of the subject 700, for example, near the occipital nerve 720.

[0064] Depending on the coupling of the primary transmission unit 230 of the external unit 200 and the secondary transmission unit 330 of the implant unit 300, a sub-modulation signal or modulation signal may be transmitted from the external unit 200 to the modulation electrode 320 of the implant unit 300. The circuitry of the external unit 200 may be configured to generate an electrical primary signal on the primary transmission unit 230 that may, for example, induce an electrical secondary signal on the secondary transmission unit 330 in the implant unit 300. The secondary signal may then be configured to generate an electric field between the modulation electrodes 320 sufficient to modulate nerve ending fibers when spaced therefrom.

[0065] 2 depicts a schematic rear view of a subject with a system 100 for bilateral nerve stimulation, comprising an implant unit 300 and an external unit 200, according to an exemplary embodiment of the present disclosure. The embodiment shown in FIG. 2 differs from that of FIG. 1 in that a long lead 310 or stimulation bridge 350 is used, which is suitable for bilateral stimulation. The lead 310 of the stimulation bridge 350 shown in FIG. 2 is about 20 cm long. Preferably, it is configured for an implantation procedure using two incisions 600.

[0066] In particular, bilateral nerve stimulation requires one small incision 600 of 3 cm length at the level of the mastoid process and a second incision 600 located 1-1.5 cm above the inion for implantation of the stimulation bridge 350. By using a stimulation bridge 350 having leads 310 longer than 10 cm, i.e. configured for bilateral stimulation, it is possible to stimulate a large nerve area of ​​the subject 700 using only the small incision 600. Thus, the medical procedure of implanting the implant unit in the subject 700 can be kept short and still allow for very efficient nerve stimulation.

[0067] 3 depicts a schematic diagram of an exemplary embodiment of an implant unit 300 comprising a unilateral modulating electrode 320 configuration. In particular, the implant unit 300 of FIG. 3 comprises a stimulation bridge 350 and a secondary transmission unit 330. The stimulation bridge 350 comprises a lead 310 approximately 10 cm long, as well as eight pairs of modulating electrodes 320 (also labeled E1-E8 in FIG. 3) ("octopole leads") attached to the lead 310. According to the embodiment shown in FIG. 3, the modulating electrodes 320 are uniformly spaced along the lead 310.

[0068] The implant unit 300 of FIG. 3 is battery-free, allowing the implant unit 300 to be a low-profile and relatively small form factor of the stimulation bridge 350 shown in FIG. 3. Such an implant unit 300 is suitable for use in the neurostimulation system 100 as disclosed herein, as it is configured for implantation within the body of the subject 700 through an incision 600 in the skin of the subject 700, the incision being 0.5-3.5 cm in length. Additionally, the implant unit 300 may be configured for implantation within a tunnel 610 in the tissue of the subject 700, leading from the incision 600 toward a location near the inion 710 of the subject 700, for example, near the occipital nerve 720.

[0069] In the electrode 320 configuration of the stimulation bridge 350 of Figure 3, any individual modulation electrode E1-E8 can be programmed as an anode (A) or a cathode (C), or it can be left unconnected (NC). According to a preferred embodiment, at least one electrode 320 may be defined as an anode and / or at least one electrode 320 may be defined as a cathode. The remaining 2 to 7 electrodes may be placed in parallel as anodes or cathodes.

[0070] Figure 4 depicts a schematic diagram of an exemplary embodiment of an implant unit 300 comprising a bilateral modulation electrode 320 configuration. The implant unit 300 of Figure 4 differs from the embodiment of Figure 3 in that the stimulation bridge 350 comprises longer leads 310 suitable for bilateral stimulation. The leads 310 of the stimulation bridge 350 shown in Figure 3 are approximately 20 cm long.

[0071] As shown in Fig. 4, the stimulation bridge 350 is composed of two connected sections, each section comprising eight pairs of modulation electrodes 320a and 320b, respectively. The modulation electrodes 320a attached to the section of the stimulation bridge 350 that is connected to the secondary transmission unit 330 are referred to as proximal electrodes 320a (also labeled PE1-PE8 in Fig. 4). Similarly, the modulation electrodes 320b attached to the section of the stimulation bridge 350 that is not directly connected to the secondary transmission unit 330 are referred to as distal electrodes 320b (also labeled DE1-DE8 in Fig. 4).

[0072] According to the electrode 320 configuration of the stimulation bridge 350 of Figure 4, any individual modulation electrode PE1-PE8 or DE1-DE8 can be programmed as an anode (A) or a cathode (C), or it can be left unconnected (NC). According to a preferred embodiment, at least one electrode 320 may be defined as an anode and / or at least one electrode 320 may be defined as a cathode.

[0073] FIG. 5 depicts a flow chart of a system 100 for treating headaches and facial pain, according to an exemplary embodiment. According to this embodiment, an external unit 200 may be attached to an external carrier 240, which is attached to the patient's skin. This "patient external unit" 200 (patient EU in FIG. 5) establishes a transmission link via its primary transmission unit 230 with an implant unit 300, which is implanted under the skin of a patient 700. Furthermore, the "patient external unit" 200 may provide power to the implant unit 300 via induction.

[0074] According to the illustrated embodiment of the system 100, the implant unit 300 is configured to communicate with the external unit 200 via wireless transmission. The implant unit may further comprise a boot loader, which initiates software programs installed on the processor of the implant unit. Finally, the implant unit 300 may be configured to perform and diagnose stimulation therapy and send alerts and warnings (A and W) to the external unit 200 if the implant unit 300 encounters a problem.

[0075] The system 100 further comprises a charging unit 400 for charging the external unit 200 via inductive coupling. However, according to the embodiment of FIG. 5, the charging unit 400 may further be configured to collect A and W data stored on the patient-external unit 200 and transmitted from the implant unit 300 to the external unit 200. Furthermore, the charging unit 400 may comprise a charger LED and an emergency LED, which may be turned on or off. For example, the charger LED may be turned on as long as the external unit 200 is charging. Similarly, the emergency LED may be turned on when the charging unit 400 receives A and W data from the external unit 200. In addition, the charging unit 400 may connect to a web server and upload log files or A and W reports.

[0076] Finally, as shown by FIG. 5, the system 100 may comprise a physician programming unit 800 connectable to the external unit 200. When the external unit 200 is connected to the physician programming unit 800, it may also be referred to as the "physician external unit" 200 (see physician EU in FIG. 5). The "physician external unit" 200 may then either be the same device as the "patient external unit" (see patient EU in FIG. 5) or it may be a different external device used only by the physician. The physician programming unit 800 may be an external computing unit, for example a PC or a similar handheld or portable device such as a tablet or smartphone. Together, the physician external unit 200 and the physician programming unit 800 are configured to prepare therapy templates and store configurations with specific names. Furthermore, the physician programming unit 800 may help in secure identification of the implant unit 300 and establish secure pairing between the implant unit 300 and the physician external unit 200. Further functions of the physician programming unit 800 and physician programming unit 200 may include verifying patient history log files stored within the implant unit 300, preparing / loading therapies and performing test stimulation sequences during a patient visit, programming the tested therapy during a patient visit, receiving status reports (e.g., alerts or warnings, history log files, etc.) from the implant unit 300 during a patient visit, and providing a user-friendly interface for visualizing the therapy prior to programming (e.g., showing electrode configuration, current amplitude, pulse duration, on / off period, etc.).

[0077] The invention is not limited to one of the embodiments described herein but may be modified in many other ways.

[0078] All features disclosed in the claims, this specification, and the drawings, as well as all advantages, including structural details, spatial arrangements, and methodological steps, may be essential to the present invention, either by themselves or in various combinations with one another.

[0079] List of reference numbers [Table 1]

Claims

1. A neurostimulation system (100) for treating headaches and facial pain, said system (100) comprising: an external unit (200) configured for a location external to the body of a subject (700); an implant unit (300) configured for implantation within the body of a subject (700); Equipped with The external unit (200) A processor (210); A power source (220); a primary transmission unit (230) in electrical communication with said power source (220) and said processor (210); Equipped with The implant unit (300) comprises: At least one electrical conductor (310); at least one pair of modulating electrodes (320) attached to said at least one conductor (310); a secondary transmission unit (330) in electrical communication with said at least one conductor (310) and said modulation electrode (320); Equipped with The system (100), wherein the processor (210) is configured to establish a coupling between the primary transmission unit (230) and the secondary transmission unit (330) and transmit power and / or data from the power source (220) to the implant unit (300) via the coupling.

2. The system (100) of claim 1, characterized in that the system (100) comprises a charging unit (400).

3. The system (100) according to any one of claims 1 to 2, characterized in that the modulating electrodes (320) are located along the at least one conductor (310), the electrodes (320) being, in particular, uniformly spaced along the conductor (310).

4. The system (100) according to any one of claims 1 to 3, characterized in that the implant unit (300) comprises tines (350) for fixation of the at least one conductor (310) to the subcutaneous tissue of the subject (700).

5. The system (100) according to any one of claims 1 to 4, characterized in that the external unit (200) is configured for attachment to the skin of the subject (700).

6. The system (100) according to any one of the preceding claims, characterized in that the external unit (200) comprises an energy harvesting unit (260) configured for deriving energy from an external source.

7. The system (100) according to any one of the preceding claims, characterized in that the power source (220) comprises a battery (221).

8. The system (100) according to any one of claims 1 to 7, characterized in that the charging unit (400) is configured for charging the battery (221) of the external unit (200).

9. The system (100) according to any one of the preceding claims, characterized in that said system (100) further comprises a remote control device (500) configured for adjusting said neurostimulation.

10. The system (100) according to any one of claims 1 to 9, characterized in that the coupling between the primary transmission unit (230) and the secondary transmission unit (330) comprises capacitive coupling, inductive coupling, optical, ultrasonic and / or radio frequency coupling.

11. An implant unit (300) for use in a neurostimulation system (100) according to any one of claims 1 to 10, comprising: the implant unit (300) is configured for implantation within a body of a subject (700) through an incision (600) in the skin of the subject (700); The implant unit (300) is further configured for implantation within a tunnel (610) within tissue of the subject (700).

12. 12. The implant unit (300) of claim 11, wherein the implant unit (300) is configured for implantation through a 0.5-3.5 cm incision (600) in the skin of the subject (700), the implant unit (300) being further configured for implantation within a tunnel (610) in tissue of the subject (700) leading from the incision (600) towards a location proximate the inion (710) of the subject (700).

13. 13. An implant unit (300) according to claim 11 or 12, characterized in that the implant unit (300) is configured for a location in the vicinity of the occipital nerve (720).

14. A method for electrical stimulation of neuromuscular tissue using a neurostimulation system (100) according to any one of claims 1 to 10, the method comprising: transmitting stimulation parameters from the external unit (200) to the implant unit (300); generating an electrical stimulation pattern using the internal unit (300), the electrical stimulation pattern comprising at least one modulated signal; delivering said electrical stimulation pattern to an implant unit (300) located within the body of a subject (700); adjusting the electrical stimulation pattern, the adjusting the electrical stimulation pattern including changing an electrode configuration, increasing or decreasing a voltage, a current amplitude, a pulse frequency, and / or a pulse width of the electrical stimulation pattern; A method comprising:

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