Methods and systems for electrical nerve stimulation

Abstract

Disclosed herein is a method for electrical nerve (510) stimulation, the method comprising: generating an electrical stimulation pattern (100) comprising a plurality of consecutive pulse sequences (110), wherein each pulse sequence (110) has a pulse sequence amplitude (111); delivering the electrical stimulation pattern (100) to a nerve (510) of a subject with a stimulator (300) having at least one electrode (310); modulating the electrical stimulation pattern (100), wherein the modulation of the electrical stimulation pattern (100) comprises gradually increasing the pulse sequence amplitude (111) from one pulse sequence (110) to consecutive pulse sequences (110) until a determined target stimulation amplitude (130) is reached at a stimulation onset (101); characterized in that the modulation of the electrical stimulation pattern (100) further comprises reducing the target stimulation amplitude (130) to a defined reduction amplitude (140) within each pulse sequence (110) after the target stimulation amplitude (130) is reached.

Description

TECHNICAL FIELD

[0001] The disclosed subject matter described below relates to methods and systems for electrical nerve stimulation, in particular to methods and systems for adjusting parameter values of the stimulation. Furthermore, it is mentioned that the electrical nerve stimulation method is used to correct sleep disordered breathing. BACKGROUND

[0002] Neural modulation, e.g., electrical stimulation of nerves, is considered in the art to be a reliable and effective type of medical treatment. It offers the opportunity to address many physiological conditions and disorders by interacting with the body’s own natural neural processes. Neural modulation includes the suppression (e.g., blocking), stimulation, modification, regulation, or therapeutic alteration of electrical or chemical activity in the central, peripheral, or autonomic nervous systems. By modulating the activity of the nervous system, several different goals can be achieved. For example, motor neurons can be stimulated at appropriate times to cause muscle contractions. In addition, sensory neurons can be blocked to reduce pain or stimulated to provide a signal to a subject. In other examples, modulation of the autonomic nervous system can be used to adjust various unconscious physiological parameters, such as heart rate and blood pressure. Neural modulation can offer the opportunity to treat several diseases or physiological conditions. Various devices and techniques have been used in an attempt to provide optimal stimulation of the tissue of interest.

[0003] Generally, a neural stimulator delivers therapy in the form of electrical pulses and includes one or more electrodes in the vicinity of a target location, such as a particular nerve or portion thereof. The electrical stimulation is programmable and is adjustable by various parameters, such as polarity of the electrode(s), voltage, current amplitude, pulse frequency, pulse width, etc., as these parameters define the electrical stimulation therapy to be delivered to a user in need of treatment. These parameters can be preprogrammed or programmable to deliver the desired stimulation and the desired end result from the stimulation therapy.

[0004] One of the conditions that can apply neural modulation is obstructive sleep apnea (OSA), which is a breathing disorder characterized by repeated episodes of partial or complete obstruction of the upper airway during sleep. One of the causes of OSA is due to the loss of muscle tone associated with sleep, and the tongue muscles are unable to resist the negative pressure of inspiration in the pharynx. When the tongue pulls back, it obstructs the upper airway, reducing ventilation, and reducing lung and blood oxygen levels. For example, stimulating the hypoglossal nerve causes the tongue muscles (e.g., genioglossus) to contract, thereby maintaining an open, unobstructed airway, as the genioglossus is responsible for forward movement of the tongue and tightening of the anterior wall of the pharynx.

[0005] Various devices, systems, and methods have been disclosed in the prior art, specifically related to electrical stimulation therapy and neurostimulation. For example, US 2013 / 0289667 Al discloses devices, systems, and techniques for increasing or decreasing one or more parameter values of electrical stimulation. An implantable medical device can increase or decrease a parameter value, e.g., amplitude or pulse width, over time to reach a target value of the parameter. SUMMARY

[0006] It is one of the objects of the present disclosure to respond to the drawbacks of the prior art and to provide an improved system and method for stimulating electrical neurostimulation of a recipient. Specifically, according to the disclosed subject matter, the system and method aim to reduce discomfort that can be caused by electrical neurostimulation and, when applied, to be energy efficient, safe, and reliable. Furthermore, to maximize the therapeutic effect on OSA patients, the use of the method along with a system for electrical neurostimulation is required.

[0007] According to one aspect of the present disclosure, a method of compensating for a change in position of an implantable electrical stimulator and an external device configured to activate the implantable electrical stimulator is provided. Such an implantable electrical stimulator can be implanted near a muscle and an associated nerve. In one example, such a muscle can be the genioglossus muscle and the nerve can be the hypoglossal nerve. The method includes generating an electrical stimulation pattern through electrical communication between the external activation device and the implantable electrical stimulator to stimulate a nerve of a subject to contract a muscle associated therewith, causing a change in position of the implantable stimulator relative to the external activation device, and adjusting stimulation parameters sent by the stimulated external activation device to compensate for the change in position of the implantable electrical stimulator relative to the activation device to substantially maintain electrical stimulation intensity by compensating for the change in position of the implant relative to the external activation device. Such an external device according to the example can be a transmitting element. The transmitting element can include an antenna or a coil, which in turn can be associated with a control unit. Such a control unit can further include a power source. In one embodiment, such a control unit can wirelessly transmit activation inputs, e.g., stimulation parameters, and power to the implant through the transmitting device. Such a combination of the external device and the control unit can constitute the external activation device.

[0008] The stimulation parameters can be automatically adjusted based on the degree of coupling between the stimulator and the external activation device, or these parameters can be preprogrammed to respond to a presumed change in position (e.g., based on a titration process to be further discussed herein). Such a change in position according to the disclosed subject matter can be a change in distance between the stimulator and the activation device, a change in angle between them, etc.

[0009] Adjustment or modulation of the electrical stimulation pattern can include reducing the target stimulation amplitude to a defined step-down amplitude within each pulse sequence after the target stimulation amplitude is reached. Variations of other parameters can also be applied, either as an alternative or in combination with changes in stimulation amplitude. It will be understood that this and other definitions apply to all aspects of the disclosed subject matter, mutatis mutandis.

[0010] According to another aspect of the disclosed subject matter, there is provided a method for electrical nerve stimulation, wherein the method comprises: generating an electrical stimulation pattern comprising a plurality of consecutive pulse sequences, wherein each pulse sequence has a stimulation amplitude; delivering the electrical stimulation pattern to a tongue of a patient with a stimulator having at least one electrode; modulating the electrical stimulation pattern, wherein the modulation of the electrical stimulation pattern comprises gradually increasing the stimulation amplitude from one pulse sequence to consecutive pulse sequences at the onset of the stimulation until a determined target stimulation amplitude is reached. The method is characterized in that the modulation of the electrical stimulation pattern further comprises reducing the target stimulation amplitude to a defined step-down amplitude within each pulse sequence after the target stimulation amplitude is reached.

[0011] As disclosed herein, reducing the target stimulation amplitude to a defined step-down amplitude within each pulse sequence can simply be referred to as “step-down”. There are at least two main advantages to step-down. One advantage is that the nerve fibers initially affected or triggered via the stimulation signal do not necessarily need to be further stimulated with the same amount of energy, i.e. a lower stimulation amplitude or frequency can be as effective as the initial amplitude or frequency to maintain the nerve affect. Furthermore, once a muscle is stimulated, it contracts. As long as this muscle contraction is activated, the distance between the external device generating the stimulation and the muscle itself will decrease, as at least part of the muscle will be closer to the patient’s skin surface due to the contraction. Thus, the distance between the external device and the stimulator decreases. At the same time, less intermediary tissue will be located between the external device and the stimulator. The intermediary tissue can include muscle tissue, connective tissue, organ tissue, or any other type of biological tissue. Again, this means that a lower stimulation amplitude or frequency can be needed to maintain the recruitment of the muscle compared to the initial amplitude or frequency.

[0012] As strong stimulation (e.g. a relatively high amplitude and / or frequency of the pulses of each pulse sequence of the stimulation pattern) can lead to discomfort, or in some cases even pain, in the patient, a lower stimulation intensity will be perceived as more comfortable by the subject. For example, if the stimulation amplitude is reduced, the subject can tolerate electrical stimulation with a higher pulse frequency and for a longer period of time. Furthermore, a lower stimulation intensity leads to a more energy efficient or battery saving method than a method with a continuously higher than actually needed stimulation intensity.

[0013] This reduction, for example, after reaching the target stimulation amplitude, can be combined with a gradual increase of the stimulation amplitude from one pulse sequence to the consecutive pulse sequence until a determined target stimulation amplitude is reached at the onset of the stimulation burst, which can be referred to as a "train ramp up". It will be appreciated that this ramp up can be implemented from the onset of the stimulation burst until the end of the stimulation, resulting in a target stimulation parameter which can be predetermined. This stimulation cycle can be throughout the whole treatment cycle, which in the case of OSA can be the cycle of the user sleeping. Such a cycle can be from 30 minutes to several hours as desired, depending on the sleep cycle of the user. It will be appreciated that the reduction can be implemented alternatively by other stimulation parameters or in combination with amplitude adjustment.

[0014] The electrical stimulation pattern comprises a pulse train stimulation, which consists of alternating ON and OFF phases or sequences. The length of the ON phase is called the sequence length, and the length of the OFF phase is called the sequence interval. The ON phase of the sequence stimulation consists of consecutive pulses, which are characterized by amplitude, duration, and interval. Two other important parameters are the frequency and the duty cycle, where the duty cycle is defined as the percentage of time a sequence is ON during stimulation.

[0015] The gradual increase of the stimulation amplitude from one pulse sequence to the consecutive pulse sequence at the onset of the stimulation burst comprises a gradual increase of the stimulation amplitude from one stimulation sequence to another stimulation sequence until a target stimulation amplitude is reached. Thus, it can be avoided to wake up the patient after the initialization of the stimulation. The gradual increase feature can comprise, for example, only one configurable parameter, namely the duration, i.e. a time period after a delay time during which the amplitude will be gradually increased.

[0016] The purpose of this feature is to increase the treatment acceptance by gradually increasing the amplitude to a target stimulation amplitude (in order to open the upper airway without waking up the patient), to maintain this target stimulation amplitude for a short period of time, and then to reduce the amplitude, since the force needed to keep the upper airway open should be lower than the force needed to open the closed upper airway.

[0017] Thus, the patient, as he or she receives the treatment over time, can select or the system can automatically select different modulation programs to change the electrical stimulation pattern.

[0018] According to one embodiment disclosed herein, the method is further characterized in that the target stimulation amplitude is reduced to a reduced amplitude in a stepwise manner. In other words, reducing the target stimulation amplitude to a defined reduced amplitude within each pulse sequence after reaching the target stimulation amplitude can comprise one distinct drop in amplitude until the defined reduced amplitude is reached. It is also possible that more drops to one or more intermediate amplitudes are performed before reaching the defined reduced amplitude, resulting in a gradual reduction of the pulses. The duration of each intermediate amplitude can be the same for each intermediate amplitude or can vary. Once the reduced amplitude is maintained for a defined duration, the amplitude is dropped, or successively dropped, to approximately 0.

[0019] The method is further characterized in that the target stimulation amplitude within each pulse sequence is reached according to a rise function comprising a rise duration, wherein the rise duration is defined as the time it takes for the stimulation amplitude to reach the target stimulation amplitude. The point in time within each pulse sequence at which the defined target stimulation amplitude is reached can be referred to as the rise point.

[0020] The target stimulation amplitude can be maintained for a defined hold duration before the target stimulation amplitude is reduced to the reduced amplitude. According to a preferred embodiment, the hold duration is in the range of 0 milliseconds to 1000 milliseconds, in particular in the range of 0 milliseconds to 500 milliseconds, wherein the hold duration is defined as the duration of the period for which the target stimulation amplitude is maintained within one stimulation sequence.

[0021] It is also possible that each successive pulse sequence is separated by a pulse sequence interval. According to a preferred embodiment, each pulse sequence comprises a plurality of successive single pulses, wherein each single pulse has a single pulse amplitude and a single pulse duration, and wherein successive pulses are separated by a single pulse interval. The method disclosed herein is further characterized in that each pulse sequence has a pulse sequence length, a single pulse frequency, and a duty cycle.

[0022] The method is further characterized in that the modulation of the electrical stimulation pattern is based on a determination of a degree of coupling between a primary antenna associated with the external device and a secondary antenna associated with the stimulator. The primary antenna can be configured as part of a circuit within the external device and can be coupled, directly or indirectly, including wirelessly, to various components in the external device. For example, the primary antenna can be configured to communicate with an amplifier, which can also be included in the external device, and which can output an amplified signal to the primary antenna.

[0023] The primary antenna can include any electrically conductive structure that can be configured to produce an electromagnetic field. The primary antenna can also be any suitable size, shape, and / or configuration. The size, shape, and / or configuration can be determined by the size of the patient, the placement location of the stimulator, the size and / or shape of the stimulator, the energy required to modulate the nerve, the location of the nerve to be modulated, the type of receiving electronics present on the stimulator, and / or the like. The primary antenna can include any suitable antenna known to those skilled in the art that can be configured to transmit and / or receive signals. Suitable antennas can include, but are not limited to, a long wire antenna, a patch antenna, a helical antenna, and / or the like. In one embodiment, for example, the primary antenna can include a coil antenna. Such a coil antenna can be made of any suitable electrically conductive material and can be configured to include any suitable electrically conductive coil arrangement.

[0024] The stimulator can include a secondary antenna mounted on or integrated with the carrier (e.g., a flexible carrier). Similar to the primary antenna, the secondary antenna can include any suitable antenna known to those skilled in the art that can be configured to transmit and / or receive signals. The secondary antenna can include any suitable size, shape, and / or configuration. The size, shape, and / or configuration can be determined by the size of the patient, the placement location of the stimulator, or the energy required to modulate the nerve. Suitable antennas can include, but are not limited to, a long wire antenna, a patch antenna, a helical antenna. For example, in some embodiments, the secondary antenna can include a coil antenna having a circular or elliptical shape. Such a coil antenna can be made of any suitable electrically conductive material and can be configured to include any suitable electrically conductive coil arrangement (e.g., diameter, number of coils, coil layout, and / or the like).

[0025] In a further development of the method, the electrical stimulation pattern further comprises an acknowledgement pulse and a delay time. The acknowledgement pulse is defined as the amplitude of a single first pulse emitted immediately after the connection between the external device and the stimulator is established. The acknowledgement pulse is described as a percentage of the total system output. Correspondingly, the delay time is defined as the time between the connection of the external device and the stimulator and the start of the stimulation.

[0026] In addition to the above, the duration of the gradual increase in stimulation amplitude from one pulse sequence to the consecutive pulse sequence at the onset of the stimulation is in the range of 0 minutes to 60 minutes, in particular in the range of 0 minutes to 30 minutes.

[0027] Furthermore, it can be expected that the rise duration is in the range of 0 milliseconds to 2000 milliseconds, in particular in the range of 0 milliseconds to 1000 milliseconds, wherein the rise duration is the duration of the gradual increase in amplitude within each stimulation sequence.

[0028] The reduction amplitude can also have an amplitude from 1% to 99% of the total system output amplitude, in particular 1% to 90% of the total system output amplitude. It is contemplated that the stimulation amplitude can have an amplitude from 1% to 100% of the total system (200) output amplitude. The method is further characterized by a pulse train interval duration in the range of 0.1 seconds to 20 seconds, in particular in the range of 0.2 seconds to 10 seconds. In addition to the above, the individual pulse duration is in the range of 5 microseconds to 500 microseconds, in particular in the range of 50 microseconds to 250 microseconds. The method disclosed herein is further characterized by a pulse train length duration in the range of 0.1 seconds to 20 seconds, in particular in the range of 0.2 seconds to 10 seconds, and an individual pulse frequency in the range of 10 Hz to 100 Hz, in particular in the range of 30 Hz to 50 Hz. According to another beneficial embodiment, the confirmation pulse has an amplitude from 1% to 100% of the total system output amplitude, and the delay time has a duration in the range of 0 minutes to 120 minutes, in particular in the range of 0 minutes to 90 minutes.

[0029] Preferably, among all the above parameters, the parameters that can be modified are as follows: individual pulse frequency, individual pulse duration, overall stimulation amplitude, pulse train length, pulse train interval, delay time, confirmation pulse, and ramp function. Once the other parameters are set, the total cycle length and duty cycle can be automatically calculated.

[0030] According to another aspect of the present disclosure, there is presented the use of the invented method for electrical neurostimulation in wakeful titration. In order to optimize the treatment of a patient, the use of the method disclosed herein is provided. According to this aspect, it is contemplated that the patient is returned to the hospital for one or more titration visits. The stimulation pattern parameters disclosed herein will be refined and / or adjusted during wakefulness and / or sleep, i.e., via sleep studies or polysomnography ("PSG"), until a set of settings is reached that does not cause the patient to wake up but at the same time maintains upper airway effectiveness, oxygenated hemoglobin saturation, and sleep continuity.

[0031] Thus, while the subject is awake, a wakeful titration is first performed according to a defined set of treatment guidelines. During the wakeful titration, one or more different stimulation thresholds can be determined. Once these thresholds are defined, the optimal wakeful parameter set for a given patient can be determined and stored based on the tongue movement characteristics of that patient.

[0032] In this way, the movement characteristics, direction, and intensity of the tongue, as well as the stimulation thresholds, can be determined without anesthesia or endoscopy, thereby helping to define the optimal treatment parameters.

[0033] The method described herein as used is further characterized in that the method is used to define a motor threshold stimulation amplitude for a defined single pulse frequency and a defined single pulse duration. The motor threshold is defined as the minimum threshold that, when applied, causes first noticeable movement or displacement of the tongue or the hypopharyngeal muscles. This can be done by, for example, a trained physician or medical doctor or any other suitable therapist.

[0034] Further, the method can be used to define a pain threshold stimulation amplitude for a defined single pulse frequency and a defined single pulse duration. The pain threshold is defined as the minimum threshold that, when applied, causes an unpleasant, uncomfortable or painful sensation in the subject. This can be determined, for example, by interrogating the subject.

[0035] As part of another embodiment, the method described herein can be used for awake endoscopy. During awake endoscopy, the airway opening amplitude at each opening site can be defined by the minimum amplitude required to observe airway opening during stimulation. Similarly, the plateau amplitude at each opening site can be defined by the threshold at which no further increase in airway opening is observed, or above which a decrease in airway opening is observed.

[0036] In addition to the above, the method can be used to define an airway opening amplitude, wherein the airway opening amplitude is the minimum stimulation amplitude required to cause airway opening in the subject during stimulation.

[0037] The method can also be used to define a plateau amplitude, wherein the plateau amplitude is the maximum stimulation amplitude beyond which no further increase in airway opening in the subject is caused.

[0038] The method can also be used for polysomnography titration. Polysomnography (PSG) titration allows for configuration and optimization of stimulation parameters until a desired set of treatment settings is reached, i.e., settings that do not wake the participant while maintaining upper airway effectiveness, oxygen saturation levels, and sleep continuity. During PSG titration, if a sleep event occurs, one stimulation parameter can be changed at a time in a defined order. For example, the stimulation amplitude can be increased, e.g., by about 5%. If the patient does not support the increased amplitude or the increased amplitude has the opposite effect, the duration of the individual pulses can be increased, e.g., by 20 microseconds. If the patient does not support the increased duration of the individual pulses, the duty cycle can be adjusted to match the patient’s respiratory cycle. For example, PSG titration stimulation can start after the patient has been asleep for at least 20 minutes. The stimulation pattern parameters can be refined according to a desired set of treatment guidelines until a specific set of settings is reached that does not wake the patient while maintaining upper airway effectiveness, oxygenated hemoglobin saturation, and sleep continuity. These settings can be stored as the optimal settings, which can be maintained throughout the night. PSG and respiration parameters can also be recorded until the patient eventually wakes up. During the night, it can be necessary to further adjust the electrical stimulation parameters.

[0039] According to yet another aspect of the present disclosure, a system for electrical nerve stimulation to correct sleep disordered breathing is provided, the system comprising a stimulator having at least one electrode; an external device, wherein the external device is configured to communicate with the stimulator, and wherein the external device comprises a processor configured to: generate an electrical stimulation pattern comprising a plurality of consecutive pulse sequences, wherein each pulse sequence has a stimulation amplitude; deliver the electrical stimulation pattern to a hypoglossal nerve of a subject by the stimulator; modulate the electrical stimulation pattern according to a stimulation program, wherein the modulation of the electrical stimulation pattern comprises gradually increasing the stimulation amplitude from one pulse sequence to consecutive pulse sequences at a stimulation onset until a determined target stimulation amplitude is reached, and wherein the modulation of the electrical stimulation pattern further comprises reducing the target stimulation amplitude to a defined reduction amplitude within each pulse sequence after the target stimulation amplitude is reached.

[0040] The system can be configured for neuromodulation of a patient's tongue muscle. More specifically, the system can be configured to deliver energy to an OSA patient. Accordingly, the system can include an external device configured for positioning outside the patient's body. The external device can also be configured to be affixed to the patient. In particular, the external device can be configured to be placed near an implanted stimulator, for example, under the patient's chin and / or in front of the patient's neck or away from the subject's body. Suitability of the placement location can be determined by communication between the external device and the stimulator. In some embodiments, the stimulator can be configured as a device implanted within the patient's body, and the external device can be configured to send signals to and / or receive signals from the stimulator. The stimulator can be formed of any suitable material. In some embodiments, the stimulator can include a flexible carrier including a flexible biocompatible material. The stimulator can also include circuitry including a conductive material, such as gold, platinum, titanium, or any other biocompatible conductive material or combination of materials. The stimulator can also be manufactured to have a thickness suitable for implantation under the patient's skin. The stimulator can have a thickness of less than about 4 millimeters or less than about 2 millimeters.

[0041] Various components can be included within a housing of the external device or otherwise associated with the external device. In particular, at least one processor is associated with the external device. For example, the at least one processor can be located within a housing of the external device. In alternative embodiments, the at least one processor can be configured to communicate with the external device from a location outside the housing, either wired or wirelessly. The housing can include any suitable receptacle configured to hold components. Further, the housing can be any suitable size and / or shape, and can be rigid or flexible. Exemplary embodiments of a housing for the external device include one or more of a patch, a button, or other receptacle having different shapes and sizes and constructed of any suitable material. For example, in one embodiment, the housing can include a flexible material such that the external device can be configured to conform to a desired location.

[0042] The at least one processor can include any circuitry that can be configured to perform logical operations on at least one input variable. Accordingly, the at least one processor can include one or more integrated circuits, microchips, microcontrollers, and microprocessors, which can be all or a portion of a central processing unit (CPU), a digital signal processor (DSP), a field programmable gate array (FPGA), or any other circuitry suitable for executing instructions or performing logical operations as known to those of skill in the art.

[0043] The stimulator can also include at least one pair or plurality of field generating electrodes. The electrodes can include any suitable shape and orientation on the stimulator so long as the electrodes can be configured to generate an electric field in the patient. The electrodes can also include any suitable electrically conductive material, such as copper, silver, gold, platinum, iridium, platinum iridium, platinum gold, electrically conductive polymers, etc., or combinations of electrically conductive materials. In some embodiments, the electrodes can include short wire electrodes, round electrodes, and / or pairs of round electrodes. Additionally, the stimulator can include electrodes positioned in multiple locations.

[0044] The system is further characterized in that the system further includes a user interface configured to enable a user to adjust and / or select a stimulation program, wherein at least one set of stimulation pattern parameters is adjustable.

[0045] It is also contemplated that the set of stimulation pattern parameters can further include a stimulation amplitude, a pulse train length, a single pulse frequency, a single pulse duration, a target stimulation amplitude, a hold duration, a decrease amplitude, a ramp up duration, a pulse train interval, a duty cycle, and / or a delay time. The external device can further include a memory configured to store at least one stimulation program. For example, patient-specific stimulation pattern parameters programmed by a therapy specialist.

[0046] According to another preferred embodiment, the external device further includes a disposable patch configured to be connectable to the processor. In particular, the processor can be attached to one or more disposable patches, which in turn can be placed on the patient's skin, for example, under the chin, and in some examples via at least one adhesive surface of the disposable patch. For activation and deactivation of the stimulation, the disposable patch connected to the processor can be placed under the chin by the subject prior to a stimulation session or before going to sleep, and removed in the morning. The power supply of the processor can be charged during the day using a charging unit.

[0047] Advantageously, the disposable patch can be a biocompatible adhesive device for one-time use, which is placed under the chin of the patient prior to entering a stimulation session or before going to sleep. The processor is mounted on the disposable patch, which allows activation of the stimulator by delivering energy. In a preferred embodiment, the energy delivery occurs wirelessly.

[0048] According to further developments of the system, the external device can comprise a power source. The power source can be removably coupled to the external device at a location external to the external device. Alternatively, the power source can also be permanently or removably coupled to a location within the external device. The power source can also comprise any suitable power source configured to be in electrical communication with the processor. In a preferred embodiment, for example, the power source can comprise a battery. The power source can be configured to power various components within the external device. It can also be configured to power the processor. Furthermore, the power source can be configured to power a signal source. The signal source can be in communication with the processor and can comprise any device configured to generate a signal (e.g., a sinusoidal signal, a square wave, a triangular wave, a microwave, a radio frequency (RF) signal, or any other type of electromagnetic signal). The signal source can include, but is not limited to, a waveform generator, which can be configured to generate an alternating current (AC) signal and / or a direct current (DC) signal. For example, in one embodiment, the signal source can be configured to generate an AC signal for transmission to one or more other components. The signal source can be configured to generate a signal of any suitable frequency. In some embodiments, the signal source can be configured to generate a signal having a frequency from about 6.5 MHz to about 13.6 MHz. In further embodiments, the signal source can be configured to generate a signal having a frequency from about 7.4 MHz to about 8.8 MHz. In further embodiments, the signal source can generate a signal having a frequency as low as 90 kHz or as high as 28 MHz.

[0049] The system disclosed herein is further characterized in that the system further comprises a remote control device. The remote control device can be implemented, for example, in a mobile device. With the remote control device, the therapist or the subject can adjust the stimulation pattern parameters of the system in a more convenient manner.

[0050] As part of another embodiment of the system, the system can further comprise a wireless control device configured to: wirelessly communicate with the processor; and wirelessly communicate with the remote control device.

[0051] Additionally, the system is characterized in that the wireless communication of the wireless control device is based on an RFID or a Bluetooth connection. Preferably, the wireless control device can be installed on a mobile device, i.e. the wireless control device can be an application (APP) on a smartphone or a smart tablet or the like.

[0052] Any one of the embodiments, examples, or features disclosed herein can be combined or used independently, in combination with any one of the aspects of the disclosed subject matter, with necessary modifications, if any, being made. BRIEF DESCRIPTION OF DRAWINGS

[0053] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate several examples of the disclosed subject matter. The drawings show the following:

[0054] Figure 1 A schematic diagram illustrating a detailed electro-stimulation pattern 100 according to an exemplary embodiment of the present disclosure is depicted;

[0055] Figure 2 A schematic diagram illustrating a detailed electro-stimulation pattern 100 according to another exemplary embodiment of the present disclosure is depicted;

[0056] Figures 3a-3d Different schematic diagrams are depicted, each illustrating a possible pattern of the pulse sequence 110 during modulation according to different exemplary embodiments of the present disclosure;

[0057] Figure 4 A partial cross-sectional side view of a patient 500 with a use system 200 according to exemplary embodiments of the present disclosure is depicted;

[0058] Figure 5 Anatomy of the tongue and associated muscles and nerves according to exemplary embodiments of the present disclosure is depicted;

[0059] Figures 6a-6b A schematic diagram of the stimulator 300 and the external device 400 according to exemplary embodiments of the present disclosure is depicted. DETAILED DESCRIPTION

[0060] Figure 1 A schematic diagram illustrating a detailed electro-stimulation pattern 100 according to an exemplary embodiment of the present disclosure is depicted. Specifically, the schematic diagram shows the following parameters of the electro-stimulation pattern 100: delay time 151; confirmation pulse 150; pulse sequence length 112; pulse sequence interval 113; pulse sequence amplitude 111; single pulse duration 121; single pulse interval 122. Furthermore, the specific duty cycle can be inferred from the graph shown. Figure 1 More specifically, as shown, one pulse sequence 110 comprises several single pulses 120, which are all separated from each other by a single pulse interval 122. The number of single pulses 120 per unit of time is defined as the single pulse frequency 123. Similarly, the individual pulse sequences 110 are separated from each other by a pulse sequence interval 113. Figure 1

[0061] As shown, the electro-stimulation pattern 100 is very basic, meaning that all single pulses have the same amplitude, with the exception of the confirmation pulse 150. Therefore, no rising or falling function is depicted in this graph. Figure 1

[0062] Figure 2 ​​A schematic drawing depicting a detailed electrical stimulation pattern 100 during modulation is illustrated according to another exemplary embodiment of the present disclosure. Specifically, an electrical stimulation pattern 100 is shown, wherein the modulation of the electrical stimulation pattern 100 comprises a gradual increase 160 of the pulse sequence amplitudes 111 from one pulse sequence 110 to the consecutive pulse sequence 110 at the onset of stimulation 101 until a determined target stimulation amplitude 130 is reached. The individual pulses making up one pulse sequence 110 can all have the same amplitude or have different amplitudes. For example, the amplitudes of the individual pulses within one pulse sequence 110 can also be incremented relative to each other (not shown in the middle). Figure 2

[0063] This feature can help to increase the acceptance of the therapy by gradually increasing the amplitude until the target stimulation amplitude 130 (in order to open the upper airway without waking up the patient 500), to maintain this target stimulation amplitude 130 for a shorter period of time and then to decrease the amplitude 111, since the force needed to keep the upper airway open should be lower than the force needed to open a closed upper airway.

[0064] In addition to the gradual increase 160 during the onset of stimulation 101, Figure 2 a modulation of the electrical stimulation pattern 100 is also shown, which is in the form of a decrease of the target stimulation amplitude 130 to a defined decrease amplitude 140 within each pulse sequence 110 after reaching the target stimulation amplitude 130 via a ramp with a defined ramp-up duration 132. Specifically, according to Figure 2 the variation shown, the target stimulation amplitude 130 is decreased in a more or less abrupt manner to the decreased amplitude 140. In other words, the decrease of the target stimulation amplitude 130 to the defined decreased amplitude 140 within each pulse sequence 110 after reaching the target stimulation amplitude 130 can comprise one distinct drop of the amplitude until the defined decreased amplitude 140 is reached. It is also possible that more drops to one or more intermediate amplitudes are performed before the defined decreased amplitude 140 is reached. Then, the duration of each intermediate amplitude can be the same for each intermediate amplitude or can be varied.

[0065] Furthermore, as Figure 2 shown, the target stimulation amplitude 130 within each pulse sequence 110 can be reached according to a ramp function comprising a ramp-up duration 132. The ramp-up duration 132 is defined as the time it takes for the pulse sequence amplitude 111 to reach the target stimulation amplitude 130. Advantageously, although Figure 2 ​The target stimulation amplitude 130 can remain defined for a defined hold duration 131 before being reduced to the reduced amplitude 140, which is not explicitly shown. According to a preferred embodiment, the hold duration 131 is in the range of 0 milliseconds to 1000 milliseconds, in particular in the range of 0 milliseconds to 500 milliseconds, wherein the hold duration 131 is defined as the duration of a time period during which the target stimulation amplitude 130 remains within one stimulation sequence.

[0066] Figures 3a-3d Different diagrams are depicted, each diagram illustrating possible patterns of the pulse sequence 110 during modulation according to different exemplary embodiments of the present disclosure. The graphs show the pulse sequence amplitude 111 (Y-axis) over time (X-axis). Specifically, different types of rising and / or falling modulation are depicted, wherein rising is defined as increasing the pulse sequence amplitude within one pulse sequence 110 according to a rising function comprising a rising duration 132 until the target stimulation amplitude 130 is reached. The point of reaching the target stimulation amplitude 130 is defined as the rising point 133 - the rising duration 132 is defined as the time taken by the pulse sequence amplitude 111 to reach the target stimulation amplitude 130. The gradual increase 160 of the pulse sequence amplitude 111 from one pulse sequence 110 to the consecutive pulse sequence 110 at the stimulation onset 101 comprises gradually increasing the pulse sequence amplitude 111 from one stimulation sequence to the other until the target stimulation amplitude 130 is reached, and wherein falling is defined as reducing the target stimulation amplitude 130 to the defined reduced amplitude 140 within each pulse sequence 110, as disclosed herein.

[0067] Rising has the effect that it can be avoided to wake up the patient 500 after stimulation initialization. The gradual increase 160 can for example comprise only one configurable parameter, namely the duration, i.e. the time period after the delay time 151 during which the amplitude is to be gradually increased.

[0068] Reducing has at least two main advantages. One advantage lies in the fact that the nerve fibers initially affected or triggered via the stimulation signal do not necessarily need to be further stimulated with the same amount of energy, i.e. a lower pulse sequence amplitude 111 or frequency can be as effective in maintaining the nerve effect as the initial amplitude or frequency. Furthermore, once a muscle is activated via the stimulation, it contracts. As long as this muscle contraction is activated, the distance between the external device 400 generating the stimulation in the muscle and the muscle itself will decrease, because due to the contraction at least a part of the muscle will be closer to the skin surface of the patient 500. Thus, the distance between the external device 400 and the stimulator 300 decreases. At the same time, less intermediary tissue will be located between the external device 400 and the stimulator 300. The intermediary tissue 530 can comprise muscle tissue, connective tissue, organ tissue or any other type of biological tissue. Again, this means that a lower pulse sequence amplitude or frequency can be needed to maintain the recruitment of the muscle compared to the initial amplitude or frequency.

[0069] According to Figure 3a In the embodiment shown, the target stimulation amplitude 130 has been reached. As shown, according to this particular embodiment, the reduction of the target stimulation amplitude 130 to the reduced amplitude 140 is achieved in a stepwise manner. In other words, reducing the target stimulation amplitude 130 to the defined reduced amplitude 140 within each pulse sequence 110 after the target stimulation amplitude 130 has been reached can comprise one distinct drop in amplitude until the defined reduced amplitude 140 is reached. When the pulse sequence 110 ends and no single pulse occurs, the reduced amplitude 140 drops abruptly to 0. According to Figure 3b In the embodiment shown, the target stimulation amplitude 130 has been reached. As shown, according to this particular embodiment, the reduction of the target stimulation amplitude 130 to the reduced amplitude 140 is achieved in a stepwise manner. In other words, reducing the target stimulation amplitude 130 to the defined reduced amplitude 140 within each pulse sequence 110 after the target stimulation amplitude 130 has been reached can comprise one distinct drop in amplitude until the defined reduced amplitude 140 is reached. When the pulse sequence 110 ends and no single pulse occurs, the reduced amplitude 140 drops abruptly to 0. According to

[0070] Figure 3c and Figure 3d show the same type of reduction modulation within a pulse sequence 110, respectively. Figure 3a and Figure 3b show the same type of reduction modulation within a pulse sequence 110, respectively. Figure 3c and Figure 3d In the exemplary embodiment shown, the target stimulation amplitude 130 is first reached by a continuous rise of the pulse sequence amplitude 111. The point in time within each pulse sequence 110 at which the defined target stimulation amplitude 130 is reached can be referred to as the rise point 133.

[0071] Figure 4A partial cross-sectional side view of a patient 500 with a system 200 for use in accordance with example embodiments of the present disclosure is depicted. The system 200 is configured for neuromodulation of a patient muscle. More specifically, the system 200 can be configured to deliver energy in a patient 500 with OSA. Accordingly, the system 200 can include an external device 400 configured for positioning outside the patient's body. As Figure 4 shown, the external device 400 can be configured to be secured to the patient 500. In particular, as Figure 4 shown, the external device 400 can be configured to be placed under the patient's chin and / or in front of the patient's neck. Suitability of the placement location can be determined by communication between the external device 400 and the stimulator 300. Other suitable locations for the external device 400 include the back of the patient's head for communication with a migraine treatment stimulator 300, the outer surface of the patient's abdomen for communication with a gastric modulation stimulator 300, the patient's back and / or any other suitable external location on the patient's skin for communication with a renal artery modulation stimulator 300, depending on the needs of the particular application.

[0072] As noted above, the stimulator 300 can be configured to be implanted in the patient (e.g., under the patient's skin). Figure 4 and Figure 5 It is shown that the stimulator 300 can be configured to be implanted for modulation of nerves associated with the genioglossus muscle. Modulation of nerves associated with a subject's tongue muscle can include stimulation to cause muscle contraction. In further embodiments, the stimulator 300 can be configured to be placed in connection with any nerves that one can wish to modulate.

[0073] Figure 5 Anatomy of the tongue and associated muscles and nerves (i.e., hypoglossal nerve (XII)) is depicted in accordance with example embodiments of the present disclosure. Figure 5The nerve 510 is further delineated. The nerve 510 innervates the tongue and other tongue muscles, including the genioglossus and hyoglossus muscles, through its lateral branch and medial branch. The horizontal compartment of the genioglossus muscle is primarily innervated by the medial trifurcated fibers of the medial branch of the nerve 510, which bifurcates from the lateral branch at the terminal bifurcation. The distal portion of the medial branch then becomes the medial terminal fibers. Contraction of the horizontal compartment of the genioglossus muscle can be used to open or maintain the airway of a subject. Contraction of other tongue muscles can contribute to other functions, such as swallowing, articulation of speech, and opening or closing of the airway. Because the hypoglossal nerve 510 innervates several tongue muscles, it can be advantageous for OSA treatment to limit modulation of the nerve 510 to the medial branch, or even to the medial terminal fibers or terminal fibers of the nerve 510. In this way, contraction-inducing neural modulation can be selectively targeted to the genioglossus muscle, which is most responsible for tongue movement and airway maintenance. Alternatively, the horizontal compartment of the genioglossus muscle can be selectively targeted.

[0074] However, the medial terminal fibers or terminal fibers can be difficult to affect neural modulation because they are located within the fibers of the genioglossus muscle. Embodiments of the present disclosure facilitate modulation of any such terminal fibers. In some embodiments, the stimulator 300, including at least one pair of modulation electrodes 310 and at least one electrical circuit, can be configured to be implanted through the dermis of the underside of the chin of a subject. When implanted through the dermis of the underside of the chin of a subject, the stimulator 300 can be located near the medial terminal fibers of the medial branch of the hypoglossal nerve 510 of the subject. Figure 5 The position of an exemplary stimulator 300 is delineated. Furthermore, the efficacy of the modulation can be increased by an electrode configuration that is suitable to generate parallel electric field lines that are partially or substantially parallel to the nerve fibers to be modulated. Figure 5 The electrodes 310 that generate electric field lines that are substantially parallel to the medial terminal fibers, as shown by the dashed lines, are delineated.

[0075] Figures 6a-6b A schematic of a stimulator 300 and external device 400 according to exemplary embodiments of the present disclosure is delineated. As shown, the stimulator 300 can be configured for implantation in a patient 500, preferably in a location that allows it to modulate a nerve. In particular, the stimulator 300 can be located in the patient 500 such that intervening tissue is present between the stimulator 300 and the hypoglossal nerve 510. Thus, the location of the stimulator 300 does not need to be in contact with the nerve for effective neural modulation. The stimulator 300 can also be located directly near the nerve 510, such that no intervening tissue is present.

[0076] In the treatment of OSA, the stimulator 300 can be located on the genioglossus muscle of the patient 500. Such a location is suitable for modulation of the hypoglossal nerve 510, which extends at the genioglossus muscle.

[0077] As Figure 6a illustrated, when the muscle is at rest, i.e. not contracted, the distance Al between the external device 400 generating the muscle stimulation and the muscle itself will be relatively large. Likewise, the distance Al between the external device 400 and the implanted stimulator 300 will also be relatively large, and a lot of tissue will be located between the external device 400 and the stimulator 300. As a result, a high intensity of stimulation is required for the initial engagement of the nerve 510.

[0078] Once a muscle contraction is achieved, the distance A2 between the external device 400 generating the stimulation in the muscle and the muscle itself will be reduced, as Figure 6b illustrated. Since at least part of the muscle will be closer to the skin surface of the patient 500 due to the contraction, the distance between the external device 400 and the stimulator 300 will also be reduced. At the same time, less intermediary tissue will be located between the external device 400 and the stimulator 300. This means that a lower amplitude 111 or frequency of the pulse train is required to maintain the recruitment of the muscle compared to the initial amplitude or frequency of the stimulation. In other words, a lower intensity stimulation is sufficient to maintain the muscle contraction.

[0079] The invention is not limited to one of the embodiments described herein, but can be modified in many other ways.

[0080] All features disclosed in the claims, specification, and drawings, and all the advantages thereof, individually and collectively, together with accompanying claims are inherent. Any

[0081] List of reference signs

[0082] 100 electrical stimulation pattern

[0083] 101 stimulation onset

[0084] 110 pulse train

[0085] 111 pulse train amplitude

[0086] 112 pulse train length

[0087] 113 pulse train interval

[0088] 120 single pulse

[0089] 121 single pulse duration

[0090] 122 single pulse interval

[0091] 130 target stimulation amplitude

[0092] 131 hold duration

[0093] 132 rise duration

[0094] 133 rise point

[0095] 140 fall amplitude

[0096] 150 confirmation pulse

[0097] 151 delay time

[0098] 160 ramp up

[0099] 200 system

[0100] 300 stimulator

[0101] 310 electrode

[0102] 400 external device

[0103] 500 patient

[0104] 510 nerve

[0105] 530 intermediary organization

[0106] 600 genioglossus muscle

[0107] A1, A2 distance

Claims

1. A system (200) for electrical nerve (510) stimulation to correct sleep-disordered breathing, said system (200) comprising: A stimulator (300) having at least one electrode assembly (310). An external device (400), wherein the external device (400) is configured to communicate with the stimulator (300), and wherein the external device (400) includes a processor configured to: An electrical stimulation pattern (100) is generated, comprising multiple consecutive pulse sequences (110), wherein each pulse sequence (110) has a pulse sequence amplitude; The electrical stimulation pattern (100) is transmitted to the nerves (510) of the subject (500) via the stimulator (300). The electrical stimulation pattern (100) is modulated according to a stimulation program, wherein the modulation of the electrical stimulation pattern (100) includes gradually increasing the amplitude of the pulse sequence (111) from one pulse sequence (110) to a continuous pulse sequence (110) during a stimulation attack (101) until a predetermined target stimulation amplitude (130) is reached, and wherein the modulation of the electrical stimulation pattern (100) further includes reducing the target stimulation amplitude (130) to a defined reduction amplitude (140) within each pulse sequence (110) after the target stimulation amplitude (130) is reached. The modulation of the electrical stimulation mode (100) includes continuously reducing the reduction amplitude (140) to zero once the target stimulation amplitude (130) drops to the reduction amplitude (140).

2. The system (200) according to claim 1, characterized in that The system (200) also includes a user interface configured to enable a user to adjust and / or select the stimulation program, wherein at least one set of stimulation mode parameters is adjustable.

3. The system (200) according to claim 2, characterized in that, The set of stimulation mode parameters includes pulse sequence amplitude (111), pulse sequence length (112), single pulse frequency, single pulse duration (121), target stimulation amplitude (130), hold duration (131), decrease amplitude (140), rise duration (132), pulse sequence interval (113), duty cycle and / or delay time (151).

4. The system (200) according to claim 1, characterized in that, The external device (400) also includes a memory configured to store at least one stimulation program.

5. The system (200) according to claim 1, characterized by The external device (400) also includes a disposable patch configured to connect to the processor.

6. The system (200) according to claim 1, characterized by The external device (400) also includes a power supply.

7. The system (200) according to claim 1, characterized in that, The system (200) also includes a remote control device.

8. The system (200) according to claim 7, characterized in that, The system (200) further includes a wireless control device configured to: Wireless communication with the processor; and It communicates wirelessly with the remote control device.

9. The system (200) according to claim 8, characterized in that, The wireless communication of the wireless control device is based on RFID or Bluetooth connection.

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