System and method to improve pharyngeal wall stiffening and diaphragmatic contraction for OSA treatment

Abstract

A system and methods for stimulating two or more nerves to treat obstructive sleep apnea includes an implantable nerve stimulator (e.g., an implantable pulse generator) with a single current source for generating a time-multiplexed signal. The time-multiplexed signal includes first pulses defined interleaved with second pulses. The first and second pulses are defined by respective sets of pulse parameters stored in memory. The processor controls at least one switch to selectively steer each first pulse to a first nerve and each second pulse to a second nerve. In some examples, the first and second nerves are selected from a group of nerves consisting of the ansa cervicalis, the phrenic nerve, and the hypoglossal nerve.

Description

SYSTEM AND METHOD TO IMPROVE PHARYNGEAL WALL STIFFENING AND DIAPHRAGMATIC CONTRACTION FOR OSA TREATMENTCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application relates to and claims priority from U.S. provisional patent application number 63 / 762,252, filed on 02-24-2025, and entitled “System and Method to Improve Pharyngeal Wall Stiffening and Diaphragmatic Contraction for OSA Treatment”.FIELD

[0002] The present disclosure relates to implantable stimulation systems and methods for stimulating two or more nerves. In particular, it relates to an implantable stimulator including a single current source for generating a temporally multiplexed stimulation signal, and a switching circuit for steering discrete pulses of the stimulation signal to either a first nerve or a second nerve.BACKGROUND

[0003] Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder characterized by repeated cessations of breathing during sleep. Obstruction or collapse of the upper airway causes arousals, desaturation events, and diminished sleep quality. If left untreated, long-term effects of OSA can include high blood pressure, heart failure, stroke, diabetes, headaches, and memory loss.

[0004] Continuous positive airway pressure (CPAP) therapy is the standard treatment for OSA. CPAP therapy uses machines that generally include a flow generator, tubing, and a mask to deliver a constant flow of air pressure to keep the airways continuously open. However, the success of CPAP therapy is limited by lack of patient compliance, with reported rates ranging from 50% to 70%.

[0005] Electrical stimulation of certain peripheral nerves, such as the hypoglossal nerve (HGN), provides a viable treatment alternative to CPAP and has shown therapeutic efficacy in managing OSA in some patients. Stimulation of the HGN extends the tongue, increases airway patency, and can reduce the frequency and severity of certain apneic events. Implantable stimulation systems suitable for such purposes often include an implantable stimulator, such as an implantable pulse generator (IPG), and an optional stimulation lead coupled to the stimulator for transmitting targeted electrical stimulation directly to a nerve.

[0006] However, single-target neural stimulation cannot sufficiently address all OSA pathologies. Some OSA types involve multi-level airway collapse and discoordination or weakness of certain respiratory muscles, suggesting simultaneous or coordinated stimulation of two or more nerves could further improve respiratory dynamics.

[0007] In some conventional stimulation systems, stimulating multiple nerves with tailored stimulation parameters for each has been accomplished using either a plurality of implanted stimulators or a single implanted stimulator containing multiple independent current sources, each used to drive stimulation to a respective nerve. Such strategies can enable targeted therapy for each nerve but often increase implant size, system cost, energy consumption, and overall complexity.SUMMARY

[0008] The following summary provides non-limiting, non-exhaustive examples of systems, methods, components, and features (collectively, “aspects”) in accordance with the present disclosure to provide a basic understanding. Any or all aspects could be interchangeably applied between examples, and no single aspect is essential to achieve the technical effects / solutions described. Many aspects are described in the context of systems and methods configured to treat OSA, but could also apply to the treatment of another medical condition, and the systems described should not be misconstrued as applicable only to a method of treatment.

[0009] Many conventional implantable stimulators are designed to deliver therapeutic electrical stimulation to a single peripheral nerve that innervates a specific muscle. However, OSA can arise from multiple pathophysiological mechanisms, and not all of these can be adequately addressed by stimulating a single nerve. Examples of nerves that may be beneficial to stimulate to treat OSA include the Hypoglossal Nerve (HGN), the Ansa Cervicalis (AC), and the Phrenic Nerve (PN).

[0010] Some conventional multi-channel IPGs include multiple independent current sources for driving stimulation to respective nerves, increasing device size, power consumption, cost, and system complexity. There is a need for an implantable stimulation architecture that, using a single current source, can selectively direct pulses to multiple distinct neural targets, while preserving nerve-specific stimulation parameters and timing, minimizing implant size and energy overhead.

[0011] In one aspect, the present disclosure provides a stimulation system configured to stimulate at least two distinct nerves to treat OSA. The at least two nerves include a first nerve and a second nerve. In some examples, the first and second nerves are each selected from a group of nerves consisting of: the Hypoglossal Nerve (HGN), the Ansa Cervicalis (AC), and / or the Phrenic Nerve (PN). Delivering stimulation to two or more of these nerves can improve the efficacy of OSA stimulation therapy by addressing multiple underlying causes, such as tongue obstruction, pharyngeal collapse, and diaphragmatic weakness / discoordination.

[0012] In some examples, the system includes an implantable stimulator, such as an implantable pulse generator (IPG). The stimulator comprises a housing containing a power source (e.g., a battery), a current source, a processor, a memory, a plurality of independent output stimulation channels including a first output stimulation channel and a second output stimulation channel, and at least one switch (e.g., an analog switch, a programmable logic controller, a demultiplexer, or the like) for selectively controlling electrical circuit continuity between the current source and the plurality of independent output stimulation channels. One or more stimulation leads may also be included as part of the stimulation channels. The stimulation lead(s) include elongate electrical conductors for electrically coupling the plurality of stimulation output channels from the IPG to a plurality of electrodes carried on the distal end of stimulation lead, which distal end of the lead may be a nerve cuff, a linear array of electrodes, or a paddle lead, among other configurations that are well known in the neuromodulation field.

[0013] In some examples, the plurality of output channels includes a first output channel and a second output channel. An elongate electrical conductor in the at least one lead couples the first output channel to a first electrode. The first electrode is carried by the body of a first nerve cuff configured for circumferential placement on the first nerve. Another elongate electrical conductor couples the second output channel to a second electrode. The second electrode is carried by the body of a second nerve cuff configured for circumferential placement on the second nerve.

[0014] In some examples, the processor instructs the current source to generate a temporally multiplexed signal comprising a plurality of interleaved electrical pulses. Each pulse is tuned, in real time or according to a programmed schedule, in accordance with either a first or second set of stimulation parameters stored in memory. The multiplexed signal is passed to the at least one switch. The at least one switch is controlled (e.g., by the processor) to selectively directdiscrete electrical pulses to either the first or second output channel, for delivery via the first electrode and the second electrode to either the first or second nerve, respectively.

[0015] In some examples, the memory is configured to store at least two distinct sets of predetermined or pre-programmed stimulation parameters, including at least a first parameter set (“first set”) and a second parameter set (“second set”). The first and second sets each contain values for stimulation parameters (such as pulse amplitude, pulse width, pulse frequency, and / or duty cycle) tailored for stimulating a respective nerve. The first and second sets may differ with respect to at least one parameter value. In a specific example, the first and second sets have different pulse amplitude values.

[0016] In some examples, the processor continuously monitors the current source's output for comparison against, e.g., the first parameter set, the second parameter set, or a predetermined safety threshold, such as a maximum allowable voltage or current of the output signal, stored in memory. In such cases, a sensing circuit (e.g., a voltage shunt) can provide continuous feedback to the processor, allowing the processor to adjust its instructions to the current source in real time to compensate for detected changes in impedance. The processor might also continuously analyze the feedback signal to verify that it complies with the anticipated stimulation parameters, to monitor the health / functionality of the switching circuit (i.e., to check if any cross-talk exists between output channels), and / or to actively control the switching circuit (i.e., to open the circuit) to prevent transmission to one or more output channels in the event that the feedback signal is determined to exceed a predetermined safety threshold. Thus, the processor could optionally serve as an active supervisory circuit or monitoring relay in some implementations.

[0017] The processor can be configured to analyze the amplitude and / or another distinguishing characteristic of each stimulus pulse, identify correspondence to either the first or second set of stimulation parameters, and activate the at least one switch to route or direct the pulse to the appropriate lead / el ectrode or electrode combination. In certain implementations, three or more parameter sets stored in memory can allow selective routing of stimulus pulses to three or more nerve targets.

[0018] In some examples, the system is configured to deliver therapy for OSA by coordinating hypoglossal nerve stimulation to maintain airway patency, ansa cervicalis stimulation to recruit infrahyoid muscle tone and laryngeal stabilization, and / or phrenic nerve stimulation to synchronize respiratory drive or augment inspiratory effort. Two of the targets may be stimulated concurrently. Or only one target may be stimulated at any one time, but twoor three targets may be stimulated at different times, i.e., through time multiplexing. Temporal multiplexing conserves hardware resources and power while enabling multi-site neuromodulation with target-specific pulse characteristics.

[0019] In various examples, stimulation could be applied unilaterally (i.e., ipsilaterally on one side of the neck) or bilaterally (i.e., contralaterally on both sides of the neck) for any given nerve. Stimulation can be delivered in a monopolar (by using the metal IPG housing as a return or indifferent electrode and a cathode electrode located on the nerve cuff, paddle, or linear electrode array) or bipolar stimulation configuration (by using two electrodes as an anodecathode pair, the pair of electrodes closely located on the nerve cuff, paddle, or linear electrode array). Any one or a combination of the electrically conductive contacts (or “electrodes”) could be configured to perform one or a combination of functions, including, but not limited to, functioning as, in first time interval, an anode or a cathode, for transmitting electrical stimulation to a nerve, or in a second time interval as a sensing electrode for sensing electrical signals emanating from a target nerve (action potential or nerve impulse) or nearby muscle (electromyogram (EMG)). Stimulation pulses generated or delivered by the system could be monophasic or biphasic.

[0020] Additional features, aspects, and examples are addressed in later portions of this disclosure.BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In the figures, similar components may be denoted using like reference numerals. This numbering scheme is provided merely for convenience and is not indicative of any relationship between like-numbered components or between examples. Like-numbered components across different examples may not be identical in all respects. Structural and functional differences may exist between like-numbered components of different example embodiments. Certain features may not be drawn to scale, and some components may be shown in a simplified block form to avoid obscuring such components.

[0022] FIG. 1 is a partial cross-section of the human neck showing the location of various nerves, including the hypoglossal nerve (HGN), the Ansa Cervicalis (AC), and the Phrenic nerve (PN).

[0023] FIG. 2 is a simplified block diagram showing select components of a stimulation system, according to one example.

[0024] FIG. 3 is a stimulation system configured for treating OSA, according to some examples.

[0025] FIG. 4 is a side view of a portion of the electrode lead shown in FIG. 3.

[0026] FIG. 5 is the nerve cuff of FIG. 3, shown in an unfurled state, in accordance with one example.

[0027] FIG. 6 is a cross-sectional view taken along line 6-6 of FIG. 3.

[0028] FIG. 7 is a cross-sectional view taken along line 7-7 of FIG. 5.

[0029] FIG. 8 is a front view of an implantable stimulator coupled to a bifurcated lead for providing ipsilateral stimulation to two nerves.

[0030] FIG. 9 is a front view of an implantable stimulator coupled to a bifurcated lead for providing contralateral (or bilateral) stimulation to two nerves.

[0031] FIG. 10 is a flowchart illustrating steps of a method for generating a multiplexed stimulation signal, in accordance with some examples.

[0032] FIG. 11 is a simplified circuit of an implantable stimulator including a single current source and at least one switch, for generating a temporally multiplexed stimulation signal and routing pulses between isolated output channels.

[0033] FIG. 12 depicts a multiplexed stimulation signal including interleaved pulses having different pulse parameters, according to one example.

[0034] FIG. 13 is a chart depicting select pulses of the multiplexed stimulation signal of FIG.12, which are defined by a first set of parameters and routed to a first output channel and first electrode.

[0035] FIG. 14 is a chart depicting select pulses of the multiplexed stimulation signal of FIG.12, which are defined by a second set of parameters and routed to a second output channel and second electrode.DETAILED DESCRIPTION

[0036] The following detailed description is made with reference to the accompanying figures to demonstrate some examples of the best-known modes of carrying out the invention. This description is not to be taken in a limiting sense but is made merely for the purpose of illustrating the general principles of the invention.

[0037] Some conventional implantable stimulators are designed to deliver therapeutic electrical stimulation to a single peripheral nerve, such as the HGN. However, OSA can arisefrom multiple pathophysiological mechanisms, and not all of these are adequately addressed by stimulating the HGN alone. Examples of other nerves that could be beneficial to stimulate include the Ansa Cervicalis (AC) and the Phrenic Nerve (PN).Some multi-channel IPGs contain multiple independent current sources for driving stimulation to multiple nerves, but having more stimulation channels generally increase IPG size, power consumption, cost, and system complexity. A need therefore exists for an implantable stimulation architecture that can use a single current source, but which can selectively route or direct stimulus pulses between multiple distinct neural targets, deliver target-specific stimulus with different parameters and specific delivery timing, while minimizing IPG size and energy consumption. Using a single current source to stimulate multiple nerves may be preferred over multiple implanted current sources, as having fewer IPG components helps to minimize the total IPG volume. Further, systems and methods in accordance with the present disclosure could, in some implementations, be used to enhance the capabilities of certain existing stimulators / IPGs that include only one current source, enabling multi-target stimulation without significant modification to existing IPG circuitry.

[0038] When a single nerve, whether the HGN, AC, or PN, is stimulated, this can be accomplished relatively easily by placing a single nerve cuff around the target nerve. However, if it is desired to stimulate two different, separately located nerves, either concurrently or at different times, this introduces complexity, requiring more stimulation leads and additional surgery to place them. In addition, it may be challenging to use an IPG with a single current source rather than multiple current sources. Several subsequent examples are provided, which pertain to stimulating two or more nerves in the neck and / or the surrounding area, which is herein referred to as the "cervical region".

[0039] Referring to FIG. 1, a partial, cross-sectional view of the human neck is provided to show the location of various peripheral nerves in the cervical region, including the Ansa Cervicalis (AC), the Phrenic Nerve (PN), and the Hypoglossal Nerve (HGN). In many of the later-described examples, a stimulation system 10 is configured to direct therapeutic stimulation to at least two of the AC, the PN, and the HGN.

[0040] The ansa cervicalis (AC) is a nerve loop in the neck that has two roots: the superior root (SR-AC) and the inferior root (IR-AC). The SR-AC extends alongside the HGN. The IR-AC extends curvilinearly below the SR-AC prior to joining therewith. Physiologically, the AC innervates the infrahyoid muscles, including the sternohyoid, sternothyroid, and omohyoid muscles. Activation of the infrahyoid muscles can help maintain airway patency by pulling thelarynx (voice box) caudally and stiffening the pharyngeal walls to prevent airway collapse. Collapse of the airway in this manner may be referred to interchangeably as “pharyngeal collapse” or “lateral wall collapse”. At least some of the later-described systems 10 could include a stimulation electrode lead 100 configured for placement on or near the AC to transmit therapeutic stimulation to the AC and to treat OSA.

[0041] The tongue can occasionally obstruct the upper airway, leading to apnea. Stimulation of the hypoglossal nerve (HGN), which innervates the tongue, has previously been shown to prevent such obstructions. By way of example and not limitation, U.S. Patent numbers 10,981,000 and 10,967,178 are each assigned to The Alfred E. Mann Foundation for Scientific Research and describe implantable stimulation systems and / or methods for stimulating the HGN to treat OSA. At least some of the later-described systems 10 include an electrode lead 100 configured for placement on or near the HGN to treat OSA.

[0042] The cervical phrenic nerve (PN) is a mixed motor-sensory nerve that arises from the union of the C3, C4, and C5 spinal nerves. Physiologically, efferent fibers of the PN provide motor innervation to the musculature of the diaphragm, which is responsible for initiating respiration. The PN also includes afferent fibers that provide sensory innervation from various thoracic body structures. Supplemental PN stimulation has been explored for the treatment of central sleep apnea (CSA) and / or associated central nervous system (CNS) dysfunctions affecting autonomic breathing regulation. Stimulation of the PN has, in the past, been largely overlooked as a means for treating OSA. However, PN activation (via supplemental electrical stimulation) can increase diaphragmatic contractile strength in a dose-dependent manner, making PN stimulation beneficial for treating OSA when, for example, a patient experiences incomplete airway obstruction. A partially blocked airway can increase airway pressure, impeding patient respiration. In such instances, stimulation of the PN can bolster the patient’s diaphragmatic contractile strength and increase respiratory effort to overcome the partial blockage and maintain regular respiration. PN stimulation can be particularly effective when stimulated in conjunction with another nerve (e.g., the AC and / or the HGN) to prevent airway obstruction. Selective stimulation of the PN would ideally involve preferentially stimulating only the motor nerve fibers innervating the diaphragm and simultaneously avoiding the stimulation of afferent (i.e., sensory) nerve fibers within the PN to prevent perceived patient discomfort. At least some of the later-described systems 10 could include an electrode lead 100 configured for placement on or near the PN to treat OSA.

[0043] Examples of implantable stimulation systems 10 in accordance with the present disclosure will now be described with reference to FIGS. 2-10.

[0044] FIG. 2 is an embodiment of a stimulation system (“system”) 10 with select components illustrated in block form. FIG. 3 is a plan view of another embodiment of system 10. System 10 includes an implantable stimulator 50, such as an implantable pulse generator (or IPG 50), electrically coupled to at least one electrode lead (“lead”) 100 for directing therapeutic electrical stimulation to two or more distinct nerves in the cervical region.

[0045] Referring to FIG. 3, system 10 is illustrated to include only a single lead 100, although other examples may include two or more leads 100. In other examples, a bifurcated lead 100 (having two or more bifurcating branches) may be used, or multiple distinct leads (not shown) could be independently connectable to separate receptacles 52 on an IPG header.

[0046] Embodiments for electrode leads 100 in accordance with systems and methods of the present disclosure could potentially include any feasible number of leads, any known type of lead (for example, nerve cuff, paddle or linear electrode array), and any configuration of electrodes, so long as the system 10 remains capable of directing stimulation to at least two distinct nerves in the cervical region. Preferably, system 10 includes a bifurcated lead having a proximal end coupled to the IPG and two distal ends, each terminating in a respective nerve cuff 102 containing a plurality of electrodes. Each electrode can operate as a sensing or stimulating electrode (cathode or anode) at different times or remain inactive at other times.

[0047] With reference to FIGS. 3-6, lead 100 includes a lead body 106 with a proximal region 108 coupled to IPG 50, and a distal region 110 coupled to nerve cuff 102. The nerve cuff 102 is discussed in greater detail below with reference to FIGS. 5-7. The lead body 106 includes a lead connector 112 with contacts 115 on the proximal region 108 for coupling to a corresponding connector receptacle 52 on IPG 50. Each contact 115 may be configured to couple with a respective output channel, and elongate electrical conductors 120 within lead body 106 may electrically couple each contact 115 to one or more electrodes 116 or 118, carried by a nerve cuff 102. The nerve cuff 102 may be pre-set (or “pre-shaped”) to a resting furled (or “curled”) state, as illustrated in FIGS. 3 and 6, and may be movable to an unfurled state, as illustrated in FIG. 5 during implantation.

[0048] Lead(s) 100, in accordance with the present disclosure, are not strictly limited to nerve cuffs 102, but could instead comprise a different style of lead, such as, e.g., a paddle lead, a linear array electrode lead, or the like. Lead body 106 may include one or more S-shaped sections to provide strain relief (as shown) or may be straight. The S-shaped sectionsaccommodate body movement at the location within the neck where the lead body 106 is implanted, thereby reducing the likelihood that the target nerve(s) will be damaged due to unavoidable pulling of the electrode lead 100 that may result from neck movements. The accommodation provided by the S-shaped sections also reduces the likelihood of fatigue damage.

[0049] Referring to FIGS. 5-7, nerve cuff 102 includes a cuff body 114, which defines a length L and a width W that is greater than the length in the unfurled state. The nerve cuff 102 includes two relatively wide electrically conductive contacts (or “electrodes”) 116 on the cuff body 114, and a plurality of relatively narrow electrically conductive contacts (“electrodes”) 118 on the cuff body 114 between the electrodes 116. Other example embodiments of nerve cuff 102 may include more or fewer electrodes 116 and / or 118, and electrodes 116 and / or 118 may differ in size, shape, orientation, or distribution from those shown in the illustrated examples. Accordingly, another potential embodiment of a nerve cuff 102 may not include any relatively wide electrodes 116 and may include a greater number of relatively narrow electrodes 118.

[0050] With reference to FIG. 7, the electrodes 116 and / or 118 may be individually electrically connected to contacts 115 on the lead connector 112 by elongate conductive members (e.g., wires) 120 that extend through the tubular member 126 of the lead body 106. Each wire 120 includes a conductor 122 and an insulator 124. The conductors 122 may be connected to the rear side of the electrodes 116 and / or 118 by welding or other suitable processes. Cables or other electrical conductors may be employed in place of wires 120 in other implementations.

[0051] The cuff body 114 includes a stimulation region 128 and a compression region 130. The electrodes 116 and / or 118 are located within the stimulation region 128, and there are no electrodes 116, 118 located within the compression region 130. The compression region 130 wraps around at least a portion of the stimulation region 128 when the nerve cuff 102 is in the pre-shaped furled state and slightly larger, expanded and less tightly furled states, thereby resisting (but not preventing) expansion of the stimulation region 128 and improving the electrical connection between the electrodes 118 and / or 116 and the target nerve(s).

[0052] Suitable cuff body 114 materials include materials that are biologically compatible, electrically insulative, elastic, and capable of functioning in the manner described herein. By way of example, suitable cuff body 114 materials include silicone, polyurethane and styrene-isobutylene-styrene (SIBS) elastomers. The cuff body 114 materials should be pliable enoughto allow a clinician to hold the cuff body 114 (and nerve cuff 102) in an unfurled state when the nerve cuff 102 is being placed around the target nerve(s), yet resilient enough to cause the nerve cuff 102 to return to the pre-shaped, resting, furled state illustrated in FIG. 6 when released. The materials should also be flexible enough to allow the cuff body 114 (and nerve cuff 102) to assume slightly larger, expanded, and less tightly furled states.

[0053] Although the present inventions are not so limited, each of the electrodes 116 is the same size and shape, i.e., a rectangle with rounded corners, while each of the electrodes 118 is the same size and shape, i.e., a square with rounded corners. In other implementations, electrodes 116 and / or 118 within a particular nerve cuff 102 could differ in number, shape, size, or orientation from those illustrated. Alternative electrode shapes could include, but are not limited to, rounded rectangles, circles, ovals, coils, and squares. Suitable materials for the electrodes 116 and / or 118 include, but are not limited to, platinum-iridium and palladium.

[0054] In some examples, system 10 may also include a clinician programming unit (“CP”) 54, a patient programmer or patient remote control (“PR”) 56, and an external inductive charger (not shown). By way of example and not limitation, suitable chargers, clinician's programming units, and patient remotes are shown and described in U.S. Pat. Pub. No. 2022 / 0313987, assigned to The Alfred E. Mann Foundation for Scientific Research.

[0055] Referring to FIG. 2, IPG 50 includes a housing 58 that contains a power source 60, such as a rechargeable battery, a processor 62, a current source (or “current generator”) 63, a memory 64, and at least one switch 68 (see FIG. 11) for controlling continuity between the current source 63 and a plurality of output channels (see FIG. 11). System 10 may also include a wireless communication unit 66, such as an RF transmitter, receiver, or transceiver, to wirelessly communicate with various external components, such as CP 54 or PR 56.

[0056] As used herein, a “processor” comprises one or more elements of hardware, software, firmware, or middleware configured to execute stored instructions. Processor 62 can provide instructions to and receive information from the other components of system 100. Processor 62 can, according to stored instructions, make decisions. Processor 62 can act according to instructions stored in memory, associated with processor 62, another system component, or a stand-alone memory unit (e.g., memory 64). In some examples, processor 62 might comprise any one or a combination of: a central processing unit (CPU), a graphics processing unit (GPU), a microprocessor (MPU), such as a microprocessor from Intel® or Advanced Micro Devices, a microcontroller (MCU), a programmable logic controller (PLC), or the like.

[0057] Processor 62 executes stored instructions to control the generation of electrical current by current source 63, and is configured to selectively control the at least one switch 68 (see FIG. 11) to route or direct pulses of electrical current to one or more of a plurality of independent stimulation output channels on the IPG for transmission to one or more electrodes (any of 116 or 118), and to deliver stimulation pulses asynchronously to multiple nerves, wherein stimulation pulses delivered to respective nerves are defined by nerve-specific stimulation parameters.

[0058] In some examples, the memory 64 is configured to store at least two distinct sets of programmed or predetermined stimulation parameters, including at least a first stimulation or stimulus parameter set (“first set”) and a second stimulation or stimulus parameter set (“second set”). The first and second sets contain values for stimulation parameters (such as pulse amplitude, pulse width, pulse frequency, and / or duty cycle) tailored for stimulating respective nerves. The first and second sets may differ with respect to at least one parameter value. In a specific example, the first and second sets have different pulse amplitude values. In various examples, the memory used for storing each stimulation group could include a cloud-based memory, a stand-alone memory (e.g. memory 64 of IPG 50), or a memory external to the IPG 50 and in wireless communication therewith, such as a memory within CP 54 or PR 56.

[0059] Non-limiting and non-exhaustive examples for suitable sets of stimulation parameters for the hypoglossal nerve, the ansa cervicalis, and the phrenic nerve are provided below.

[0060] Hypoglossal nerve exemplary stimulation parameters: (i) current amplitude: 0.5-3.5 mA, (ii) pulse width: 60-300 ps per phase, (iii) waveform: biphasic, cathodic (-) phase first followed by an anodic (+) phase commonly preferred, (iv) frequency: 20-60 Hz (v) duty cycle: 0.05-0.3 Hz or timed with respiratory phase.

[0061] Ansa Cervicalis exemplary stimulation parameters: (i) current amplitude: 0.3-2.0 mA, (ii) pulse width: 100-400 ps, (iii) waveform: biphasic, optionally asymmetrical (e.g., cathodic phase amplitude and anodic phase amplitudes are different e.g. anodic phase amplitude is much smaller but is lasts longer in time), (iv) frequency: 20-50 Hz and (v) duty cycle: continuous or timed with respiratory phase.

[0062] Phrenic nerve exemplary stimulation parameters :(i) current amplitude: 0.3-5.0 mA, (ii) pulse width: 100-300 ps, (iii) waveform: biphasic, charge balanced, (iv) frequency: 10-30 Hz (v) duty cycle of a train of stimulus pulses: 0.05-0.3 Hz or timed with the respiratory phase.

[0063] In some examples, processor 62 instructs the current source 63 to generate a temporally multiplexed signal comprising a plurality of interleaved electrical stimulus pulses,generated in rapid succession. Each stimulus pulse is tuned - that is, optimized for best efficacy and minimum power consumption by adjusting one or more stimulus parameters for the specific circumstance or treatment, in real time (which is not pre-determined) or according to a predetermined or programmed schedule, in accordance with either a first or second set of stimulation parameter sets stored in memory. The multiplexed signal is passed to at least one switch 68, and the at least one switch 68 is controlled (e.g., by the processor 62) to selectively route or direct discrete stimulus pulses to either the first or second output channel, for delivery of the first stimulation and second stimulation to either the first and second nerve, respectively, asynchronously - for example, successively, but not concurrently.

[0064] In the memory (e.g. memory 64), each nerve is programmatically assigned a respective set of stimulation parameters, each set of which may include the following: (a) stimulation amplitude, frequency, pulse width, and variable duty cycling; (b) and one or more output channels corresponding to at least a sub-set of electrodes 116 and / or 118 on a given nerve cuff to achieve optimal stimulation field delivery; and (c) various patient-convenient timing and delay parameters (time-to-sleep, time-to-wake up, etc.). The stimulation groups can be programmatically sequenced to deliver asynchronous stimulation, such that a plurality of stimulation pulses may be applied to the target nerves over non-overlapping stimulation intervals, or the stimulation intervals of both nerves could be interleaved to accommodate the delivery of pulses to each nerve in, for example, an alternating manner. The parameters for each nerve may be determined based on user inputs to the graphical user interface (GUI) of CP 54 or PR 56, or automatically determined via a titration algorithm executed by the processor.

[0065] Stimulation of any nerve could optionally be conducted in an open-loop or closed-loop manner. For closed-loop stimulation, the system 10 may include one or more sensors for detecting a patient biomarker, which may, for example, trigger stimulation or modulate a stimulation parameter. In various examples, patient-specific biomarkers might relate to detection of a respiratory event, a qualitative or quantitative indication of patient respiratory effort, or could generally relate to patient cardiovascular data (heart rate, blood oxygen concentration, blood pressure, etc.), patient respiratory data, patient activity level, patient positioning, or commands that are transmitted to IPG 50 from an external device, such as CP 54 or PR 56, among other examples.

[0066] Detection of patient biomarkers can be accomplished using any known sensor or a combination of known sensors including, e.g., an accelerometer, a gyroscope, a magnetometer, an inertial measurement unit (IMU), a pulse oximeter, a light-based sensor (e.g. an IR sensor),a microphone, a GPS sensor, a pressure sensor, an electrocardiogram (ECG), an impedancebased measuring circuit, and / or any one of the system’s 10 electrodes 116, 118 could be configured for sensing impedance, or for sensing electrical activity emanating from a target nerve or muscle of the patient.

[0067] FIGS. 8 and 9 provide two more exemplary embodiments of system 10, including an electrode lead 100 with first and second bifurcated lead branches (100a and 100b, respectively). The first and second lead branches (100a, 100b) each include a nerve cuff 102 and are respectively implanted on distinct nerves in the cervical region. In FIG. 9, the first and second lead branches 100a and 100b are disposed on contralateral sides of the patient’s neck, whereas the lead branches 100a and 100b in FIG. 8 are implanted upon different nerves on the same (ipsilateral) side of the patient’s neck.

[0068] Depending on the particular example, stimulation therapy for any given nerve target could be applied unilaterally (i.e. when any one nerve, e.g., the hypoglossal nerve, is stimulated on only one side of the neck) or bilaterally (i.e. when any one type of nerve, e.g., the hypoglossal nerve, is stimulated on both sides of the neck), and stimulation of the two different nerve targets could also be applied on the same side of the neck (i.e. ipsilaterally), e.g. FIG. 8, or on opposing sides (i.e. contralaterally), e.g. FIG 9.

[0069] The present disclosure further provides systems and associated methods for treating OSA by using an implantable stimulator to selectively stimulate only certain nerve fibers of a given nerve target. For example, selective stimulation of a given nerve target may be directed from system 10 to activate efferent motor nerve fibers innervating muscles that, e.g., move the tongue or the diaphragm, while preferentially avoiding afferent nerve fibers in the same nerve target that provide sensory signals back to the brain. In one exemplary implementation, the system is configured to stimulate efferent nerve fibers of the phrenic nerve (PN) to elicit diaphragm contractions while preferentially avoiding its sensory afferent nerve fibers.

[0070] Selective stimulation may be achieved by actively selecting, via the processor 62, only a subset of electrodes 116, 118 (being selected from a plurality of electrodes 116, 118 associated with a respective nerve cuff 102), wherein only this subset of electrodes 116, 118 is actively used to transmit therapeutic stimulation to the nerve. Further, following circumferential implantation of the nerve cuff 102 about the nerve, circumferential distribution of electrodes 116, 118 about the nerve allows for the subset of electrodes 116, 118 to be used to supply stimulation at discrete locations about its circumference.

[0071] Any two or more electrodes 116, 118 of the plurality of electrodes 116, 118 in the cuff 102 could be selected as an anode-cathode pair for transmitting multi-polar (e.g. bipolar and / or tripolar) stimulation to the nerve, whereby selection of electrodes 116, 118 as either anodes or cathodes allows the system to purposefully steer stimulative current (i.e. “current steering”) though the nerve body to target desirable nerve fibers, such as efferent motor nerve fibers, that may be contained within relatively deeper fascicles of the nerve, while preferentially steering current away from fascicles containing undesirable nerve fibers, such as afferent nerve fibers (i.e., sensory nerve fibers), which may cause discomfort, or efferent nerve fibers (i.e., motor nerve fibers) that innervate off-target musculature.

[0072] Referring to FIG. 10, a flowchart is provided depicting steps in accordance with a method 200 for delivering asynchronous stimulation to two distinct nerves using a single current source. This flowchart provides only one example method and should therefore not be interpreted as limiting. Other examples may include more or fewer steps, and any one of the steps shown in FIG. 10 could be modified, reorganized, or altogether absent from other embodiments without departing from the scope of the invention.

[0073] A first step 202 of method 200 includes selecting a first set of stimulation parameters for stimulating a first nerve. In this instance, the first nerve is selected from a group of nerves consisting of the AC, the PN, and the HGN. Selecting stimulation parameters for the first nerve can involve manually entering them into a graphical user interface of an external controller, such as the CP 54 or PR 56. A first lead 100a is placed on or proximate to the first nerve in the cervical region of a patient.

[0074] A second step 204 includes selecting a second set of stimulation parameters for stimulating a second nerve. Optionally, the first and second nerves are both selected from the group of nerves consisting of the AC, the PN, and the HGN. Selecting stimulation parameters for the second nerve can involve manually entering them in the graphical user interface of CP 54 or PR 56. A second electrode lead 100b is placed on or proximate the second nerve in the cervical region. Stimulation parameters for each of the first and second nerves are stored in a memory that is accessible by processor 62.

[0075] A third step 206 includes using the processor 62 to retrieve the first and second sets of stimulation parameters, and sending a signal from the processor 62 to the signal generator 63 to generate a multiplexed stimulation signal comprising first pulses, defined by the first set of parameters, interleaved with second pulses, defined by the second set of parameters.

[0076] A fourth step 208 includes controlling (e.g., via processor 62) at least one switch 68 (or “switch” 68) upstream from the signal generator 63. The switch is coupled between the signal generator and a plurality of output channels. In a particular embodiment, the switch 68 routes or directs each of the first pulses to a first output channel 70, which is electrically coupled to the first lead 100a, so that each of the first pulses is routed to the first nerve.

[0077] A fifth step 209 includes controlling (e.g., via processor 62) the switch 68 to route or direct each of the second pulses to a second output channel 72. The second output channel is electrically coupled to the second lead 100b, so each of the second pulses is routed to the second nerve.

[0078] FIG. 11 provides a simplified circuit architecture for generating a temporally multiplexed stimulation signal and routing discrete pulses to either a first or a second stimulation output channel (70 and 72, respectively) for delivery to either a first electrode or a second electrode and to either a first nerve target or second nerve target, respectively. The processor 64 generates instructions that are passed through a digital-to-analog converter (D.A.C.) and sent to the current source 63. The instructions cause the current source 63 to generate a multiplexed signal 300 (shown in FIG. 12), and at least one switch 68 is controlled by the processor to route pulses of the multiplexed signal to either the first or second output channel. Pulses having first stimulus parameters (“first pulses”) are directed to the first output channel 70, and pulses having second stimulus parameters (“second pulses”) are directed to the second output channel 72. The first output channel 70 and the second output channel 72 are coupled to respective contacts 115 or subsets of contacts 115 on lead 106 for delivery to either the first nerve or the second nerve. Accordingly, pulses routed to the first output channel are transmitted to the first nerve, and pulses routed to the second output channel are transmitted to the second nerve.

[0079] In example embodiments, the at least one switch 68 could comprise one or more analog switches, a programmable logic controller (PLC), or a power demultiplexer coupled between the single generator and at least two selectable stimulation output channels.

[0080] Additional components, such as a voltage source, one or more filters, amplifiers, and / or current mirrors, could be included in other implementations but are excluded from this discussion to highlight the particular features that enable the single current source 63 to generate the temporally multiplexed signal. Any of the output channels (70, 72) in FIG. 11 could include one or more parallel branches to, for example, enable bipolar stimulation using two or more electrodes (for example, two electrodes located within the same nerve cuff) withflipped biphasic stimulation pulses (i.e. first phase of the stimulus is anodic and the second phase of the same stimulus is cathodic), or to otherwise modulate the pulses of the multiplexed output signal to more precisely suit the needs of a given implementation.

[0081] FIG. 12 is an example graph of a multiplexed output signal 300 from the current source 63, showing the pulse amplitude over time. The signal 300 comprises first pulses 302 interleaved with second pulses 304 defined by respective sets of pulse parameters stored in memory. In this example, the first pulses 302 have relatively smaller pulse amplitude (e.g., 2.5 mA) than the second pulses 304 (e.g., 5.0 mA). In other implementations, the amplitude values for the first and second pulses could differ from those shown. Further, first pulses 302 and second pulses 304 could vary with respect to any one or more of stimulus pulse amplitude, pulse frequency, pulse width, pulse shape, or duty cycle, rather than just pulse amplitude, as shown.

[0082] FIGS. 13 and 14 are example graphs showing the pulses of the multiplexed signal 300 of FIG 12 that are selectively routed or directed (via the processor 64, by controlling at least one switch 68) to either the first output channel 70 (FIG. 13) or the second output channel 72 (FIG. 14). As shown, the switch 68 is controlled to direct first pulses 302 to the first output channel 70 for delivery to the first nerve, and second pulses 304 to the second output channel 72 for delivery to the second nerve.

[0083] The subject matter of the present disclosure may be embodied in various forms and should not be construed as being limited to only the illustrated and described examples herein. Rather, these examples are provided so that this disclosure will be thorough and complete and will fully convey certain aspects and features of the present disclosure to those skilled in the art. Accordingly, processes, elements, and techniques that are not necessary to those having ordinary skill in the art for a complete understanding of aspects and features of the present disclosure may not be described. In the drawings, the relative sizes of elements and regions may be exaggerated for clarity.

[0084] Groupings of alternative embodiments, elements, or steps of the present disclosure are not to be construed as limitations. Each group member may be referred to and claimed individually or in any combination with other group members disclosed herein. It is anticipated that one or more members of a group may be included in, or deleted from, a group for reasons of convenience and / or patentability. When any such inclusion or deletion occurs, the specification is deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims.

[0085] When used in the claims, whether as filed or added per amendment, the open-ended transitional term “comprising” (and equivalent open-ended transitional phrases thereof like including, containing and having) encompasses all the expressly recited elements, limitations, steps and / or features alone or in combination with unrecited subject matter; the named elements, limitations and / or features are essential, but other unnamed elements, limitations and / or features may be added and still form a construct within the scope of the claim. Specific embodiments disclosed herein may be further limited in the claims using the closed-ended transitional phrases “consisting of’ or “consisting essentially of’ in lieu of or as an amended for “comprising.” When used in the claims, whether as filed or added per amendment, the closed-ended transitional phrase “consisting of’ excludes any element, limitation, step, or feature not expressly recited in the claims. The closed-ended transitional phrase “consisting essentially of’ limits the scope of a claim to the expressly recited elements, limitations, steps and / or features and any other elements, limitations, steps and / or features that do not materially affect the basic and novel character! stic(s) of the claimed subject matter. Thus, the meaning of the open-ended transitional phrase “comprising” is being defined as encompassing all the specifically recited elements, limitations, steps and / or features as well as any optional, additional unspecified ones. The meaning of the closed-ended transitional phrase “consisting of’ is being defined as only including those elements, limitations, steps and / or features specifically recited in the claim whereas the meaning of the closed-ended transitional phrase “consisting essentially of’ is being defined as only including those elements, limitations, steps and / or features specifically recited in the claim and those elements, limitations, steps and / or features that do not materially affect the basic and novel characteristic(s) of the claimed subject matter. Therefore, the open-ended transitional phrase “comprising” (and equivalent open-ended transitional phrases thereof) includes within its meaning, as a limiting case, claimed subject matter specified by the closed-ended transitional phrases “consisting of’ or “consisting essentially of.” As such, embodiments described herein or so claimed with the phrase “comprising” are expressly or inherently unambiguously described, enabled, and supported herein for the phrases “consisting essentially of’ and “consisting of.”

[0086] It will be understood that, although the terms “first”, “second”, “third”, etc., may be used herein to describe various elements, processes, or other features, these elements, processes, or features should not be limited by these terms. These terms are only used to distinguish one element, process, or feature from another element, process, or feature. Thus, afirst element, process, or feature discussed herein could be termed a second element, process, or feature, without departing from the spirit and scope of the present disclosure.

[0087] The foregoing disclosure provides illustration and description but is not intended to be exhaustive or to limit the implementations to the precise form disclosed. Modifications may be made in light of the above disclosure or may be acquired from practice of the implementations. As used herein, the term “component” is intended to be broadly construed as hardware, firmware, or a combination of hardware and software. It will be apparent that systems and / or methods described herein may be implemented in different forms of hardware, firmware, and / or a combination of hardware and software. The actual specialized control hardware or software code used to implement these systems and / or methods is not limiting of the implementations. Thus, the operation and behavior of the systems and / or methods are described herein without reference to specific software code - it being understood that software and hardware can be used to implement the systems and / or methods based on the description herein. As used herein, satisfying a threshold may, depending on the context, refer to a value being greater than the threshold, greater than or equal to the threshold, less than the threshold, less than or equal to the threshold, equal to the threshold, and / or the like, depending on the context. Although particular combinations of features are recited in the claims and / or disclosed in the specification, these combinations are not intended to limit the disclosure of various implementations. In fact, many of these features may be combined in ways not specifically recited in the claims and / or disclosed in the specification.

[0088] Although each dependent claim listed below may directly depend on only one claim, the disclosure of various implementations includes each dependent claim in combination with every other claim in the claim set. No element, act, or instruction used herein should be construed as critical or essential unless explicitly described as such. Also, as used herein, the articles “a” and “an” are intended to include one or more items and may be used interchangeably with “one or more.” Further, as used herein, the article “the” is intended to include one or more items referenced in connection with the article “the” and may be used interchangeably with “the one or more.” Furthermore, as used herein, the term “set” is intended to include one or more items (e.g., related items, unrelated items, a combination of related and unrelated items, and / or the like), and may be used interchangeably with “one or more.” Where only one item is intended, the phrase “only one” or similar language is used. Also, as used herein, the terms “has,” “have,” “having,” or the like are intended to be open-ended terms. Further, the phrase “based on” is intended to mean “based, at least in part, on” unless explicitlystated otherwise. Also, as used herein, the term “or” is intended to be inclusive when used in a series and may be used interchangeably with “and / or,” unless explicitly stated otherwise (e.g., if used in combination with “either” or “only one of’).

Claims

CLAIMSWHAT IS CLAIMED IS:

1. A stimulation system configured for stimulating two or more nerves to treat OSA, the system comprising:an implantable stimulator including a housing, the housing containing:a processor in communication with a current source; and at least one switch that selectively controls the continuity between the current source and a first and second output channels,wherein the processor causes the current source to generate a time-multiplexed signal including first pulses interleaved with second pulses, the first and second pulses being defined by respective sets of pulse parameters stored in memory.

2. The system of claim 1, wherein the processor is electrically coupled to the at least one switch.

3. The system of claim 1, wherein the processor controls the at least one switch to route each pulse to either the first or second output channels.

4. The system of claim 1, wherein the first pulses and the second pulses are routed to different output channels.

5. The system of claim 4, wherein each of the first pulses is routed to the first output channel.

6. The system of claim 5, wherein each of the second pulses is routed to the second output channel.

7. The system of claim 6, including at least one lead coupled to the stimulator, the at least one lead including a first elongate conductor electrically coupling the first output channel to a first electrode configured for placement near a first nerve.

8. The system of claim 7, wherein the at least one lead includes a second elongate conductor electrically coupling the second output channel to a second electrode configured for placement near a second nerve that differs from the first nerve.

9. The system of claim 8, wherein the stimulator housing comprises an electrically conductive material that behaves as an anode when the system is in a monopolar stimulation mode and forms an anode-cathode pair with the first or second electrode.

10. The system of claim 8, wherein the first nerve is selected from a group of nerves consisting of a hypoglossal nerve, an ansa cervicalis, and a phrenic nerve.

11. The system of claim 10, wherein the second nerve is selected from the group of nerves consisting of the hypoglossal nerve, the ansa cervicalis, and the phrenic nerve.12 The system of claim 1, including a sensor in the stimulator for detecting a biomarker.

13. The system of claim 12, wherein the sensor is an accelerometer.

14. The system of claim 1, including an external controller in wireless communication with the stimulator.

15. The system of claim 14, wherein first and second sets of pulse parameters are wirelessly transmitted from the external controller to the stimulator.

16. An implantable stimulator configured for stimulating two or more nerves to treat OSA, the stimulator comprising:a housing, the housing containing a processor in communication with a memory, a current source, and at least one switch,wherein the memory stores first and second sets of pulse parameters defining first pulses and second pulses, and the processor is configured to cause the current source to generate a time-multiplexed signal comprising first pulses interleaved with second pulses.

17. The stimulator of claim 16, wherein the at least one switch comprises an analog switch.

18. The stimulator of claim 16, including a first output channel coupled to a first electrode lead, and a second output channel coupled to a second electrode lead.

19. The stimulator of claim 18, wherein the at least one switch is controlled by the processor to route first pulses to the first output channel and second pulses to the second output channel.

20. The stimulator of claim 19, wherein the first electrode lead includes a first nerve cuff configured for implantation on the hypoglossal nerve.

21. The stimulator of claim 20, wherein the second electrode lead includes a second nerve cuff configured for implantation on either the ansa cervicalis or the phrenic nerve.

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