Patent Description:
Implantable medical devices capable of delivering electrical stimulation pulses have been proposed or are available for treating a variety of medical conditions, such as cardiac arrhythmias and chronic pain as examples. Obstructive sleep apnea (OSA), which encompasses apnea and hypopnea, is a serious disorder in which breathing is irregularly and repeatedly stopped and started during sleep, resulting in disrupted sleep and reducing blood oxygen levels. OSA is caused by complete or partial collapse of the pharynx during sleep. In particular, muscles in a patient's mouth and throat intermittently relax thereby obstructing the upper airway while sleeping. Airflow into the upper airway can be obstructed by the tongue or soft pallet moving to the back of the throat and covering a smaller than normal airway. Loss of air flow also causes unusual inter-thoracic pressure as a person tries to breathe with a blocked airway. Lack of adequate levels of oxygen during sleep can contribute to abnormal heart rhythms, heart attack, heart failure, high blood pressure, stroke, memory problems and increased accidents. Additionally, loss of sleep occurs when a person is awakened during an apneic episode. Implantable medical devices capable of delivering electrical stimulation pulses have been proposed for treating OSA by electrically stimulating muscles around the upper airway that may block the airway during sleep.

The invention provides an implantable neurostimulator according to claim <NUM>. For better understanding of the invention, the present disclosure provides also further, non-claimed, aspects, which do not form part of the invention but are provided for illustrative purposes. One aspect of the disclosure is directed to an implantable neurostimulator (INS) including: an electrical lead having formed thereon at least a pair of bi-polar electrodes, where the electrical lead is configured for placement of the pair of bi-polar electrodes proximate protrusor muscles of a patient and configured to receive electromyography (EMG) signals; a pulse generator electrically connected to the electrical lead and configured to deliver electrical energy to the pair of bi-polar electrodes, the pulse generator having therein a sensor and a control circuit, where the sensor and control circuit are configured to receive the EMG signals and determine a tonal state of the protrusor muscles in which the lead is placed. Other embodiments of this aspect include corresponding computer systems, apparatus, and computer programs recorded on one or more computer storage devices, each configured to perform the actions of the methods and systems described herein.

Implementations of this aspect of the disclosure may include one or more of the following features. The implantable neurostimulator where the control circuit is in electrical communication with a therapy delivery circuit and causes the therapy delivery circuit to deliver electrical energy to the bi-polar electrodes upon a determination that the EMG signal is below a threshold value. The implantable neurostimulator where the control circuit is in electrical communication with a therapy delivery circuit and causes the therapy delivery circuit to deliver electrical energy to the bi-polar electrodes upon a determination that the EMG signal is below a threshold value and a heart rate detected by the sensor is below a threshold. The implantable neurostimulator where the control circuit is in electrical communication with a therapy delivery circuit and causes the therapy delivery circuit to deliver electrical energy to the bi-polar electrodes upon a determination that the EMG signal is below a threshold value and a motion sensor determines that the INS is not moving. The implantable neurostimulator where the control circuit is in electrical communication with a therapy delivery circuit and causes the therapy delivery circuit to deliver electrical energy to the bi-polar electrodes upon a determination that the EMG signal is below a threshold value and an acoustic sensor detects sounds consistent with snoring. The implantable neurostimulator where the control circuit is in electrical communication with a therapy delivery circuit and causes the therapy delivery circuit to deliver electrical energy to the bi-polar electrodes upon a determination that the EMG signal is below a threshold value and a temperature sensor detects a body temperature consistent with sleeping. The implantable neurostimulator where the control circuit is in electrical communication with a therapy delivery circuit and causes the therapy delivery circuit to deliver electrical energy to the bi-polar electrodes upon a determination that the EMG signal is below a threshold value and a breathing rate sensor detects a breathing rate consistent with sleeping.

A further aspect of the disclosure is directed to a system including: an implantable neurostimulator (INS), including a lead having at least one pair of bi-polar electrodes, and a pulse generator in electrical communication with the bi-polar electrodes, the pulse generator including a sensor, a memory, a control circuit, and a telemetry circuit; an external programmer in communication with the INS via the telemetry circuit; a server in communication with the external programmer and including thereon an application configured to receive sensor data from the INS from the external programmer and assess a quality of the sleep of a patient in which the INS is implanted based on the received sensor data; and a remote computer in communication with the server and configured to present an assessment of the quality of sleep of the patient. Other embodiments of this aspect include corresponding computer systems, apparatus, and computer programs recorded on one or more computer storage devices, each configured to perform the actions of the methods and systems described herein.

Implementations of this aspect of the disclosure may include one or more of the following features. The system further including a user interface presented on the external programmer and configured to receive a variety of self-reported data entered by the patient. The system where the application is further configured to assess the quality of the sleep of a patient in which the INS is implanted based on the received sensor data and the self-reported data. The system where the assessment of the quality of sleep is presented in the form of a sleep score. The system where the application is configured to assess the quality of the sleep of a patient in which the INS is implanted based on the received sensor data and self-reported data entered via a user interface on the external programmer and to determine a set of suggested updated stimulation parameters for the INS. The system where the received sensor data includes one or more of a tonal state of protrusor muscles, heartrate, blood pressure, blood oxygen saturation, patient temperature, arousals, awakenings, and electromyography data. The system where the updated stimulation parameters are available of review, acceptance, modification, or rejection on the remote computer. The system where upon acceptance or modification of the updated stimulation parameters, the updated stimulation parameters are transmitted to the external programmer. The system where the external programmer transmits the updated stimulation parameters to the INS.

Still a further aspect of the disclosure is directed to a non-claimed method of providing feedback for an implantable neurostimulator (INS), including receiving sensor data from an INS having at least one lead implanted in a protrusor muscle of a patient. The method also includes receiving self-reporting data entered via a user interface. The method also includes analyzing the sensor and self-reported data to determine a sleep score. The method also includes recording the sleep score. The method also includes presenting the sleep score for analysis. Other embodiments of this aspect include corresponding computer systems, apparatus, and computer programs recorded on one or more computer storage devices, each configured to perform the actions of the methods and systems described herein.

Implementations of this aspect of the disclosure may include one or more of the following features. The method further including providing suggestions for updating stimulation parameters of the INS. The method further including transmitting updated stimulation parameters to an external programmer associated with the INS and updating the INS. The method further including analyzing with an artificial intelligence the self-reported data and sensor to determine whether a reversion to the stimulation parameters of the INS prior to the update is necessary. Implementations of the described techniques may include hardware, a method or process, or computer software on a computer-accessible medium, including software, firmware, hardware, or a combination of them installed on the system that in operation causes or cause the system to perform the actions. One or more computer programs can be configured to perform particular operations or actions by virtue of including Instructions that, when executed by data processing apparatus, cause the apparatus to perform the actions.

An implantable neurostimulator (INS) system for delivering electrical stimulation to the lingual muscles of the tongue, in particular the protrusor muscles, for the treatment of OSA is described herein. Electrical stimulation is delivered to cause the tongue of a patient to be in a protruded state, during sleep, to avoid or reduce upper airway obstruction. As used herein, the term, "protruded state" with regard to the tongue refers to a position that is moved forward and/or downward compared to the non-stimulated position or a relaxed position. Those of skill in the art will recognize that to be in a protruded state does not require the tongue to be coming out of the mouth of the patient, indeed it is preferable that the tongue not extend out of the mouth of the patient, but only be advanced forward to a point where obstruction of the airway is mitigated or eliminated. The protruded state is a state associated with the recruitment of protrusor muscles of the tongue (also sometimes referred to as "protruder" muscles of the tongue) including the genioglossus and geniohyoid muscles. A protruded state may be the opposite of a retracted and/or elevated position associated with the recruitment of the retractor muscles, e.g., styloglossus and hyoglossus muscles, which retract and elevate the tongue. Electrical stimulation is delivered to cause the tongue to move to and maintain a protruded state to prevent collapse, open or widen the upper airway of a patient to promote unrestricted or at least reduced restriction of airflow during breathing.

Current INS systems must be turned on and off manually by the patient when they go to sleep and wake up. As will be appreciated, manual switching is not always a desirable feature in an implantable device associated with sleeping. In accordance with one aspect of the disclosure the INS only need to be turned on when there is a loss of lingual muscle tone (i.e., the protruder muscles are not being sufficiently stimulated naturally). The loss of lingual muscle tone increases the susceptibility of the patient to experience an OSA event. Accordingly, one aspect of the disclosure is directed to systems and methods for assessing the muscle tone of the protruder muscles, based on the tonal state determining that the patient is in need of therapy, and applying the needed therapy. The result is a therapy system which will be more "natural" and convenient for the patient and increase therapy compliance.

A further aspect of the disclosure is directed to systems and methods (non-claimed) of utilizing the sensed tonal state of the protrusor muscles along with a variety of self-reported and detected patient data to develop a patient feedback sleep score for consultation, stimulation modification, and health care reimbursement support.

<FIG> is a conceptual diagram of an implantable neurostimulator (INS) system for delivering OSA therapy. The INS system <NUM> includes at least one electrical lead <NUM> and a pulse generator <NUM>. Pulse generator <NUM> includes a housing <NUM> enclosing circuitry including a control circuit, therapy delivery circuit, optional sensor, a battery, and telemetry circuit as described below in conjunction with <FIG>. A connector assembly <NUM> is hermetically sealed to housing <NUM> and includes one or more connector bores for receiving at least one medical electrical lead used for delivering OSA therapy and, in some examples, for sensing physiological conditions such as electromyogram (EMG) signals and the like. As depicted in <FIG> the pulse generator <NUM> is implanted in the neck of the patient <NUM>. The instant disclosure is not so limited, and the pulse generator <NUM> may be located in other locations such as in the chest area or other areas known to those of skill in the art.

Lead <NUM> includes a flexible, elongate lead body <NUM> that extends from a lead proximal end <NUM> to a lead distal end <NUM>. At least two electrodes <NUM> are carried along a lead distal portion adjacent lead distal end <NUM> that are configured for insertion within the protrusor muscles 42a, 42b and <NUM> of the patient's tongue <NUM>. The electrodes <NUM> are configured for implantation within soft tissue such as musculature proximate to the medial branches of one or both hypoglossal nerves (HGN) that innervate the protrusor muscles of the tongue. The electrodes may be placed approximately <NUM> (e.g., from <NUM> to <NUM>) from a major trunk of the HGN. As such, the electrodes <NUM> may be referred to herein as "intramuscular electrodes," in contrast to an electrode that is placed on or along a nerve trunk or branch, such as a cuff electrode, used to directly stimulate the nerve trunk or branch. Lead <NUM> may be referred to herein as an "intramuscular lead" since the lead distal end and electrodes <NUM> are configured for advancement through the soft tissue, which may include the protrusor muscle tissue, to anchor electrodes <NUM> in proximity of the HGN branches that innervate the protrusor muscles 42a, 42b and <NUM>. The term "intramuscular" with regard to electrodes <NUM> and lead <NUM> is not intended to be limiting, however, since the electrodes <NUM> may be implanted in connective tissue or other soft tissue proximate the medial HGN and its branches. One or more electrodes <NUM> may be placed in an area of protrusor muscles 42a, 42b and <NUM> that include motor points, where each nerve axon terminates in the muscle (also called the neuromuscular junction). The motor points are not at one location but spread out in the protrusor muscles. Leads <NUM> may be implanted such that one or more electrodes <NUM> may be generally in the area of the motor points (e.g., such that the motor points are within <NUM> to <NUM> from one or more electrodes <NUM>).

The protrusor muscles are activated by electrical stimulation pulses generated by pulse generator <NUM> and delivered via the intramuscular electrodes <NUM> to move tongue <NUM> forward, to promote a reduction in obstruction or narrowing of the upper airway <NUM> during sleep. As used herein, the term "activated" with regard to the electrical stimulation of the protrusor muscles refers to electrical stimulation that causes depolarization or an action potential of the cells of the nerve (e.g., hypoglossal nerve(s)) innervating the protrusor muscles and motor points and subsequent depolarization and mechanical contraction of the protrusor muscle cells. In some cases, the muscles may be activated directly by the electrical stimulation pulses. The protrusor muscles that may be activated by stimulation via intramuscular electrodes <NUM> may include at least one or both of the right and/or left genioglossus muscle (GG) <NUM>, which includes the oblique compartment (GGo) 42a and the horizontal compartment (GGh) 42b (referred to collectively as GG <NUM>) and/or the right and/or left geniohyoid muscle (GH) <NUM>. The GG muscle and GH muscle are innervated by a medial branch of the HGN (also referred to as the XIIth cranial nerve), while the hyoglossus and styloglossus muscles, which cause retraction and elevation of the tongue, are innervated by a lateral branch of the HGN.

The multiple distal electrodes <NUM> may be used to deliver bilateral or unilateral stimulation to the GG <NUM> and/or the GH <NUM> muscles via the medial branch of the HGN or branches thereof, also referred to herein as the "medial HGN. " Distal electrodes <NUM> may be switchably coupled to output circuitry of pulse generator <NUM> to enable delivery of electrical stimulation pulses in a manner that selectively activates the right and left protrusor muscles in a cyclical or alternating pattern to avoid muscle fatigue while maintaining upper airway patency. Additionally or alternatively, electrical stimulation may be delivered to selectively activate the GG <NUM> and/or GH <NUM> muscles or portions thereof during unilateral stimulation of the left or right protrusor muscles.

The lead proximal end <NUM> includes a connector (not shown in <FIG>) that is coupleable to connector assembly <NUM> of pulse generator <NUM> to provide electrical connection between circuitry enclosed by the housing <NUM> of pulse generator <NUM>, e.g., including therapy delivery circuitry and control circuitry as described below in conjunction with <FIG>. The lead body <NUM> encloses electrical conductors extending from each of the distal electrodes <NUM> to the proximal connector at proximal end <NUM> to provide electrical connection between output circuitry of pulse generator <NUM> and the electrodes <NUM>.

Though shown in <FIG> as separate from and extending from the pulse generator <NUM>, the lead <NUM> could be integrated into a portion of the pulse generator <NUM>, and merely be an exposed surface of the pulse generator <NUM>. In such an embodiment, the pulse generator would be implanted proximate the lingual muscles under the chin of the patient. In contrast the embodiment shown in <FIG> allows for more flexibility in the placement of the pulse generator in the neck or pectoral region of the patient.

<FIG> is a schematic diagram of pulse generator <NUM>. Pulse generator <NUM> includes a control circuit <NUM>, memory <NUM>, therapy delivery circuit <NUM>, a sensor <NUM>, telemetry circuit <NUM> and power source <NUM>. Power source <NUM> may include one or more rechargeable or non-rechargeable batteries for supplying electrical current to each of the control circuit <NUM>, memory <NUM>, therapy delivery circuit <NUM>, sensor <NUM> and telemetry circuit <NUM>. While power source <NUM> is shown in communication only with control circuit <NUM> for the sake of clarity, it is to be understood that power source <NUM> provides power as needed to each of the circuits and components of pulse generator <NUM> as needed. For example, power source <NUM> provides power to therapy delivery circuit <NUM> for generating electrical stimulation pulses.

Sensor <NUM> may include one or more separate sensors for monitoring a patient condition. These sensors may include one or more accelerometers, inertial measurement units (IMU), fiber-Bragg gratings (e.g., shape sensors), optical sensors, acoustic sensors, pulse oximeters, and others without departing from the scope of the disclosure and as will be described in greater detail below. In one aspect of the disclosure sensor <NUM> is configured as, among other things, a patient posture sensor. Patient posture data may be stored in memory <NUM> from the detected posture states of patient when sensor <NUM> is included, and may be presented on a display of external programmer <NUM>, e.g., as generally described in <CIT>).

Additionally or alternatively, the sensor <NUM> may detect a signal that is correlated to the movement of the patient's tongue into and out of a protruded state. This signal may be used to detect adequate protrusion and/or fatigue of the stimulated muscle for use in controlling the duty cycle, pulse amplitude and/or stimulating electrode vector of the electrical stimulation therapy delivered by therapy delivery circuit <NUM>.

The functional blocks shown in <FIG> represent functionality included in a pulse generator <NUM> configured to delivery an OSA therapy and may include any discrete and/or integrated electronic circuit components that implement analog and/or digital circuits capable of producing the functions attributed to a pulse generator herein. The various components may include an application specific integrated circuit (ASIC), an electronic circuit, a processor (shared, dedicated, or group) and memory that execute one or more software or firmware programs, a combinational logic circuit, state machine, or other suitable components or combinations of components that provide the described functionality. Providing software, hardware, and/or firmware to accomplish the described functionality in the context of any modern medical device system, given the disclosure herein, is within the abilities of one of skill in the art.

Control circuit <NUM> communicates, e.g., via a data bus, with memory <NUM>, therapy delivery circuit <NUM>, telemetry circuit <NUM> and sensor <NUM> (when included) to control OSA therapy delivery and other pulse generator functions. As disclosed herein, control circuit <NUM> may pass control signals to therapy delivery circuit <NUM> to cause therapy delivery circuit <NUM> to deliver electrical stimulation pulses via electrodes <NUM> according to a therapy protocol that may include selective stimulation patterns of right and left portions of the GG and GH muscles and/or proximal and distal portions of the GG and GH muscles. Control circuit <NUM> may further be configured to pass therapy control signals to therapy delivery circuit <NUM> including stimulation pulse amplitude, stimulation pulse width, stimulation pulse number and frequency of a stimulation pulse train.

Memory <NUM> may store instructions for execution by a processor included in control circuit <NUM>, stimulation control parameters, and other device-related or patient-related data. Control circuit <NUM> may retrieve therapy delivery control parameters and a therapy delivery protocol from memory <NUM> to enable control circuit <NUM> to pass control signals to therapy delivery circuit <NUM> for controlling the OSA therapy. Memory <NUM> may store historical data relating to therapy delivery for retrieval by a user via telemetry circuit <NUM>. Therapy delivery data or information stored in memory <NUM> may include therapy control parameters used to deliver stimulation pulses as well as delivered therapy protocol(s), hours of therapy delivery or the like. Patient related data, such as that received from the sensor <NUM> signal may be stored in memory <NUM> for retrieval by a user.

Therapy delivery circuit <NUM> may include a charging circuit <NUM>, an output circuit <NUM>, and a switching circuit <NUM>. Charging circuit <NUM> may include one or more holding capacitors that are charged using a multiple of the battery voltage of power source <NUM>, for example. The holding capacitors are switchably connected to output circuit <NUM>, which may include one or more output capacitors that are coupled to a selected bipolar electrode pair via switching circuit <NUM>. The holding capacitor(s) are charged to a programmed pacing pulse voltage amplitude by charging circuit <NUM> and discharged across the output capacitor for a programmed pulse width. Charging circuit <NUM> may include capacitor charge pumps or an amplifier for the charge source to enable rapid recharging of holding capacitors included in charging circuit <NUM>. Therapy delivery circuit <NUM> responds to control signals from control circuit <NUM> for generating and delivering trains of pulses to produce sustained tetanic contraction of the GG and/or GH muscles or portions thereof to move the tongue forward and avoid upper airway obstruction.

Output circuit <NUM> may be selectively coupled to bipolar pairs of electrodes 30a-30d via switching circuit <NUM>. Switching circuit <NUM> may include one or more switches activated by timing signals received from control circuit <NUM>. Electrodes 30a-30d may be selectively coupled to output circuit <NUM> in a time-varying manner to deliver stimulation to different portions of the protrusor muscles at different time to avoid fatigue, without requiring stimulation to be withheld completely. Switching circuit <NUM> may include a switch array, switch matrix, multiplexer, or any other type of switching device(s) suitable to selectively couple therapy delivery circuit <NUM> to bipolar electrode pairs selected from electrodes <NUM>. Bipolar electrode pairs may be selected one at a time or may be selected two or more at time to allow overlapping stimulation of two or more different portions of the protrusor muscles. Overlapping stimulation times of two portions of the protrusor muscles, for example left and right or proximal and distal may maintain a forward position of the tongue and allow a ramping up and ramping down of the electrical stimulation being delivered to two different portions of the protrusor muscles.

Telemetry circuit <NUM> is optional but may be included to enable bidirectional communication with an external programmer <NUM>. A user, such as the patient <NUM>, may manually adjust therapy control parameter settings, e.g., as described in Medtronic's Patient Programmer Model <NUM>. The patient may make limited programming changes such as small changes in stimulation pulse amplitude and pulse width. The patient may turn the therapy on and off or set timers to turn the therapy on or off using external programmer <NUM> in wireless telemetric communication with telemetry circuit <NUM>.

In other examples, a user, such as a clinician, may interact with a user interface of an external programmer <NUM> to program pulse generator <NUM> according to a desired OSA therapy protocol. For example, a Physician Programmer Model <NUM> available from Medtronic, Inc. , Minneapolis, MN, may be used by the physician to program pulse generator <NUM> for delivering electrical stimulation.

Programming of pulse generator <NUM> may refer generally to the generation and transfer of commands, programs, or other information to control the operation of pulse generator <NUM>. For example, external programmer <NUM> may transmit programs, parameter adjustments, program selections, group selections, or other information to control the operation of pulse generator <NUM>, e.g., by wireless telemetry. As one example, external programmer <NUM> may transmit parameter adjustments to support therapy changes. As another example, a user may select programs or program groups. A program may be characterized by an electrode combination, electrode polarities, voltage or current amplitude, pulse width, pulse rate, therapy duration, and/or pattern of electrode selection for delivering patterns of alternating portions of the protrusor muscles that are being stimulated. A group may be characterized by multiple programs that are delivered simultaneously or on an interleaved or rotating basis. These programs may adjust output parameters or turn the therapy on or off at different time intervals.

External programmer <NUM> may present patient related and/or device related data retrieved from memory <NUM> via telemetry circuit <NUM>. Additionally or alternatively, external programmer <NUM> may present sleep sound or motion data stored in memory <NUM> as determined from signals from sensor <NUM>. Further, the time periods in which the patient is lying down can be acquired based on patient posture detection using sensor <NUM> and a history of such data can be stored into memory <NUM> and retrieved and displayed by external programmer <NUM>.

<FIG> depicts a single intramuscular lead <NUM> inserted into the tongue <NUM> of a patient. Lead <NUM> may include two or more electrodes, and in the example shown lead <NUM> includes four electrodes 30a, 30b, 30c, and 30d (collectively referred to as "electrodes <NUM>") spaced apart longitudinally along lead body <NUM>. Lead body <NUM> is a flexible lead body which may define one or more lumens within which insulated electrical conductors extend to a respective electrode 30a-30d. The distal most electrode 30a may be adjacent or proximate to lead distal end <NUM>. Each of electrodes 30b, 30c and 30d are spaced proximally from the respective adjacent electrode 30a, 30b and 30c by a respective interelectrode distance <NUM>, <NUM> and <NUM>.

Each electrode 30a-30d is shown have equivalent electrode lengths <NUM>. In other examples, however, electrodes 30a-30d may have electrode lengths <NUM> that are different from each other in order to optimize placement of the electrodes <NUM> or the resulting electrical field of stimulation relative to targeted stimulation sites corresponding to left and right portions of the HGN or branches thereof and/or motor points of the GG and GH muscles. The interelectrode spacings between electrodes 30a, 30b, 30c, and 30d are shown to be approximately equal in <FIG>, however they may also be different from each other in order to optimize placement of electrodes <NUM> relative to the targeted stimulation sites or the resulting electrical field of stimulation relative to targeted stimulation sites corresponding to left and right hypoglossal nerves or branches of hypoglossal nerves and/or motor points of protrusor muscles 42a, <NUM>, or <NUM>.

In some examples, electrodes 30a and 30b form an anode and cathode pair for delivering bipolar stimulation in one portion of the protrusor muscles, e.g., either the left or right GG and/or GH muscles or either a proximal or distal portion of the GG and/or GH muscles. Electrodes 30c and 30d may form a second anode and cathode pair for delivering bipolar stimulation in a different portion of the protrusor muscles (e.g., the other of the left or right portions or the other of the proximal or distal portions). Accordingly, the interelectrode spacing <NUM> between the two bipolar pairs 30a-30b and 30c-30d may be different than the interelectrode spacing <NUM> and <NUM> between the anode and cathode within each bipolar pair 30a-30b and 30c-30d.

In one example, the total distance encompassed by electrodes 30a-30d along the lead body <NUM> may be about <NUM> millimeter, <NUM> millimeters, or <NUM> millimeters as examples. In one example, the total distance is between <NUM> and <NUM> millimeters. The interelectrode spacings between a proximal electrode pair 30c-30d and a distal electrode pair 30a-30b, respectively, may be between <NUM> and <NUM>, including all integer values therebetween. The interelectrode spacing separating the distal and proximal pairs 30a-30b and 30c-30d may be the same or different from each other and the spacing between individual electrodes of any such pair.

In the example shown, each of electrodes 30a-30d is shown as a circumferential ring electrode which may be uniform in diameter with lead body <NUM>. In other examples, electrodes <NUM> may include other types of electrodes such as a tip electrode, a helical electrode, a coil electrode, a segmented electrode, a button electrode as examples. For instance, the distal most electrode 30a may be provided as a tip electrode at the lead distal end <NUM> with the remaining three electrodes 30b, 30c and 30d being ring electrodes. When electrode 30a is positioned at the distal end <NUM>, electrode 30a may be a helical electrode configured to screw into the muscle tissue at the implant site to additionally serve as a fixation member for anchoring the lead <NUM> at the targeted therapy delivery site. In other examples, one or more of electrodes 30a-d may be a hook electrode or barbed electrode to provide active fixation of the lead <NUM> at the therapy delivery site.

Lead <NUM> may include one or more fixation member <NUM> for minimizing the likelihood of lead migration. In the example shown, fixation member <NUM> includes multiple sets of tines which engage the surrounding tissue when lead <NUM> is positioned at the target therapy delivery site. The tines of fixation member <NUM> may extend radially and proximally at an angle relative to the longitudinal axis of lead body <NUM> to prevent or reduce retraction of lead body <NUM> in the proximal direction. Tines of fixation member <NUM> may be collapsible against lead body <NUM> when lead <NUM> is held within the confines of a lead delivery tool, e.g., a needle or introducer, used to deploy lead <NUM> at the target implant site. Upon removal of the lead delivery tool, the tines of fixation member <NUM> may spread to a normally extended position to engage with surrounding tissue and resist proximal and lateral migration of lead body <NUM>. In other examples, fixation member <NUM> may include one or more hooks, barbs, helices, or other fixation mechanisms extending from one or more longitudinal locations along lead body <NUM> and/or lead distal end <NUM>. Fixation member <NUM> may partially or wholly engage the GG, GH muscles and/or other muscles below the tongue, and/or other soft tissues of the neck, e.g., fat and connective tissue, when proximal end of lead body <NUM> is tunneled to an implant pocket of pulse generator <NUM>. In other examples, fixation member <NUM> may include one or more fixation mechanisms located at other locations than the location shown in <FIG>, including at or proximate to distal end <NUM>, between electrodes <NUM>, or otherwise more distally or more proximally than the location shown. The implant pocket of pulse generator <NUM> may be along the patient's neck <NUM> (see <FIG>) in the chest, or in another location as deemed appropriate by the surgeon performing the implantation. Accordingly the length of the elongated lead body <NUM> from distal end <NUM> to the lead proximal end <NUM> (<FIG>) may be selected to extend from the target therapy delivery site in the protrusor muscles to a location along the patient's neck where the pulse generator <NUM> is implanted. This length may be up to <NUM> or up to <NUM> as examples but may generally be <NUM> or less, though longer or shorter lead body lengths may be used depending on the anatomy and size of the individual patient.

<FIG> is a conceptual diagram <NUM> of the lead <NUM> deployed for delivering OSA therapy according to another example. In this example, lead <NUM> carrying electrodes <NUM> is advanced approximately along or parallel to midline <NUM> of tongue <NUM>. In the example shown, lead body <NUM> is shown approximately centered along midline <NUM>, however in other examples lead body <NUM> may be laterally offset from midline <NUM> in the left or right directions but is generally medial to both of the left HGN <NUM> and the right HGN 104R. The distal end <NUM> of lead <NUM> may be inserted inferiorly to the body of tongue <NUM>, e.g., at a percutaneous insertion point along the submandibular triangle, in the musculature below the floor of the oral cavity. The distal end <NUM> is advanced to position electrodes <NUM> medially to the left and right HGNs <NUM> and 104R, e.g., approximately midway between the hyoid bone the mental protuberance (chin). An electrical field produced by stimulation pulses delivered between any bipolar pair of electrodes selected from electrodes <NUM> may encompass a portion of both the left target region <NUM> and the right target region 106R to produce bilateral stimulation of the HGNs <NUM> and 104R and therefore bilateral recruitment of the protrusor muscles. Bilateral recruitment of the protrusor muscles may provide greater airway opening than unilateral stimulation that is generally performed using a nerve cuff electrode along the HGN. For example, electrical stimulation pulses delivered using electrodes 30a and 30b may produce electrical field <NUM> (shown conceptually) encompassing a portion of both of the left and right target regions <NUM> and 106R. Electrical stimulation pulses delivered using electrodes 30c and 30d may produce electrical field <NUM> (shown conceptually) encompassing a portion of both of the left and right target regions <NUM> and 106R. The portions of the left and right target regions <NUM> and 106R encompassed by electrical field <NUM> are posterior portions relative the portions of the left and right target regions <NUM> and 106R encompassed by electrical field <NUM>.

In some examples, electrical stimulation is delivered by pulse generator <NUM> by sequentially selecting different electrode pairs from among the available electrodes <NUM> to sequentially recruit different bilateral anterior and bilateral posterior portions of the HGNs <NUM> and 104R. This electrode selection may result in recruitment of different anterior and posterior portions of the protrusor muscles. The sequential selection of different electrode pairs may be overlapping or non-overlapping. The electrical stimulation is delivered throughout an extended time period encompassing multiple respiratory cycles independent of the timing of respiratory cycles to maintain a protruded state of tongue <NUM> from the beginning of the time period to the end of the time period. The electrodes <NUM> may be selected in bipolar pairs comprising the most distal pair 30a and 30b, the outermost pair 30a and 30d, the innermost pair 30b and 30c, the most proximal pair 30c and 30d or alternating electrodes along lead body <NUM>, e.g., 30a and 30c or 30b and 30d. Sequential selection of two or more different electrode pairs allows for sequential recruitment of different portions of the protrusor muscles to reduce the likelihood of fatigue.

In some examples, electrical stimulation delivered using an electrode pair, e.g., 30a and 30b, that is relatively more distal along distal lead portion <NUM> and implanted relatively anteriorly along tongue <NUM> may recruit a greater portion of anterior muscle fibers, e.g., within the GG muscle. Electrical stimulation delivered using an electrode pair, e.g., 30c and 30d, that is relatively more proximal along distal lead portion <NUM> and implanted relatively posteriorly along tongue <NUM> may recruit a greater portion of posterior muscle fibers, e.g., within the GH muscle. Sequential selection of electrodes <NUM> for delivering electrical stimulation pulses allows sequential recruitment in overlapping or non-overlapping patterns of anterior and posterior portions of the protrusor muscles to sustain the tongue in a protruded state throughout the extended time period while reducing or avoiding muscle fatigue.

<FIG> is a conceptual diagram of the distal portion of a dual lead system for delivering OSA therapy. In this example, one lead <NUM> is advanced anteriorly approximately parallel to midline <NUM> and offset, e.g. by <NUM>-<NUM> millimeters to the left of midline <NUM>, to position distal portion <NUM> and electrodes <NUM> in or adjacent to the left target region <NUM>. A second lead <NUM> is advanced anteriorly approximately parallel to midline <NUM> but offset laterally to the right of midline <NUM> to position distal portion <NUM> and electrodes <NUM> in or adjacent the right target region 106R. Lead <NUM> may be inserted from a left lateral or posterior approach of the body of tongue <NUM>, and lead <NUM> may be inserted from a right lateral or posterior approach of the body of tongue <NUM>. In other examples, both leads <NUM> and <NUM> may be inserted from only a left or only a right approach with one lead traversing midline <NUM> to position the electrodes <NUM> or <NUM> along the opposite side of midline <NUM> from the approaching side. Lead <NUM> and/or lead <NUM> may be advanced at an oblique angle relative to midline <NUM> but may not cross midline <NUM>. In other examples, one or both leads <NUM> and <NUM> may approach and cross midline <NUM> at an oblique angle such that one or both of distal portions <NUM> and <NUM> extend in or adjacent to both the right and left target regions <NUM> and 106R, similar to the orientation shown in <FIG>.

In the example shown, relatively more localized control of the recruitment of left, right, anterior and posterior portions of the protrusor muscles may be achieve by selecting different electrode pairs from among the electrodes 30a through 30d and 230a through 230d. For example, any combination of electrodes 30a through 30d may be selected for delivering electrical stimulation pulses to the left portions of the protrusor muscles. More distal electrodes 30a and 30b may be selected for stimulation of more anterior portions of the left protrusor muscles (corresponding to electrical field <NUM>) and more proximal electrodes 30c and 30d may be selected for stimulation of more posterior portions of the left protrusor muscles (corresponding to electrical field <NUM>). Any combination of electrodes 230a through 230d may be selected for delivering electrical stimulation pulses to the right portions of the protrusor muscles. More distal electrodes 230a and 230b may be selected for stimulation of more anterior portions of the right protrusor muscles (corresponding to electrical field <NUM>) and more proximal electrodes 230c and 230d may be selected for stimulation of more posterior portions of the right protrusor muscles (corresponding to electrical field <NUM>).

Switching circuit <NUM> may be configured to select electrode pairs that include one electrode on one of leads <NUM> or <NUM> and another electrode on the other lead <NUM> or <NUM> to produce an electrical field (not shown) that encompasses portions of both the left target region <NUM> and the right target region 106R simultaneously for bilateral stimulation. Any combination of the available electrodes 30a through 30d and electrodes 230a through 230d may be selected as two or more bipolar pairs, which are selected in a repeated, sequential pattern to sequentially recruit different portions of the two target regions <NUM> and 106R. The sequential selection of electrode pairs may be overlapping or non-overlapping, but electrical stimulation pulses are delivered without interruption at one or more selected frequencies throughout an extended time period to maintain tongue <NUM> in a protruded state from the beginning of the time period to the end of the time period, encompassing multiple respiratory cycles.

In the example of <FIG> including two leads, two pairs of electrodes may be selected simultaneously and sequentially with one or more other pairs of electrodes. For example, electrodes 30a and 30b may be selected as one bipolar pair and electrodes 230c and 230d may be selected as a second bipolar pair for simultaneous stimulation of the left, anterior portion of the target region <NUM> and the right posterior portion of the target region 106R. The electrodes 30c and 30d may be selected as the next bipolar pair from lead <NUM>, simultaneously with electrodes 230a and 230b selected as the next bipolar pair from lead <NUM>. In this way, electrical stimulation may be delivered bilaterally, alternating between posterior and anterior regions on each side. The anterior left (30a and 30b) and posterior right (230c and 230d) bipolar pairs may be selected first, and the posterior left (30c and 30d) and anterior right (230a and 230b) bipolar pairs may be selected second in a repeated, alternating fashion to maintain tongue <NUM> in a protruded state continuously during an extended time period encompassing multiple respiratory cycles. In other examples, both of the anterior pairs (30a-30b and 230a-230b) may be selected simultaneously first, and both the posterior pairs (30c-30d and 230c-230d) may be selected simultaneously second, sequentially following the anterior pairs. In this way, continuous bilateral stimulation may be achieved while sequentially alternating between posterior and anterior portions to avoid or reduce fatigue. In contrast to other OSA therapy systems that rely on a sensor for sensing the inspiratory phase of respiration to coordinate the therapy with the inspiratory phase, the intramuscular electrodes <NUM> positioned to stimulate different portions of the protrusor muscles do not require synchronization to the respiratory cycle. Alternation of stimulation locations within the protrusor muscles allows different portions of the muscles to rest while other portions are activated to avoid collapse of the tongue against the upper airway while also avoiding muscle fatigue.

It is to be understood that more or fewer than the four electrodes shown in the examples presented herein may be included along the distal portion of a lead used in conjunction with the OSA therapy techniques disclosed herein. A lead carrying multiple electrodes for delivering OSA therapy may include <NUM>, <NUM>, <NUM>, <NUM> or other selected number of electrodes. When the lead includes only two electrodes, a second lead having at least one electrode may be included to provide at least two different bipolar electrode pairs for sequential stimulation of different portions of the right and/or left medial HGNs. Furthermore, while the selected electrode pairs are generally referred to herein as "bipolar pair" including one cathode and one return anode, it is recognized that three or more electrodes may be selected at a time to provide desired electrical field or stimulation vector for recruiting a desired portion of the protrusor muscles. Accordingly, the cathode of a bipolar "pair" may include one or more electrodes selected simultaneously from the available electrodes and/or the anode of the bipolar "pair" may include one or more electrodes selected simultaneously from the available electrodes.

<FIG> timing diagram illustrating a method performed by pulse generator <NUM> for delivering selective stimulation to the protrusor muscles for promoting upper airway patency during sleep according to one example. Electrical stimulation is delivered over a therapy time period <NUM> having a starting time <NUM> and an ending time (not shown). Electrical stimulation pulses that are delivered when pulse generator sequentially selects a first bipolar electrode pair <NUM> and a second bipolar electrode pair <NUM> in an alternating, repeating manner are shown. The first and second bipolar electrode pairs <NUM> and <NUM> may correspond to any two different electrode pairs described in the examples above in conjunction with <FIG>.

A first train of electrical pulses <NUM> is shown starting at the onset <NUM> or therapy time period <NUM>. The first train of electrical pulses <NUM> is delivered using bipolar electrode pair <NUM> for a duty cycle time interval <NUM>. The first train of electrical pulses <NUM> has a pulse amplitude <NUM> and pulse frequency, e.g., <NUM> to <NUM>, defined by the interpulse intervals <NUM>. The first train of electrical pulses <NUM>, also referred to as "pulse train" <NUM>, may have a ramp on portion <NUM> during which the pulse amplitude is gradually increased from a starting voltage amplitude up to pulse voltage amplitude <NUM>. In other examples, the pulse width may be gradually increased. In this way the delivered pulse energy is gradually increased to promote a gentle transition from the relaxed, non-stimulated state to the protruded state of the tongue.

The train of electrical pulses <NUM> may include a ramp off portion <NUM> during which the pulse amplitude (and/or pulse width) is decremented from the pulse voltage amplitude <NUM> to an ending amplitude at the expiration of the duty cycle time interval <NUM>. In other examples, pulse train <NUM> may include a ramp on portion <NUM> and no ramp off portion <NUM>. In this case, the last pulse of pulse train <NUM> delivered at the expiration of duty cycle time interval <NUM> may be delivered at the full pulse voltage amplitude <NUM>. Upon expiration of the duty cycle time interval <NUM>, electrical stimulation delivery via bipolar electrode pair <NUM> is terminated.

In the example shown, a second electrode pair <NUM> is selected when duty cycle time interval <NUM> is expiring. The second electrode pair <NUM> may be selected such that delivery of electrical stimulation pulse train <NUM> starts a ramp on portion <NUM> that is simultaneous with the ramp off portion <NUM> of train <NUM>. In other examples, the ramp on portion <NUM> of pulse train <NUM> may start at the expiration of the first duty cycle time interval <NUM>. When pulse train <NUM> does not include a ramp off portion <NUM>, the pulse train <NUM> may be started such that the ramp on portion <NUM> ends just before, just after or coincidentally with the expiration of duty cycle time interval <NUM>. The second pulse train <NUM> has a duration of duty cycle time interval <NUM> and may end with an optional ramp off portion <NUM>, which may overlap with the ramp on portion of the next pulse train delivered using the first electrode pair <NUM>.

In this example, pulse trains <NUM> and <NUM> are shown to be equivalent in amplitude <NUM> and <NUM>, pulse width, pulse frequency (and inter pulse interval <NUM>), and duty cycle time interval <NUM> and <NUM>. It is contemplated, however, that each of the stimulation control parameters used to control delivery of the sequential pulse trains <NUM> and <NUM> may be separately controlled and set to different values as needed to achieve a desired sustained protrusion of tongue <NUM> while avoiding or minimizing fatigue.

The sequential pulse trains <NUM> and <NUM> are delivered using two different electrode pairs <NUM> and <NUM> such that different portions of the protrusor muscles are recruited by the pulse trains <NUM> and <NUM> allowing one portion to rest while the other is being stimulated. However, pulse trains <NUM> and <NUM> occur in a sequential overlapping or non-overlapping manner such that electrical pulses are delivered at one or more selected frequencies for the entire duration of the therapy time period <NUM> to sustain the tongue in a protruded state throughout time period <NUM>. It is to be understood that the relative down and/or forward position of the protruded tongue may shift or change as different electrode pairs are selected but the tongue remains in a protruded state throughout therapy time period <NUM>.

At times, the pulse trains <NUM> and <NUM> may be overlapping to simultaneously recruit the left and right GG and/or GH muscles to create a relatively greater force (compared to recruitment of a single side) to pull the tongue forward to open an obstructed upper airway. In some cases, the overlapping pulse trains <NUM> and <NUM> may cause temporary fatigue of the protrusor muscles along the left or right side but the temporary fatigue may improve the therapy effectiveness to ensure an open upper airway during an apneic episode. Recovery from fatigue will occur between duty cycles and at the end of an apneic episode. Duty cycle lengths may vary between patients depending on the fatigue properties of the individual patient. Control circuit <NUM> may control the duty cycle on time in a manner that minimizes or avoids fatigue in a closed loop system using a signal from sensor <NUM>, e.g., a motion sensor signal and or electromyography (EMG) signal correlated protrusor muscle contraction force and subsequent fatigue.

<FIG> is a timing diagram <NUM> of a non-claimed method for delivering OSA therapy by pulse generator <NUM> according to another example. In this example, a therapy delivery time period <NUM> is started at <NUM> with a ramp on interval <NUM> delivered using a first bipolar electrode pair <NUM>. The ramp on interval <NUM> is followed by a duty cycle time interval <NUM>. Upon expiration of the duty cycle time interval <NUM>, a second bipolar electrode pair <NUM> is selected for delivering electrical stimulation pulses for a second duty cycle time interval <NUM>. A third duty cycle time interval <NUM> starts upon the expiration of the second duty cycle time interval <NUM>, and stimulation pulses are delivered by selecting a third bipolar electrode pair <NUM> different than the first two pairs <NUM> and <NUM>. A fourth bipolar pair <NUM> is selected upon expiration of the third duty cycle time interval <NUM> and used to deliver stimulation pulses over the fourth duty cycle time interval <NUM>. Upon expiration of the fourth duty cycle time interval <NUM>, the sequence is repeated beginning with duty cycle time interval <NUM> again.

In this example, four different bipolar pairs are selected in sequence. The four different bipolar electrode pairs may differ by at least one electrode and/or the polarity of another bipolar electrode pair. For example, when a single quadripolar lead <NUM> is used, the four bipolar pairs may include 30a-30b, 30b-30c, 30c-30d and 30a-30d. The portions of the protrusor muscles recruited by the four different pairs may not be mutually exclusive since the electrical fields of the four different pairs may stimulate some of the same nerve fibers. Four different portions of the protrusor muscles may be recruited, which may include overlapping portions. The relatively long recovery periods <NUM>, <NUM>, <NUM> and <NUM> between respective duty cycle time intervals allows each different portion of the protrusor muscles to recover before the next duty cycle. When recruited muscle portions overlap between selected electrode pairs, the bipolar electrode pairs may be selected in a sequence that avoids stimulating the overlapping recruited muscle portions consecutively. All recruited muscle portions are allowed to recover during at least a portion of each respective recovery period <NUM>, <NUM>, <NUM> and/or <NUM>. For example, if the bipolar electrode pair <NUM> and the bipolar electrode pair <NUM> recruit overlapping portions of the protrusor muscles, the recruited portions may still recover during the second duty cycle time interval <NUM> and during the fourth duty cycle time interval <NUM>.

The duration of each duty cycle time interval, <NUM>, <NUM>, <NUM> and <NUM>, may be the same or different from each other, resulting in the same or different overall duty cycles. For example, when four bipolar electrode pairs are sequentially selected, stimulation delivery for each individual pair may be a <NUM>% duty cycle. In other examples, a combination of different duty cycles, e.g., <NUM>%, <NUM>%, <NUM>% and <NUM>%, could be selected in order to promote sustained protrusion of the tongue with adequate airway opening while minimizing or avoiding fatigue. The selection of duty cycle may depend on the particular muscles or muscle portions being recruited and the associated response (position) of the tongue to the stimulation for a given electrode pair selection.

The stimulation control parameters used during each of the duty cycle time intervals <NUM>, <NUM>, <NUM>, and <NUM> for delivering electrical pulses using each of the different bipolar electrode pairs <NUM>, <NUM>, <NUM> and <NUM> may be the same or different. As shown, a different pulse voltage amplitude and a different interpulse interval and resulting pulse train frequency may be used. The pulse amplitude, pulse width, pulse frequency, pulse shape or other pulse control parameters may be controlled according to settings selected for each bipolar electrode pair.

In the example shown, one ramp on portion <NUM> of the stimulation protocol is shown at the onset of the therapy delivery time period <NUM>. Once the stimulation is ramped up to position the tongue in a protruded position, no other subsequent duty cycle time intervals <NUM> (other than the first one), <NUM>, <NUM> and <NUM> may include or be proceeded by a ramp on portion. In other examples, a ramp on portion may precede each duty cycle time interval (or be included in the duty cycle time interval as shown in <FIG>) and may overlap with the preceding duty cycle time interval. No ramp off portions are shown in the example of <FIG>. In other examples, ramp off portions may follow or be included in each duty cycle time interval <NUM>, <NUM>, <NUM> and <NUM> and may overlap with the onset of the next duty cycle time interval as shown in <FIG>. In some examples, only the last duty cycle time interval (not shown in <FIG>) may include or be immediately followed by a ramp off portion to gently allow the tongue to return to a relaxed position at the end of the therapy delivery time period <NUM>.

Following implantation as depicted in <FIG> and <FIG> and calibration by the surgeon or other caregiver, the INS <NUM> is ready for use. In accordance with one aspect of the disclosure, the INS system <NUM> is manually switched on by the patient as part of their routine prior to sleeping. This may be a function of the external programmer <NUM>, or another similar device that can communicate with the pulse generator <NUM> via the telemetry circuit <NUM>. A delay period may be programmed into the software or firmware employed by the control circuit <NUM>. The delay period allows the patient a period to fall asleep before therapy is begun. The period may be established for the patient based on a variety of factors, including an average time to sleep observed during, for example, a sleep study and may be adjusted by the patient via the external programmer <NUM>. Without the delay period, the patient would immediately begin to experience the effects of stimulating the protrusor muscles, which though not dangerous or painful, can be observed and may be considered annoying to experience while awake.

As will be appreciated, manual switching as described above, is not always a desirable feature in an implantable device associated with sleeping. In a further aspect of the disclosure, OSA therapy may be started and stopped at scheduled times of day. Control circuit <NUM> may include a clock for scheduling the time that OSA therapy is started and stopped by therapy delivery circuit <NUM>. Many patients, however, are not as rigorous regarding their schedules as would be desired to make the scheduling most effective. Further, the patient may find themselves at a social gathering or other affair at a time where they are normally scheduled for sleeping. Additionally, or alternatively, the patient may find themselves taking an unscheduled nap in a motor vehicle, plane, or train, and not have an opportunity to initiate or schedule therapy. Since OSA is often co-morbid with heart related diseases any instances of experiencing OSA can have complicating factors affecting the patient's heart. Thus, sensing of sleeping conditions and initiation of therapy are desirable. One aspect of the disclosure is directed to a mechanism of initiating therapy based on a detected state of the tone of the protrusor muscles.

In accordance with the disclosure, and as noted above, the electrodes <NUM> either alone or in combination with the sensor <NUM> can be configured to detect electromyography (EMG) signals. Electromyography is a technique of evaluating and recording the electrical activity produced by skeletal muscles. An electromyograph detects the electrical potential generated by muscle cells when the cells are electrically or neurologically activated. <FIG>, in an upper plot depicts an EMG signal observed in a genioglossus muscle (GG) <NUM>, in a patient during normal breathing. The lower plot in <FIG> depicts the pharyngeal pressure during the same period as the EMG signal in the upper plot. As can be seen in <FIG>, during breathing as the pharyngeal pressure drops, consistent with inhalation, the EMG signal significantly increases. Those of skill in the art will recognize that this increase in EMG signal during breathing, signifying stimulation of the muscles of the tongue such as the genioglossus muscle (GG) <NUM>, ensures that the airway is not closed or collapsed easing the ability of the subject to take a breath. That is, at periods of high EMG signal the protrusor muscles have a contracted tonal state. At periods where there is a low EMG signal, the protrusor muscles have a relaxed tonal state.

<FIG> depicts a comparison of observed EMG signals observed in the protrusor muscles of two sets of subjects. For all subjects, the EMG signal declines when the subject is in a sleeping state as compared to a wakeful state. However, significantly for the instant disclosure, subjects who are experiencing an OSA episode have a dramatically lower EMG signal. This reduced EMG signal is evidence of a reduced tonal state of the protrusor muscles of the subjects experiencing OSA. <FIG> depicts similar data for comparison of the EMG signals during REM, non-REM, quiet wakefulness, and active wakefulness of subjects. This data confirms the top line of <FIG> that when asleep, the EMG signals are reduced, and as noted in <FIG>, that reduction is more pronounced and in subjects experiencing an OSA event.

In accordance with one aspect of the disclosure, when a stimulation pulse is not being delivered by electrodes 30a-30d, the electrodes can be employed to detect the electrical potential of muscles. That is, the electrodes 30a-30d can detect the EMG signals that are being applied to the protrusor muscles by the patient's neural system. These signals can be communicated to the control circuit <NUM> for monitoring and application of rules in the software or firmware stored therein. In other examples, dedicated EMG sensing electrodes may be carried by housing <NUM> and/or lead body <NUM> and coupled to sensor <NUM> for EMG signal monitoring. EMG signal monitoring by control circuit <NUM> allows for detection of a low tonal state of the GG and/or GH muscles. With reference to <FIG> a low tonal state (i.e., low incidence of EMG signals) indicates both a likelihood of the patient being asleep and a susceptibility to upper airway collapse. Detection of low tonal state of the protrusor muscles may either alone or in combination with other sensor data, e.g., detection of the pose of the patient indicating that they are in a reclined position or the detection of a heart rate consistent with sleeping, be used to initiate therapy and prevent the onset of an OSA event. Thus, the EMG signals may be used by control circuit <NUM> to detect a sleep state and/or low tonal state of the protrusor muscles for use in controlling therapy delivery circuit <NUM> for delivering stimulation pulses to cause protrusion of the patient's tongue. As will be appreciated, in the detection of the EMG signals a variety of bandpass filtering, rectification, and normalization may be employed by the control circuit <NUM>, or intervening hardware to produce a useable signal providing a clear indication of the state of the protrusor muscles. An example of such processing of the EMG signal is depicted in <FIG>.

EMG monitoring may further be used in monitoring for fatigue of the stimulated GG and/or GH muscles. If fatigue of the muscles is detected, control circuit <NUM> may alter to control the duty cycle of electrical stimulation pulse trains delivered by therapy delivery circuit <NUM> to minimize or avoid fatigue and/or allow adequate fatigue recovery time between duty cycle on times. In this manner, Sensor <NUM> may be configured to produce a signal that is correlated to protrusor muscle tonal state for use by control circuit <NUM> for detecting a low tonal state predictive of upper airway obstruction, detecting protrusor muscle fatigue, and/or detecting a protruded state of tongue <NUM>. Therapy delivery circuit <NUM> may be configured to respond to a detection of the protrusor muscle tonal state by control circuit <NUM> by adjusting one or more control parameters used to control stimulation pulse delivery.

As noted above, the EMG monitoring may not be the only signal employed by the pulse generator <NUM>, and particularly the control circuit <NUM> in determining the level of wakefulness. As an example, sensor <NUM> may include an accelerometer that can provide an indication of motion of the patient. Further, where the accelerometer <NUM> is a three-axis accelerometer, a posture of the patient may be determined. Additionally, an accelerometer may be employed to detect snoring sounds and physical movements of the patient. Still further, a temperature sensor may be employed in which the diurnal temperature of a patient is measured and stored in memory as are sleeping temperatures. The sensor <NUM> may also be one or more accelerometers employed to detect the heartrate of a patient. In another example, sensor <NUM> may be an accelerometer employed to detect the rate of breathing or the volume of airflow, into or out of the patient. Volume of airflow may be determined by placing the accelerometer at a point on a patient's chest and comparing the travel of the accelerometer to previously observed lung volume data that has been correlated to the sensor <NUM> movement data. Breathing rate can be determined by simply monitoring the change in direction of the accelerometer.

Still further, the sensor <NUM> may be an implantable pulse-oximeter useable to measure the blood oxygen saturation levels. In one example the pulse-oximeter is a cuff placed substantially around a blood vessel and measuring the blood-oxygenation levels using a light source as is known in the art. As described herein, the sensor <NUM> may be one or several of the various types of sensors described herein.

The sensor <NUM> may be an ECG sensor. ECG is a recording of the electrical activity of the heart over a period of time. While an ECG typically employs sensors placed on the skin, an effective ECG can be employed in an implantable device wherein at least two electrodes separated by a distance (e.g., at least about <NUM>) are employed to detect electrical changes caused by the cardiac depolarization and repolarization during each cardiac cycle.

A further aspect of the disclosure is described in connection with <FIG> and <FIG> in which a simplified diagram of an INS system is depicted, and a method of the systems operation are described. The system <NUM> includes an INS device <NUM>, an external programmer <NUM>, a server <NUM> in communication with the external programmer and a remote computer <NUM> in communication with the server <NUM>. Prior to implantation of an INS <NUM>, patients typically undergo a patient assessment (step <NUM>) one or more analyses in conjunction with their doctor. During this analysis a variety of self-reported issues may be identified including daytime sleepiness, interrupted snoring, gasping, co-morbidities, etc. The data related to these issues may be stored on the server <NUM> as part of the patient electronic medical records (EMR) or as part of a specific OSA treatment and remediation file. The discussions with the medical provider may lead to an initial diagnosis of OSA. This initial diagnosis is typically confirmed through the use of one or more sleep studies of the patient. During the sleep study a wide variety of physiological data is gathered as well as some self-reported data. For example, the heart rate, blood oxygen saturation levels, temperature, an electroencephalogram (EEG), electrocardiogram (ECG), total sleep, quality of sleep, sleep efficiency, sleep stages, number of arousals (less than <NUM>), number of awakenings (greater than <NUM>), Apnea Hypopnea Index as well as others. These data may be recorded by remote computer <NUM>, either directly or via additional hardware, and saved on the remote server <NUM> (step <NUM>).

These collected data from the sleep study, along with the data collected by the medical provider may be used to generate an initial set of stimulation parameters (e.g., pulse width, frequency, amplitude, pairing of electrodes, etc.) for the INS <NUM> (step <NUM>). This may be in part based on larger population studies to identify some aspects of more global therapy parameters. The initial stimulation parameters may be set either at remote computer <NUM> or directly at external programmer <NUM>, and in either event may be saved a server <NUM> (e.g., a cloud computer storage device), for access by either device. And the external programmer <NUM> can be employed to install the initial stimulation parameters in the INS <NUM> (step <NUM>). Often, the patient is permitted to utilize the INS <NUM> for a period of time, and a subsequent sleep study may be performed. From this second sleep study, the initial stimulation parameters may be altered, or additional surgery may be recommended to those who do not respond to stimulation therapy. Further sleep studies may be required periodically to adjust the stimulation parameter settings in an effort to improve the therapy of the individual patient.

In accordance with the present disclosure, the data collected from the sensor <NUM> may be combined with various self-reported data that a user may input via a user interface on the external programmer <NUM> and utilized to replace at least the second sleep study, and possibly the first as well. The external programmer <NUM>, or another device in communication with the server <NUM>, presents the patient with a user interface. The user interface may be presented to the user on a periodic basis including daily, weekly, bi-weekly, or monthly. In accordance, with the daily embodiment, the user interface may request that the patient input various self-reporting data. This can include nightly alcohol intake, smoking, stress, the time the patient went to bed, the patient's perception of the quality of the last night's sleep, tiredness, discomfort, pain or soreness of the protrusor muscles potentially caused by the stimulation, etc. Additionally, data from other appliances may also be reported. For example, may patients suffering from OSA also suffer from high blood pressure, and may be on a regimen of periodically testing their blood pressure. This blood pressure data may be self-reported via the user interface. Similarly, if the patient is a diabetic, they may need to test their blood sugar levels both before and after sleep. These data too may be self-reported via the user interface. In addition, the patient may be asked to answer the inquiries of the Eppsworth Sleepiness Scale (ESS). In one embodiment, the ESS inquiry may be requested of the patient at a different interval that the other data. In this way the ESS can be used as one gauge of the effectiveness of the therapy.

As noted above, the sensor <NUM> can provide a variety of data dependent upon how it is configured. As one example using the EMG data, a sleep start and end time may be determined. Using one or more accelerometers and a variety of bandpass filtering position, activity (arousals vs awakenings), sleep stages, respiration rate, and heart rate can be collected. This data can be reported to the control circuit <NUM> and stored in memory <NUM> at least temporarily. The external programmer <NUM> can be set to automatically interface with the INS <NUM> every day, or at another periodic interval. The external programmer <NUM> can then download the sensor data via the telemetry circuit and communicate the sensor data from the INS and self-reported data entered via the user-interface to the server <NUM> (step <NUM>).

The server <NUM> may include thereon one or more software applications. One of these applications may review the data received from the external programmer <NUM> and assign a value to each datapoint received. These values can be analyzed, and a sleep score determined based on the received sensor and self-reported data (step <NUM>). The sleep score provides an overall assessment of the patient's sleep that can be assessed by both the patient and the medical provider. As will be apparent some data points may be more important to assessing the overall sleep of the patient thus some form of scaling of the values may be required. The application will also be able to flag any relevant data significant to a poor sleep score. For example, if the patient reported several alcoholic drinks the evening before the data resulting in the poor sleep score was recorded, this might be a highly relevant factor, and indicate that the sleep score for that day is not an accurate indicator of the effectiveness of the current stimulation parameters.

Regardless, the sleep score may then be recorded as part of the patient's sleep record and the score reported to a medical provider via the remote computer <NUM> (step <NUM>). This data may be viewed in a variety of ways to provide the medical provider an assessment of the current stimulation parameters. For example, the medical provider may view the daily results, an average over a period of time, a graphical representation of the sleep score or a percentage or rate of change (if any) from the preceding reporting period. By periodically assessing the effectiveness of the parameters and comparing the effectiveness to the additional self-reported data a multi-pronged analysis can be undertaken. In one example if the patient's data indicates that the therapy is effective in achieving quality sleep with few incidents of OSA, but the patient expresses a feeling of soreness or fatigue of the protrusor muscles, the stimulation parameters may be changed to increase the frequency of the switching between bi-polar pairs and to prolong the interval between any set of bi-polar pairs being stimulated. Alternatively, the amplitude of the signal may be reduced. Further, following further sampling of the data collected by the sensor <NUM> and self-reported by the patient via the user interface, if the first of these is not effective, the second may be attempted. In this way, the medical provider is able to proceed in a stepwise fashion of altering the stimulation parameters, make adjustments, and observing the results of those adjustments while considering not just the self-reported data. This collection of data and reporting of a sleep score (steps <NUM>-<NUM>) may be iterative repeated prior to advancing to the next step. One of skill in the art will recognize that the remote computer may in fact be an external programmer <NUM> configured for physician or medical care provider's use.

In a further aspect of the disclosure, the server <NUM> may collect or be in communication one or more further servers receiving similar data from other patients. The entirety of the collected data may then be analyzed by one or more neural networks to assess the combined data and to identify patterns within the data to provide a global assessment of stimulation parameters and effectiveness of the stimulation pattens when applied across a wide array of patients. Some of these patients will have similar comorbidities, and others will not. By further assessment of the data the neural network can seek out similar groups of patients and provide refined initial stimulation parameters for the subgroup based on these similarities (e.g., age, demographics, weight, heart disease, blood pressure, etc.). The neural network may also be employed to assess an individual patient to provide individualized guidance on updating stimulation parameters. In a similar fashion, the server may include one or more applications employing fuzzy logic to analyze the data from both an individual and from the broader community of patients to provide suggestions for updating the stimulation parameters (step <NUM>). In both the use of neural networks and fuzzy logic the application on the server <NUM> may present the medical provider with the option to reject the suggested updated stimulation parameters (step <NUM>) or to accept or modify the suggested updated stimulation parameters (step <NUM>). As will be appreciated, the medical provider may forgo the use of either the neural network or fuzzy logic and update or modify the stimulation parameters. Once the updated stimulation parameters are accepted/modified by the medical provider the updated stimulation parameters are communicated to the external programmer <NUM> (step <NUM>). Once received at the external programmer <NUM>, the patient again may have the option to accept the updated stimulation parameters (step <NUM>) or reject the updated stimulation parameters (step <NUM>). If accepted by the patient the external programmer <NUM> can update the stimulation parameters on the INS (step <NUM>). If at step <NUM> or <NUM> the updated stimulation parameters are rejected, the method simply returns to step <NUM>. Similarly, after updating the stimulation parameters on the INS <NUM>, the process similarly returns to step <NUM>.

These updated stimulation parameters may be stored on the server <NUM> until the next communication with the remote programmer <NUM>, at which time the improved stimulation parameters may be downloaded to the external programmer <NUM>. During the next collection of data from the INS <NUM>, the external programmer <NUM> may then download the updated stimulation parameters to the INS <NUM>. In this way, the stimulation parameters of the INS updated, and the patient's sleep score improved. As would be expected the user interface on the external programmer <NUM> would indicate to the patient that the new stimulation parameters are ready for installing on the INS, and it is at this point that steps <NUM> and <NUM> may be performed.

A further aspect of the present disclosure is the presence of an artificial intelligence (AI) within the external programmer <NUM>. The AI may have a limited mandate for purposes of safety of the patient to limit the number of successive nights resulting in a poor sleep score. In one aspect of the disclosure, following the update of the stimulation parameters and receiving the data from the following night's sleep, the AI could analyze the data from sensor <NUM> and the self-reported data and make an immediate assessment regarding the sleep score (step <NUM>). If the sleep score is bad the user interface may present the patient with the ability to revert to the prior stimulation parameters until they can interface with their medical provider regarding the prior bad night's sleep (step <NUM>). Of course, the AI may require more than a single night's data to identify the issue or have sufficient data to raise concerns with the patient. Further, the AI may be enabled to communicate a request for intervention directly to the medical provider via the server <NUM> and remote computer <NUM>.

In this way real actionable feedback on the effectiveness of stimulation parameters is provided to both the medical provider and to the patient. A continuum of care and assessment of the patient's experience with the INS device is enabled so that adverse results from therapy can be rectified and behavioral modifications can be suggested to the patient based on their self-reported data.

It will be appreciated by those of skill in the art that one or more of the calculations, assessments, and user interfaces described herein above with respect to the server <NUM> and the remote computer <NUM> may also be performed directly at the external programmer <NUM>. In some embodiments this may provide for near instant feedback to the patient regarding a prior night's sleep via a user interface on the external programmer. In other embodiments, where the external programmer <NUM> is of a type typically used by the physician during an office visit, the capabilities and functions of the external programmer <NUM> can be more robust and potentially even eliminate or at least reduce the use of the server <NUM> and remote computer <NUM>. As a further, example, in applications employing an AI, the AI may be trained to perform all of the assessments and analyses of the server and offer up the suggestions for modification of the stimulation parameters to the patient or care provider. allowing a greater depth of understanding of the therapy, efficacy, and assessment of possible changes, without necessarily requiring access to the data stored on the server <NUM> or the applications operating thereon. And in yet a further example, the AI on the external programmer <NUM> may assess the data received from the INS <NUM> and make adjustments to the stimulation parameters either autonomously or present them to the patient for acceptance. As will be appreciated, these updates may be bounded to prevent large changes in the stimulation parameters from occurring without intervention from a medical provider.

It should be understood that, depending on the example, certain acts or events of any of the methods described herein can be performed in a different sequence, may be added, merged, or left out altogether (e.g., not all described acts or events are necessary for the practice of the method).

Computer-readable media may include computer-readable storage media, which corresponds to a tangible medium such as data storage media (e.g., RAM, ROM, EEPROM, flash memory, or any other medium that can be used to store desired program code in the form of instructions or data structures and that can be accessed by a computer).

Claim 1:
An implantable neurostimulator INS, comprising:
an electrical lead (<NUM>) having formed thereon at least a pair of bipolar intramuscular ring electrodes (<NUM>), wherein the electrical lead is configured for placement of the ring electrodes within protrusor muscles of a patient in an area of a medial branch of a hypoglossal nerve, that includes motor points of the one or more protrusor muscles of the patient, wherein the motor points are where each nerve axon of the hypoglossal nerve terminates in the muscle, and wherein the ring electrodes are configured to receive electromyography. EMG resulting from signals applied to the protrusor muscles by the patient's neural system from the intramuscular electrodes;
a pulse generator (<NUM>) electrically connected to the electrical lead and configured to deliver electrical energy to the ring electrodes to activate the protrusor muscles to move the tongue of the patient forward, the pulse generator having therein a sensor (<NUM>) and a control circuit (<NUM>),
wherein the sensor and control circuit are configured to receive the EMG signals sensed with the ring electrodes from the one or more protrusor muscles and determine a tonal state of the protrusor muscles in which the lead is placed based on the EMG signals; and wherein the pulse generator (<NUM>) includes a therapy delivery circuit (<NUM>) and the control circuit (<NUM>) is in electrical communication with the therapy delivery circuit (<NUM>) and causes the therapy delivery circuit to deliver electrical energy to the ring electrodes upon a determination that the EMG signal is below a threshold value.