Sleep apnea treatment system and method

Abstract

The present disclosure provides a method of treating sleep apnea in a patient by manipulating an implanted nerve stimulator implant to stimulate genioglossus nerve branches and / or genioglossus. The present disclosure also provides a method of implanting a nerve stimulator implant in the genioglossus muscle near the genioglossus muscle nerve branch. The invention further provides a sleep apnea treatment system and a guide used for the sleep apnea treatment system.

Description

background

[0001] There are many treatments for sleep apnea, such as continuous positive airway pressure devices (CPAP), surgically implanted neurostimulators, oral tubes, and medications. Typically, known devices have poor efficacy in reducing the apnea-hypopnea index (AHI) and / or they are highly invasive device procedures that can only be performed by a surgeon. Additionally, neurostimulators and positive airway pressure (PAP) devices on the market are primarily stand-alone devices that are only partially able to treat OSA or CSA.

[0002] US2022370797A1 discloses a technique for implanting a signal delivery device to treat sleep apnea. Specifically, US2022370797A1 teaches a method of percutaneously implanting a signal delivery device to target the medial branch of the hypoglossal nerve. As described in US2022370797A1, stimulating the medial branch of the hypoglossal nerve can innervate oral muscles, such as the genioglossus and geniohyoid muscles, which tend to pull the tongue forward (forward), thereby reducing the tendency of the soft tissue of the palate to prolapse into the patient's airway. However, the medial branch also includes retractors (retrusers) that innervate muscles (such as the styloglossus and hyoglossus), which tend to pull the soft tissue backward (backward), and / or can cause the tongue to curl to the left or right in the oral cavity---both are motor responses that can block the patient's airway. Therefore, it is important to stimulate the medial branch in a manner that causes a net positive protrusive effect or a net protrusive motor response. This may include, for example, stimulation of the medial branch to avoid full activation of the retractor muscles.

[0003] The problem with the method taught in US2022370797A1 is that the implant position and the electrical stimulation signal relative to the medial branch of the hypoglossal nerve will determine the balance of protrusion-retraction stimulation. Therefore, the implantation procedure requires a high degree of accuracy and calibration, resulting in a relatively complex and invasive procedure, which usually requires surgical intervention, such as the use of an endoscope during calibration.

[0004] US20130218230A1 discloses a method for stimulating the hypoglossal nerve for controlling the position of a patient's tongue, for example to prevent obstructive sleep apnea. US20130218230A1 proposes that stimulating the distal branch of the hypoglossal nerve can generate only the desired tongue movement by targeting only some tongue muscles, particularly those muscles that cause the tongue to protrude.

[0005] As explained in US20130218230A1, one problem with targeting the distal branches of the hypoglossal nerve is that surgical approaches to these distal branches are more difficult, and as the branches get progressively smaller, the electrodes are placed further away, making it more difficult to design appropriate electrodes for such small branches, and the systems used to stimulate them are less stable and more likely to damage these more delicate structures. This also makes the implantation procedure difficult.

[0006] Therefore, it would be advantageous to provide an implantable neurostimulator system that targets the distal branches of the hypoglossal nerve and an implantation procedure that addresses the above-mentioned difficulties. Brief Overview

[0007] According to the present invention, a method of treating sleep apnea in a patient is provided, the method comprising operating an implanted neurostimulator implant to stimulate a branch of a hypoglossal nerve. In examples, the implanted neurostimulator implant is operable to stimulate a distal branch of the hypoglossal nerve, particularly a genioglossus nerve branch. In other examples, the implanted neurostimulator implant is operable to stimulate a medial branch of the hypoglossal nerve.

[0008] In an example, the method includes operating an implanted neurostimulator implant to stimulate genioglossus nerve branches and / or the genioglossus muscle. Stimulating the genioglossus nerve branches and / or the genioglossus muscle may cause tongue protrusion, alleviating sleep apnea.

[0009] In an example, an implanted neurostimulator implant is operable to directly stimulate the genioglossus nerve branches and / or the genioglossus muscle. Such direct stimulation can be provided by implanting the electrodes of the neurostimulator implant into the genioglossus muscle in close proximity to the genioglossus nerve branches. By implanting the electrodes in close proximity to the genioglossus nerve branches, for example implanting the electrodes at a position no more than 2 cm or no more than 1 cm from the genioglossus nerve branches, the amplitude of the stimulation signal can be limited so that only the genioglossus nerve branches are stimulated. This can avoid stimulating other parts of the hypoglossal nerve and other muscles, thereby avoiding retraction of the tongue. In an example, an implanted neurostimulator implant is operable to stimulate only the genioglossus nerve branches and / or the genioglossus muscle. In an example, an implanted neurostimulator implant is operable to not stimulate the medial branches of the hypoglossal nerve.

[0010] In an example, an implanted neurostimulator implant is operated to stimulate the genioglossus nerve branch with a first stimulation signal and the genioglossus muscle with a second stimulation signal. The first stimulation signal and the second stimulation signal can be generated simultaneously or sequentially. The first stimulation signal and the second stimulation signal can be generated in response to a detected physiological parameter or movement of the patient, as further described below.

[0011] In an example, the implanted neurostimulator implant is operated to stimulate the genioglossus muscle with a stimulation signal having a frequency between about 2 Hz and about 150 Hz, for example, between about 2 Hz and about 100 Hz, for example, between about 2 Hz and about 50 Hz, for example, between about 2 Hz and about 40 Hz, for example, between about 2 Hz and about 30 Hz, for example, between about 2 Hz and about 20 Hz, for example, between about 2 Hz and about 15 Hz, for example, between about 2 Hz and about 10 Hz.

[0012] In an example, the stimulation signal for stimulating the genioglossus muscle has a peak amplitude between 0.1 mA and 10 mA, for example, between 0.1 mA and 5 mA. Such low-frequency, low-amplitude muscle stimulation can avoid discomfort to the patient.

[0013] In an example, the implanted neurostimulator implant is operated to stimulate branches of the genioglossus nerve with a stimulation signal having a frequency between about 20 Hz and about 1500 Hz, for example, between about 20 Hz and about 1000 Hz, for example, between about 20 Hz and about 500 Hz, for example, between about 20 Hz and about 400 Hz, for example, between about 20 Hz and about 300 Hz, for example, between about 20 Hz and about 200 Hz, for example, between about 20 Hz and about 150 Hz, for example, between about 20 Hz and about 100 Hz.

[0014] In an example, stimulation of the genioglossus nerve branches and / or the genioglossus muscle comprises a stimulation signal having a plurality of pulses, each pulse having a pulse width between 30 microseconds and 2000 microseconds. In an example, the pulse interval may be between 30 microseconds and 2000 microseconds.

[0015] In an example, an electrode that provides a stimulation signal to a nerve or muscle may be operated as an anode or a cathode. The neurostimulator implant may be controllable to change between anodal stimulation and cathodal stimulation.

[0016] In an example, the neurostimulator implant may include an electrode lead having an electrode. The method may include implanting the electrode lead into the genioglossus muscle near a branch of the genioglossus nerve of the patient. Thus, the neurostimulator implant may directly stimulate the genioglossus nerve branch within the genioglossus muscle. In an example, the electrode may be implanted at a position no more than about 2 cm from the genioglossus nerve branch, preferably implanted at a position no more than about 1 cm from the genioglossus nerve branch.

[0017] In an example, the neurostimulator implant may further include a housing portion. The electrode lead may extend from the housing portion. The method may include implanting the housing portion into subcutaneous tissue of the patient.

[0018] In an example, the method may further include transmitting wireless power from the external device to the implanted neurostimulator implant. In an example, the neurostimulator implant includes a wireless power receiver (e.g., an antenna). The wireless power receiver may be disposed in the housing portion and / or in the electrode lead. In an example, the wireless power transmitted to the implanted neurostimulator implant includes a frequency between 300 MHz and 3 GHz, for example, between 400 MHz and 2.5 GHz, for example, between 433 MHz and 2.4 GHz.

[0019] In an example, the method may further include detecting at least one physiological parameter by a sensor. In an example, the at least one physiological parameter may include at least one of the following:

[0020] The patient's breathing rate, The patient's electromyography (EMG) The patient's electrocardiogram (ECG). The patient's oxygen saturation, The patient's temperature, The patient's heart rate, The patient's blood pressure.

[0021] In an example, the method may include generating a stimulation signal in response to the detected at least one physiological parameter.The method may include adapting the stimulation signal based on the detected at least one physiological parameter.

[0022] In an example, the method may further include detecting, by a sensor, at least one movement of the patient, such as at least one of the following: The patient's breathing movements, The patient's jaw movement, The patient's chest movement, The patient's diaphragm moves.

[0023] In an example, the method may include generating a stimulation signal in response to the detected at least one motion.The method may include adjusting the stimulation signal based on the detected at least one motion.

[0024] In an example, the method may further include detecting, by a sensor, a physiological parameter or movement of the patient indicative of sleep apnea, such as at least one of: A lapse in breathing rate, Electromyography (EMG) curves indicating sleep apnea, ECG curve indicating sleep apnea, Decreased oxygen saturation, Increased body temperature, Increased heart rate, Increased blood pressure, or Breathing movement, jaw movement, rib cage movement or diaphragm movement.

[0025] In an example, the method may include generating a stimulation signal in response to at least one detected physiological parameter or movement of the patient indicative of sleep apnea. The method may include adjusting the stimulation signal based on at least one detected physiological parameter or movement of the patient indicative of sleep apnea.

[0026] In an example, the method may further include controlling a neurostimulator implant to stimulate the genioglossus nerve branches and / or the genioglossus muscle in response to at least one detected physiological parameter of the patient and / or at least one detected movement of the patient and / or at least one physiological parameter or movement of the patient indicative of sleep apnea. Thus, the neurostimulator implant may be operated to provide stimulation at a time determined based on parameters detected by the sensor and / or using a stimulation signal configured based on parameters detected by the sensor. In response to the parameters detected by the sensor, the stimulation signal may be configured to have a specific period and / or frequency and / or amplitude and / or duration and / or pulse width and / or pulse interval. A stimulation signal may be generated for stimulating the genioglossus nerve branches and / or the genioglossus muscle.

[0027] In one example, the method includes detecting a patient's respiratory rate via a sensor and stimulating genioglossus nerve branches and / or the genioglossus muscle in sync with the detected respiratory rate. In another example, the method includes stimulating genioglossus nerve branches and / or the genioglossus muscle in sync with a predetermined target respiratory rate. In an example, the method may include stimulating genioglossus nerve branches and / or the genioglossus muscle at the beginning of the patient's inspiratory cycle.

[0028] In an example, the method may further include determining a classification of sleep apnea based on at least one detected physiological parameter and / or at least one movement of the patient, in particular whether the detected sleep apnea includes obstructive sleep apnea OSA, central sleep apnea CSA, or a combination of OSA and CSA. The method may include adjusting the stimulation signal based on the determined classification of sleep apnea.

[0029] In an example, the method may further include operating an implanted second neurostimulator implant to stimulate the patient's phrenic nerve and / or cervical loop nerve. Stimulation of the phrenic nerve and / or cervical loop may be responsive to a detected physiological parameter, patient movement, or classification of sleep apnea as described above. Stimulation of the phrenic nerve and / or cervical loop may be responsive to a detected apneic event. Stimulation of the phrenic nerve and / or cervical loop may be synchronized with stimulation of the genioglossus nerve branches and / or the genioglossus muscle.

[0030] In an example, the method may further include operating a continuous positive airway pressure (CPAP) device to provide positive air pressure to the patient's airway. The operation of the CPAP device may be responsive to a detected physiological parameter, patient movement, or classification of sleep apnea as described above. The operation of the CPAP device may be responsive to a detected apnea event. The operation of the CPAP device may be synchronized with stimulation of the genioglossus nerve branches and / or the genioglossus muscle.

[0031] In an example, the method may further include controlling the or each neurostimulator implant and optionally the CPAP device based on at least one detected physiological parameter of the patient and / or at least one detected movement of the patient. In an example, the method may include operating the neurostimulator implant and / or a second neurostimulator implant and / or the CPAP device based on the determined classification of sleep apnea. In an example, the method may include, if the classification of sleep apnea is determined to be obstructive sleep apnea OSA, operating the neurostimulator device to stimulate the genioglossus nerve branches and / or the genioglossus muscle. In an example, if the classification of sleep apnea is determined to be central sleep apnea CSA, the method may include operating the second neurostimulator implant to stimulate the phrenic nerve and / or the cervical nerve. In an example, if the classification of sleep apnea is determined to be obstructive sleep apnea OSA, the method may include operating the CPAP device to provide positive air pressure to the patient. In an example, if the classification of sleep apnea is determined to be a combination of obstructive sleep apnea and central sleep apnea, the method may include operating:

[0032] a nerve stimulator device to stimulate the genioglossus nerve branches and the genioglossus muscle, and At least one of the following: A second neurostimulator implant is used to stimulate the phrenic nerve and / or the cervical nerve, and a CPAP device for providing positive air pressure to the patient.

[0033] In examples, the sensor may be integrated with the neurostimulator implant. In other examples, the sensor may be an external sensor. In examples, there may be more than one sensor arranged to detect more than one physiological parameter or movement of the patient, and each sensor may be integrated with the neurostimulator implant or an external device. In one example, the neurostimulator implant includes an oxygen saturation sensor and / or an ECG sensor, and an external accelerometer is provided to detect movement of the patient, such as jaw or head movement.

[0034] According to another aspect of the present invention, there is also provided a system for treating sleep apnea in a patient, the system comprising a neurostimulator implant implantable proximate to a branch of a hypoglossal nerve of the patient and operable to stimulate the branch of the hypoglossal nerve.

[0035] In an example, the implanted neurostimulator implant is operable to stimulate the patient's genioglossus nerve branches and / or the genioglossus muscle. In other examples, the implanted neurostimulator implant is operable to stimulate the medial branch of the hypoglossal nerve.

[0036] In an example, the implanted neurostimulator implant is operable to stimulate the genioglossus muscle with a stimulation signal having a frequency between about 2 Hz and about 150 Hz, for example, between about 2 Hz and about 100 Hz, for example, between about 2 Hz and about 50 Hz, for example, between about 2 Hz and about 40 Hz, for example, between about 2 Hz and about 30 Hz, for example, between about 2 Hz and about 20 Hz, for example, between about 2 Hz and about 15 Hz, for example, between about 2 Hz and about 10 Hz.

[0037] In an example, the stimulation signal for stimulating the genioglossus muscle has a peak amplitude between 0.1 mA and 10 mA, for example, between 0.1 mA and 5 mA. Such low-frequency, low-amplitude muscle stimulation can avoid discomfort to the patient.

[0038] In an example, the implanted neurostimulator implant is operable to stimulate branches of the genioglossus nerve with a stimulation signal having a frequency between about 20 Hz and about 1500 Hz, for example, between about 20 Hz and about 1000 Hz, for example, between about 20 Hz and about 500 Hz, for example, between about 20 Hz and about 400 Hz, for example, between about 20 Hz and about 300 Hz, for example, between about 20 Hz and about 200 Hz, for example, between about 20 Hz and about 150 Hz, for example, between about 20 Hz and about 100 Hz.

[0039] In an example, the neurostimulator implant is operable to stimulate the genioglossus nerve branches and / or the genioglossus muscle with a stimulation signal having a plurality of pulses, each pulse having a pulse width between 30 microseconds and 2000 microseconds. In an example, the pulse interval may be between 30 microseconds and 2000 microseconds.

[0040] In an example, the neurostimulator implant includes an electrode implantable into the genioglossus muscle proximate to a genioglossus nerve branch of the patient, and includes a signal generator for generating a stimulation signal to stimulate the genioglossus nerve branch and / or the genioglossus muscle of the patient. In an example, the neurostimulator implant may be implanted into the genioglossus muscle proximate to a genioglossus nerve branch for directly stimulating the genioglossus muscle and / or the genioglossus nerve branch.

[0041] In an example, the neurostimulator implant is a battery-free implant and includes a wireless power receiver. In an example, the system also includes an external device. The external device may include a wireless power transmitter. The wireless power transmitter is used to transmit wireless power to the neurostimulator implant when the neurostimulator implant is implanted in the genioglossus muscle. The neurostimulator implant may include a wireless power antenna for receiving wireless power. In some examples, the external device includes a signal generator that generates a stimulation signal. In other examples, the signal generator is provided in the neurostimulator implant.

[0042] In an example, the system may further comprise a sensor arranged to detect at least one physiological parameter of the patient and / or at least one movement of the patient.

[0043] In an example, the at least one physiological parameter includes one or more of the following: The patient's breathing rate, The patient's electromyography (EMG) The patient's electrocardiogram (ECG). The patient's oxygen saturation, The patient's temperature, The patient's heart rate, The patient's blood pressure.

[0044] In an example, the stimulation signal generated by the signal generator may be generated in response to the detected at least one physiological parameter.The stimulation signal may be adjusted based on the detected at least one physiological parameter.

[0045] In an example, the at least one movement of the patient includes at least one of: The patient's breathing movements, The patient's jaw movement, The patient's chest movement, The patient's diaphragm moves.

[0046] In an example, the stimulation signal generated by the signal generator may be generated in response to at least one movement of the patient.The stimulation signal may be adjusted based on the detected at least one movement of the patient.

[0047] In an example, the system may further include a controller configured to determine the onset or occurrence of sleep apnea based on detected physiological parameters and / or detected movements of the patient, such as at least one of: Decline in respiratory rate, Electromyography (EMG) curves indicating sleep apnea, ECG curve indicating sleep apnea, Decreased oxygen saturation, Increased body temperature, Increased heart rate, Increased blood pressure, or Breathing movement, jaw movement, rib cage movement or diaphragm movement.

[0048] In an example, the stimulation signal generated by the signal generator may be generated in response to a detected onset or occurrence of sleep apnea.The stimulation signal may be adjusted based on the detected onset or occurrence of sleep apnea.

[0049] In an example, the signal generator can be configured to generate a stimulation signal in response to at least one detected physiological parameter of the patient and / or at least one detected movement of the patient and / or at least one physiological parameter or movement of the patient indicative of sleep apnea. Thus, the neurostimulator implant can be operated to provide stimulation at a time determined based on the parameters detected by the sensor and / or using a stimulation signal configured based on the parameters detected by the sensor. In response to the parameters detected by the sensor, the stimulation signal can be adjusted or configured to have a specific period and / or frequency and / or amplitude and / or duration and / or pulse width and / or pulse interval.

[0050] In an example, the system may further include a second neurostimulator implant, the second neurostimulator implant comprising: A neurostimulator implant comprising an electrode; a signal generator for generating a stimulation signal, and A wireless power system for providing power to a neurostimulator implant, The electrodes may be implanted to stimulate the patient's phrenic nerve and / or cervical nerve.

[0051] In an example, the system may further include a continuous positive airway pressure (CPAP) device operable to provide positive air pressure to the patient.

[0052] In an example, the system may further include a controller configured to control the or each neurostimulator implant and optionally the CPAP device based on at least one detected physiological parameter of the patient and / or at least one detected movement of the patient. The controller may be disposed in one of the neurostimulator implant, the CPAP device, or an external device.

[0053] In an example, the controller can be configured to determine a classification of sleep apnea based on at least one detected physiological parameter and / or at least one movement of the patient, in particular whether the detected sleep apnea includes obstructive sleep apnea OSA, central sleep apnea CSA, or a combination of OSA and CSA.

[0054] In an example, the controller may be configured to operate the neurostimulator implant and / or the second neurostimulator implant and / or the CPAP device based on the determined classification of sleep apnea.

[0055] According to another aspect of the present invention, there is also provided a method of implanting a neurostimulator implant into a patient for treating sleep apnea, wherein the neurostimulator implant comprises a housing portion and a flexible elongated electrode lead extending from the housing portion and having an electrode, the method comprising: providing a delivery device having a first needle holding a housing portion of a neurostimulator implant and a second needle holding an electrode lead, wherein the second needle has a higher gauge than the first needle, wherein the second needle extends beyond the first needle, and wherein the second needle is retractable in a direction toward the first needle, Insert a second needle into the patient at the insertion point below the patient's chin. advancing a second needle through the patient's tissue in an insertion direction toward the patient's genioglossus muscle, When the second needle is within the patient's genioglossus muscle, retracting the second needle to implant an electrode lead having electrodes into the genioglossus muscle near a branch of the genioglossus nerve, and The housing portion is withdrawn from the first needle to implant the housing portion beneath the skin.

[0056] In an example, the insertion point is near the posterior edge of the patient's mandibular symphysis.

[0057] In an example, the insertion direction includes a first angle β in the mandibular plane of the patient's chin and a second angle θ in the sagittal plane of the patient. In an example, the first angle β is between about ±15 degrees and about ±30 degrees, such as between about ±18 degrees and about ±25 degrees, such as between about ±20 degrees and about ±23 degrees, such as about ±22 degrees, and in particular about ±21.8 degrees. In an example, the second angle is between about 40 degrees and about 65 degrees, such as between about 45 degrees and about 55 degrees, such as between about 40 degrees and about 50 degrees, such as between about 47 degrees and about 49 degrees, and in particular about 48.1 degrees.

[0058] In an example, the method includes scanning the patient and determining the insertion direction based on the scan.

[0059] In an example, the method further comprises rotating the delivery device before withdrawing the housing portion from the first needle so that the housing portion is implanted in a different orientation relative to the electrode lead. In an example, the delivery device is rotated toward a position where the first needle is parallel to the skin surface and the tip of the first needle is located below the skin. In an example, rotating the delivery device causes the electrode lead to bend. In an example, the first needle includes a slot, and wherein a portion of the electrode lead passes through the slot when the delivery device is rotated.

[0060] In an example, the method further comprises monitoring the position of the second needle using an ultrasound device.

[0061] In an example, the method further comprises positioning a guide on the patient, the guide having a guide channel defining an insertion direction of the second needle, and the method further comprises positioning the second needle in the guide channel. In an example, the method further comprises removing the guide when the second needle is percutaneously positioned.

[0062] According to another aspect of the present invention, there is also provided a sleep apnea treatment system, comprising: a neurostimulator implant having electrodes; a delivery device for implanting a neurostimulator implant such that an electrode is implanted in the genioglossus muscle of a patient proximal to a branch of the genioglossus nerve; and A guide is positionable on a patient and includes a guide channel configured to receive a portion of a delivery device and define an insertion direction of the delivery device to implant a neurostimulator implant within the genioglossus muscle proximal to a branch of the genioglossus nerve.

[0063] In an example, a neurostimulator implant includes a housing portion and a flexible, elongated electrode lead extending from the housing portion. In an example, a delivery device includes a first needle adapted to hold the housing portion of the neurostimulator implant and a second needle adapted to hold the electrode lead, the second needle having a higher gauge than the first needle and extending beyond the first needle.

[0064] In an example, the second needle is retractable in a direction toward the first needle for implantation of the electrode lead.

[0065] In an example, the guide channel can be moved to align the guide channel with an insertion point on the patient. In an example, the guide channel can be rotated to change the insertion direction. Thus, the guide can be adjusted according to the patient's specific anatomy.

[0066] In an example, the guide also includes an attachment for an ultrasound scanner. The ultrasound scanner can be attached to the guide so that the ultrasound sensor window is directed toward the implantation site for monitoring the position of the neurostimulator implant during implantation.

[0067] In an example, the guide channel includes a slot for removing the guide when the delivery device is percutaneously implanted. Thus, the delivery device can be rotated during implantation, such as after implantation of the electrode.

[0068] In an example, the guide includes a positioning portion that can be positioned against the patient. In an example, the positioning portion is shaped to be positioned on the patient's chin. In an example, the positioning portion is shaped to be received in the patient's mouth. In an example, the positioning portion is configured to engage the patient's mandible. In an example, the positioning portion includes a bracket configured to engage the patient's mandible and the patient's neck and / or shoulders.

[0069] According to another aspect of the present invention, there is provided a guide for a delivery device for percutaneously implanting a neurostimulator implant into the genioglossus muscle of a patient near a branch of the genioglossus nerve, wherein the guide comprises: a positioning portion capable of being positioned against a patient; and A guide channel is configured to receive a portion of a delivery device and define an insertion direction of the delivery device to implant the neurostimulator implant into the genioglossus muscle near a branch of the genioglossus nerve.

[0070] In an example, the delivery device includes a first needle adapted to hold a housing portion of a neurostimulator implant and a second needle adapted to hold an electrode lead, and wherein the guide channel is configured to receive the second needle.

[0071] In an example, the guide channel can be moved to align the guide channel with an insertion point on the patient. In an example, the guide channel can be rotated to change the insertion direction.

[0072] In an example, the guide also includes an attachment for an ultrasound scanner.

[0073] In an example, the guide channel includes a slot for removing the guide when the delivery device is percutaneously implanted.

[0074] In an example, the positioning portion is shaped to be positioned on the chin of the patient. In an example, the positioning portion is shaped to be received in the mouth of the patient. In an example, the positioning portion is configured to engage the mandible of the patient. In an example, the positioning portion includes a cervical collar configured to engage the mandible of the patient and the neck of the patient.

[0075] According to one aspect of the present disclosure, a method for percutaneously implanting one or more neurostimulator implants is provided, so that the electrodes of the neurostimulator implants are implanted near the genioglossus nerve branches, particularly the genioglossus horizontal nerve branches. The percutaneous implantation avoids the submandibular gland and ductal and vascular structures. The neurostimulator implant can be implanted under combined anatomical landmarks and ultrasound guidance.

[0076] According to another aspect of the present disclosure, an integrated biosensor in a neurostimulator implant can detect signs of inspiration to trigger device activation and / or general patient diagnostics. Such biosensors can include bioimpedance or biopotential based sensing devices, whose respective signals are converted into ECG, EMG, EDA formats for interpretation of heart rate, blood pressure, and / or electromyographic detection of inspiratory muscle contraction. The neurostimulator implant can communicate with an external wearable device or an external power supply unit to combine data sets and / or trigger device activation in sync with the patient's natural breathing rate.

[0077] According to one aspect of the present disclosure, a method of treating a patient is provided, comprising: A) detecting a physiological parameter of the patient, and B) activating neural stimulation in synchronization with the patient's respiratory rate. In one example, the method comprises detecting the patient's respiratory rate. In one example, the method comprises stimulating the patient's hypoglossal nerve, particularly the genioglossus nerve branch, in synchronization with the patient's respiratory rate.

[0078] According to another aspect of the present disclosure, an integrated biosensor in a wearable device is used to detect signs of inspiration to trigger device activation and / or general patient diagnostics. Such biosensors may include bioimpedance or biopotential based sensing devices, with respective signals converted into ECG, EMG, EDA formats for interpretation of heart rate, blood pressure and / or electromyographic detection of inspiratory muscle contraction, as well as oxygen, carbon dioxide (to detect signs of hypoxia or anoxia), and the use of microphones and / or accelerometers to detect signs of airway obstruction. BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

[0079] To easily identify the discussion of any particular element or action, the most significant digit(s) in a reference number refers to the figure number in which the element is first introduced.

[0080] Figure 1 The anatomical location of the patient's hypoglossal nerve is shown.

[0081] Figure 2 An example neurostimulator implant for treating sleep apnea is shown.

[0082] Figure 3A Shown for Figure 2 Side view of a first example implant position of a neurostimulator implant.

[0083] Figure 3B Shows Figure 3A Anterior view of an example implant location.

[0084] Figure 4 A front view of a second example implant location with two neurostimulator implants is shown.

[0085] Figure 5A A front view of a third example implant location with three neurostimulator implants is shown.

[0086] Figure 5B Shows Figure 5A Side view of a third example implant position.

[0087] Figure 6 A front view of a fourth example implant location with four neurostimulator implants is shown.

[0088] Figure 7 Shown for implantation Figure 2 An example delivery device for a neurostimulator implant.

[0089] Figure 8 Shows Figure 7 A cross-sectional view of a conveying device.

[0090] Fig.9A Shows Figure 7 A first needle and a second needle of a delivery device.

[0091] Fig. 9B Shows Fig.9A Cross-sectional view of .

[0092] FIG. 10A to FIG. 10L Shows the use of Figure 7 Implantation of delivery device Figure 2 A method of implanting a neurostimulator to target the genioglossus nerve branch of the hypoglossal nerve in a patient.

[0093] Fig.11 Electrode leads of a neurostimulator implant and first and second needles of a delivery device are shown during an implantation method.

[0094] Fig. 12A Example insertion points and insertion orientations for implanting a neurostimulator implant are shown.

[0095] Fig. 12B Shows Fig. 12A Bottom view of the insertion point and insertion orientation shown in .

[0096] Fig. 12C Shows Fig. 12A Side view of the insertion point and insertion orientation shown in .

[0097] Fig.12D The patient's mandibular and muscle planes are shown.

[0098] Fig.12E The measurement of the patient's principal distances using the images is shown.

[0099] Fig.13A Shown for FIG. 10A to FIG. 10L Example guide for implantation method.

[0100] Fig. 13B Shows Fig.13A Details of the sample guide.

[0101] Fig.14A Shows Fig.13A and Fig. 13B An example bootloader with Figure 7 Use of delivery device.

[0102] Fig. 14B Shows Fig.13A and Fig. 13B An example bootloader with Figure 7 Use of delivery device.

[0103] Fig.15A Shows Fig.13A and Fig. 13B An example bootloader with Figure 7 Use of delivery device.

[0104] Fig. 15B Shows Fig.13A and Fig. 13B An example bootstrap with Figure 7 Use of delivery device.

[0105] Fig.16 A guide with a bracket is shown.

[0106] Fig.17 An example guide is shown.

[0107] Fig.18 Another example guide is shown.

[0108] Fig.19 A method of operating a sleep apnea therapy system is shown. Detailed Description

[0109] Figure 1Portions of the nervous system in the area of ​​the head 102 and neck 104 of the patient 100 are shown. As shown, the left hypoglossal nerve 108 is a motor nerve that originates from the obligate medulla of the brainstem and extends toward the chin of the patient 100. The hypoglossal nerve 108 innervates all extrinsic and intrinsic muscles of the tongue, except the palatoglossus. The hypoglossal nerve 108 includes a medial branch 110 and more distal branches. The medial branch of the hypoglossal nerve 108 innervates oral muscles, such as the genioglossus 112, as well as the geniohyoid, styloglossus, and hyoglossus muscles. Some of these muscles cause the tongue to protrude forward, while others cause the tongue to retract. The most distal branches of the hypoglossal nerve 108 form the genioglossus nerve branch 106, which innervates the genioglossus 112. Contraction of the genioglossus 112 causes the tongue to protrude forward. It will be appreciated that the right hypoglossal nerve is present on the contralateral side and has the same anatomical structure.

[0110] As described below, the present invention provides a neurostimulator implant that can be implanted to target the genioglossus nerve branches 106 within the genioglossus muscle 112. The difficulties in providing such an implant are that the active stimulation device (electrode) needs to be implanted close enough to the genioglossus nerve branches 106 for effective stimulation, the neurostimulator implant needs to have the required electronics implanted close enough to the skin surface to send / receive wireless communications, and the neurostimulator implant needs to be oriented so that it can receive wireless power. The neurostimulator implant, delivery device, and implantation procedure described herein address these challenges and provide an implantable system for treating sleep apnea that includes stimulating the genioglossus nerve branches 106 within the genioglossus muscle 112.

[0111] Figure 2 An example neurostimulator implant 200 is shown having a housing portion 202 and electrode leads 204 extending from the housing portion 202. The housing portion 202 can house the electronic components of the neurostimulator implant 200. The electronic components within the housing portion 202 can include a wireless power receiver (e.g., an antenna) and a signal generator. Additionally, the electronic components can include a wireless communicator receiver / transmitter. Additionally, the electronic components can include sensor electronics. In an example, the electronic components can include a printed circuit board (PCB). In an example, the housing portion 202 is hermetically sealed. In an example, the neurostimulator implant 200 is battery-free.

[0112] The electrode lead 204 extends from the housing portion 202 and is flexible. The electrode lead 204 is joined to the housing portion 202 by a lead connector 210. The electrode lead 204 includes at least one electrode 206a, in this example, four electrodes 206a, 206b, 206c, 206d. In other examples, the electrode lead 204 may include one, two, three, five, six or more electrodes. The electrodes 206a, 206b, 206c, 206d are spaced apart from each other at the distal end of the electrode lead 204. The electrodes 206a, 206b, 206c, 206d are connected to the electronic devices in the housing portion 202. The electrodes 206a, 206b, 206c, 206d are metals, preferably platinum-iridium alloys or titanium.

[0113] In an example, the electrodes 206a, 206b, 206c, 206d are operated by an electronic device assembly disposed in the housing portion 202 to provide electrical stimulation to stimulate the patient's nerves. In other examples, the electrodes 206a, 206b, 206c, 206d are operated by an electronic device assembly disposed in the housing portion 202 to sense or detect neural signals. In other examples, the electrodes 206a, 206b, 206c, 206d are operated by an electronic device assembly disposed in the housing portion 202 to detect other (non-neural) parameters of the patient, such as bioimpedance, blood pressure, or heart rate. In an example, at least two of the electrodes 206a, 206b, 206c, 206d may include different materials, particularly different metals, and may be operated to detect differential bioimpedance. In an example, the electrodes 206a, 206b, 206c, 206d are operable to detect neural signals in a first mode and to stimulate the patient's nerves in a second mode. In an example, some of the electrodes 206a, 206b, 206c, 206d are operable to detect neural signals and other electrodes are operable to stimulate nerves. In an example, some of the electrodes 206a, 206b, 206c, 206d are operable to detect / stimulate nerves and other electrodes are operable to sense other (non-neural) parameters. In an example, the neurostimulator implant 200 may be implanted to sense and / or stimulate Figure 1 The hypoglossal nerve 108 is shown, and in particular the genioglossus nerve branch 106 within the genioglossus muscle 112. In other examples, the neurostimulator implant 200 can be implantable to sense and / or stimulate the phrenic nerve and / or the loop cervical nerve. Sensing and stimulating the hypoglossal nerve and / or the phrenic nerve and / or the loop cervical nerve can provide treatment for sleep apnea. In other examples, the neurostimulator implant 200 can be implantable to sense and / or stimulate other nerves, including the greater occipital nerve, the tibial nerve, the sacral nerve (e.g., to treat urinary incontinence), or the vagus nerve (e.g., to regulate pancreatic secretions).

[0114] In an example, in operation, the electrodes 206a, 206b, 206c, 206d of the neurostimulator implant 200 are provided with an electrical signal, such as an electric current, to stimulate a nerve. In an example, the electrical signal may be a voltage-regulated stimulation.

[0115] In other examples, the neurostimulator implant 200 can be additionally operable as a diagnostic implant, such as a neurodiagnostic implant, which is operable to detect one or more neural signals in a nerve. In such an example, the electrodes 206a, 206b, 206c, 206d are operable to detect neural signals. The neural signals can be analyzed for the purpose of detecting, monitoring, and / or diagnosing a condition.

[0116] In other examples, the neurostimulator implant 200 may be additionally operable as a diagnostic implant operable to detect one or more physiological parameters, such as body temperature, heart rate, electromyogram (EMG), electrocardiogram (ECG), respiratory rate, blood pressure, oxygen saturation, and / or blood gas concentration (e.g., oxygen, carbon dioxide, carbon monoxide).

[0117] In an example, the housing portion 202 can have an outer diameter of less than about 5 mm, such as between about 1 mm and about 5 mm, such as between about 1 mm and about 3 mm, such as about 3 mm. The housing portion 202 can have a length of at most about 30 mm, such as at most about 25 mm, such as at most about 20 mm, such as about 20 mm. In an example, the electrode lead 204 can have a diameter of between about 0.3 mm and about 1.5 mm, such as between about 0.5 mm and 1.3 mm, such as about 0.8 mm. The electrode lead 204 can have a length of at most about 200 mm, such as at most about 150 mm, such as at most about 120 mm, such as about 120 mm. The electrodes 206a, 206b, 206c, 206d can each have a length (along the electrode lead 204) of at most about 15 mm, such as at most about 10 mm, such as at most about 5 mm, such as at most about 3 mm. The electrodes 206a, 206b, 206c, 206d may be spaced apart from each other along the electrode lead 204 by at least 2 mm, such as at least 3 mm, such as at least 5 mm.

[0118] However, it will be appreciated that the dimensions of the housing portion 202 will correspond to the dimensions of the electronic device components within the housing portion 202, and the length of the electrode lead 204 will correspond to the anatomy surrounding the target nerve, and thus a shorter or longer electrode lead 204 may be appropriate depending on the depth of the nerve within the patient's tissue.

[0119] Also like Figure 2As shown, the housing portion 202 also includes one or more ring electrodes 208a, 208b, 208c, 208d. The ring electrodes 208a, 208b, 208c, 208d are spaced apart from each other and extend at least partially around the housing portion 202 circumferentially. In this example, the housing portion 202 includes four ring electrodes 208a, 208b, 208c, 208d. In other examples, the housing portion 202 may include one, two, three, five, six or more ring electrodes. The ring electrodes 208a, 208b, 208c, 208d are connected to the electronic devices within the housing portion 202, for example, via a feedthrough. The ring electrodes 208a, 208b, 208c, 208d are metal, preferably a platinum-iridium alloy or titanium.

[0120] In an example, the ring electrodes 208a, 208b, 208c, 208d are operable to sense and / or stimulate nerves of a patient in the same manner as the electrodes 206a, 206b, 206c, 206d described above. In an example, the ring electrodes 208a, 208b, 208c, 208d are operable to detect one or more physiological parameters, such as body temperature, heart rate, electromyogram (EMG), electrocardiogram (ECG), respiratory rate, blood pressure, oxygen saturation, and / or blood gas concentration (e.g., oxygen, carbon dioxide, carbon monoxide).

[0121] Figure 3A and Figure 3B Shows Figure 2 Neurostimulator implants 200 in Figure 1 A first example implant is shown in patient 100. Figure 3A As shown, the neurostimulator implant 200 is implanted under the chin of the patient 100. The electrode lead 204 extends within the genioglossus muscle 112 to the vicinity of the genioglossus nerve branch 106 of the hypoglossal nerve 108, in this example, the genioglossus nerve branch 106 of the right hypoglossal nerve 108. The housing portion 202 is implanted in subcutaneous tissue in the neck 104. As further described below, the housing portion 202 is implanted substantially parallel to the skin of the neck 104. The external device 302 is attached to the neck 104 in alignment with the housing portion 202. The external device 302 can provide wireless power transmission to the neurostimulator implant 200 and / or wireless communication with the neurostimulator implant 200. The external device 302 can be operable to control the neurostimulator implant 200. In a preferred example, the neurostimulator implant 200 is battery-free and the external device 302 provides power for operating the neurostimulator implant 200.

[0122] Figure 3A and Figure 3BThe neurostimulator implant 200 shown can be used to detect and / or treat sleep apnea. For example, the neurostimulator implant 200 can be operable to detect one or more indicators of sleep apnea, such as heart rate, respiratory rate, jaw movement, thoracic movement, diaphragm movement, and / or electromyography (EMG). In particular, one or more of the electrodes 206a, 206b, 206c, 206d and / or one or more of the ring electrodes 208a, 208b, 208c, 208d can be operable to detect one or more indicators of sleep apnea. In an example, the neurostimulator implant 200 can be operable to stimulate the genioglossus nerve branch 106 of the right hypoglossal nerve 108 within the genioglossus muscle 112. In particular, one or more of the electrodes 206a, 206b, 206c, 206d can be operable to stimulate the genioglossus nerve branch 106 of the right hypoglossal nerve 108 within the genioglossus muscle 112. This stimulation results in innervation of the genioglossus muscle 112 to pull the tongue forward (anteriorly) to treat obstructive sleep apnea (OSA). The stimulation may innervate the genioglossus muscle 112 directly (particularly the portion of the genioglossus muscle 112 proximal to the electrode lead 204), and / or the genioglossus nerve branches 106 may be stimulated to innervate the genioglossus muscle 112.

[0123] It will be appreciated that the neurostimulator implant 200 may alternatively be implanted at the other hypoglossal nerve (the left hypoglossal nerve). Stimulation of a single hypoglossal nerve (eg, the right or left hypoglossal nerve 108) may be referred to as unilateral hypoglossal nerve stimulation.

[0124] Figure 4 Shows Figure 2 Neurostimulator implants 200 in Figure 1 Another example implantation in patient 100 is shown. In this example, the first neurostimulator implant 200 is implanted with a reference Figure 3A and Figure 3B The second neurostimulator implant 200 is implanted at the right hypoglossal nerve 402 in the same manner as described above, and the second neurostimulator implant 200 is implanted at the left hypoglossal nerve 404. The neurostimulator implant 200 implanted at the left hypoglossal nerve 404 is implanted at the same manner as described above. Figure 3A and Figure 3B Implantation is performed in the same manner as described above, but the electrode lead 204 is implanted near the left hypoglossal nerve 404.

[0125] As shown, a single external device 302 may be provided to power and / or communicate with both neurostimulator implants 200. Alternatively, different external devices 302 may be provided for the two neurostimulator implants 200. In some examples, the two neurostimulator implants 200 may wirelessly communicate directly with each other, or they may both wirelessly communicate with the external device 302.

[0126] The neurostimulator implant 200 is similar to the reference Figure 3A and Figure 3B The invention also provides a method for controlling the genioglossus muscle 112 and the tongue. The method may be performed in the same manner as described above, for example to detect one or more indicators of sleep apnea, and / or to stimulate the right hypoglossal nerve 402 and the left hypoglossal nerve 404 and / or the genioglossus muscle 112. Such stimulation may result in innervation of the genioglossus muscle 112 to pull the tongue forward (anteriorly) to relieve obstructive sleep apnea (OSA). The stimulation may directly innervate the genioglossus muscle 112 (particularly the portion of the genioglossus muscle 112 proximal to the electrode lead 204), and / or the genioglossus nerve branch 106 may be stimulated to innervate the genioglossus muscle 112.

[0127] Stimulation of both the left hypoglossal nerve 404 and the right hypoglossal nerve 402 may be referred to as bilateral hypoglossal nerve stimulation.

[0128] Figure 5A and Figure 5B Shows Figure 2 Neurostimulator implants 200 in Figure 1 Another example implantation in a patient 100 is shown. In this example, two neurostimulator implants 200 are implanted at the right hypoglossal nerve 402 and the left hypoglossal nerve 404, respectively, as shown in FIG. Figure 4 Optionally, a single neurostimulator implant 200 may be provided at the right hypoglossal nerve 402 or the left hypoglossal nerve 404. A third neurostimulator implant 504 is implanted in the patient's neck, with electrode leads 508 implanted near the phrenic nerves 502 (particularly the right phrenic nerve 502). The neurostimulator implant 504 may be implanted to stimulate the phrenic nerve 502 within the cervical loop, or at a location where the phrenic nerve 502 has branched from the cervical loop. The neurostimulator implant 504 is similar to the reference Figure 2 The neurostimulator implant 200 is the same as described and is implanted to sense and / or stimulate the phrenic nerve 502. The phrenic nerve 502 innervates the diaphragm, and stimulation of the phrenic nerve 502 can trigger inspiration, thereby helping to relieve central sleep apnea (CSA) by improving the regulation of the patient's breathing. Stimulating the phrenic nerve 502 in addition to or in place of the right hypoglossal nerve 402 and the left hypoglossal nerve 404 can provide treatment for combined obstructive sleep apnea (OSA) and central sleep apnea (CSA) or provide treatment for one or the other of obstructive sleep apnea (OSA) and central sleep apnea (CSA).

[0129] like Figure 5A and Figure 5BAs shown, a housing portion 506 of a neurostimulator implant 504 can be implanted in subcutaneous tissue, and an external device 510 can be attached to the patient's skin in alignment with the housing portion 506 to provide wireless power and / or communication to the neurostimulator implant 504. In examples, the external device 510 can be separate from the external device 302, or it can be an antenna for the external device 302. In other examples, the external device 302 can directly power and / or communicate with the neurostimulator implant 504. In examples, each of the neurostimulator implant 200 and the neurostimulator implant 504 can wirelessly communicate with each other, or they can both wirelessly communicate with the external device 302 or each external device 302.

[0130] It will be appreciated that the neurostimulator implant 504 may alternatively be implanted at the other phrenic nerve (the right phrenic nerve).Stimulating a single phrenic nerve (eg, the right phrenic nerve or the left phrenic nerve) may be referred to as unilateral phrenic nerve stimulation.

[0131] Figure 6 Another example is shown in which a second neurostimulator implant 504 is implanted at the left phrenic nerve 602 in addition to the first neurostimulator implant 504 implanted at the right phrenic nerve 604 and the two neurostimulator implants 200 implanted at the right hypoglossal nerve 402 and the left hypoglossal nerve 404, respectively. The second neurostimulator implant 504 may be implanted to stimulate the left phrenic nerve 602 and the right phrenic nerve 604 within the cervical loop, or at a location where the left phrenic nerve 602 and the right phrenic nerve 604 have branched from the cervical loop.

[0132] The external device 510 and / or the external device 302 may provide power to and / or communicate with the second neurostimulator implant 504 as well as the first neurostimulator implant 504 .

[0133] Stimulating the left phrenic nerve 602 and / or the right phrenic nerve 604 in addition to or in lieu of the hypoglossal nerves 402, 404 may provide treatment for combined obstructive sleep apnea (OSA) and central sleep apnea (CSA) or provide treatment for one or the other of obstructive sleep apnea (OSA) and central sleep apnea (CSA).

[0134] Stimulation of both the left phrenic nerve 602 and the right phrenic nerve 604 may be referred to as bilateral phrenic nerve stimulation.

[0135] In some examples, the first and / or second neurostimulator implants 504 may be implanted to stimulate the loop cervical nerve proximal to the phrenic nerve 502 .

[0136] Figure 7 Shown is the Figure 2The neurostimulator implant 200 is implanted in Figures 3A to 6 The delivery device 700 may be used to implant the neurostimulator implant 200 at the phrenic nerve 502 and / or the cervical nerve, such as at any of the hypoglossal nerves 108 shown in FIG. FIG. 5A to FIG. 6 shown.

[0137] like Figure 7 As shown, the delivery device 700 includes a handle 702 and a first needle 704 fixed to the handle 702 and extending from the handle 702. A second needle 706 extends from the first needle 704 in a direction away from the handle 702. The second needle 706 can be retracted relative to the first needle 704 by operating a control slider 708, as further described below. The first needle 704 is larger (has a lower gauge) than the second needle 706. In an example, the first needle 704 can have a gauge number between 6 and 15, such as 10. In an example, the second needle 706 can have a gauge number between 15 and 25, such as 20.

[0138] Figure 8 Shown through Figure 7 A cross-section of the conveying device 700, and Fig.9A and Fig. 9B Details of the first needle 704 and the second needle 706 are shown. The second needle 706 is slidably received in the first needle 704 and extends beyond the first needle 704 away from the handle 702. The second needle 706 can be retracted into the first needle 704 during operation, as described in detail below. The control slide 708 is operable to retract and extend the second needle 706 relative to the first needle 704 and the handle 702. The control slide 708 is operably coupled to the second needle 706 by a rack and pinion transmission mechanism. The rack and pinion transmission mechanism includes a first rack portion 802 coupled to the control slide 708 and extending into the handle 702. The second rack portion 806 is coupled to the second needle 706 and extends into the handle 702. The gear 804 is rotatably mounted in the handle 702 and acts between the first rack portion 802 and the second rack portion 806. Thus, moving the control slide 708 toward the handle 702 will cause the second rack portion 806 and the second needle 706 to move toward the handle 702 , ie, retract the second needle 706 into the first needle 704 .

[0139] like Figure 8As shown, the handle 702 includes a guide portion 810 extending from the handle 702 in a direction opposite to the first needle 704. The control slider 708 can slide along the guide portion 810. The guide portion 810 includes one or more (four in this example) stop positions 808a, 808b, 808c, 808d, which provide predefined operating positions of the control slider 708. The stop positions 808a, 808b, 808c, 808d may include holes or grooves, and the control slider 708 may include a ball detent for engaging the hole or groove to stop the control slider 708 at the stop positions 808a, 808b, 808c, 808d. Thus, the control slide 708 may be moved along the guide portion 810 between different stop positions 808a, 808b, 808c, 808d to move the second needle 706 between different predefined positions during use of the delivery device 700, as will be described in detail below.

[0140] like Figure 8 , Fig.9A and Fig. 9B As shown, Figure 2 The neurostimulator implant 200 is shown housed in a delivery device 700. In particular, the housing portion 202 is housed in a first needle 704, and the electrode lead 204 is housed in a second needle 706. During use, as further described below, in a two-stage implantation process, retraction of the second needle 706 implants the electrode lead 204 into the patient, after which the housing portion 202 can be withdrawn from the first needle 704.

[0141] In this example, the housing portion 202 is oriented so that the lead connector 210 is directed toward the handle 702. The electrode lead 204 extends from the lead connector 210 and covers the housing portion 202 before entering the second needle 706. Figure 7 and Figure 8 As shown, the first needle 704 includes a slot 710 to receive a portion of the electrode lead 204 overlying the housing portion 202 within the first needle 704. The slot 710 advantageously allows the housing portion 202 to be implanted at different angles relative to the electrode lead 204 without applying excessive bending stress to the electrode lead 204, as described below.

[0142] FIG. 10A to FIG. 10L Shows the use of reference Figures 7 to 9B The method of implanting a neurostimulator implant 200 into a patient using a delivery device 700 is described. In this example, the neurostimulator implant 200 is implanted to target a Figure 1 The genioglossus nerve branch 106 of the hypoglossal nerve 108 within the genioglossus muscle 112 is shown.

[0143] like Fig. 10A As shown, originally with reference Figures 7 to 9B The described manner places the neurostimulator implant 200 in the delivery device 700. In particular, the second needle 706 is in an extended position. The ultrasound device 1002 is used to guide the second needle 706 to the genioglossus nerve branch 106 of the hypoglossal nerve 108 during implantation.

[0144] The second needle 706 enters the patient's tissue at an insertion point 1010. The insertion point 1010 is located in the following manner: With the patient's head tilted back and the neck in hyperextension, the operator identifies the posterior edge of the mandibular symphysis at the midline. This point is the insertion point 1010 of the second needle 706. FIG. 13A to FIG. 15B As further described, the insertion point 1010 may be located using a guide 1302 and / or scanning (particularly ultrasound or X-ray).

[0145] The second needle 706 is inserted at the insertion point 1010 in a predefined insertion orientation relative to the patient. In particular, the insertion orientation is defined by two angles: θ and β. FIG. 12A to FIG. 12C The method for determining insertion orientation is described in more detail.

[0146] Once the insertion point 1010 and insertion orientation are determined, the second needle 706 is advanced into the patient's tissue, through the skin 1006 and into the subcutaneous tissue 1004, as shown in FIG. Fig. 10B The second needle 706 is advanced toward the genioglossus muscle 112 , specifically the genioglossus nerve branch 106 of the hypoglossal nerve 108 . The ultrasound device 1002 provides an image of the position of the second needle 706 and can be used to guide the second needle 706 toward the genioglossus nerve branch 106 .

[0147] like Fig. 10C As shown, the position of the second needle 706, and therefore the position of the electrode lead 204, can be tested by partially retracting the second needle 706 to expose at least some of the electrodes 206a, 206b, 206c, 206d on the electrode lead 204. In this example, as shown in enlarged detail, the second needle 706 is retracted to expose electrodes 206c and 206d. Figure 8 , the second needle 706 can be retracted to this position by moving the control slide 708 from the first stop position 808a to the second stop position 808b.

[0148] exist Fig. 10CIn the position shown, the position of the electrode lead 204 can be tested by powering the neurostimulator implant 200. The neurostimulator implant 200 can be powered by a power system disposed in the delivery device 700, or by an external device. The neurostimulator implant 200 can be powered and controlled to provide sensing or stimulation to determine whether the electrode lead 204 is properly positioned relative to the genioglossus nerve branch 106. The test can include monitoring the patient's response to the stimulation of the neurostimulator implant 200.

[0149] like Fig. 10D As shown, if the position of the electrode lead 204 is determined to be unacceptable, the second needle 706 can be re-extended, particularly by moving the control slider 708 back to the first stop position 808a. The delivery device 700 can then be manipulated to move the second needle 706 to a better position relative to the genioglossus nerve branch 106, such as Fig.10E Repositioning the second needle 706 can include rotating the delivery device 700 so that the second needle 706 is more closely aligned with the genioglossus nerve branch 106 .

[0150] Preferably, one end of the electrode lead 204 having electrodes 206a, 206b, 206c, 206d is substantially parallel to the genioglossus nerve branch 106, such that each of the electrodes 206a, 206b, 206c, 206d can be operated to sense and / or stimulate the genioglossus nerve branch 106. Repositioning the second needle 706 can also include percutaneously positioning the tip of the first needle 704 within the patient, for example, in the skin 1006 or subcutaneous tissue 1004.

[0151] Once it is determined that the second needle 706 is properly positioned relative to the genioglossus nerve branch 106 within the genioglossus muscle 112, as shown in FIG. Fig.10E As shown, the second needle 706 can be more fully retracted to implant the electrode lead 204. The second needle 706 can be retracted by moving the control slider 708 to Figure 8 The fourth stop position 808d is shown fully retracted.

[0152] Preferably, if Fig.10F As shown, the retraction of the second needle 706 deploys an anti-migration tine 1008 to anchor the electrode lead 204 in place. In particular, the anti-migration tine 1008 can be a spring tine attached to the electrode lead 204 between the housing portion 202 and the electrodes 206a, 206b, 206c, 206e. Fig. 10CThe anti-displacement tines 1008 are not released during the described position testing. However, when the second needle 706 is more fully retracted, the anti-displacement tines 1008 are released from within the second needle 706 and deployed outwardly to anchor the electrode lead 204 in place.

[0153] like Figure 10G As shown, once the electrode lead 204 has been implanted and preferably anchored, the delivery device 700 is partially withdrawn from the patient's body so that the first needle 704 is removed from the subcutaneous tissue 1004 and the skin 1006. The delivery device 700 can be rotated simultaneously or subsequently. Due to the arrangement of the electrode lead 204 in the second first needle 704 and the second needle 706 and the groove 710 in the first needle 704 (see Figures 7 to 9B ), the slack in the electrode lead 204 allows the delivery device 700 to be retracted and rotated without applying tensile or bending stress to the electrode lead 204. Advantageously, this prevents displacement of the electrode lead 204 from the implanted position. Specifically, as Fig.11 As shown, when the delivery device 700 is rotated, the portion of the electrode lead 204 that initially covers the housing portion 202 within the first needle 704 can move out of the first needle 704 through the slot 710.

[0154] like Figure 10G and Fig. 10H As shown, the delivery device 700 is rotated so that the first needle 704 is closer to parallel to the skin 1006. Advantageously, this allows the housing portion 202 to be implanted at a different angle relative to the electrode lead 204, particularly an angle closer to parallel to the skin 1006.

[0155] like Fig. 10H As shown, once the delivery device 700 has been rotated, the first needle 704 is percutaneously repositioned for implantation into the housing portion 202 .

[0156] like Fig.10I As shown, preferably, the second needle 706 is partially redeployed to help the first needle 704 move through the patient's skin 1006 and subcutaneous tissue 1004. The second needle 706 can be moved by moving the control slider 708 to Figure 8 The third stop position 808c is shown partially retracted.

[0157] like Fig.10J As shown in FIG, the first needle 704 is pushed into the patient's skin 1006 and subcutaneous tissue 1004 at a location for implanting the housing portion 202. During this movement, the electrode lead 204 bends and passes through the slot 710 in the first needle 704, thereby preventing displacement of the implanted end of the electrode lead 204.

[0158] Figure 10K202 is shown withdrawn from the first needle 704. The housing portion 202 is withdrawn from the first needle 704 by moving the control slider 708 toward the handle 702 to the maximum position. In this position, as shown in FIG. Figure 8 As is most clearly shown in FIG. 8 , one end of the first rack portion 802 pushes the housing portion 202 out of the end of the first needle 704, as shown in FIG. Figure 10K When the operator pushes the control slider 708 to the maximum position, the operator can gradually withdraw the delivery device 700 from the patient's tissue so that the housing portion 202 is implanted in the space created by the first needle 704 .

[0159] The delivery device 700 may then be removed from the patient, and Fig.10L An implanted neurostimulator implant 200 is shown. As shown, one end of an electrode lead 204 having an electrode has been implanted and anchored near the genioglossus nerve branch 106 within the genioglossus muscle 112. The housing portion 202 has been implanted in the skin 1006, and the electrode lead 204 is bent between the housing portion 202 and the electrode.

[0160] Advantageously, the housing portion 202 is oriented substantially parallel to the skin 1006, which can facilitate wireless power transmission and / or wireless communication between the housing portion 202 and an external device. Additionally, this implantation location enables the neurostimulator implant 200 to target the genioglossus nerve branches 106 within the genioglossus muscle 112, where minimal tissue suitable for implanting the housing portion 202 exists.

[0161] Therefore, reference FIG. 10A to FIG. 10L The described method advantageously allows for targeting of the neurostimulator implant 200 to the genioglossus nerve branches 106 within the genioglossus muscle 112 using minimally invasive surgery.

[0162] FIG. 12A to FIG. 12C As shown in the reference FIG. 10A to FIG. 10KA method for determining an insertion point 1010 and an insertion orientation 1202 of a delivery device 700 during the described implantation method. The method for determining the insertion point 1010 and the insertion orientation 1202 can be based on Benbassat et al. (Benbassat B, Cambronne C, Gallini A, Chaynes P, Lauwers F, deBonnecaze G. The specific branches leading to the genioglossus muscle: three-dimensional localisation using skin reference points. Surg Radiol Anat. 2020 May; 42(5): 547-555. doi: 10.1007 / s00276-019-02390-w. Epub 2019 Dec 9. PMID: 31820050.).

[0163] Insertion point 1010 is located at the posterior edge of the mandibular symphysis at the midline. The operator can find and mark this point by feeling the mandibular symphysis through the patient's skin. Ultrasound and / or X-ray scanning can provide additional information for locating insertion point 1010.

[0164] like FIG. 12A to FIG. 12C As shown, the insertion orientation is defined by a first angle 1206 in the transverse plane 1204. When the neck 104 is in the hyperextended position, the transverse plane 1204 approximates the muscle plane of the patient's chin, which also approximates the skin plane on the chin, as shown in FIG. Fig.12D 12. The first angle 1206 is positive or negative, depending on whether the left or right hypoglossal nerve is targeted. The first angle 1206 is an angular offset in the transverse plane 1204 relative to the longitudinal plane 1208 of the patient. As described below, the longitudinal plane 1208 is the median or sagittal plane of the patient 100.

[0165] like FIG. 12A to FIG. 12C As shown, the insertion orientation is also defined by a second angle 1210 in the longitudinal plane 1208. The longitudinal plane 1208 is the median (sagittal) plane of the patient and is perpendicular to the transverse plane 1204. The second angle 1210 is an angular offset in the longitudinal plane 1208 from the transverse plane 1204.

[0166] In an example, the first angle 1206 can be between about ±15 degrees and about ±30 degrees, such as between about ±18 degrees and about ±25 degrees, such as between about ±20 degrees and about ±23 degrees. In a specific example, the first angle 1206 can be about ±22 degrees, particularly about ±21.8 degrees.

[0167] In an example, the second angle 1210 can be between about 40 and about 65 degrees, such as between about 45 and about 55 degrees, such as between about 40 and about 50 degrees. In a specific example, the second angle 1210 is, for example, between about 47 and about 49 degrees, particularly about 48.1 degrees.

[0168] However, it will be appreciated that the first angle 1206 and the second angle 1210 may be different for different patients, and the first angle 1206 and the second angle 1210 may be determined for a particular patient prior to an implantation procedure, for example based on ultrasound scan or other scan information.

[0169] In some examples, the insertion depth is also determined. The insertion depth is approximately the distance from the skin to the genioglossus nerve branches 106 within the genioglossus muscle 112. If the insertion depth is determined, it can be based on the following equation defined by Benbassat et al. (Benbassat B, Cambronne C, Gallini A, Chaynes P, Lauwers F, de Bonnecaze G, The specific branches leading to the genioglossus muscle: three-dimensional localisation using skin reference points, Surg Radiol Anat, 2020 May; 42(5): 547-555. doi: 10.1007 / s00276-019-02390-w, Epub 2019 Dec 9, PMID: 31820050.).

[0170]

[0171]

[0172] in: L is the insertion depth.

[0173] GH was the measured variable and was defined as the distance from the posterior edge of the mandibular symphysis to the hyoid bone along the midline (in the transverse plane). Fig.12E Shown in.

[0174] In other examples, the insertion depth can be determined based on medical images (e.g., X-rays or ultrasound scans) prior to the implantation procedure. In other examples, the operator can use a scanner, particularly an ultrasound scanner, to monitor the insertion depth and location. In other examples, the insertion depth is not determined, but the operator can insert the delivery device 700 to a predetermined depth. In other examples, the insertion depth can be tested and / or verified by generating stimulation signals and testing the patient's response to the stimulation signals, and / or by using bioimpedance sensing to detect when the electrode is implanted near a nerve.

[0175] like Fig.12D and Fig.12E As shown, to help determine the proper insertion orientation for a particular patient, a scan, in this case a cephalogram, may be performed prior to the implantation procedure. As shown, the radiograph may be used to determine the angle 1212 between the mandibular plane and the muscle plane on the patient's chin, thereby allowing for proper positioning of the transverse plane 1204 as described above. Additionally, if desired, the transverse plane 1204 may be positioned as described above. Fig.12E The variable GH is shown measured from radiographs.

[0176] FIG. 13A to FIG. 15B Shown for reference FIG. 10A to FIG. 10L The first example guide 1302 in the implantation method described. Fig.13A and Fig. 13B As shown, the guide 1302 includes a positioning portion 1304 that is shaped to fit the patient's chin for positioning the guide 1302 relative to the patient. The positioning portion 1304 is mounted on a track 1306 via a slider 1308, and the ultrasound device 1002 is also attached to the track 1306. Therefore, the position of the positioning portion 1304 is adjustable relative to the ultrasound device 1002. In this way, the ultrasound sensor window 1310 of the ultrasound device 1002 is properly positioned relative to the patient during implantation.

[0177] like Fig. 13B As shown, track 1306 includes Figure 7 The guide channel 1312 of the second needle 706 of the delivery device 700 is shown. The size and shape of the guide channel 1312 are determined to be defined for reference FIG. 10A to FIG. 10F The insertion point and insertion orientation of the second needle 706 for implanting the neurostimulator implant 200 at the genioglossus nerve branch 106 of the hypoglossal nerve 108. The guide channel 1312 includes a guide channel 1312 for inserting the second needle 706 at the reference Figure 10G The rotating delivery device 700 previously removes the groove 1314 of the guide 1302. Thus, the guide 1302 is used to guide the second needle 706 to the insertion point 1010 (see Fig. 10A) and maintain the insertion orientation until the second needle 706 is properly positioned relative to the genioglossus nerve branch 106.

[0178] The track 1306 may be moved based on the image obtained from the ultrasound device 1002 to align the guide channel 1312 with the insertion point. Fig.14A and Fig. 14B As shown, the slider 1308 includes a locking member 1402 for fixing the position of the positioning portion 1304 along the track 1306 once the guide channel 1312 has been aligned with the insertion point. Thus, the guide 1302 is adjustable for a particular patient.

[0179] Track 1306 includes a guide channel portion 1404 through which guide channel 1312 extends. As described above, guide channel 1312 thereby defines an insertion orientation for second needle 706.

[0180] Specifically, Fig.15A and Fig. 15B As shown, the insertion orientation is determined based on the reference FIG. 12A to FIG. 12C The described method determines the first angle 1206 and the second angle 1210 defined.

[0181] According to reference FIG. 12A to FIG. 12C In the method described, the first angle 1206 can be between about ±15 degrees and about ±30 degrees, such as between about ±18 degrees and about ±25 degrees, such as between about ±20 degrees and about ±23 degrees. In a specific example, the first angle 1206 can be about ±22 degrees, particularly about ±21.8 degrees. In the example, the guide 1302 is adjustable so that the first angle 1206 defined by the guide channel portion 1404 can be adjusted, such as within the above range.

[0182] In an example, the second angle 1210 can be between about 40 degrees and about 60 degrees, such as between about 45 degrees and about 55 degrees, such as between about 40 degrees and about 50 degrees. In a specific example, the second angle 1210 is, for example, between about 47 degrees and about 49 degrees, particularly about 48.1 degrees. In an example, the guide 1302 is adjustable so that the second angle 1210 defined by the guide channel portion 1404 can be adjusted, such as within the above range.

[0183] Before use, a scan (e.g., such as Fig.12D and Fig.12E ) to determine the appropriate first angle 1206 and second angle 1210.

[0184] Figures 16 to 18 Additional examples of guides 1602 , 1702 , 1802 are shown.

[0185] exist Fig.16 In the example of FIG. 1 , the guide 1602 includes a bracket 1604 positionable between a patient's mandible 1606 and neck / shoulder 1608. A guide channel portion 1610 having a guide channel is mounted to the bracket 1604 via a mounting portion 1612. The mounting portion 1612 is movably mounted to the bracket 1604 so that the position and orientation of the guide channel portion 1610 is adjustable.

[0186] Advantageously, the support 1604 is positioned against the patient's mandible 1606 so that the mandibular plane and the muscle plane (see Fig.12D ) are less significant. In addition, guide 1602 allows the operator to fully adjust the position and orientation of guide channel portion 1610, and therefore also the position and orientation of delivery device 700, to provide an optimal position and orientation for insertion of delivery device 700. Bracket 1604 is also advantageously used to limit patient movement during implantation.

[0187] exist Fig.17 In the example of , the guide 1702 includes a mouthpiece 1704. The mouthpiece 1704 is inserted into the patient's mouth and is firmly fixed there by the patient biting the mouthpiece 1704. The mouthpiece 1704 extends over the patient's chin and includes a guide channel portion 1706 located approximately at the rear edge of the mandibular symphysis. The guide channel portion 1706 can be movably mounted (e.g., rotatably mounted) to the mouthpiece 1704 to provide adjustability of the position and orientation of the guide channel portion 1706. The ultrasound device 1002 is also mounted to the guide 1702 in a manner similar to that described above. The ultrasound device 1002 is attached to the guide 1702 so that it is directed toward the patient to image the implant position during use.

[0188] In this example, a first inclinometer 1708 is provided on the ultrasound device 1002. The first inclinometer 1708 measures the inclination of the ultrasound device 1002. During use, based on the ultrasound image obtained by the ultrasound device 1002, the ultrasound device 1002 is moved so that it is substantially parallel to the transverse plane (1204, see FIG. 12A to FIG. 12C ). A second inclinometer 1710 is disposed on the guide channel portion 1706. Thus, the angular difference between the angle measurement at the first inclinometer 1708 and the insertion point 1010 gives the angular offset between the transverse plane and the guide channel portion 1706. In this manner, the guide channel portion 1706 can be properly positioned and oriented for implantation.

[0189] exist Fig.18In the example of , the guide 1802 includes a mouthpiece 1804. The mouthpiece 1804 is inserted into the patient's mouth and is firmly held there by the patient biting the mouthpiece 1804. The mouthpiece 1804 extends over the patient's chin and includes a guide channel portion 1806 located approximately at the rear edge of the mandibular symphysis. In this example, the guide channel portion 1806 is fixedly mounted to the mouthpiece 1804, and the guide 1802 does not provide adjustability of the insertion position and orientation. However, the guide 1802 can be configured for a specific patient, such as by 3D printing based on an earlier scan. Alternatively, multiple guides 1802 of different sizes and dimensions can be provided, and the most appropriate guide 1802 can be selected based on the scan.

[0190] Fig.19 A neurostimulator implant system 1900 is shown, which includes a hypoglossal nerve stimulator implant 1904, a phrenic nerve neurostimulator implant 1906, and a continuous positive airway pressure device CPAP device 1908. The hypoglossal nerve stimulator implant 1904 may include a phrenic nerve neurostimulator implant 1906, and a continuous positive airway pressure device CPAP device 1908. FIG. 3A to FIG. 4 The one or two neurostimulator implants 200. The phrenic nerve neurostimulator implant 1906 may include a FIG. 5A to FIG. 6 The one or two neurostimulator implants 504 can stimulate the phrenic nerve and / or the cervical nerve. The CPAP device 1908 is a separate device and is not an implanted device. The CPAP device 1908 includes a pump and a mask worn over the patient's mouth and nose, and is operable to provide continuous positive air pressure to the patient to assist breathing and help regulate the breathing rate.

[0191] The neurostimulator implant system 1900 also includes a controller 1902. The controller 1902 may be provided in an external device, such as Figures 3A to 6 Alternatively, the controller 1902 may be part of at least one of the neurostimulator implants, or may be provided in a separate device, such as a computing device that communicates with the neurostimulator implants 1904, 1906 and the CPAP device 1908.

[0192] The neurostimulator implant system 1900 also includes a sensor 1910. The sensor 1910 is arranged to detect at least one indicator of sleep apnea. The sensor 1910 may include one or more sensors. In an example, the sensor 1910 is arranged to detect at least one of the following items: respiratory rate, heart rate, jaw movement, thoracic movement, diaphragm movement, oxygen saturation, and / or EMG. The sensor 1910 can be disposed in one or more of the neurostimulator implants 1904, 1906, and / or the sensor 1910 can be disposed in the CPAP device 1908, and / or the sensor 1910 can be disposed in the external device 302, 510, and / or the sensor 1910 can be a separate sensor that can be attached to the patient at different locations.

[0193] The controller 1902 is configured to operate the hypoglossal nerve stimulator implant 1904 and / or the phrenic nerve neurostimulator implant 1906 and / or the CPAP device 1908 in response to an apnea event detected by the sensor 1910. The controller 1902 may be configured to determine whether the apnea event may be classified as OSA, CSA, or a combination of OSA and CSA based on data provided by the sensor 1910. The controller 1902 may be configured to operate one or more of the hypoglossal nerve stimulator implant 1904, the phrenic nerve neurostimulator implant 1906, and / or the CPAP device 1908 based on the classification of the apnea event.

[0194] For example, in the event that the controller 1902 detects an OSA event, the controller 1902 can be configured to operate the hypoglossal nerve stimulator implant 1904 to stimulate the left genioglossus nerve branch 106 and / or the right genioglossus nerve branch 106. Such stimulation can cause tongue protrusion and relieve OSA.

[0195] In another example, if the controller 1902 detects a CSA event, the controller 1902 can be configured to operate the phrenic nerve neurostimulator implant 1906 to stimulate the phrenic nerve. Figure 6 The left phrenic nerve 602 and / or the right phrenic nerve 604 (and / or the loop cervical nerve) are shown. Such stimulation may relieve CSA.

[0196] Additionally or alternatively, in the event that the controller 1902 detects an OSA event, the controller 1902 can be configured to operate the CPAP device 1908 to provide positive air pressure and regulate the patient's breathing rate. Such positive air pressure can alleviate OSA.

[0197] In another example, where the controller 1902 detects a combined OSA and CSA event, the controller 1902 can be configured to operate the hypoglossal nerve stimulator implant 1904 to stimulate at least one of the right hypoglossal nerve 402 and the left hypoglossal nerve 404, and also operate the phrenic nerve neurostimulator implant 1906 to stimulate at least one of the left phrenic nerve 602 and the right phrenic nerve 604 (and / or the loop cervical nerve). This combined stimulation can alleviate the apnea event. Additionally or alternatively, the controller 1902 can be configured to control the CPAP device 1908 to provide continuous positive air pressure to the patient to further alleviate the apnea event.

[0198] Advantageously, the neurostimulator implant system 1900 can thereby use information from one or more sensors 1910 to determine the onset or presence of sleep apnea and determine the classification of sleep apnea (i.e., OSA, CSA, or a combination of OSA and CSA). Different forms and combinations of neurostimulation and positive air pressure therapy can then be provided to alleviate sleep apnea.

[0199] In an example, the therapy delivered by the neurostimulator implant system 1900 can be modulated with respect to amplitude and / or frequency. Specifically, in some examples, the CPAP device 1908 and / or the hypoglossal nerve stimulator implant 1904 and / or the phrenic nerve neurostimulator implant 1906 can be operated via a sequential pulse sequence, whereby each sequence, pulse train, and pulses (within each pulse train) can be individually modulated according to a determined therapy. In addition, the start time, stop time, and any delay time can be adjusted as needed based on information provided by the sensor 1910. Adjustments to the therapy can be made manually and / or automatically in response to information provided by the sensor 1910.

[0200] In some examples, the sensor 1910 detects jaw movement (e.g., rotational movement of the mandible), and the neurostimulator implant system 1900 configures therapy provided by the hypoglossal nerve stimulator implant 1904, the phrenic nerve neurostimulator implant 1906, and / or the CPAP device 1908 based on the detected jaw movement. In such examples, the sensor 1910 may include a gyroscope and / or an accelerometer and / or a magnetometer, which may be in one or more of the hypoglossal nerve stimulator implant 1904 or the phrenic nerve neurostimulator implant 1906, and / or in an external device, and / or in a separate sensor unit. Based on the detected jaw movement, the therapy may be configured to have different periods and / or frequencies and / or amplitudes and / or durations, and / or different combinations of positive air pressure and neurostimulation.

[0201] In some examples, sensor 1910 is arranged to detect other movements, such as chest movement and / or head movement, in a similar manner as described above. Therapy can be configured in the same manner as described above based on the detected chest and / or head movement, in particular by adjusting the period, frequency and / or amplitude and / or duration and / or different combinations of positive air pressure and neural stimulation based on the detected movement.

[0202] In some examples, sensor 1910 is arranged to detect oxygen saturation and / or EMG. In such examples, therapy can be configured based on oxygen saturation and / or EMG by adjusting the period and / or frequency and / or amplitude and / or duration and / or different combinations of positive air pressure and neural stimulation based on the detected oxygen saturation and / or EMG.

[0203] In some examples, sensor 1910 is arranged to detect the patient's respiratory rate, in particular a decay in the respiratory rate. In such examples, therapy can be configured in the same manner as described above based on the detected respiratory rate. In particular, based on the detected respiratory rate, therapy can be configured to have different periods and / or frequencies and / or amplitudes and / or durations, and / or different combinations of positive air pressure and neural stimulation. In some examples, therapy (in particular positive air pressure and / or neural stimulation) can be provided synchronously with the patient's respiratory rate detected by sensor 1910. In an example, therapy (in particular, positive air pressure and / or neural stimulation) can be provided at a predetermined respiratory rate in order to regulate the patient's respiratory rate.

[0204] In some examples, the controller 1902 is configured to configure therapy such that the CPAP device 1908 and / or the hypoglossal nerve stimulator implant 1904 and / or the phrenic nerve neurostimulator implant 1906 operate at a particular phase of the respiratory cycle. For example, one or more may be activated during the inspiratory cycle and deactivated during exhalation, or vice versa. In some examples, the controller 1902 is configured to operate the hypoglossal nerve stimulator implant 1904 and / or the phrenic nerve neurostimulator implant 1906 and / or the CPAP device 1908 synchronously (in phase with each other or out of phase with each other). For example, neural stimulation may be provided at the beginning of the inspiratory cycle, and positive air pressure may be provided during the inspiratory cycle.

[0205] In an example, the sensor 1910 is configured to continuously or intermittently detect one or more parameters of the patient, and the controller 1902 is configured to continuously or intermittently (re)configure the therapy provided to the patient. This provides a closed loop system for treating sleep apnea.

[0206] In an example, the controller 1902 can be configured to operate the hypoglossal nerve stimulator implant 1904, the phrenic nerve nerve stimulator implant 1906, and / or the CPAP device 1908 in response to detected respiratory decline, a detected respiratory rate falling below a threshold, detection of one or more indicators of sleep apnea (e.g., based on detected respiratory decline and / or jaw, chest and / or head movement and / or oxygen saturation and / or EMG).

[0207] In the various examples described above, the neurostimulator implant 200 provides neurostimulation to nerves, particularly to the genioglossus nerve branches 106 and / or the phrenic nerve 502 and / or the loop cervical nerve. The stimulation provided by the electrodes 206a, 206b, 206c, 206d of the neurostimulator implant 200 is based on a stimulation signal generated by a signal generator within the housing portion 202. The stimulation signal characteristics may be determined by the signal generator in the neurostimulator implant 200, or they may be determined by an external controller and transmitted to the neurostimulator implant 200.

[0208] The stimulation signal may include random signal generation combining high frequencies and low frequencies. The high-frequency and low-frequency stimulation signals may be generated sequentially or simultaneously. Depending on whether the stimulation is directed to a muscle or a nerve, the stimulation signal may have a frequency in a range between 2 Hz and 1500 Hz. In one example, the stimulation signal may include a low-frequency component for stimulating a muscle (e.g., the genioglossus muscle). In such an example, the low-frequency component may have a frequency between 2 Hz and 150 Hz. In an example, the stimulation signal may have a high-frequency component for stimulating a nerve (e.g., a branch of the genioglossus nerve). In such an example, the high-frequency component may have a frequency between 20 Hz and 1500 Hz.

[0209] In some examples, the stimulation signal has a variable pulse width. The pulse width can be between 20 microseconds and 10,000 microseconds. The pulse can be charge balanced. The stimulation signal can be unipolar, bipolar, or a combination of unipolar and bipolar. The amplitude of the stimulation signal can be up to 10.5 V in amplitude and up to 25 mA in amplitude.

[0210] In an example, an electrode that provides a stimulation signal to a nerve or muscle may be operated as an anode or a cathode. The neurostimulator implant may be controllable to change between anodal stimulation and cathodal stimulation.

[0211] Throughout the description and claims of this specification, the words "comprise" and "contain" and their variations mean "including but not limited to", and they are not intended to (and do not) exclude other components, integers or steps. Throughout the description and claims of this specification, the singular encompasses the plural, unless the context requires otherwise. In particular, where the indefinite article is used, this specification should be understood as contemplating the plural as well as the singular, unless the context requires otherwise.

[0212] Features, integers, characteristics or combinations described in conjunction with a particular aspect, embodiment or example of the invention will be understood to be applicable to any other aspect, embodiment or example described herein unless incompatible therewith. All features disclosed in this specification (including any accompanying claims, abstract and drawings) and / or all steps of any method or process so disclosed may be combined in any combination, except combinations where at least some of such features and / or steps are mutually exclusive. The invention is not limited to the details of any foregoing embodiments. The invention extends to any novel one or any novel combination of features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one or any novel combination of steps of any method or process so disclosed.

Claims

1. A method of treating sleep apnea in a patient, the method comprising operating an implanted neurostimulator implant to stimulate branches of the hypoglossal nerve.

2. The method according to claim 1, wherein: The method includes operating the implanted neurostimulator implant to stimulate the genioglossus nerve branches and / or the genioglossus muscle.

3. The method according to claim 2, wherein: The implanted neurostimulator implant is operated to stimulate the genioglossus nerve branches with a first stimulation signal and to stimulate the genioglossus muscle with a second stimulation signal.

4. The method according to claim 2 or 3, wherein: The implanted neurostimulator implant is operated to stimulate the genioglossus muscle with a stimulation signal having a frequency between about 2 Hz and about 150 Hz, for example between about 2 Hz and about 100 Hz, for example between about 2 Hz and about 50 Hz, for example between about 2 Hz and about 40 Hz, for example between about 2 Hz and about 30 Hz, for example between about 2 Hz and about 20 Hz, for example between about 2 Hz and about 15 Hz, for example between about 2 Hz and about 10 Hz.

5. The method according to claim 4, wherein: The stimulation signal for stimulating the genioglossus muscle has a peak amplitude between 0.1 mA and 10 mA, for example between 0.1 mA and 5 mA.

6. The method according to any one of claims 2 to 5, wherein: The implanted neurostimulator implant is operated to stimulate the genioglossus nerve branches with a stimulation signal having a frequency between about 20 Hz and about 1500 Hz, for example between about 20 Hz and about 1000 Hz, for example between about 20 Hz and about 500 Hz, for example between about 20 Hz and about 400 Hz, for example between about 20 Hz and about 300 Hz, for example between about 20 Hz and about 200 Hz, for example between about 20 Hz and about 150 Hz, for example between about 20 Hz and about 100 Hz.

7. The method according to any one of claims 2 to 6, wherein: Stimulation of the genioglossus nerve branches and / or the genioglossus muscle comprises a stimulation signal having a plurality of pulses, each pulse having a pulse width between 30 microseconds and 2000 microseconds.

8. The method according to any one of claims 2 to 7, wherein: The neurostimulator implant includes an electrode lead having electrodes, and wherein the method includes implanting the electrode lead in the genioglossus muscle of the patient proximal to a branch of the genioglossus nerve.

9. The method according to claim 8, wherein: The neurostimulator implant also includes a housing portion, and wherein the electrode leads extend from the housing portion, and wherein the method includes implanting the housing portion in subcutaneous tissue of a patient.

10. The method of any one of claims 1 to 9, further comprising transmitting wireless power from an external device to the implanted neurostimulator implant.

11. The method according to claim 10, wherein: The wireless power transmitted to the implanted neurostimulator implant includes frequencies between 300 MHz and 3 GHz, such as between 400 MHz and 2.5 GHz, such as between 433 MHz and 2.4 GHz.

12. The method according to any one of claims 1 to 11, further comprising detecting at least one physiological parameter by means of a sensor, such as at least one of the following: The patient's breathing rate, The patient's electromyography (EMG) The patient's electrocardiogram (ECG). The patient's oxygen saturation, The patient's temperature, The patient's heart rate, The patient's blood pressure.

13. The method according to any one of claims 1 to 12, further comprising detecting at least one movement of the patient by a sensor, such as at least one of the following: The patient's breathing movements, The patient's jaw movement, The patient's chest movement, The patient's diaphragm moves.

14. The method according to any one of claims 1 to 13, further comprising detecting by a sensor a physiological parameter or movement of the patient indicative of sleep apnea, such as at least one of the following: Decline in respiratory rate, Electromyography (EMG) curves indicating sleep apnea, ECG curve indicating sleep apnea, Decreased oxygen saturation, Increased body temperature, Increased heart rate, Increased blood pressure, or Breathing movement, jaw movement, rib cage movement or diaphragm movement.

15. The method according to any one of claims 12 to 14 further comprises controlling the neurostimulator implant to stimulate the genioglossus nerve branches and / or the genioglossus muscle in response to at least one detected physiological parameter of the patient and / or at least one detected movement of the patient.

16. The method according to any one of claims 12 to 15, comprising detecting the patient's breathing rate by means of a sensor and stimulating the genioglossus nerve branches and / or the genioglossus muscle in synchrony with the detected breathing rate.

17. The method of claim 16, comprising stimulating the genioglossus nerve branches and / or the genioglossus muscle at the onset of the patient's inspiratory cycle.

18. The method according to any one of claims 12 to 17, further comprising determining a classification of sleep apnea based on at least one detected physiological parameter and / or at least one movement of the patient, in particular whether the detected sleep apnea includes obstructive sleep apnea OSA, central sleep apnea CSA or a combination of OSA and CSA.

19. The method of claim 18, further comprising operating an implanted second neurostimulator implant to stimulate the patient's phrenic nerve and / or loop cervical nerve.

20. The method of claim 18 or 19, further comprising operating a continuous positive airway pressure (CPAP) device to provide positive air pressure to the patient's airway.

21. The method according to claim 19 or 20 further comprises controlling the or each neurostimulator implant, and optionally the CPAP device, based on at least one detected physiological parameter of the patient and / or at least one detected movement of the patient.

22. The method of any one of claims 18 to 20, further comprising operating the neurostimulator implant and / or the second neurostimulator implant and / or the CPAP device based on the determined classification of sleep apnea.

23. The method according to claim 22, comprising: If the classification of sleep apnea is determined to be obstructive sleep apnea OSA, the neurostimulator device is operated to stimulate the genioglossus nerve branches and / or the genioglossus muscle.

24. The method according to claim 22 or 23, comprising: If the classification of sleep apnea is determined to be central sleep apnea CSA, the second neurostimulator implant is operated to stimulate the phrenic nerve and / or the cervical nerve.

25. A method according to any one of claims 22 to 24, comprising: If the classification of sleep apnea is determined to be obstructive sleep apnea OSA, the CPAP device is operated to provide positive air pressure to the patient.

26. A method according to any one of claims 22 to 25, comprising: If the classification of sleep apnea is determined to be a combination of obstructive and central sleep apnea, then the procedure is: the nerve stimulator device to stimulate the genioglossus nerve branches and the genioglossus muscle, and At least one of the following: The second neurostimulator implant is used to stimulate the phrenic nerve and / or the cervical nerve, and the CPAP device for providing positive air pressure to the patient.

27. The method according to any one of claims 12 to 26, wherein: The sensor is integrated with the neurostimulator implant.

28. A system for treating sleep apnea in a patient, the system comprising a neurostimulator implant implantable in proximity to a branch of a hypoglossal nerve of the patient and operable to stimulate the branch of the hypoglossal nerve.

29. The system of claim 28, wherein: The implanted neurostimulator implant is operable to stimulate branches of the genioglossus nerve and / or the genioglossus muscle of the patient.

30. The system of claim 29, wherein: The neurostimulator implant includes an electrode implantable into the genioglossus muscle of a patient near branches of the genioglossus nerve and a signal generator for generating stimulation signals to stimulate the branches of the genioglossus nerve and / or the genioglossus muscle of the patient.

31. The system of claim 29, wherein: The neurostimulator implant is a battery-free implant and includes a wireless power receiver.

32. The system of claim 31 , further comprising an external device comprising a wireless power transmitter for transmitting wireless power to the neurostimulator implant when the neurostimulator implant is implanted in the genioglossus muscle.

33. The system according to claim 28 or 32, further comprising a sensor arranged to detect at least one physiological parameter of the patient and / or at least one movement of the patient.

34. The system of claim 33, wherein: The at least one physiological parameter includes one or more of the following: The patient's breathing rate, The patient's electromyography (EMG) The patient's electrocardiogram (ECG). The patient's oxygen saturation, The patient's temperature, The patient's heart rate, The patient's blood pressure.

35. A system according to claim 33 or 34, wherein: The at least one movement of the patient comprises at least one of the following: The patient's breathing movements, The patient's jaw movement, The patient's chest movement, The patient's diaphragm moves.

36. The system according to any one of claims 33 to 35, further comprising a controller configured to determine the onset or occurrence of sleep apnea based on the detected physiological parameters and / or detected movements of the patient, such as at least one of: Decline in respiratory rate, Electromyography (EMG) curves indicating sleep apnea, ECG curve indicating sleep apnea, Decreased oxygen saturation, Increased body temperature, Increased heart rate, Increased blood pressure, or Breathing movement, jaw movement, rib cage movement or diaphragm movement.

37. The system of any one of claims 28 to 36, further comprising a second neurostimulator implant implantable to stimulate the patient's phrenic nerve and / or cervical nerve.

38. The system of any one of claims 28 to 37, further comprising a continuous positive airway pressure (CPAP) device operable to provide positive air pressure to the patient.

39. A system according to any one of claims 33 to 38, further comprising a controller configured to control the or each neurostimulator implant, and optionally the CPAP device, based on at least one detected physiological parameter of the patient and / or at least one detected movement of the patient.

40. A system according to any one of claims 33 to 39, wherein: The controller is configured to determine a classification of sleep apnea based on at least one detected physiological parameter and / or at least one movement of the patient, in particular whether the detected sleep apnea includes obstructive sleep apnea OSA, central sleep apnea CSA or a combination of OSA and CSA.

41. The system of claim 40, wherein: The controller is configured to operate the neurostimulator implant and / or the second neurostimulator implant and / or the CPAP device based on the determined classification of sleep apnea.

42. A method of implanting a neurostimulator implant into a patient for treating sleep apnea, wherein the neurostimulator implant comprises a housing portion and a flexible elongated electrode lead extending from the housing portion and having electrodes, the method comprising: providing a delivery device having a first needle holding the housing portion of the neurostimulator implant and a second needle holding the electrode lead, wherein the second needle has a higher gauge than the first needle, wherein the second needle extends beyond the first needle, and wherein the second needle is retractable in a direction toward the first needle, Insert the second needle into the patient at an insertion point below the patient's chin, advancing the second needle through tissue of the patient in an insertion direction toward the genioglossus muscle of the patient, retracting the second needle to implant the electrode lead having the electrode into the genioglossus muscle near a branch of the genioglossus nerve when the second needle is in the genioglossus muscle of the patient, and The housing portion is withdrawn from the first needle to implant the housing portion beneath the skin.

43. The method of claim 42, wherein: The insertion point is proximal to the posterior edge of the patient's mandibular symphysis.

44. The method according to claim 42 or 43, wherein: The insertion direction includes a first angle β in the mandibular plane of the patient's chin and a second angle θ in the sagittal plane of the patient.

45. The method of claim 44, wherein: The first angle β is between about ±15 degrees and about ±30 degrees, such as between about ±18 degrees and about ±25 degrees, such as between about ±20 degrees and about ±23 degrees, such as about ±22 degrees, in particular about ±21.8 degrees.

46. ​​The method according to claim 44 or 45, wherein: The second angle is between about 40 degrees and about 65 degrees, such as between about 45 degrees and about 55 degrees, such as between about 40 degrees and about 50 degrees, such as between about 47 degrees and about 49 degrees, in particular about 48.1 degrees.

47. A method according to any one of claims 44 to 46, comprising scanning a patient and determining the insertion direction based on the scan.

48. The method of any one of claims 42 to 47, further comprising rotating the delivery device prior to withdrawing the housing portion from the first needle so that the housing portion is implanted in a different orientation relative to an electrode lead.

49. The method of claim 48, wherein: The delivery device is rotated toward a position where the first needle is parallel to the skin surface and the tip of the first needle is positioned beneath the skin.

50. The method of claim 48 or 49, wherein: Rotating the delivery device causes the electrode lead to bend.

51. The method of claim 50, wherein: The first needle includes a slot, and wherein a portion of the electrode lead passes through the slot when the delivery device is rotated.

52. The method of any one of claims 42 to 51 further comprising monitoring the position of the second needle using an ultrasonic device.

53. The method of any one of claims 42 to 52, further comprising positioning a guide on a patient, the guide having a guide channel defining the insertion direction of the second needle, and the method further comprising positioning the second needle in the guide channel.

54. The method of claim 53, further comprising removing the guide when the second needle is percutaneously positioned.

55. A sleep apnea treatment system comprising: a neurostimulator implant, the neurostimulator implant comprising an electrode; a delivery device for implanting the neurostimulator implant such that the electrode is implanted in the genioglossus muscle of the patient near a branch of the genioglossus nerve; and A guide is positionable on a patient and includes a guide channel configured to receive a portion of the delivery device and define an insertion direction of the delivery device to implant the neurostimulator implant into the genioglossus muscle proximal to a branch of the genioglossus nerve.

56. The sleep apnea treatment system of claim 55, wherein: The neurostimulator implant includes a shell portion and a flexible, elongated electrode lead extending from the shell portion, and wherein the delivery device includes a first needle adapted to hold the shell portion of the neurostimulator implant and a second needle adapted to hold the electrode lead, the second needle having a higher gauge than the first needle and extending beyond the first needle.

57. The sleep apnea treatment system of claim 56, wherein: The second needle is retractable in a direction toward the first needle for implantation of the electrode lead.

58. A sleep apnea treatment system according to any one of claims 55 to 57, wherein: The guide channel is movable to align the guide channel with an insertion point on a patient.

59. A sleep apnea treatment system according to any one of claims 55 to 58, wherein: The guide channel is rotatable to change the insertion direction.

60. A sleep apnea treatment system according to any one of claims 55 to 59, wherein: The guide also includes attachments for an ultrasound scanner.

61. A sleep apnea treatment system according to any one of claims 55 to 60, wherein: The guide channel includes a slot for removing the guide when the delivery device is percutaneously implanted.

62. A sleep apnea treatment system according to any one of claims 55 to 61, wherein: The guide includes a positioning portion positionable against a patient.

63. The sleep apnea treatment system of claim 62, wherein: The locating portion is shaped to be located on the chin of a patient.

64. The sleep apnea treatment system of claim 62, wherein: The locating portion is shaped to be received in the mouth of a patient.

65. The sleep apnea treatment system of claim 62, wherein: The positioning portion is configured to engage a mandible of the patient.

66. The sleep apnea treatment system of claim 63, wherein: The positioning portion includes a bracket configured to engage the patient's mandible and the patient's neck.

67. A guide for a delivery device for percutaneously implanting a neurostimulator implant into the genioglossus muscle of a patient near a branch of the genioglossus nerve, wherein: The guide member comprises: a positioning portion positionable against a patient; and A guide channel is configured to receive a portion of the delivery device and define an insertion direction of the delivery device to implant the neurostimulator implant into the genioglossus muscle near a branch of the genioglossus nerve.

68. The guide member of claim 67, wherein: The delivery device includes a first needle adapted to hold a housing portion of the neurostimulator implant and a second needle adapted to hold an electrode lead, and wherein the guide channel is configured to receive the second needle.

69. A guide according to claim 67 or 68, wherein The guide channel is movable to align the guide channel with an insertion point on a patient.

70. A guide according to any one of claims 67 to 69, wherein The guide channel is rotatable to change the insertion direction.

71. A guide according to any one of claims 67 to 70, wherein The guide also includes attachments for an ultrasound scanner.

72. A guide according to any one of claims 67 to 71, wherein The guide channel includes a slot for removing the guide when the delivery device is percutaneously implanted.

73. A guide according to any one of claims 67 to 72, wherein The locating portion is shaped to be located on the chin of a patient.

74. A guide according to any one of claims 67 to 73, wherein The locating portion is shaped to be received in the mouth of a patient.

75. A guide according to any one of claims 67 to 74, wherein The positioning portion is configured to engage a mandible of the patient.

76. The guide of claim 75, wherein: The positioning portion includes a bracket configured to engage the patient's mandible and the patient's neck.

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