Implantable device for selective stimulation in peripheral nerves, and system using the implantable device in obstructive sleep apnea therapy

Abstract

The invention relates to an implantable stimulation device (1) for implantation in a human body and for stimulation of a nervous tissue, wherein the implantable stimulation device (1) comprises at least one stimulation unit (2), wherein the stimulation unit (2) comprises at least three ring level electrodes (4) configured to be arranged in a row along a nerve fiber (3), wherein at least two neighboring ring level electrodes (4) form an electrode group (5), and wherein two neighboring ring level electrodes (4) within each electrode group (5) are both an anodal electrode (6) or both a cathodal electrode (7).

Description

[0001] 15.01.2026

[0002] 30214-0111-PWO - Bac / Bac

[0003] Applicant: Nyxoah SA

[0004] 12, Rue Edouard Belin

[0005] 1435 Mont Saint Guibert

[0006] Implantable device for selective stimulation in peripheral nerves, and system using the implantable device in obstructive sleep apnea therapy

[0007] Disclosed herein is an implantable device for spatially-selective and fiber-selective stimulation in peripheral nerves. The disclosure further refers to a system comprising the implantable device for use in stimulation therapy.

[0008] Main features of the implantable device are specified by claim 1. Special embodiments or beneficial variants of the device are presented in claims 2 to 10. Main features of the system are specified by claim 11.

[0009] Neuromodulation, i.e. electrical stimulation of nerves, is well-known in the prior art as a reliable and effective type of medical treatment. It presents the opportunity to tackle many physiological conditions and disorders by interacting with the body's own natural neural processes. Neural modulation includes inhibition (e.g. blockage), stimulation, modification, regulation, or therapeutic alteration of activity, electrical or chemical, in the central, peripheral, or autonomic nervous system. By modulating the activity of the nervous system, several different goals may be achieved. For instance, motor neurons may be stimulated at appropriate times to cause muscle contractions. Further, sensory neurons can be blocked to relieve pain or stimulated to provide a signal to a subject. In yet other examples, modulation of the autonomy nervous system may be used toadjust various involuntary physiological parameters, such as heart rate and blood pressure. Neural modulation may provide the opportunity to treat several diseases or physiological conditions. Various devices and techniques have been used in attempts to provide optimum stimulation of a tissue of interest.

[0010] Within the content of this disclosure, the expressions “nerve stimulation”, “neural stimulation”, “nerve modulation”, “neuromodulation” and “neural modulation” are used synonymously unless something else is apparent from the respective context. In general, the above expressions refer to the process of generating an electric field in the vicinity of a nerve or a group of nerves. Likewise, the expressions “subject” and “patient” are used synonymously unless something else is apparent from the respective context. Both terms refer to a person potentially suffering from obstructive sleep apnea (OSA), or other medical indications.

[0011] One of the conditions to which neural modulation can be applied to is obstructive sleep apnea (OSA), a respiratory disorder characterized by recurrent episodes of partial or complete obstruction of the upper airway during sleep. One of the major causes of OSA is the inability of the tongue muscles to resist negative inspiratory pressure in the pharynx due to the sleep-related loss in muscle tone. As the tongue is pulled backwards, it obstructs the upper airway, decreasing ventilation and lowering lung and blood oxygen levels. Stimulation of the hypoglossal nerve 15 (“Hypoglossal Nerve Stimulation” or HGNS) causes the tongue muscles to contract, thereby maintaining an open, unobstructed airway. When a person without OSA is sleeping, the pharyngeal muscles - a group of muscles that form the pharynx - relax and gradually collapse, narrowing the airway. Narrowing of the airway in turn limits the effectiveness of the sleeper's breathing, causing a rise in CO2 levels in the blood of the sleeper. The increase in CO2 results in the pharyngeal muscles contracting to open the airway to restore proper breathing. The larger of the pharyngeal muscles responsible for upper airway dilation is the genioglossus muscle, which is one of several different muscles in the tongue.

[0012] A neuromodulation device for treating OSA is for example known from EP 2760537 A2. However, the device described therein does not allow for spatially and fiber-selective stimulation of a target nerve, and may results in muscle fatigue, and discomfort for the patient.

[0013] Selective nerve stimulation is known in the prior, e.g. from EP 3085414 A1. There, Vagus nerve stimulation is demonstrated using a ring or a cuff electrode comprised of a plurality of smaller electrode contacts. In order to selectively stimulate the target nerve, EP 3085414 A1 discloses minimizing undesired recruitment of large-diameter fibers by a pulse train composed of an initial selective-arrest phase followed by a phase where a charge-balanced alternating current (AC) is applied between a selected contact and an electrode ring. However, the solution described in theprior relies on an ‘all or nothing’ approach - dynamic recruitment of individual nerve fibers is not known from EP 3085414 A1.

[0014] The objective technical problem of the present invention is to eliminate the disadvantages of the prior art and to improve selective nerve stimulation, in particular to provide an improved implantable stimulation device for use in the treatment of OSA.

[0015] The problem is solved by an implantable stimulation device for implantation in a human body and for stimulation of a nervous tissue, wherein the implantable stimulation device comprises at least one stimulation unit, wherein the stimulation unit comprises at least three ring level electrodes configured to be arranged in a row along a nerve fiber, wherein at least two neighboring ring level electrodes form an electrode group, and wherein two neighboring ring level electrodes within each electrode group are both an anodal electrode or both a cathodal electrode.

[0016] With a device as described above, it is possible to virtually change the center of the cathode or of the anode along the nerve, since either of the two can comprise two or more electrodes in an electrode group, wherein each electrode group can function as a virtual cathode (or as a virtual anode). Depending on the distance of the neighboring electrodes within an electrode group, as well as on a distribution of current between those electrodes, the center of the virtual cathode or virtual anode can be shifted, thus changing the virtual distance between anode and cathode.

[0017] In accordance with this disclosure, a ring level electrode can be a continuous circular electrode contact, an interrupted circular electrode contact, or a segmented ring consisting of two or more electrode contacts, that is positioned around the nerve , i.e. at a certain ring level. In other words: A ring level electrode is defined as an electrode contact or a combination of electrode contacts positioned around the circumference of a peripheral nerve at a distinct position along said nerve.

[0018] The device as described above allows for selective nerve stimulation. In particular, it is possible for spatially select parts of the nerve for stimulation (“spatially-selective stimulation”), and / or to select a subset of fibers within a nerve or fascicle for stimulation (“fiber-selective stimulation”). For example, small nerve fibers may be recruited first, with larger fibers of the nerve being dynamically and gradually added with subsequent stimulation events. Such a dynamic recruitment can be especially useful for stimulation of motoneurons for muscle contraction, since it closely resembles actual physiological recruitment of muscle fibers - the advantage being that the muscle force can be more gradually increased for stimulated muscles, while muscle fatigue and soreness are reduced. For example, more fatigue-resistant muscle fibers, which are first activated in physiological contraction, are innervated by small nerve fibers. This is opposed to regular peripheral nervestimulation, which is known to first recruit larger nerve fibers, i.e. in order opposite to physiological recruitment.

[0019] Furthermore, using the implantable device as described herein for stimulation therapy will lead to fewer side effects. For example, spatially selective nerve stimulation prevents unintended stimulation of nerve fascicles or a group of nerve fibers that may be involved in functions other than required for the treatment. Likewise, fiber-selective stimulation prevents side effects resulting in unintended stimulation of fibers that may be involved in functions other that required for the treatment.

[0020] According to an embodiment, the stimulation unit may be configured for a distribution of current between the two or more neighboring ring level electrodes within one electrode group, thereby shifting the “position” of the virtual electrode. In particular, distribution of current between neighboring ring level electrodes of an electrode group may be freely chosen. For example, it is possible that a first electrode of the electrode group delivers 100% of the total current of the electrode group, and that the second electrode of the electrode group delivers 0%. Likewise, the first electrode may deliver 0% of the current, with the second electrode delivering 100%. However, any intermediate distribution of current between the electrodes is also possible, e.g. a distribution of 80% and 20%, or of 50% and 50%.

[0021] According to another possible embodiment, the stimulation unit may comprise at least four ring level electrodes. In particular, the stimulation unit may have a first electrode group comprising at least two cathodal electrodes, and a second electrode group comprising at least two anodal electrodes. This allows for two or more anodal ring levels to be used in combination with two or more cathodal ring levels, wherein the two or more anodal ring levels form a virtual anode and wherein the two or more cathodal ring levels form a virtual cathode. This way, the level of selectivity can be increased, since the distance between (virtual) anode and (virtual) cathode for each stimulation can be varied to an even bigger extent.

[0022] According to another possible embodiment, the stimulation unit may comprise at least one anodal electrode that functions as an anodal block. An anodal block can be used to achieve directional fiber activation in nerve stimulation, thus allowing for a level of directional and / or fiber selectivity. If a nerve is stimulated with two fixed electrode contacts with the anode being distal (i.e. close to the muscle), some fibers can be inactivated depending on the distance between the two electrode contacts. However, this distance is fixed, and cannot be changed after implantation of the stimulation unit. By adding a third ring level electrode, it is possible to create a virtual anode (or a virtual cathode, for that matter). Thus, while the electrode contacts are fixed, the virtual anode centerand / or the virtual cathodal center may be moved relative to each other (i.e. closer to each other or further apart from each other).

[0023] According to another possible embodiment, the stimulation unit may have one electrode group comprising at least two cathodal electrodes, wherein said electrode group is flanked to each side along the nerve fiber by a single anodal electrode. This configuration leads to the stimulation unit having a possible anodal block in both directions of the nerve, i.e. away from the brain or towards the brain. This way, it is possible to avoid unintended stimulation in one direction, which can otherwise sometimes occur. As a result, the risk of unwanted side effects can be significantly lowered.

[0024] According to another possible embodiment, the implantable stimulation device may be configured to deliver a pulse train to the nervous tissue. In particular, the implantable stimulation device may be configured to adjust at least one parameter of a group of parameters of the pulse train, the group of parameters comprising: a pulse amplitude, a pulse width, a pulse frequency, and a pulse shape. Furthermore, the parameters may comprise movement of the virtual center of the anode and / or movement of the virtual center of the cathode. Moreover, the stimulation parameters can be different for each of the pulses of the pulse train for optimal nerve fiber recruitment and thus for improved therapeutic effects. This way, different nerve fiber types can be recruited dynamically throughout the pulse train, e.g. for more physiological recruitment of muscle fibers. This would result in smoother contraction and thus in better control of muscle force, with fewer side effects such as muscle fatigue and discomfort.

[0025] According to another possible embodiment, each ring level electrode may be a continuous circular electrode contact, or that the ring level electrode is an interrupted circular electrode contact, or that ring level electrode is a segmented ring of two or more electrode contacts. According to this disclosure, an “interrupted circular electrode contact” may still comprise a gap or some other sort of opening in order for the ring level electrode to be wrapped around the nerve. Segmented circular contacts are in particular useful spatially-selective stimulation, i.e. for selective stimulation of one side of the nerve. Depending on the nerve, this allows for more selective activation of certain muscles. By adding fiber-selective stimulation (e.g. with anodal block, preferentially with a virtual anode or with a virtual cathode as described herein), certain nerve fibers may be activated on one side of the nerve, while nerve fibers on the other side of the same nerve remain inactivated. The combination of spatially- and fiber-selective activation reduces the risk of overactivation of the target muscle, which in turn reduces stimulation-induced muscle fatigue. As a result, the overall comfort of the stimulation therapy can be increased.According to another possible embodiment, each of the electrode contacts of the segmented ring may be configured for independently generating an electrical pulse. This facilitates shifting the center of the electrical field and stimulating a different part of the nerve. For example, independent use of the electrode contacts of a segmented ring may allow for different depths of the nerve to be recruited, or for different parts or sections around the nerve

[0026] Another aspect of the invention refers to a system for electrical nerve stimulation for use in stimulation therapy, in particular for use in obstructive sleep apnea therapy, wherein the system comprises an implantable stimulation device as described herein, and one or more external devices configured for communication with the implantable stimulation device, among others for setting stimulation parameters. The system may, for example, comprise two external devices: a clinician programming unit, allowing a clinician to program a broad set of stimulation parameters, and a patient remote control, which only allows limited control overstimulation parameters. The external device or devices may include a processor, a power source, and / or a remote control.

[0027] Each of the embodiments, examples or features disclosed herein may be used in combination or separately and in conjunction with any one of the aspect of the disclosed subject matter.

[0028] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate several examples of the disclosed subject matter. The drawings show the following:

[0029] Figs. 1a-e show schematic cross sections of different types of ring level electrodes in accordance with this disclosure;

[0030] Figs. 2a-c show schematic cross sections of a segmented ring level electrode at different stimulation events;

[0031] Figs. 3a-c show schematic illustrations of a nerve with a stimulation group according to one embodiment;

[0032] Figs. 4a-c show schematic illustrations of a nerve with a stimulation group according to another embodiment;

[0033] Figs. 5 shows a schematic illustration of a nerve with a stimulation group according to yet another embodiment;

[0034] Figs. 6 shows a schematic illustration of a nerve with a stimulation group according to yet another embodiment.Fig. 1 shows schematic cross sections of different types of ring level electrodes 4 each placed around a nerve 3, such that the respective electrode contacts are in contact with the nerve. Fig.

[0035] 1a depicts a fully closed circular ring level electrode 4. Fig. 1b depicts an essentially circular ring level electrode 4. However, the ring level electrode 4 of Fig. 1b has an opening to facilitate placement of the electrode 4 around the nerve 3. Fig. 1c depicts a segmented ring level electrode 4 comprising two equally sized and equidistantly placed segments 9. Fig. 1d depicts a segmented ring level electrode 4 comprising three equally sized and equidistantly placed segments 9. Fig.

[0036] 1e depicts a segmented ring level electrode 4 comprising four equally sized and equidistantly placed segments 9.

[0037] According to this disclosure, on each ring level, the individual electrode contacts 8 of a segmented ring level electrode 4 may be independently used for electrical stimulation. For example, a ring level electrode 4 with three segments 9 and therefore with three separate electrode contacts 8 (as depicted in Fig. 1d) can be used such that current flows through either of the segments 9. Alternatively, current may flow through two or all segments, which case the distribution of current may be split arbitrarily such that the total amount of current delivered by each ring level electrode 4 equals 100%. This way, the field of electrical stimulation can be moved in accordance with given requirements or personal preferences. An example is shown in Figs. 2a-c, which depict schematic cross sections of a segmented ring level electrode 4 at different stimulation events.

[0038] Figs. 3a-c show schematic illustrations of a nerve 3 with a stimulation group 2 according to one embodiment. The depicted stimulation group 2 comprises three ring level electrodes 4, one of which being circular, and the remaining two being segmented. The two segmented ring level electrodes 4 form an electrode group 5. The electrode group 5 may then be used as a cathode, and the other remaining ring level electrode 4 may function as an anode 6. Distribution of current between the cathodal 7 ring level electrodes 4 allows to virtually change the center of the cathode 7 (depicted by the shaded circle). Hence, the distance between the anode 6 and the virtual center of the cathode 7 may be altered, thereby allowing selective stimulation of fibers within the nerve respectively. Individual nerve fibers are not shown on the figures. In particular, in Fig. 3a, spatially-selective stimulation of one side of the nerve is shown, i.e. of the side of the contacts closest to the viewer. More importantly, however, the figure shows the principle of dynamic anodal block by having a virtual cathode of which the center can be moved closer or farther away from the blocking anode, cathodal stimulation on the ring level electrode 4 closest to the anodal 6 ring level electrode 6 results in a short distance between the anode 6 and the virtual center of the cathode 7, and will lead to stimulation of only the smallest fibers 3a. In Fig. 3b, cathodal stimulation the ring level electrode 4 farthest away from the anodal 6 ring level electrode 6 results in a long distancebetween the anode 6 and the virtual center of the cathode 7, and lead to stimulation of small and large fibers 3a. Lastly, in Fig. 3c, the current is distributed between the proximal ring level electrodes 4 of the cathode 7, which results in an intermediate distance between the anode 6 and the virtual center of the cathode 7, thereby recruiting fibers in a more selective manner than in the example of Fig. 3b, but in a less selective manner than in the example of Fig. 3b. The anodal block can be away from the brain (i.e. in a distal direction D, as shown in Figs. 3a-c), or also towards the brain (i.e. in a proximal direction P, not shown in Figs. 3a-c).

[0039] Figs. 4a-c show schematic illustrations of a nerve 3 with a stimulation group 2 according to another embodiment. Here, the virtual center of the anode 6 is changed, rather than of the cathode 7. This is achieved by the anode 6 comprising an electrode group 2 of two ring level electrodes 4, which in the example of Figs. 4a-c are circular ring level electrodes 4. The cathode 7 only comprises one, segmented ring level electrode 4.

[0040] In accordance with the embodiments of Figs. 3 and 4, it is also possible to provide virtual centers for both the anode 6 and the cathode 7 of a respective stimulation unit 2. This allows for an even higher level of selectivity. An example for such an embodiment is shown in Fig. 5.

[0041] Figs. 6 shows a schematic illustration of a nerve 3 with a stimulation group 2 according to yet another embodiment. The two ring level electrodes that are located in the middle are each segmented in 3 separate segments 9 having their own contacts 8. The embodiment shown in Fig. 6 allows for anodal block of pulses in a proximal direction P (with the ring electrode level 4 at the right end of the depicted nerve 3 section), and for anodal block of pulses in a distal direction D (with the ring electrode level 4 at the left end of the depicted nerve 3 section).

[0042] The invention is not limited to one of the embodiments described herein but may be modified in numerous other ways.

[0043] All features disclosed by the claims, the specification and the figures, as well as all advantages, including constructive particulars, spatial arrangements and methodological steps, can be essential to the invention either on their own or by various combinations with each other.List of reference numerals

[0044] 1 Implantable stimulation device

[0045] 2 Stimulation unit

[0046] 3 Nerve

[0047] 3a Nerve fascicle

[0048] 4 Ring level electrode

[0049] 5 Electrode group

[0050] 6 Anodal electrode

[0051] 7 Cathodal electrode

[0052] 8 Electrode contacts

[0053] 9 Segmented ring

[0054] D Distal direction

[0055] P Proximal direction

[0056] M Direction towards target muscle

Claims

Claims1. Implantable stimulation device (1) for implantation in a human body and for stimulation of a nervous tissue, wherein the implantable stimulation device (1) comprises at least one stimulation unit (2), wherein the stimulation unit (2) comprises at least three ring level electrodes (4) configured to be arranged in a row along a nerve fiber (3), wherein at least two neighboring ring level electrodes (4) form an electrode group (5), and wherein two neighboring ring level electrodes (4) within each electrode group (5) are both an anodal electrode (6) or both a cathodal electrode (7).

2. Implantable stimulation device (1) according to claim 1 , characterized in that the stimulation unit (2) is configured for a distribution of current between two or more neighboring ring level electrodes (4) within each electrode group (5).

3. Implantable stimulation device (1) according to any of the preceding claims, characterized in that the stimulation unit (2) comprises at least three ring level electrodes (4), wherein the stimulation unit (2) in particular comprises at least four ring level electrodes (4).

4. Implantable stimulation device (1) according to claim 2, characterized, in that the stimulation unit (2) has one electrode group (5) comprising at least two cathodal electrodes (7), wherein said electrode group (5) is flanked to each side along the nerve fiber (3) by a single anodal electrode (6).

5. Implantable stimulation device (1) according to claim 2, characterized in that the stimulation unit (2) has a first electrode group (5) comprising at least two cathodal electrodes (7), and a second electrode group (5) comprising at least two anodal electrodes (6).

6. Implantable stimulation device (1) according to any of the preceding claims, characterized in that the stimulation unit (2) comprises at least one anodal electrode (6) that functions as an anodal block.

7. Implantable stimulation device (1) according to any of the preceding claims, characterized in that the implantable stimulation device (1) is configured to deliver a pulse train to the nervous tissue.

8. Implantable stimulation device (1) according to any of the preceding claims, characterized in that the implantable stimulation device (1) is configured to adjust at least one parameter of a group of parameters of the pulse train, the group of parameters comprising: a pulse amplitude, a pulse width, a pulse frequency, and a pulse shape.

9. Implantable stimulation device (1) according to any of the preceding claims characterized in that the ring level electrode (4) is a continuous circular electrode contact (8), or that the ring level electrode (4) is an interrupted circular electrode contact (8), or that ring level electrode (4) is a segmented ring (9) of two or more electrode contacts (8).

10. Implantable stimulation device (1) according to claim 9, characterized in that each of the electrode contacts (8) of the segmented ring (9) is configured for independently generating an electrical pulse.

11. System for electrical nerve stimulation for use in stimulation therapy, in particular for use in obstructive sleep apnea therapy, wherein the system comprises an implantable stimulation device (1) according to any of the preceding claims, and an external device configured for communication with the implantable stimulation device (1).

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