METHOD AND SYSTEM FOR ELECTRICAL NERVE STIMULATION

Abstract

Disclosed herein is a method for electrical nerve (510) stimulation, the method comprising: generating an electrical stimulation pattern (100) comprising a plurality of successive pulse trains (110), wherein each pulse train (110) has a pulse train amplitude (111); delivering the electrical stimulation pattern (100) to a subjects hypoglossal nerve (510) with a stimulator (300) having at least one electrode (310); modulating the electrical stimulation pattern (100), wherein modulation of the electrical stimulation pattern (100) comprises gradually increasing the pulse train amplitude (111) from one pulse train (110) to a successive pulse train (110) at stimulation onset (101) until a determined target stimulation amplitude (130) is reached; characterized in that modulation of the electrical stimulation pattern (100) further comprises decreasing the target stimulation amplitude (130) to a defined step-down amplitude (140) within each pulse train (110) after the target stimulation amplitude (130) was reached.

Claims

1. A method for electrical nerve stimulation, the method comprising: generating an electrical stimulation pattern comprising a plurality of successive pulse trains, wherein each pulse train has a pulse train amplitude; delivering the electrical stimulation pattern to a subject's nerve with a stimulator having at least one electrode set; modulating the electrical stimulation pattern, wherein modulation of the electrical stimulation pattern comprises gradually increasing the pulse train amplitude from one pulse train to a successive pulse train at a stimulation onset until a determined target stimulation amplitude is reached; wherein modulation of the electrical stimulation pattern further comprises decreasing the target stimulation amplitude to a defined step-down amplitude within each pulse train after the target stimulation amplitude was reached.

2. The method of claim 1, wherein the target stimulation amplitude is decreased to the step-down amplitude in an abrupt manner.

3. The method of claim 1, wherein the target stimulation amplitude within each pulse train is reached according to a ramp-up function comprising a ramp-up duration, wherein the ramp-up duration is defined as the time it takes for the pulse train amplitude to reach the target stimulation amplitude.

4. The method of claim 1, wherein the target stimulation amplitude is maintained for a defined hold duration before it is de creased to the step-down amplitude.

5. The method of claim 1, wherein each the successive pulse trains are separated by pulse train intervals.

6. The method of claim 1, wherein each pulse train comprises a plurality of successive pulses, wherein each pulse has a single pulse amplitude and a single pulse duration and wherein successive pulses are separated by single pulse intervals.

7. The method of claim 1, wherein each pulse train has a pulse train length and a pulse train interval, together defining a pulse train frequency and a duty cycle.

8. The method of claim 1, wherein the modulation of the electrical stimulation pattern is based on determination of a degree of coupling between a primary antenna associated with an external device and a secondary antenna associated with the implantable stimulator.

9. The method of claim 1, wherein the electrical stimulation pattern further comprises a confirmatory pulse and a delay time.

10. The method of claim 1, wherein the duration of the gradual increase of the pulse train amplitude from one pulse train to a successive pulse train at stimulation onset ranges from 0 min to 90 min, in particular from 0 min to 30 min.

11. The method of claim 1, wherein the ramp-up duration ranges from 0 msec to 2000 msec, in particular from 0 msec to 1000 msec.

12. The method according to claim 4, wherein the hold duration ranges from 0 msec to 1000 msec, in particular from 0 msec to 500 msec.

13. The method of claim 1, wherein the step-down amplitude has an amplitude from 1% to 99%, in particular from 1% to 90%, of the total system output amplitude.

14. The method of claim 1, wherein the pulse train amplitude has an amplitude from 1% to 100% of a total system output amplitude.

15. The method of claim 1, wherein the duration of the pulse train interval ranges from 0.1 sec to 20 sec, in particular from 0.2 sec to 10 sec.

16. The method of claim 1, wherein the single pulse duration ranges from 5 psec to 500 psec, in particular from 50 psec to 250 psec.

17. The method of claim 1, wherein the duration of the pulse train length ranges from 0.1 sec to 20 sec, in particular from 0.2 sec to 10 sec and that the pulse frequency within train ranges from 10 Hz to 100 Hz, in particular from 30 to 50 Hz.

18. The method of claim 1, wherein the confirmatory pulse has an amplitude from 1% to 100% of the total system output amplitude and that the duration of the delay time ranges from 0 min to 120 min, in particular from 0 min to 90 min.

19. The method of claim 1, wherein the method is used in a wakeful titration.

20. The method of claim 19, wherein the method is used to define a motor threshold stimulation amplitude for a defined single pulse frequency and a defined single pulse duration.

21. The method of claim 19, wherein the method is used to define a discomfort threshold stimulation amplitude for a defined single pulse frequency and a defined single pulse duration.

22. The method of claim 1, wherein the method is used in a wakeful endoscopy.

23. The method of claim 22, wherein the method is used to define an airway opening amplitude, wherein the airway opening amplitude is the minimum stimulation amplitude required to cause an opening of the subject's airway during stimulation.

24. The method of claim 22, wherein the method is used to a define plateau amplitude, wherein the plateau amplitude is the maximum stimulation amplitude above which no further increase of the opening of the subject's airway is caused.

25. The method of claim 1, wherein the method is used in a polysomnography titration.

26. A system for electrical nerve stimulation to correct sleep disordered breathing, the system comprising a stimulator having at least one electrode set; an external device, wherein the external device is configured for communication with the stimulator and wherein the external device comprises a processor configured to: generate an electrical stimulation pattern comprising a plurality of successive pulse trains, wherein each pulse train has a pulse train amplitude; deliver the electrical stimulation pattern to a subject's nerve through the stimulator; modulate the electrical stimulation pattern according to a stimulation program, wherein modulation of the electrical stimulation pattern comprises gradually increasing the pulse train amplitude from one pulse train to a successive pulse train at stimulation onset until a determined target stimulation amplitude is reached and wherein the modulation of the electrical stimulation pattern further comprises decreasing the target stimulation amplitude to a defined step-down amplitude within each pulse train after the target stimulation amplitude was reached.

27. The system according to claim 26, wherein the system further comprises a user interface configured to enable a user to adjust and/or select the stimulation program, wherein at least of a group of stimulation pattern parameters is adjustable.

28. The system according to claim 26, wherein the group of stimulation pattern parameters comprises a pulse train amplitude, a pulse train length, a single pulse frequency, a single pulse duration, a target stimulation amplitude, a hold duration, a step-down amplitude, a ramp-up duration, a pulse train interval, a duty cycle and/or a delay time.

29. The system according to claim 26, wherein the external device further comprises a memory configured to store at least one stimulation program.

30. The system according to claim 26, wherein the external device further comprises a disposable patch configured to be connectable to the processor.

31. The system according to claim 26, wherein the external device further comprises a power source.

32. The system according to claim 26, wherein the system further comprises a remote control device.

33. The system according to claim 26, wherein the system further comprises a wireless control device configured to: wirelessly communicate with the processor; and wirelessly communicate with the remote control device.

34. The system according to claim 26, wherein the wireless communication of the wireless control device is based on RFID or a Bluetooth connection.

35. A method of compensating for a positional change of an stimulator, the stimulator being implantable in a vicinity of a muscle and an associated nerve, and an external device configured to activate the stimulator, the method comprising: generating an electrical stimulation pattern through an electrical communication between the external device and the stimulator to stimulate a subject's nerve thereby eliciting the muscle contraction associated therewith, resulting in position change of the stimulator respective to the external device adjusting stimulation parameters transmitted by the external device to compensate for the positional change of the stimulator with respect to the external device to substantially maintain an electrical stimulation intensity by compensating the positional change of the implant with respect to the external device.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0054] 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:

[0055] FIG. 1 depicts a schematic graph illustrating a detailed electrical stimulation pattern 100 100 according to an exemplary embodiment of the present disclosure;

[0056] FIG. 2 depicts a schematic graph illustrating a detailed electrical stimulation pattern 100 100 during modulation according to another exemplary embodiment of the present disclosure;

[0057] FIG. 3a-3d depict different schematic graphs each illustrating a possible pattern of a pulse train 110 during modulation according to different exemplary embodiments of the present disclosure;

[0058] FIG. 4 depicts a partially cross-sectioned side view of a patient 500 with a system 200 according to an exemplary embodiment of the present disclosure;

[0059] FIG. 5 depicts anatomy of the tongue and associated muscles and nerves according to an exemplary embodiment of the present disclosure;

[0060] FIG. 6a-6b depict schematic illustrations of an stimulator 300 and an external device 400 according to an exemplary embodiment of the present disclosure.

DETAILED DESCRIPTION OF THE EXEMPLARY EMBODIMENTS

[0061] FIG. 1 depicts a schematic graph illustrating a detailed electrical stimulation pattern 100 according to an exemplary embodiment of the present disclosure. In particular, the schematic graph shows the following parameters of the electrical stimulation pattern 100: delay time 151; confirmatory pulse 150; pulse train length 112; pulse train interval 113; pulse train amplitude 111; single pulse duration 121; single pulse intervals 122. Furthermore, a specific duty cycle may be inferred from the graph shown in FIG. 1. More particular, as shown in FIG. 1, one pulse train 110 comprises several single pulses 120, which are all separated from each other by single pulse intervals 122. The number of single pulses 120 per unit time is defined as the single pulse frequency 123. Likewise, the individual pulse trains 110 are separated from each other by pulse train intervals 113.

[0062] The electrical stimulation pattern 100 as shown in FIG. 1 is very basic, meaning that all single pulses have the same amplitude, with the confirmatory pulse 150 being the sole exception. Thus, no ramp-up or step-down functions are depicted in this graph.

[0063] FIG. 2 depicts a schematic graph illustrating a detailed electrical stimulation pattern 100 during modulation according to another exemplary embodiment of the present disclosure. In particular, an electrical stimulation pattern 100 is shown where modulation of the electrical stimulation pattern 100 comprises a gradual increase 160 of the pulse train amplitude 111 from one pulse train 110 to a successive pulse train 110 at stimulation onset 101, until a determined target stimulation amplitude 130 is reached. It is possible for the single pulses making up one pulse train 110 to either all have the same amplitude or to have different amplitudes. For example, the amplitudes of the single pulses within one pulse train 110 may also be increased incrementally with respect to each other (not shown in FIG. 2).

[0064] This feature can assist in increasing therapy acceptance by gradually increasing the amplitude up to the target stimulation amplitude 130 (in order to open the upper airway without waking up the patient 500), to hold this target stimulation amplitude 130 during a shorter period of time and then decrease the amplitude 111 as the force needed to maintain the upper airway open should be lower than the one needed to open a closed upper airway.

[0065] In addition to the gradual increase 160 during stimulation onset 101, FIG. 2 also shows modulation of the electrical stimulation pattern 100 in form of decreasing the target stimulation amplitude 130 to a defined Step-down amplitude 140 within each pulse train 110 after the target stimulation amplitude 130 was reached via a ramp-up having a defined ramp-up duration 132. In particular, according to the variation shown in FIG. 2, the target stimulation amplitude 130 is decreased to the Step-down amplitude 140 in a more or less abrupt manner. In other words, decreasing the target stimulation amplitude 130 to a defined Step-down amplitude 140 within each pulse train 110 after the target stimulation amplitude 130 was reached may involve one distinct drop in amplitude until the defined Step-down amplitude 140 is reached. It is also possible that more drops to one or more intermediate amplitudes are executed before the defined Step-down amplitude 140 is reached. The duration of each intermediate amplitude may then be the same for each intermediate amplitude, or it may vary.

[0066] Further, as depicted in FIG. 2, the target stimulation amplitude 130 within each pulse train 110 may be reached according to a ramp-up function comprising a ramp-up duration 132. The ramp-up duration 132 is defined as the time it takes for the pulse train amplitude 111 to reach the target stimulation amplitude 130. Advantageously, although not expressly shown by FIG. 2, the target stimulation amplitude 130 may be maintained for a defined hold duration 131 before it is decreased to the Step-down amplitude 140. According to a preferred embodiment, the hold duration 131 ranges from 0 msec to 1000 msec, in particular from 0 msec to 500 msec, wherein the hold duration 131 is defined as the duration of the period during which a target stimulation amplitude 130 is maintained within one stimulation train.

[0067] FIG. 3a-3d depict different schematic graphs each illustrating a possible pattern of a pulse train 110 during modulation according to different exemplary embodiments of the present disclosure. The graphs display a pulse train amplitude 111 (Y-axis) over time (X-axis). In particular, different types of ramp-up and/or step-down modulations are depicted, wherein a ramp-up is defined as increasing the pulse train amplitude within one pulse train 110 until the target stimulation amplitude 130 is reached according to a ramp-up function comprising a ramp-up duration 132. The point, at which target stimulation amplitude 130 is reached is defined as ramp-up point 133—The ramp-up duration 132 is defined as the time it takes for the pulse train amplitude 111 to reach the target stimulation amplitude 130 a gradual increase 160 of the pulse train amplitude 111 from one pulse train 110 to a successive pulse train 110 at stimulation onset 101 consists of gradually increasing the pulse train amplitude 111 from one stimulation train to another until a target stimulation amplitude 130 is reached and wherein a step-down is defined as decreasing the target stimulation amplitude 130 to a defined Step-down amplitude 140 within each pulse train 110 as disclosed herein.

[0068] A ramp-up has the effect that awaking the patient 500 after initialization of the stimulation might be avoided. The gradual increase 160 may, for example, include only one configurable parameter, namely duration, i.e. a period a time just after the delay time 151 during which the amplitude will increase gradually.

[0069] A step-down has at least two major advantages. One advantage lies in the fact that nerve fibers that have been initially affected or triggered via a stimulation signal need not necessarily be further stimulated with the same amount energy, i.e. a lower pulse train amplitude 111 or frequency might be as efficient in maintaining nerve affection as the initial amplitude or frequency. Also, once a muscle has been engaged via stimulation it will contract. As soon as such a muscle contraction has been activated, the distance between an external device 400 generating the stimulation in the muscle and the muscle itself will be decreased, since at least a part of the muscle will be closer to the skin surface of a patient 500 due to contraction. Thus, the distance between the external device 400 and the stimulator 300 is decreased. At the same time, less intervening tissue will be located between the external device 400 and the stimulator 300. Intervening tissue 530 may include muscle tissue, connective tissue, organ tissue, or any other type of biological tissue. Again, this means that a lower pulse train amplitude 111 or frequency might be needed to maintain recruitment of the muscle as compared to the initial amplitude or frequency.

[0070] According to the embodiment shown in FIG. 3a, the target stimulation amplitude 130 is already reached. As shown, according to this particular embodiment, a decrease of the target stimulation amplitude 130 to the step-down amplitude 140 is achieved in an abrupt manner. In other words, decreasing the target stimulation amplitude 130 to a defined step-down amplitude 140 within each pulse train 110 after the target stimulation amplitude 130 has been reached may involve one distinct drop in amplitude until the defined step-down amplitude 140 is reached. When the pulse train 110 ends and no single pulses occur, the step-down amplitude 140 abruptly drops to 0. According to the embodiment shown in FIG. 3b, after the target stimulation amplitude 130 has dropped to the step-down amplitude 140, the step-down amplitude 140 is further reduced to 0 in a continuous manner.

[0071] FIG. 3c and FIG. 3d show the same types of step-down modulations within a pulse train 110 as FIG. 3a and FIG. 3b, respectively. However, in the exemplary embodiments shown in FIG. 3c and FIG. 3d, the target stimulation amplitude 130 is first reached through a continuous ramp-up of the pulse train amplitude 111. The point time in time within each pulse train 110, at which the defined target stimulation amplitude 130 is reached, may be referred to as ramp-up point 133.

[0072] FIG. 4 depicts a partially cross-sectioned side view of a patient 500 with a system 200 according to an exemplary embodiment of the present disclosure. The system 200 is configured for neuromodulation of a patient's muscle. More particularly, the system 200 may be configured to deliver energy in a patient 500 with OSA. The system 200 may therefore include an external device 400 configured for location external to the patient's body. As depicted in FIG. 4, the external device 400 may be configured to be affixed to the patient 500. In particular, as shown in FIG. 4, the external device 400 may be configured for placement underneath the patient's chin and/or on the front of the patient's neck. The suitability of placement locations may be determined by communication between the external device 400 and the stimulator 300. Further suitable locations of the external device 400 include the back of a patient's head for communication with a migraine treatment stimulator 300, the outer portion of a patient's abdomen for communication with a stomach modulating stimulator 300, a patient's back for communication with a renal artery modulating stimulator 300 and/or any other suitable external location on a patient's skin, depending on the requirements of a particular application.

[0073] As noted, the stimulator 300 may be configured to be implanted in a patient's body (e.g. beneath the patient's skin). FIG. 4 and FIG. 5 illustrate that the stimulator 300 may be configured to be implanted for modulation of a nerve associated with the genioglossal muscle. Modulating a nerve associated with a muscle of the subject's tongue may include stimulation to cause a muscle contraction. In further embodiments, the stimulator 300 may be configured to be placed in conjunction with any nerve that one may desire to modulate.

[0074] FIG. 5 depicts anatomy of the tongue and associated muscles and nerves (i.e. hypoglossal nerve (XII)) according to an exemplary embodiment of the present disclosure. FIG. 5 further depicts nerve 510. The nerve 510, through its lateral branch and medial branch, innervates the muscles of the tongue and other glossal muscles, including the genioglossus muscle and the geniohyoid muscle. The horizontal compartment of the genioglossus is mainly innervated by the medial terminal fibers of the medial branch of the nerve 510, which diverges from the lateral branch at terminal bifurcation. The distal portion of the medial branch then variegates into the medial terminal fibers. Contraction of the horizontal compartment of the genioglossus muscle may serve to open or maintain a subject's airway. Contraction of other glossal muscles may assist in other functions, such as swallowing, articulation and opening or closing of the airway. Because the hypoglossal nerve 510 innervates several glossal muscles, it may be advantageous for OSA treatment, to confine modulation of the nerve 510 to the medial branch, or maybe even to the medial terminal fibers or the terminal fibers of the nerve 510. This way, the genioglossus muscle, most responsible for tongue movement and airway maintenance, may be selectively targeted for contraction inducing neuromodulation. Alternatively, the horizontal compartment of the genioglossus muscle may be selectively targeted.

[0075] The medial terminal fibers or the terminal fibers may, however, be difficult to affect with neuromodulation, since they are located within the fibers of the genioglossus muscle. Embodiments of the present disclosure facilitate modulation of any such terminal fibers. In some embodiments the stimulator 300, including at least one pair of modulation electrodes 310 and at least one circuit may be configured for implantation through derma on an underside of a subject's chin. When implanted through derma on an underside of a subject's chin, the stimulator 300 may be located proximate to medial terminal fibers of the medial branch of a subject's hypoglossal nerve 510. An exemplary stimulator 300 location is depicted in FIG. 5. Furthermore, the efficacy of modulation may be increased by an electrode configuration suitable for gene rating parallel electric field lines that run partially or substantially parallel to the nerve fibers to be modulated. FIG. 5 depicts electrodes 310 generating electric field lines (shown as dashed lines) substantially parallel to medial terminal fibers.

[0076] FIG. 6a-6b depict schematic illustrations of a stimulator 300 and an external device 400 according to an exemplary embodiment of the present disclosure. As is shown, the stimulator 300 may be configured for implantation in a patient 500, preferably in a location that permits it to modulate a nerve. The stimulator 300 may, in particular, be located in a patient 500 in such way that intervening tissue exists between the stimulator 300 and the hypoglossal nerve 510. Thus, the location of the stimulator 300 does not require contact with the nerve for effective neuromodulation. The stimulator 300 may also be located directly adjacent to the nerve 510, such that no intervening tissue exists.

[0077] In treating OSA, the stimulator 300 may be located on a genioglossus muscle of a patient 500. Such a location is suitable for modulation of the hypoglossal nerve 510, branches of which run at the genioglossus muscle.

[0078] As is shown in FIG. 6a, when the muscle is at rest, i.e. not contracted, the distance A1 between an external device 400 generating the stimulation of the muscle and the muscle itself will be relatively large. Likewise, the distance A1 between the external device 400 and the implanted stimulator 300 is relatively large, too, and much tissue is located between the external device 400 and the stimulator 300. Therefore, initial engagement of the nerve 510 requires a high intensity of stimulation.

[0079] Once a muscle contraction has been achieved, the distance A2 between the external device 400 generating the stimulation in the muscle and the muscle itself will be decreased, as depicted in FIG. 6b. Since at least a part of the muscle will be closer to the skin surface of a patient 500 due to contraction, the distance between the external device 400 and the stimulator 300 is decreased, as well. At the same time, less intervening tissue will be located between the external device 400 and the stimulator 300. This means that a lower pulse train amplitude 111 or frequency is needed to maintain recruitment of the muscle as compared to the initial amplitude or frequency of the stimulation. In other words, a stimulation with a lower intensity is sufficient to maintain muscle contraction.

[0080] The invention is not limited to one of the embodiments described herein but may be modified in numerous other ways.

[0081] 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

[0082] 100 Electrical stimulation pattern [0083] 101 Stimulation onset [0084] 110 Pulse train [0085] 111 Pulse train amplitude [0086] 112 Pulse train length [0087] 113 Pulse train interval [0088] 120 Single pulse [0089] 121 Single pulse duration [0090] 122 Single pulse interval [0091] 130 Target stimulation amplitude [0092] 131 Hold duration [0093] 132 Ramp-up duration [0094] 133 Ramp-up point [0095] 140 Step-down amplitude [0096] 150 Confirmatory pulse [0097] 151 Delay time [0098] 160 Gradual increase [0099] 200 System [0100] 300 Stimulator [0101] 310 Electrodes [0102] 400 External device [0103] 500 Patient [0104] 510 Nerve [0105] 530 Intervening tissue [0106] 600 Genioglussos muscle [0107] A1, A2 Distance