Tripolar lead systems for vagus nerve stimulation

Abstract

An implantable tripolar lead assembly includes a flexible lead body that extends from a header of an implantable device housing to multiple distal electrodes. Conductors disposed within the lead body transmit respective electrical signals to the electrodes. The conductors include at least one outer conductor positioned radially outermost relative to one or more inner conductors inside the lead body. In an example, a first distal electrode of the multiple distal electrodes is coupled to the at least one outer conductor, and a second distal electrode of the multiple distal electrodes is coupled to one of the inner conductors. A flexure resilience characteristic of the outer and inner conductors can be different. Lead fault conditions can be identified by measuring electrical characteristics of the lead. In response to a lead fault condition, a therapy delivery or sensing vector can be automatically updated or therapy parameters can be updated.

Description

TRIPOLAR LEAD SYSTEMS FOR VAGUS NERVE STIMULATIONCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is related to and claims priority to United States Provisional Application No. 63 / 528,156, filed on July 21, 2023, and entitled “TRIPOLAR LEAD VECTOR SELECTION FOR VAGUS NERVE STIMULATION BASED ON IMPEDANCE ASSESSMENT,” the entirety of which is incorporated herein by reference; and this application is related to and claims priority to United States Provisional Application No.63 / 528,157, filed on July 21, 2023, and entitled “ELECTROSTIMULATION VECTOR OPTIMIZATION FOR TRIPOLAR LEAD AND EPILEPSY TREATMENT,” the entirety of which is incorporated herein by reference; and this application is related to and claims priority to United States Provisional Application No. 63 / 528,162, filed on July 21, 2023, and entitled “TRIPOLAR LEAD STRUCTURES FOR RELIABLE VAGUS NERVE STIMULATION,” the entirety of which is incorporated herein by reference.BACKGROUND

[0002] Implantable medical devices can be provided to electrically stimulate the central and peripheral nervous systems (e.g., including the autonomic system), cardiac muscle tissue, and other muscle tissues.Electrical signals delivered to neural tissue or muscle tissue can be used to treat various bodily dysfunctions and disorders by blocking, masking, stimulating, or replacing electrical signals within the body. In a particular example, electrical signals delivered to the vagus nerve can be used to treat epilepsy, seizures, depression, anxiety, obesity, and other disorders.

[0003] Vagus Nerve Stimulation (VNS) for treatment of epilepsy can involve stimulating the left cervical vagus nerve using one or more electrodes on an implanted lead. A neurostimulation lead can include one or more electrodes that are implanted or installed at or adjacent to the target tissue (e.g., the vagus nerve) such that electrical energy from the electrodescan be delivered to the target tissue. In an example, an epilepsy therapy can comprise a bipolar, biphasic electrical stimulation pulse, or series of such pulses, delivered to a nerve target using the implanted lead and electrodes.

[0004] In an example, an implantable electrode can comprise a cuff type electrode or a helical electrode, among others. A cuff type electrode comprises a substantially or partially cylindrical structure that can be open at one side, and can be placed around the nerve target and closed with a suture or other device. A helical electrode can comprise a flexible structure that can, in some examples, expand or contract to help size the electrode around the nerve target. Cuff or helical electrodes can be used together with other lead or electrode anchoring features to help maintain the electrode at or near the nerve target over time.BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

[0005] To easily identify the discussion of any particular element or act, the most significant digit or digits in a reference number refer to the figure number in which that element is first introduced. The drawings are not drawn to scale.

[0006] FIG. 1 illustrates generally an example of a neurostimulation system.

[0007] FIG. 2A illustrates generally an example that includes implantable electrodes.

[0008] FIG. 2B illustrates generally an example of electrodes disposed at a nerve target.

[0009] FIG. 3 illustrates generally an example of a first tripolar lead assembly.

[0010] FIG. 4 illustrates generally an example of a first method for lead fault identification.

[0011] FIG. 5 illustrates generally an example of a second method for lead fault identification.

[0012] FIG. 6 illustrates generally an example of a third method for lead fault identification.

[0013] FIG. 7 illustrates generally an example of a fourth method for adverse effect detection.

[0014] FIG. 8 illustrates generally an example of a fifth method for adverse effect detection.

[0015] FIG. 9 illustrates generally a schematic example of an implantable lead assembly.

[0016] FIG. 10 illustrates generally an example of a machine in the form of a computer system within which a set of instructions may be executed for causing the machine to perform any one or more of the methodologies discussed herein, according to an example embodiment.DETAILED DESCRIPTION

[0017] A therapy for the treatment of drug-resistant epilepsy includes vagus nerve stimulation. An implantable device can be implanted in a patient with one or more electrodes positioned proximate the vagus nerve to deliver the stimulation therapy. Discussed herein are systems and methods for making and using a tripolar lead for vagus nerve stimulation or other therapeutic neurostimulation or neuromodulation. In an example, the tripolar lead includes three separately-addressable electrodes that can be used to deliver neurostimulation using multiple different stimulation vectors. Use of a tripolar lead enables various benefits including more robust and reliable lead fault identification, and enhanced control over a direction or location of an electrostimulation field provided by the electrodes of the lead, such as to a target portion of a nerve target. In an example, the tripolar lead structure itself can be used to detect wear or fatigue and indicate replacement ahead of a fault condition.

[0018] An illustrative (but non-restrictive) example, as shown in FIG. 1, includes a system 100 for providing neurostimulation (or neuromodulation) to a vagus nerve 102, or vagus nerve stimulation (VNS). In an example, the system 100 can be configured to sense nerve activity or other electrical activity or motion. The example of the system 100 includes an implantable device 112 such as can comprise a processor circuit 114 and a signalgenerator 116. The processor circuit 114, or control circuit, can control operation of the signal generator 116 according to various therapy delivery algorithms or therapy signal-defining parameters. The signal generator 116 can be configured to generate stimulation signals or pulses according to parameters or instructions from the control circuit. In an example, the signal generator 116 includes independent current sources and controllers to enable independent and simultaneous output of multiple respective therapy signals.

[0019] In an example, the implantable device 112 comprises or is coupled to one or more physiologic status sensors that are configured to sense information about a patient. For example, the system can include a sensor 118. The implantable device 112 can further include a recording unit 120 configured to record information from the sensor 118. The sensor 118 can comprise a portion of the implantable device 112 or can be coupled to a lead that is coupled to the implantable device 112. In other examples, the sensor 118 can be an external sensor that is coupled to, or otherwise configured to receive information from, the patient. In an example, the sensor 118 comprises an accelerometer configured to sense motion information about the patient. In an example, the sensor 118 comprises one or more electrodes configured to sense electrical signals from the patient. In an example, the one or more electrodes can be implanted at or near a vagus nerve of the patient and can be configured to deliver electrical signals to, or receive electrical signals from, the vagus nerve (or other neural target). For example, the one or more electrodes can be configured to sense vagal activity information from the patient.

[0020] In an example, the system 100 includes an external device 122 that can communicate with the implantable device 112. The external device 122 can include a patient device or clinician device that is configured to receive information from, or provide information to, the implantable device 112. In an example, the external device 122 can include a display configured to receive and display data from the implantable device 112, including individual sensor data and seizure detection annotations. The system 100 or the external device 122 may calculate and display seizure burden, and / ordisplay an event log. In an example, the external device 122 includes an interface that allows patients to confirm events and / or add comments or annotations to detected events.

[0021] For example, the external device 122 can be used to set one or more parameters for a stimulation therapy that is provided by the implantable device 112. In an example, the external device 122 can be used to report information to a patient or clinician about one or more therapies provided by the implantable device 112. In an example, the external device 122 includes one or more sensors that are configured to monitor physiologic or behavioral information about the patient.

[0022] The interaction between the external device 122 and the implantable device 112 is facilitated through a bidirectional communication link using a wireless coupling 124 that allows for the continuous exchange of data and commands between the two devices. The communication is established using wireless technology protocols that are specifically designed for medical devices, ensuring secure and reliable data transmission.

[0023] The external device 122 is equipped with various sensors, including a high-resolution camera, a microphone, and an accelerometer, which collect a wide array of physiological and environmental data, as described below. This data includes visual and audio records of the patient's movements, vocalizations, and surrounding environment, as well as quantitative measurements such as detected motion patterns, heart rate, and / or respiration rate. The collected data is then processed (e.g., at the external device 122, at the implantable device 112, or elsewhere) using advanced algorithms to identify potential seizure events.

[0024] In an example, the processor circuit 114 is programmed with a set of parameters that define thresholds for initiating or adjusting VNS therapy. Upon receiving a therapy-indicating signal from the external device 122 or based on information from the sensor 118, the processor circuit 114 can be configured to analyze the sensor data against the predefined parameters. If the data indicates that a seizure is occurring or imminent, the implantable device 112 adjusts the therapy parameters accordingly. This adjustment mayinvolve changing the intensity, frequency, duration, or other characteristic of the electrical impulses delivered to the vagus nerve to provide an appropriate therapeutic response.

[0025] In an example, seizure detection and VNS can include or use one, two, three, or more vagus nerve sensing electrodes (e.g., “recording cuff” or helical electrodes), such as located in different longitudinal positions along the cervical vagus region, relative to a stimulation site. Separate stimulating electrodes (e.g., an anode and a cathode) can be positioned to provide VNS. In the example of FIG. 1, the system 100 includes a first electrode 104, a separate second electrode 106, a separate third electrode 108, and a separate nth electrode 110 positioned at or near the vagus nerve 102. The various electrodes can be used in various combinations to provide an epilepsy therapy or to sense activity from the vagus nerve or other nerve. In an example, the multiple electrodes comprise respective portions of a single lead, or multiple leads can be used, with each lead comprising one or more electrode.

[0026] The count and position of electrodes in the example of FIG. 1 is merely illustrative. For example, an implantable device can include circuitry for sensing (e.g., recording) neural activity (e.g., an action potential or compound action potential), along with circuitry for generating VNS. In such an example, a machine learning approach, such as an instance of a machine learning -based model (e.g., such as can be referred to as an artificial intelligence or “AI”-based technique) can be instantiated by the implant circuitry or the processor circuit 114. Such a machine learning-based model can be used for detection of a seizure, or for therapy control in response thereto, or both.

[0027] In an example, the sensing electrodes and related circuitry can be separate from the stimulating electrodes and the sensing electrodes can be monitored by a separate unit (e.g., an external assembly) that can be used in an acute or temporary manner, such as supporting the implant procedure or implantable device configuration. For example, in the case that the sensing and stimulating electrodes are separate, the sensing electrode may beexplanted acutely as a portion of a first procedure or soon after the first procedure. In yet another example, there can be three or more electrodes, each configurable as either a stimulating electrode or a sensing electrode at any time. For example, two electrodes closest to a brain of a patient could be assigned as an anode and a cathode, respectively, and another electrode that is located more distally could be assigned as a sensing electrode to detect efferent nerve activation. As another illustration, two electrodes most distal to the brain could be assigned as an anode and a cathode, respectively, and an electrode more or most proximal to the brain could be assigned as a sensing electrode to detect afferent activity.

[0028] FIG. 2A illustrates generally components of an electrode assembly. The components can include a first electrode array 202 and ring electrode 208. The first electrode array 202 can comprise multiple, separately addressable electrodes, such as including a first electrode 204 and a second electrode 206. One or more of the first electrode array 202 and the ring electrode 208 can optionally be coupled to a support structure 210 or scaffold, and the support structure 210 can be provided about a target nerve or tissue. The first electrode array 202 or the ring electrode 208 can comprise examples or embodiments of any one or more of the first electrode 104, the second electrode 106, the third electrode 108, and / or the nth electrode 110 from the example system 100 of FIG. 1.

[0029] FIG. 2B illustrates generally an example of an electrode assembly 212. The electrode assembly 212 includes a first electrode array 218, a second electrode array 220, a third electrode array 222, and a fourth electrode array 224. Each of the arrays can comprise multiple, separately addressable electrodes. Each of the arrays comprise an example or embodiment of the electrodes of the example system 100 of FIG. 1.

[0030] The electrode assembly 212 can be provided about a nerve 214. In an example, the nerve 214 comprises a portion of a vagus nerve, such as in a cervical region of a patient. In an example, the electrode assembly 212 can be secured about the nerve 214 using one or more sutures 216.

[0031] The electrodes of the electrode assembly 212 can be supported by a monolithic, shared scaffold or support, or the electrodes can be individually supported at their respective locations along the nerve 214. Implanting a monolithic structure at, near, or around a nerve has the advantage of generally being easier and faster for the implanting physician, as compared to implantation of individual discrete electrode structures.

[0032] In an example, the first electrode array 218 comprises electrodes that are configured to be arranged or disposed at discrete locations about a circumference of a nerve. The electrodes can optionally be arranged about a twisted or helical path. The electrodes can be selectively energized to stimulate nearby nerve fibers.

[0033] The use of a plurality of electrodes in an array, or in a series of ring structures, or in other arrangements, facilitates the programmability of different spatial arrangements of neural activity sensing, stimulation, or both. In various examples, an array configuration provides redundancy in case of loss of sensing or a reduction of stimulation efficacy of a particular electrode. Such a multi-electrode configuration can be used to provide sensing modalities or stimulation electrode configurations that can vary over time to maintain the effectiveness of VNS therapy, seizure detection, or both.

[0034] In another example, instead of having a contiguous circular or round electrode, an array including multiple discrete electrodes can be provided at various positions of one ring of a cuff or on one or more helical supports. The electrodes can be configured to selectively stimulate the vagus fibers. Using multiple electrodes in an array, or a series of ring structures, can facilitate programmability of different spatial arrangements of neural activity sensing or stimulation (or both). As an illustration, such an array configuration can provide redundancy in case of loss of sensing or loss of stimulation efficacy of a particular electrode. Such a multi-electrode configuration can be used to provide sensing modalities or stimulation electrode configurations that can vary over time to maintain effectiveness of VNS therapy or seizure detection, or both.

[0035] In an example, a lead can comprise one or more electrodes and can optionally comprise a retention or affixation feature. The affixation feature can be provided at a proximal or distal end of the lead, or can be provided at an intermediate location along the length of the lead. The affixation feature can be electrically functional (e.g., comprising one or more electrodes for sensing or delivery of electrical neurostimulation) or electrically nonfunctional (e.g., without conductive materials or without electrodes). In some examples, an electrode can be coupled to, or integrated with, a retention feature.

[0036] FIG. 3 illustrates generally an example of a first tripolar lead assembly 300. with a first retention feature 318. The first tripolar lead assembly 300 can be coupled to a stimulator circuit (e.g., via a header in an implantable housing) and can be configured for implantation at a neural target, such as at the vagus nerve 302. The first tripolar lead assembly 300 can comprise a lead body 304 and one or more distal electrodes, anchors, or affixation features.

[0037] The first tripolar lead assembly 300 includes multiple helical anchors, and each of the anchors comprises a separately addressable electrode. For example, the first tripolar lead assembly 300 includes a first helical anchor 306 with a first electrode 308, a second helical anchor 310 with a second electrode 312, and a third helical anchor 314 with a third electrode 316. Any one or more of the anchors can optionally comprise an array of multiple, separately-addressable electrodes. Each of the helical anchors can be configured to receive a respective portion of the vagus nerve 302 (or other nerve) and can be adjustable in size to accommodate variations in width of the vagus nerve 302 and other tissue. For ease of reference herein, the first electrode 308 can be referred to as “electrode A” or “A,” the second electrode 312 can be referred to as “electrode B” or “B,” and the third electrode 316 can be referred to as “electrode C” or “C.” Combinations or pairs of the electrodes used for electrostimulation can be referred to by letters, for example, electrode pair A-B can refer to one of the first electrode 308 and the second electrode 312 configured as an anode and the other of theelectrodes configured as a cathode for use in an electrostimulation vector. In other examples, two or more of the electrodes can be electrically coupled to provide an anode or cathode for another electrostimulation vector. For example, the first electrode 308 and the second electrode 312 can be electrically coupled to provide an anode and the third electrode 316 can be used as a cathode. Other combinations can similarly be used to provide other electrostimulation vectors for neurostimulation therapy delivery or sensing. In an example, a stimulation or sensing vector can include or use at least one of the electrodes of the first tripolar lead assembly 300 and can optionally use one or more “can” electrodes, or electrodes coupled to (or integrated with) a housing of the implantable device 112.

[0038] In the example of FIG. 3, the electrodes are illustrated schematically as having discrete locations, however, other locations in, on, or around the helical anchors can be used. In an example, one or more of the electrodes can comprise a ring electrode or conductive ribbon that extends partially or entirely around a revolution of its respective helical anchor, such as to encircle the target tissue (e.g., the vagus nerve 302). Other configurations can similarly be used.

[0039] In an example, the first retention feature 318 comprises a mesh or other structure. In the example of FIG. 3, the mesh structure can be coupled to a distal portion of the lead body 304 and configured to grow into tissue at, near, adjacent to, or around the vagus nerve 302 or other nerve tissue. In an example, additionally or alternatively to providing the first retention feature 318 at the distal portion of the lead body 304, one or more other instances of the first retention feature 318 can be coupled to a proximal or intermediate portion of the lead body 304.

[0040] In an example, a VNS therapy can be provided using bipolar stimulation delivered using a selected pair of two of the available three (or more) electrodes of the first tripolar lead assembly 300. In the case of fracture or dislodgment of either one of the two electrodes or their helical anchors, the system can be configured to automatically detect a lead impedance error and can then take a remedial action such as reconfiguringthe stimulation vector, such as by selecting a different pair of the available three electrodes, or selecting a “can” or housing electrode of the implantable device 112. In an example, the impedance error can include an impedance range error (e.g., high or low impedance), or an impedance change by greater than a specified threshold impedance change amount, among others. In an example, a faulty electrode among the three available electrodes can be automatically identified and removed from service. VNS therapy can then continue substantially uninterrupted using the remaining electrode(s) and using the same or different stimulation parameters.

[0041] In an example, the signal generator 116 can be configured to intermittently or periodically (e.g., hourly, twice daily, daily, weekly, or at another specified interval) perform a lead impedance measurement using each of the available electrodes. The system can be configured to identify a faulty electrode if multiple (e.g., two or more, and preferably three) consecutive impedance measurements are out of range relative to a baseline or reference (e.g. the impedance is measured to be less than 1100 Q or greater than 5000 Q; other threshold values can similarly be used). Additionally or alternatively, the system can be configured to identify a faulty electrode upon detecting an abrupt and sustained increase or decrease in lead impedance (e.g., an impedance change of greater than 2000 Q; other threshold values can similarly be used). The specific reference impedance values used herein are provided as examples only. In use, reference or baseline impedance values may vary from patient to patient, and can be established automatically or manually by the system 100.

[0042] In an example, the system can be configured to intermittently or periodically perform lead impedance tests on one, multiple, or all available electrode combinations and then select the electrode combination with the most desirable lead impedance (e.g., to maximize therapy or to minimize battery usage). In an example, lead impedance testing may be used in combination with an automated test of physiological response to stimulation.

[0043] FIG. 4 illustrates generally an example of a first method 400 that can include identifying a lead fault for an implantable lead, such as the firsttripolar lead assembly 300. In operation 402, the first method 400 can include or use a lead integrity assessment routine that is initiated by a control circuit (e.g., the processor circuit 114) in an implantable medical device housing. Operation 402 can include measuring a first impedance characteristic at a first time using a first pair of electrodes of a first implantable lead where the first implantable lead includes at least first, second, and third electrodes configured to be disposed at or around a nerve, such as the vagus nerve 302. In an example, the first pair of electrodes comprises the first and second electrodes.

[0044] In an example, a stimulation therapy can be provided to the nerve following the operation 402. The therapy can be provided using the first pair of electrodes or using a different second pair of electrodes, such as can comprise the first and third electrodes of the first implantable lead. That is, in an example, the therapy can be provided using a stimulation vector that excludes at least one of the electrodes used to make the first impedance measurement at operation 402. Following the therapy, the first method 400 can continue at operation 404. In other examples, at least a portion of the therapy can be provided concurrently with the impedance measurement at operation 402 and / or operation 404.

[0045] At operation 404, the first method 400 includes measuring a second impedance characteristic at a second time, subsequent to the first time, using the same first pair of electrodes of the first implantable lead. At operation 406, the first method 400 includes identifying a lead fault for the first implantable lead based on a relationship between a specified threshold impedance characteristic and the measured first and second impedance characteristics. In an example, identifying the lead fault at operation 406 includes determining that each of the measured first and second impedance characteristics exceeds the specified threshold impedance characteristic.

[0046] In an example, the specified threshold impedance characteristic is a specified impedance magnitude amount. In this example, identifying the lead fault at operation 406 includes determining whether a difference between themeasured first and second impedance characteristics exceeds the specified impedance magnitude amount.

[0047] In an example, in response to identifying a lead fault or other error condition, such as at operation 406, the first method 400 can include notifying the patient, a caregiver, or clinician about the fault or error condition. In an example, the notification can be provided using a patient interface device that is communicatively coupled with the patient's implantable device, or can be provided using another monitoring and / or programming device that is communicatively coupled with the patient’s implantable device.

[0048] In an example, operation 406 can include or use trend information, such as collected over time, about the impedance measured using the first pair of electrodes. The trend information can be based on impedance characteristic measurements that occur over a time that can include seconds, minutes, days, weeks, or longer. If the trend indicates an impedance change that exceeds a threshold change amount for a particular time interval, then a fault condition can be indicated. That is, the fault determination can be based on longer-term information about an impedance characteristic of the lead, or can be based on shorter-term information about abrupt changes in the impedance characteristic of the lead.

[0049] In an example, operation 406 can include identifying the lead fault based on a difference between the measured first and second impedance characteristics, and the difference can be compared to the specified threshold impedance characteristic. The specified threshold impedance characteristic can be based on a duration of a time interval elapsed between the first and second impedance measurements. For example, a first threshold impedance characteristic can be used when the first and second impedance characteristic measurements are performed within minutes or hours of each other, and a different second threshold impedance characteristic can be used when the measurements are performed weeks or months apart.

[0050] At operation 408, the first method 400 includes, in response to identifying the lead fault at operation 406, selecting a different second pairof electrodes of the first implantable lead for impedance testing and / or for therapy delivery. In an example, the different second pair of electrodes includes the third electrode and only one of the first and second electrodes. If the second electrode pair is a known-good pair (e.g., as-determined from results of other testing), then operation 408 can include using the second electrode pair for therapy delivery without additional testing. In an example, operation 408 can further include selecting one or more other pairs of available electrodes of the first implantable lead for impedance testing, and subsequently performing an impedance test (or test sequence) using one or more of the available electrode pairs of the first implantable lead.

[0051] Although the example of the first method 400 is discussed generally with respect to a single lead, the impedance measurements and comparisons discussed herein can be similarly applied to test for faults between electrodes of multiple separate leads.

[0052] FIG. 5 illustrates generally an example of a second method 500 that can include providing an indication of a lead fault for an implantable lead, such as the first tripolar lead assembly 300. At operation 502, the second method 500 includes performing a series of at least three discrete impedance measurements for a first electrode pair of multiple electrode pairs that are available on a multipolar lead.

[0053] In an example, the impedance measurements are time-adjacent impedance measurements that are received from or during non-overlapping measurement intervals with zero time between intervals or with a non-zero blanking time between intervals. During a blanking time, no energy is provided by the implantable system to the electrodes of the first electrode pair.

[0054] In an example, the impedance measurements are time-adjacent with respect to measurement activity, and are interleaved with one or more therapy delivery events and / or physiologic sensing events. In an example, operation 502 includes a time series of events that can include (i) performing a first impedance measurement using the first electrode pair, (ii) delivering a first neurostimulation therapy using at least one electrode of the firstelectrode pair or using another electrode pair, (iii) performing a second impedance measurement using the first electrode pair, (iv) delivering a second neurostimulation therapy using at least one electrode of the first electrode pair or using another electrode pair, and (v) performing a third impedance measurement using the first electrode pair.

[0055] In an example, the impedance values for the at least three impedance measurements can be recorded and compared to each other or to a specified threshold impedance value. The specified threshold impedance value can be a value (or range of values) that indicates a lead fault or a likelihood of a lead fault condition.

[0056] At operation 504, the second method 500 can include determining which, if any, of the impedance measurements from operation 502 are outside of a specified impedance range. Operation 504 can include, in response to each of the at least three impedance measurements being outside of a specified impedance value range, providing an indication of a lead fault for the implantable lead. By performing a series of measurements, an out-of- range condition can be identified and verified. A remedial action can be taken, such as can include testing additional electrode pairs or inhibiting the electrode pair with the out-of-range condition from delivering therapy or sensing physiologic information.

[0057] In an example that includes interleaving the series of impedance measurements with therapy delivery events, if a successful therapy event occurs following the first or second impedance measurements in the second method 500, then the routine can be restarted. The success of a therapy event can be determined by, for example, a patient-reported therapy efficacy or an automatic determination of autonomic engagement.

[0058] FIG. 6 illustrates generally an example of a third method 600 that can include providing an indication of a lead fault for an implantable lead, such as the first tripolar lead assembly 300. At operation 602, the third method 600 can include performing a series of at least two discrete impedance measurements for a first electrode pair of multiple electrode pairs that are available on a multipolar lead. For example, operation 602 caninclude measuring first and subsequent second impedance values from a first electrode pair of the first tripolar lead assembly 300 or other implantable lead assembly.

[0059] At operation 604, the third method 600 can include determining an impedance difference between the impedance values of the first and subsequent second impedance measurements. At decision block 606, the third method 600 includes determining a relationship between the impedance difference and a specified threshold impedance. For example, decision block 606 can include determining whether the determined impedance difference exceeds a specified threshold impedance value.

[0060] If the impedance difference value exceeds the specified threshold impedance value, then the third method 600 continues at operation 608. At operation 608, for example, the third method 600 can include selecting a different second electrode pair for subsequent impedance testing (e.g., using the first method 400, the second method 500 and / or the third method 600) or for use in a neurostimulation therapy and / or for use in physiologic sensing. The different second electrode pair can comprise a different pair on the same electrode lead assembly as the first pair. The additional impedance testing can be performed for one or more of the other available electrode pairs on the same electrode lead assembly or on multiple leads, and the testing can be performed until a suitable, functional electrode pair is identified for use in therapy or sensing.

[0061] If the impedance difference value does not exceed the specified threshold impedance value, then the first electrode pair can be deemed or considered nominal, and the third method 600 continues at operation 610. Operation 610 can include, for example, using the first electrode pair in a neurostimulation therapy or for physiologic sensing, or can include using the first electrode pair for another purpose.

[0062] In an example, the implantable device 112 can be configured to automatically select a particular one of multiple available electrode pairs on an implantable lead assembly, such as the first tripolar lead assembly 300. For example, the implantable device 112 can be configured to test and selectan electrode pair from the groups comprising electrodes A-B, A-C, and B-C, among others, such as after implantation, such as to determine a most therapeutically advantageous configuration.

[0063] In an example, the implantable device 112 can be configured to measure or detect physiologic status information about the patient. The physiologic status information can include one or more indicators of autonomic engagement, such as heart rate, heart rate variability, or sensed neural traffic. The physiologic status information can additionally or alternatively include one or more indicators of a therapy side effect, such as coughing, laryngeal vibration, or other side effect. In an example, the implantable device 112 can be configured to automatically adjust an electrode configuration used for therapy and / or sensing in response to the physiologic status information. In an example, the electrode configuration can be updated manually such as by a health care provider in a hospital or clinic. In an example, the measurement and configuration adjustment can be performed at the time of implantation, or can be performed intermittently or periodically during chronic therapy to ensure that a maximum therapeutic benefit is provided to the patient and side effects experienced by the patient are minimized.

[0064] In an example, the implantable device 112 is configured to use one or more electrodes of the first tripolar lead assembly 300 for intermittent stimulation. The stimulation can comprise one or more bursts of pulses delivered to a target nerve, such as the vagus nerve, with an interburst blanking interval when no therapy is delivered. The pulses used can have various pulse width, shape (waveform morphology), and frequency characteristics. In an example, the interburst interval can include a monitoring interval when the implantable device 112 or other sensors are configured to monitor a patient physiologic status or patient response to the preceding therapy delivery event. In an example, the monitoring interval can begin immediately after cessation of energy delivery, or can begin following a delay after cessation of energy delivery. For example, the monitoring interval can begin several seconds (e.g., one or more seconds) after cessationof energy delivery and the monitoring interval can conclude about 10-15 seconds after cessation of energy delivery. In other examples, the monitoring interval can be differently timed or can overlap with a therapy delivery interval.

[0065] In an example, the monitoring interval comprises a time window of, e.g., 5 to 15 seconds that begins at the onset of intermittent stimulation. The implantable device 112 can be configured to monitor one or more physiologic status-indicating signals (e.g., from the sensor 118, such as can comprise an accelerometer or other sensor) to detect a signal indicative of a side effect that occurs during this window. In an example that includes using a signal from an accelerometer, the signal can be analyzed in the time and / or frequency domain to discern its contents and characteristics thereof. In some examples, the signal can include a sudden perturbation that indicates a patient cough, or the signal can include vibration information that indicates muscle capture.

[0066] In an example, the side effect detected using the sensor signal can occur on a specified minimum number of consecutive therapy event cycles (e.g., two or more therapy event cycles) before being declared as a stimulation-related side effect. In an example, the system can be configured to determine an ensemble average of the signal for a specified number of cycles to improve signal-to-noise ratio and generate a high-quality signal that can be used to determine a stimulation-related side effect.

[0067] In an example, the implantable device 112 can be configured to respond to the side effect automatically, such as by updating a neurostimulation therapy parameter (e.g., a stimulation signal magnitude, frequency, burst pattern or pulse shape, or other characteristic) or by changing the combination of electrodes used to provide the neurostimulation therapy. Following the response, the implantable device 112 can be configured to continue monitoring for side effects.

[0068] FIG. 7 illustrates generally an example of a fourth method 700 that can include determining whether a sensor signal indicates an adverse effect or side effect and, optionally, taking a remedial action to reduce theincidence or severity of, or avoid, further effects. At operation 702, the fourth method 700 includes delivering a first neurostimulation therapy to a nerve target using a first electrode pair. In an example, the first electrode pair comprises a pair of electrodes of the first tripolar lead assembly 300. Delivering the first neurostimulation therapy at operation 702 includes using first neurostimulation therapy parameters that can include, among other things, a particular pulse magnitude, shape, frequency, or pulse pattern.

[0069] At operation 704, the fourth method 700 includes measuring a first portion of a sensor signal for a specified first duration following delivery of the first neurostimulation therapy. For example, operation 704 can include measuring a signal from an accelerometer (e.g., comprising an example of the sensor 118) or measuring an electrical signal (e.g., an impedanceindicating signal) using electrodes of the first tripolar lead assembly 300. In an example, operation 704 can include or use a patient-reported physiologic response, such as additionally or alternatively to using the sensor signal.

[0070] At operation 706, the fourth method 700 includes delivering a second neurostimulation therapy to the nerve target using the first electrode pair. In the example of the fourth method 700, the first and second neurostimulation therapies can use the same or substantially the same therapy signal parameters.

[0071] At operation 708, the fourth method 700 includes measuring a second portion of a sensor signal for a specified second duration following delivery of the second neurostimulation therapy. For example, operation 708 can include measuring a signal from the accelerometer (or other sensor) or measuring an electrical signal using electrodes of the first tripolar lead assembly 300. Generally, the signals measured at operation 704 and operation 708 are from the same source sensor but are measured at different times and following different therapy delivery events. In an example, the specified first duration and the specified second duration can have substantially the same length or time interval. In an example, operation 708 can include or use a patient-reported physiologic response, such as additionally or alternatively to using the sensor signal. The patient-reportedresponse can include, for example, an indication of cough, discomfort, muscle spasm, or other characteristic.

[0072] At decision block 710, the fourth method 700 includes determining whether each of the first and second portions of the sensor signal indicates an adverse effect, or a likelihood of an adverse effect. If an adverse effect is indicated, then the fourth method 700 proceeds to operation 712. If an adverse effect is not indicated, then the fourth method 700 continues at operation 714 with using the first electrode pair for additional neurostimulation therapy.

[0073] In an example, at decision block 710, the fourth method 700 can include determining whether an adverse effect identified in the first portion of the sensor signal indicates the same type of adverse effect identified in the second portion of the sensor signal. If the same type of adverse effect is identified in first and second portions of the sensor signal, then the fourth method 700 can continue at operation 712 or operation 714. If different types of adverse effects are identified, then other remedial actions can be taken.

[0074] In an example, the fourth method 700 can include determining an ensemble average of the first and second portions of the sensor signal. The ensemble average can, in some examples, indicate a presence or absence of an adverse effect. Accordingly, at decision block 710, an example can include determining whether an adverse effect is present in the ensemble average information.

[0075] At operation 712, the fourth method 700 includes taking a remedial action to update or adjust a therapy parameter before providing a subsequent stimulation therapy, such as a third neurostimulation therapy. For example, operation 712 can include selecting a different second electrode pair to use for the third neurostimulation therapy, where the second electrode pair is a known-good electrode pair or is a pair that is known to be unlikely to elicit the same adverse effect detected at decision block 710 or to elicit another adverse effect. In an example, the second electrode pair can use substantially the same therapy signal parameters as used in the first neurostimulationtherapy, or different therapy signal parameters can be used. Alternatively to selecting the second electrode pair, operation 712 can include using the first electrode pair for the third neurostimulation therapy, however, the third neurostimulation therapy can use updated or adjusted second therapy signal parameters that are different than the first therapy signal parameters. For example, a magnitude or duration of a pulse signal can be different for the first and second therapy signal parameters.

[0076] In an example, the fourth method 700 can further include identifying autonomic engagement (e.g., with a therapeutic benefit) using the information in the first and / or second portions of the sensor signal. Selection of the first or second electrode pair at operation 712 can optionally be influenced by the presence of absence of autonomic engagement.

[0077] FIG. 8 illustrates generally an example of a fifth method 800 that can include determining whether a sensor signal indicates an adverse effect or side effect in response to a therapy delivery event and, optionally, taking a remedial action to avoid further adverse effects.

[0078] At operation 802, the fifth method 800 includes providing doses of a neurostimulation therapy to a portion of a vagus nerve such as using the first tripolar lead assembly 300. In an example, the doses are separated in time by at least an inter-dose duration, and the doses are delivered using a first electrode pair of multiple available electrode pairs on the first tripolar lead assembly 300. The doses of the neurostimulation therapy can optionally include doses that comprise stimulation pulses that progressively ramp up or ramp down in amplitude and / or frequency. Other stimulation parameters can similarly be varied for each dose, or in an intra-dose manner.

[0079] At operation 804, the fifth method 800 includes using a first sensor to measure respective physiologic responses to the doses of the therapy. The measurements can be performed during respective inter-dose durations. In other examples, the measurements can be performed concurrently with therapy dose delivery.

[0080] In an example, the first sensor comprises the sensor 118, such as can comprise an accelerometer. Other sensors can similarly be used, such as canbe configured to measure electrogram information, cardiac activity information, electroneurogram information, impedance information, posture information, thoracic or abdominal motion information, or other information. In an example, operation 804 can include or use a patient-reported physiologic response.

[0081] At operation 806, the fifth method 800 includes determining whether each response measured at operation 804 indicates a presence or absence of an adverse effect. In some examples, the fifth method 800 can further include determining whether each response indicates a therapeutic effect on the patient.

[0082] At operation 808, the fifth method 800 includes determining a number of consecutive responses that indicate an adverse effect. In an example, in response to identifying N (e.g., N is an integer greater than 1) consecutive responses that indicate an adverse effect, operation 808 can include at least one of (1) changing a parameter of the neurostimulation therapy for a subsequent neurostimulation therapy, and (2) selecting a different second electrode pair of the multiple available electrode pairs for the subsequent neurostimulation therapy. At operation 810, the fifth method 800 can include providing a dose of the subsequent neurostimulation therapy to the vagus nerve using the changed parameters or different electrode pair.

[0083] In an example, the fifth method 800 includes determining an ensemble average of the N (or more) responses that indicate the adverse effect. In response to determining the ensemble average meets a threshold condition for the adverse effect, the fifth method 800 can include selecting the different second electrode pair for the subsequent neurostimulation therapy, and in response to determining the ensemble average fails to meet the threshold condition for the adverse effect, the fifth method 800 can include selecting the first electrode pair for the subsequent neurostimulation therapy.

[0084] Determining whether the ensemble average meets a threshold condition can be accomplished in various ways. For example, the ensemble average can be compared to a template. In another example, a characteristic(e.g., magnitude, frequency content, etc.) of the ensemble average can be compared to a reference or baseline characteristic of the same type.

[0085] The present inventors have recognized that a problem to be solved includes early detection of implantable lead deterioration or failure. The problem can include identifying lead stress or fatigue, or lead insulation wear or breach, or other structural issue that can compromise lead integrity. If a lead is fatigued (e.g., worn, breached, etc.) due to, for example, repeated flexing or other motion, then one or more conductors or insulators that comprise the lead may degrade or otherwise be compromised. The present inventors have recognized that a solution to the problem can include or use a multipolar lead, such as the first tripolar lead assembly 300, and can include monitoring various characteristics of the assembly, to provide early detection and thereby enable early intervention or remediation.

[0086] In an example, the first tripolar lead assembly 300 comprises multiple conductors (e.g., wires) that extend from circuitry in a housing of the implantable device 112, along a lead body portion of the assembly, to distal addressable electrodes such as the first electrode 308, the second electrode 312, and the third electrode 316, etc. In an example, the conductors comprise one or more substantially straight or linear conductors, or can comprise wound or helical conductors, or ribbons, that extend along all or a portion of the lead body. In an example, some conductors can comprise a twisted pair of conductors (or twisted arrangement of three or more conductors) that extends along all or a portion of the lead body.

[0087] In an example, the implantable system can be configured to conduct measurements of electrical properties such as capacitance and inductance along the signal paths formed by the conductors extending to the electrodes. The measurement and monitoring of electrical properties or characteristics can help assess the integrity of the lead assembly in real-time. Changes in the electrical characteristics may indicate potential issues such as insulation degradation, conductor fatigue, or other structural compromises within the lead assembly.

[0088] In an example, predefined baseline values can be used for capacitance and inductance characteristics of the leads or conductors, such as can represent the expected normal ranges under typical operating conditions. Any deviation from these baseline values can trigger an alert within the system, indicating a potential compromise in lead integrity. This proactive monitoring allows for early detection of faults, enabling timely intervention measures such as adjustments in therapy delivery or recommendations for lead maintenance or replacement.

[0089] The conductors inside the first tripolar lead assembly 300 can be configured such that at least one of the conductors can be relatively more susceptible to fatigue, or more likely to be exposed from a breach in the outermost layer(s) of the lead body, than the other conductor(s) in the same lead assembly. For example, a conductor that occupies an outermost portion of the lead body may experience a greatest amount of bending fatigue stress as the patient goes about their daily activities. Accordingly, characteristics of the outermost conductor can be tested or monitored most closely, and any problem or anomaly detected in the outermost conductor can provide an early indication that the lead assembly may be compromised or may imminently need replacement. In an example, the anomaly can be detected through routine impedance measurements (or other tests) that include or use the electrode that is coupled to the outermost conductor of the lead body.

[0090] In an example, the outermost conductor can be configured to exhibit a different flexure durability or resilience relative to the inner conductor(s), wherein the outer conductor is more susceptible to flexural stress due to its radial positioning furthest from the lead body central axis. The configuration enables the outer conductor to experience relatively more bending and flexing during normal patient activities, thereby providing an early indication of structural compromise through enhanced sensitivity to fatigue and mechanical wear. In some examples, the outer conductor can be configured to have an inferior flexure resilience relative to one or more other conductors of the same lead assembly. In other words, a flexure resiliencecharacteristic of the one or more inner conductors exceeds a flexure resilience characteristic of the outer conductor.

[0091] Flexure resilience, or a flexure resilience characteristic, in the context of implantable lead assemblies refers to the ability of the lead components, such as the conductors and the supporting structures such as the inner lumen, to withstand repeated bending and flexing without degrading in performance or integrity. Resilience to flexure or bending stress ensures that the device maintains its functional reliability and longevity, reducing the risk of device failure and the need for surgical interventions.

[0092] Flexure resilience can be quantified through mechanical testing that measures the ability of a material or assembly to return to its original shape and / or retain an original property (e.g., conductivity, resistance, etc.) after being bent or flexed. Common metrics include the number of flex cycles the material can endure before failure and the degree of deformation or damage after a specified number of cycles. Testing can be conducted using a flexure testing machine which repeatedly bends a sample at a controlled angle, speed, and number of cycles. For example, a cyclic flexure test can include clamping the lead assembly (or a component thereof) at both ends and then cyclically bending it through a specified angle for a number of cycles. The test continues until the lead shows signs of mechanical fatigue or breaks. The number of cycles survived before failure provides a direct measure of a flexure resilience characteristic of the assembly or component under test.

[0093] Several factors can influence the flexure resilience characteristic of implantable leads. For example, the choice of materials for the conductors and the insulating sheaths impacts resilience. Materials with higher ductility and elastic modulus typically exhibit better flexure resilience. In an example, the geometry and arrangement of conductors within the lead body, such as twisted pairs or coiled designs, can enhance flexural endurance by distributing mechanical stress more evenly. Thicker or multi-layered insulation can provide additional mechanical protection and improve the overall resilience of a lead. In an example, methods used to fabricate the lead components, including curing processes for polymers and annealing formetals, can affect the mechanical properties of the materials, thereby influencing their flexure resilience.

[0094] FIG. 9 illustrates generally a schematic example of an implantable lead assembly 900, such as can comprise a portion of the first tripolar lead assembly 300 from FIG. 3. For example, the implantable lead assembly 900 can comprise the first electrode 308 coupled with the first helical anchor 306, the second electrode 312 coupled with the second helical anchor 310, and the third electrodes 316 coupled with the third helical anchor 314. In an example, the helical anchors and electrodes of the implantable lead assembly 900 can be configured to be disposed at or around a portion of the vagus nerve 302, as similarly described in the example of FIG. 3. For ease of illustration and clarity, various components or aspects of the implantable lead assembly 900 are not drawn to scale.

[0095] The implantable lead assembly 900 includes a lead body 902 that is configured to extend from an implantable device housing (e.g., comprising the implantable device 112) to the electrodes of the implantable lead assembly 900, or to a coupler (or one or more couplers) that electrically and mechanically connects conductors of the lead to the electrodes. The coupler is omitted from the illustration of the implantable lead assembly 900, and instead the electrical connections between the conductors and the electrodes are shown schematically. The illustrated portion of the lead body 902 includes a cut-away view to show various spatial relationships between components of the implantable lead assembly 900.

[0096] In an example, the lead body 902 comprises a lead body sheath 904 that includes a biocompatible flexible coating. The lead body 902 further comprises multiple conductors inside the lead body sheath 904 and a lead body lumen 910 inside the lead body sheath 904. In an example, one or more of the conductors are provided inside the lead body lumen 910, and the lead body lumen 910 can extend substantially coaxially with a lead body central axis 916. In other examples, the lead body lumen 910 can be offset radially from the lead body central axis 916. In an example, the lead body lumen 910 is omitted and one or more conductors are otherwise positioned or mountedinside the lead body 902. In other examples, the implantable lead assembly 900 can include multiple lumens that extend in parallel along a length of the lead body 902.

[0097] In the example of FIG. 9, the lead body 902 comprises an outer lead conductor 908. The outer lead conductor 908 can be a particular conductor, of multiple conductors in the lead body 902, that is located most distal to the lead body central axis 916, or is most radially distant from the lead body central axis 916 relative to the other conductor(s). In an example, the outer lead conductor 908 is a cylindrical conductor, a conductive sheath, a wound or helical conductor, a film or ribbon conductor, or other conductor. The outer lead conductor 908 can be coupled to any one or more of the electrodes of the implantable lead assembly 900. In the example of FIG. 9, the outer lead conductor 908 is coupled to the first electrode 308, and the first electrode 308 is the electrode that is most proximal to the housing of the implantable device 112. In an example, the outer lead conductor 908 is coupled to the first electrode 308 using a first conductor 906. In an example, the first conductor 906 can comprise a portion of the outer lead conductor 908 or vice versa.

[0098] In the example of FIG. 9, a second conductor 912 and a third conductor 914 are respectively coupled to the second electrode 312 and the third electrode 316. The second conductor 912 and the third conductor 914 can be positioned at or near, and can extend along, the lead body central axis 916. In an example, the second conductor 912 and the third conductor 914 comprise a twisted pair of conductors that extends through the lead body lumen 910. In an example, the lead body lumen 910 comprises a conductive shield, such as can comprise a conductive film or woven conductor. Other conductor types and configurations can similarly be used. Generally, however, the outer lead conductor 908, which can comprise or can be coupled to the first conductor 906, is provided radially more distant from the lead body central axis 916 than the second conductor 912 and the third conductor 914.

[0099] In an example, one or more insulators can be provided inside the lead body 902. For example, each of the conductors can be separately insulated, or other electrically insulating materials can be provided between the conductors. For example, a first electrical insulator can be provided between the lead body sheath 904 and the outer lead conductor 908, and a second electrical insulator can be provided between the outer lead conductor 908 and one or more of the inner conductors, such as the second conductor 912 and the third conductor 914. In an example, the second electrical insulator can be provided between the outer lead conductor 908 and the lead body lumen 910, or the lead body lumen 910 can comprise an insulator. Various other insulators, such as having different dielectric and flexibility characteristics, can be used.

[0100] In an example, the lead body lumen 910 is configured to organize and protect one or more conductors extending therein. The lead body lumen 910 can serve as a dedicated channel within the lead body 902 configured to ensure that the inner conductors are securely positioned and isolated from external mechanical stresses. That is, the lead body lumen 910 can help minimize exposure of the inner conductors to direct mechanical stresses, such as bending and twisting, which are common during the routine movements of the patient. The lead body lumen 910 can be configured to augment the flexure resilience of the inner conductors. Flexure resilience refers to the ability of the conductors to withstand repeated bending and flexing without sustaining damage. The design of the lead body lumen 910 supports this by providing a buffer around the conductors to help absorb and distribute mechanical forces more evenly across the conductors.

[0101] In an example, the lead fault identification techniques discussed herein can be used together with the implantable lead assembly 900 to provide early identification of a functionally compromised lead. For example, the outer lead conductor 908 (and, correspondingly, the first electrode 308 coupled to the outer lead conductor 908) can be selected for use with the first electrode pair in any of the first method 400, the second method 500, or the third method 600. If an error or fault is detected when theelectrode coupled to the outer lead conductor 908 is used, then the detected error or fault can be an early indicator of lead deterioration or imminent lead failure. Furthermore, the detected error or fault can indicate a need to switch the electrode pair that is selected for use in therapy delivery and / or sensing.

[0102] In an example, the lead body 902 and / or the helical anchors of the implantable lead assembly 900 can comprise a material having a color that contrasts with body tissue. For example, the lead body or helical structures can be made of a white or black biocompatible polymer. In an example, the lead body 902 can comprise a cable inside the lead and / or inside the helical structures coupled to the lead. The cable can have a high tensile strength such that it can be pulled to remove it from the patient, and the cable will stay together instead of unravel during explantation. It may be particularly advantageous to provide a lead assembly (e.g., comprising one or multiple electrodes) with the cable and with an anti-ingrowth agent that is applied to, or integrated with, one or more components of the lead assembly, to help facilitate later removal of the lead assembly.

[0103] FIG. 10 is a diagrammatic representation of a machine 1000 within which instructions 1008 (e.g., software, a program, an application, an applet, an app, or other executable code) for causing the machine 1000 to perform any one or more of the methodologies discussed herein may be executed. The machine 1000 can optionally comprise the implantable devices, systems, and components discussed herein, such as the implantable device 112, the first tripolar lead assembly 300, the implantable lead assembly 900, or others, or components or devices that can be coupled to at least one of the implantable systems or components discussed herein.

[0104] In an example, the instructions 1008 may cause the machine 1000 to execute any one or more of the methods, controls, therapy algorithms, signal generation routines, or other processes described herein. The instructions 1008 transform the general, non-programmed machine 1000 into a particular machine 1000 programmed to carry out the described and illustrated functions in the manner described. The machine 1000 may operate as a standalone device or may be coupled (e.g., networked) to other machines. Ina networked deployment, the machine 1000 may operate in the capacity of a server machine or a client machine in a server-client network environment, or as a peer machine in a peer-to-peer (or distributed) network environment. The machine 1000 can comprise, but is not limited to, various systems or devices that can communicate with the implantable system, such as can include a server computer, a client computer, a personal computer (PC), a tablet computer, a laptop computer, a netbook, a set-top box (STB), a PDA, an entertainment media system, a cellular telephone, a smart phone, a mobile device, a wearable device (e.g., a smart watch), a smart home device (e.g., a smart appliance), other smart devices, a web appliance, a network router, a network switch, a network bridge, or any machine capable of executing the instructions 1008, sequentially or otherwise, that specify actions to be taken by the machine 1000. Further, while only a single machine 1000 is illustrated, the term “machine” shall also be taken to include a collection of machines that individually or jointly execute the instructions 1008 to perform any one or more of the methodologies discussed herein.

[0105] The machine 1000 may include processors 1002, memory 1004, and I / O components 1042, which may be configured to communicate with each other via a bus 1044. In an example embodiment, the processors 1002 (e.g., a Central Processing Unit (CPU), a Reduced Instruction Set Computing (RISC) processor, a Complex Instruction Set Computing (CISC) processor, a Graphics Processing Unit (GPU), a Digital Signal Processor (DSP), an ASIC, a Radio-Frequency Integrated Circuit (RFIC), another processor, or any suitable combination thereof) may include, for example, a processor 1006 and a processor 1010 that execute the instructions 1008. The term “processor” is intended to optionally include multi-core processors that may comprise two or more independent processors (sometimes referred to as “cores”) that may execute instructions contemporaneously. Although FIG. 10 shows multiple processors 1002, the machine 1000 may include a single processor with a single core, a single processor with multiple cores (e.g., a multi-core processor), multiple processors with a single core, multiple processors with multiples cores, or any combination thereof.

[0106] The memory 1004 includes a main memory 1012, a static memory 1014, and a storage unit 1016, both accessible to the processors 1002 via the bus 1044. The main memory 1004, the static memory 1014, and storage unit 1016 store the instructions 1008 embodying any one or more of the methodologies or functions described herein. The instructions 1008 may also reside, completely or partially, within the main memory 1012, within the static memory 1014, within a machine-readable medium 1018 within the storage unit 1016, within at least one of the processors 1002 (e.g., within the processor’s cache memory), or any suitable combination thereof, during execution thereof by the machine 1000.

[0107] The I / O components 1042 may include a variety of components to receive input, provide output, produce output, transmit information, exchange information, capture measurements, and so on. The specific I / O components 1042 that are included in a particular machine will depend on the type of machine. For example, portable machines such as device programmers or mobile phones may include a touch input device or other such input mechanisms, while a headless server machine will likely not include such a touch input device. It will be appreciated that the I / O components 1042 may include other components that are not shown in FIG. 10. In various example embodiments, the I / O components 1042 may include output components 1028 and input components 1030. The output components 1028 may include visual components (e.g., a display such as a plasma display panel (PDP), a light emitting diode (LED) display, a liquid crystal display (LCD), a projector, or a cathode ray tube (CRT)), acoustic components (e.g., speakers), haptic components (e.g., a vibratory motor, resistance mechanisms), other signal generators, and so forth. The input components 1030 may include alphanumeric input components (e.g., a keyboard, a touch screen configured to receive alphanumeric input, a photo- optical keyboard, or other alphanumeric input components), point-based input components (e.g., a mouse, a touchpad, a trackball, a joystick, a motion sensor, or another pointing instrument), tactile input components (e.g., a physical button, a touch screen that provides location and / or force of touches or touch gestures, or other tactile input components), audio inputcomponents (e.g., a microphone), physiologic sensor components, and the like.

[0108] In further example embodiments, the I / O components 1042 may include biometric components 1032, motion components 1034, environmental components 1036, or position components 1038, among others. For example, the biometric components 1032 can include components to detect expressions (e.g., hand expressions, facial expressions, vocal expressions, body gestures, or eye tracking), measure biosignals (e.g., blood pressure, heart rate, body temperature, perspiration, or brain waves), identify a person (e.g., voice identification, retinal identification, facial identification, fingerprint identification, or electroencephalogram-based identification), and the like. The motion components 1034 can include an acceleration sensor (e.g., an accelerometer comprising an example of the sensor 118), gravitation sensor components, rotation sensor components (e.g., a gyroscope), or similar. The environmental components 1036 can include, for example, illumination sensor components (e.g., photometer), temperature sensor components (e.g., one or more thermometers that detect ambient temperature), humidity sensor components, pressure sensor components (e.g., barometer), acoustic sensor components (e.g., one or more microphones that detect background noise), proximity sensor components (e.g., infrared sensors that detect nearby objects), gas sensors (e.g., gas detection sensors to detection concentrations of hazardous gases for safety or to measure pollutants in the atmosphere), or other components that may provide indications, measurements, or signals corresponding to a surrounding physical environment. The position components 1038 can include location sensor components (e.g., a GPS receiver component), altitude sensor components (e.g., altimeters or barometers that detect air pressure from which altitude may be derived), orientation sensor components (e.g., magnetometers), and the like.

[0109] Communication may be implemented using a wide variety of technologies. The I / O components 1042 further include communication components 1040 operable to couple the machine 1000 to anetwork 1020 or other devices 1022 via a coupling 1024 and a coupling 1026, respectively. For example, the communication components 1040 may include a network interface component or another suitable device to interface with the network 1020. In further examples, the communication components 1040 may include wired communication components, wireless communication components, cellular communication components, Near Field Communication (NFC) components, Bluetooth components, or Wi-Fi components, among others. The devices 1022 may be another machine or any of a wide variety of peripheral devices such as can include other implantable or external devices.

[0110] The various memories (e.g., memory 1004, main memory 1012, static memory 1014, and / or memory of the processors 1002) and / or storage unit 1016 can store one or more sets of instructions and data structures (e.g., software) embodying or used by any one or more of the methodologies or functions described herein. These instructions (e.g., the instructions 1008), when executed by processors 1002, cause various operations to implement the disclosed embodiments, including various neuromodulation or neurostimulation therapies or functions supportive thereof.

[0111] The following Examples provide a non-limiting overview of the tripolar lead, neurostimulation vector selection, and neurostimulation vector optimization devices, systems and methods discussed herein.

[0112] Example 1 is a system comprising: an implantable lead assembly comprising: a flexible lead body configured to extend from a header of an implantable device housing to multiple distal electrodes; a plurality of conductors disposed within the lead body, the conductors configured to transmit respective electrical signals to the electrodes, wherein the conductors include, at least one outer conductor positioned radially outermost relative to one or more inner conductors inside the lead body, wherein each of the conductors extends along an axis of the lead body; an insulator provided between the outer conductor and the one or more inner conductors; a first distal electrode of the multiple distal electrodes, wherein the first distal electrode is coupled to the at least one outer conductor; and asecond distal electrode of the multiple distal electrodes, wherein the second distal electrode is coupled to one of the inner conductors; wherein a flexure resilience characteristic of the outer conductor is different than a flexure resilience characteristic of the one or more inner conductors.

[0113] In Example 2, the subject matter of Example 1 optionally includes a flexure resilience characteristic of the outer conductor is inferior to a flexure resilience characteristic of the one or more inner conductors. Stated differently, in Example 2, a flexure resilience characteristic of the one or more inner conductors exceeds a flexure resilience characteristic of the outer conductor.

[0114] In Example 3, the subject matter of any one or more of Examples 1- 2 optionally includes a processor circuit configured to: measure electrical characteristics of respective signal paths that include the first and second distal electrodes; and provide an indication of an integrity of the implantable lead assembly based on the measured electrical characteristics.

[0115] In Example 4, the subject matter of Example 3 optionally includes the processor circuit is configured to provide an indication of lead failure for the implantable lead assembly when the measured electrical characteristic of the signal path that includes the first electrode deviates from a specified reference characteristic.

[0116] In Example 5, the subject matter of any one or more of Examples 3-4 optionally includes the processor circuit is configured to measure impedance along the respective signal paths, and wherein the indication of integrity is based on changes in the measured impedance relative to a baseline impedance value.

[0117] In Example 6, the subject matter of any one or more of Examples 3-5 optionally includes the processor circuit is configured to measure capacitance and / or inductance of the respective signal paths, and the indication of integrity is based on variations in capacitance and / or inductance that deviate from specified expected values.

[0118] In Example 7, the subject matter of any one or more of Examples 3-6 optionally includes a memory storing a history of the electricalcharacteristics measured over time, and the processor circuit is configured to compare current measurements with the history of the electrical characteristics to detect changes in the electrical characteristics indicative of deterioration of the lead assembly.

[0119] In Example 8, the subject matter of any one or more of Examples 1-7 optionally includes a processor circuit configured to execute a lead integrity assessment routine by measuring a first impedance characteristic at a first time using a first pair of electrodes comprising the first and second distal electrodes, measuring a second impedance characteristic at a second time using the same first pair of electrodes, and identifying a lead fault based on a relationship between a specified threshold impedance characteristic and the measured first and second impedance characteristics.

[0120] In Example 9, the subject matter of any one or more of Examples 1-8 optionally includes a processor circuit configured to perform a series of at least three discrete impedance measurements for a first electrode pair comprising the first and second distal electrodes, wherein the processor circuit is configured to determine if each of the impedance measurements is outside of a specified impedance value range and, in response, provide an indication of a lead fault for the implantable lead assembly.

[0121] In Example 10, the subject matter of any one or more of Examples 1-9 optionally includes a processor circuit configured to perform a series of at least two discrete, time-adjacent impedance measurements for a first electrode pair comprising the first and second distal electrodes, determine an impedance difference between impedance values of the first and subsequent second impedance measurements, and, in response to the impedance difference exceeding a specified threshold value, select a different second electrode pair from the multiple distal electrodes for use in neurostimulation therapy, wherein the different second electrode pair excludes the first distal electrode.

[0122] In Example 11, the subject matter of any one or more of Examples 1-10 optionally includes an inner lumen, wherein the one or more inner conductors are disposed inside in the inner lumen.

[0123] In Example 12, the subject matter of Example 11 optionally includes the inner lumen is configured to augment a flexure resilience of the one or more inner conductors in the lead assembly.

[0124] In Example 13, the subject matter of any one or more of Examples 1-12 optionally includes a processor circuit configured to: coordinate delivery of a first neurostimulation therapy to a vagus nerve using a first electrode pair of the implantable lead assembly, wherein the first electrode pair comprises the first distal electrode; detect an error associated with the first distal electrode; and in response to detecting the error associated with the first distal electrode: provide an indication of a lead fault condition to a patient or clinician; and coordinate delivery of a second neurostimulation therapy to the vagus nerve using a second electrode pair of the implantable lead assembly, wherein the second electrode pair comprises the second distal electrode and excludes the first distal electrode.

[0125] Example 14 is an implantable lead assembly comprising: a lead body having a proximal end configured to be coupled with a header of an implantable device housing, and a distal portion comprising multiple electrodes; a first helical structure comprising a first electrode of the multiple electrodes; a second helical structure comprising a second electrode of the multiple electrodes; a third helical structure comprising a third electrode of the multiple electrodes, wherein the second helical structure is more proximal to the proximal end of the lead body than the third helical structure, and wherein the first helical structure is more proximal to the proximal end of the lead body than the second helical structure; wherein the lead body comprises: a first conductor extending axially along the lead from the proximal end and coupled to the first electrode; a second conductor extending axially along the lead from the proximal end and coupled to the second electrode; and a third conductor extending axially along the lead from the proximal end and coupled to the third electrode; wherein the second and third conductors are disposed radially nearer to a central axis of the lead body relative to the first conductor.

[0126] In Example 15, the subject matter of Example 14 optionally includes the first conductor has a different flexure resilience characteristic than the second and / or third conductors.

[0127] In Example 16, the subject matter of any one or more of Examples 14-15 optionally includes the second and third conductors comprise a twisted pair of conductors, and the first conductor is radially spaced apart from the twisted pair of the second and third conductors by an insulator.

[0128] In Example 17, the subject matter of Example 16 optionally includes the first conductor extends along a helical path from the proximal end of the lead body to the first electrode.

[0129] In Example 18, the subject matter of any one or more of Examples 14-17 optionally includes the first conductor comprises a conductive sheath.

[0130] In Example 19, the subject matter of any one or more of Examples 14-18 optionally includes the second and third conductors are disposed within an inner lumen, and wherein the first conductor is outside of the inner lumen.

[0131] In Example 20, the subject matter of any one or more of Examples 14-19 optionally includes the first conductor comprising a twisted pair of conductors.

[0132] Example 21 is a system comprising: the implantable lead assembly of Example 14; and a controller circuit configured to: deliver a first neurostimulation therapy to a vagus nerve using a first electrode pair of the implantable lead assembly, wherein the first electrode pair comprises the first electrode; detect an error associated with the first electrode; and in response to detecting the error associated with the first electrode: provide an indication of a lead fault condition to a patient or clinician; and deliver a second neurostimulation therapy to the vagus nerve using a second electrode pair of the implantable lead assembly, wherein the second electrode pair comprises the second and third electrodes and excludes the first electrode.

[0133] Example 22 is a lead fault identification method for an implantable lead, the method comprising: using a lead integrity assessment routine initiated by a control circuit in an implantable medical device housing,measuring a first impedance characteristic at a first time using a first pair of electrodes of a first implantable lead, the first implantable lead comprising at least first, second, and third electrodes configured to be disposed at or around a nerve, wherein the first pair of electrodes comprises the first and second electrodes; measuring a second impedance characteristic at a second time, subsequent to the first time, using the first pair of electrodes of the first implantable lead; and identifying a lead fault for the first implantable lead based on a relationship between a specified threshold impedance characteristic and the measured first and second impedance characteristics.

[0134] In Example 23, the subject matter of Example 22 optionally includes providing a neurostimulation therapy to the nerve using a second pair of electrodes that comprises the first and third electrodes of the first implantable lead.

[0135] In Example 24, the subject matter of Example 23 optionally includes providing the neurostimulation therapy including providing the neurostimulation therapy during an interval that follows the first impedance characteristic measurement at the first time and precedes the second impedance characteristic measurement at the second time.

[0136] In Example 25, the subject matter of any one or more of Examples 22-24 optionally includes providing a neurostimulation therapy to the nerve using the first pair of electrodes, wherein providing the neurostimulation therapy includes providing the neurostimulation therapy during an interval that follows the first impedance characteristic measurement at the first time and precedes the second impedance characteristic measurement at the second time.

[0137] In Example 26, the subject matter of any one or more of Examples 22-25 optionally includes, relative to an implantable housing coupled to the implantable lead, the first electrode is a proximal electrode, the second electrode is an intermediate electrode, and the third electrode is a distal electrode.

[0138] In Example 27, the subject matter of Example 26 optionally includes the electrodes are provided on respective helical supports configured to wrap around at least a portion of a target nerve.

[0139] In Example 28, the subject matter of any one or more of Examples 22-27 optionally includes identifying the lead fault for the first implantable lead including determining that each of the measured first and second impedance characteristics exceeds the specified threshold impedance characteristic.

[0140] In Example 29, the subject matter of any one or more of Examples 22-28 optionally includes the specified threshold impedance characteristic is a specified impedance magnitude amount; and wherein identifying the lead fault includes determining whether a difference between the measured first and second impedance characteristics exceeds the specified impedance magnitude amount.

[0141] In Example 30, the subject matter of any one or more of Examples 22-29 optionally includes identifying the lead fault based on a trend of the measured first and second impedance characteristics.

[0142] In Example 31, the subject matter of any one or more of Examples 22-30 optionally includes identifying the lead fault based on a difference between the measured first and second impedance characteristics, and the specified threshold impedance characteristic is based on a duration of a time interval elapsed between the first and second impedance measurements.

[0143] In Example 32, the subject matter of any one or more of Examples 22-31 optionally includes, in response to identifying the lead fault, selecting a different second pair of electrodes of the first implantable lead for impedance testing, wherein the different second pair of electrodes includes the third electrode and only one of the first and second electrodes.

[0144] In Example 33, the subject matter of any one or more of Examples 22-32 optionally includes, in response to identifying the lead fault, selecting a different second pair of electrodes of the first implantable lead for therapy delivery.

[0145] In Example 34, the subject matter of any one or more of Examples 22-33 optionally includes, in response to identifying the lead fault, providing a notification to a patient, caregiver, or clinician about the identified lead fault.

[0146] Example 35 is a system comprising: an implantable lead assembly including a flexible lead body configured to extend from a header of an implantable device housing to multiple distal electrodes, wherein the lead body optionally includes at least first, second, and third electrodes configured to be disposed at or around a nerve; and a processor circuit configured to perform a lead integrity assessment routine, the assessment routine including measuring a first impedance characteristic at a first time using a first pair of electrodes comprising the first and second electrodes, measuring a second impedance characteristic at a second time using the same first pair of electrodes, and identifying a lead fault based on a relationship between a specified threshold impedance characteristic and the measured first and second impedance characteristics.

[0147] In Example 36, the subject matter of Example 35 optionally includes the processor circuit is further configured to provide neurostimulation therapy to the nerve using a second pair of electrodes comprising the first and third electrodes of the implantable lead.

[0148] In Example 37, the subject matter of Example 36 optionally includes the processor circuit is configured to provide the neurostimulation therapy during an interval that follows the first impedance characteristic measurement and precedes the second impedance characteristic measurement.

[0149] In Example 38, the subject matter of any one or more of Examples 35-37 optionally includes the processor circuit is configured to provide neurostimulation therapy to the nerve using the first pair of electrodes during an interval that follows the first impedance characteristic measurement and precedes the second impedance characteristic measurement.

[0150] In Example 39, the subject matter of any one or more of Examples 35-38 optionally includes the first electrode is a proximal electrode, thesecond electrode is an intermediate electrode, and the third electrode is a distal electrode, and wherein the electrodes are provided on respective helical supports configured to wrap around at least a portion of a target nerve.

[0151] In Example 40, the subject matter of any one or more of Examples 35-39 optionally includes the processor circuit is configured to identify the lead fault by determining that each of the measured first and second impedance characteristics exceeds the specified threshold impedance characteristic, and the specified threshold impedance characteristic is a specified impedance magnitude amount.

[0152] In Example 41, the subject matter of any one or more of Examples 35-40 optionally includes the processor circuit is configured to, in response to identifying the lead fault, select a different second pair of electrodes of the implantable lead for impedance testing or therapy delivery, wherein the different second pair of electrodes includes the third electrode and only one of the first and second electrodes.

[0153] Example 42 is a lead fault identification method for an implantable lead, the method comprising: performing a series of at least three discrete impedance measurements for a first electrode pair of multiple electrode pairs, wherein the multiple electrode pairs comprise electrodes coupled to an electrostimulation circuit in an implantable device housing using a single implantable lead; and in response to each of the at least three impedance measurements being outside of a specified impedance value range, providing an indication of a lead fault for the single implantable lead.

[0154] In Example 43, the subject matter of Example 42 optionally includes the impedance measurements are interleaved with therapy delivery events.

[0155] In Example 44, the subject matter of any one or more of Examples 42-43 optionally includes the specified impedance value range is based on a baseline impedance measurement taken during an initial setup or calibration phase of the implantable device.

[0156] In Example 45, the subject matter of any one or more of Examples 42-44 optionally includes, in response to the indication of a lead fault, automatically adjusting one or more therapy delivery parameters to mitigate potential impacts on therapy effectiveness until the lead fault is resolved.

[0157] Example 46 is a lead fault identification method for an implantable lead, the method comprising: performing a series of at least first and subsequent second discrete impedance measurements for a first electrode pair of multiple electrode pairs, wherein the multiple electrode pairs comprise electrodes coupled to an electrostimulation circuit in an implantable device housing using a single implantable lead; determining an impedance difference between impedance values of the first and subsequent second impedance measurements; and in response to the impedance difference exceeding a specified threshold value, selecting a different second electrode pair, from the multiple electrode pairs, for use in a neurostimulation therapy.

[0158] In Example 47, the subject matter of Example 46 optionally includes determining whether one or both of the electrodes of the first electrode pair is faulty.

[0159] In Example 48, the subject matter of any one or more of Examples 46-47 optionally includes the first discrete impedance measurement immediately precedes a blanking interval and the subsequent second discrete impedance measurement immediately follows the blanking interval.

[0160] In Example 49, the subject matter of any one or more of Examples 46-48 optionally includes the first discrete impedance measurement immediately precedes a therapy delivery event and the subsequent second discrete impedance measurement immediately follows the same therapy delivery event.

[0161] In Example 50, the subject matter of any one or more of Examples 46-49 optionally includes the specified threshold value is based on historical impedance measurements for the first electrode pair.

[0162] In Example 51, the subject matter of any one or more of Examples 46-50 optionally includes, in response to the impedance differenceexceeding the specified threshold value, notifying a healthcare provider via a connected health monitoring system that the implantable lead may be faulty.

[0163] Example 52 is a method comprising: delivering a first neurostimulation therapy to a nerve target using a first electrode pair, wherein the first electrode pair comprises one of multiple electrode pairs available on a lead that is coupled to a stimulation circuit in an implantable device housing; measuring a first portion of a sensor signal for a specified first duration following delivery of the first neurostimulation therapy; delivering a second neurostimulation therapy to the nerve target using the first electrode pair, wherein the first and second neurostimulation therapies have substantially the same first therapy signal parameters; measuring a second portion of a sensor signal for a specified second duration following delivery of the second neurostimulation therapy ; and in response to determining each of the first and second portions of the sensor signal indicates an adverse effect, delivering a third neurostimulation therapy to the nerve target (1) using a second electrode pair, wherein the second electrode pair comprises a different one of the multiple electrode pairs available on the lead, or (2) using the first electrode pair and second therapy signal parameters that are different than the first therapy signal parameters.

[0164] In Example 53, the subject matter of Example 52 optionally includes identifying an indication of autonomic engagement in the first and / or second portions of the sensor signal; and selecting for use, in the third neurostimulation therapy, the first or the second electrode pair based on the indication of autonomic engagement.

[0165] In Example 54, the subject matter of any one or more of Examples 52-53 optionally includes determining an ensemble average of the first and second portions of the sensor signal; wherein determining the first and second portions of the sensor signal indicate an adverse effect includes determining the ensemble average indicates the adverse effect.

[0166] In Example 55, the subject matter of any one or more of Examples 52-54 optionally includes the adverse effect is a laryngeal vibration or cough.

[0167] In Example 56, the subject matter of any one or more of Examples 52-55 optionally includes measuring the first and second portions of the sensor signal including measuring acceleration information from an accelerometer.

[0168] In Example 57, the subject matter of any one or more of Examples 52-56 optionally includes the first duration and the second duration are substantially the same length.

[0169] In Example 58, the subject matter of any one or more of Examples 52-57 optionally includes wherein the first duration and the second duration are each at least 5 seconds and less than 15 seconds.

[0170] In Example 59, the subject matter of any one or more of Examples 52-58 optionally includes determining the first and second portions of the sensor signal each indicate an adverse effect including determining the first and second portions of the sensor signal each indicate the same adverse effect.

[0171] In Example 60, the subject matter of any one or more of Examples 52-59 optionally includes determining the first and second portions of the sensor signal each indicate an adverse effect including determining the first and second portions of the sensor signal indicate respective different adverse effects.

[0172] In Example 61, the subject matter of any one or more of Examples 52-60 optionally includes the therapy signal parameters comprise one or more of a pulse waveform parameter, a pulse magnitude parameter, and a pulse frequency.

[0173] Example 62 is a system comprising: an implantable lead assembly including a flexible lead body configured to extend from a header of an implantable device housing to multiple distal electrodes; a stimulation circuit configured to provide a neurostimulation therapy signal to a nerve target using a first electrode pair that comprises first and second electrodes of the multiple distal electrodes; a sensor configured to measure portions of a sensor signal for specified durations following delivery of the neurostimulation therapy signal; and a processor circuit configured todetermine if each measured portion of the sensor signal indicates an adverse effect and, in response, to control the stimulation circuit to provide a subsequent neurostimulation therapy using either a different second electrode pair or the same first electrode pair with altered therapy signal parameters.

[0174] In Example 63, the subject matter of Example 62 optionally includes the processor circuit is configured to identify indications of autonomic engagement in the sensor signal and, in response, select the first or second electrode pair for subsequent neurostimulation therapy based on the identified indication of autonomic engagement.

[0175] In Example 64, the subject matter of any one or more of Examples 62-63 optionally includes the processor circuit is configured to calculate an ensemble average of the measured portions of the sensor signal and determine presence of an adverse effect based on the ensemble average.

[0176] In Example 65, the subject matter of any one or more of Examples 62-64 optionally includes the sensor is an accelerometer configured to measure thoracic acceleration information.

[0177] In Example 66, the subject matter of any one or more of Examples 62-65 optionally includes the sensor is an implantable sensor configured to monitor a physiologic status signal.

[0178] Example 67 is a method comprising: providing doses of a neurostimulation therapy to a portion of a vagus nerve, wherein the doses are separated in time by at least an inter-dose duration, and wherein the doses are delivered using a first electrode pair of multiple available electrode pairs on an implantable lead; using a first sensor, and during respective inter-dose durations, measuring respective responses to the doses of the neurostimulation therapy; determining whether each response indicates a presence or absence of an adverse effect; in response to identifying N consecutive responses that indicate an adverse effect, at least one of (1) changing a parameter of the neurostimulation therapy for a subsequent neurostimulation therapy, and (2) selecting a different second electrode pair of the multiple available electrode pairs for the subsequent neurostimulationtherapy; and providing a dose of the subsequent neurostimulation therapy to the vagus nerve.

[0179] In Example 68, the subject matter of Example 67 optionally includes determining whether each response indicates a therapeutic effect.

[0180] In Example 69, the subject matter of any one or more of Examples 67-68 optionally includes providing the doses of the neurostimulation therapy including providing doses comprises pulses that progressively ramp up or ramp down in amplitude and / or frequency.

[0181] In Example 70, the subject matter of any one or more of Examples 67-69 optionally includes determining an ensemble average of N or more consecutive responses that indicate the adverse effect; and in response to determining the ensemble average meets a threshold condition for the adverse effect, selecting the different second electrode pair for the subsequent neurostimulation therapy, and in response to determining the ensemble average fails to meet the threshold condition for the adverse effect, selecting the first electrode pair for the subsequent neurostimulation therapy.

[0182] In Example 71, the subject matter of Example 70 optionally includes determining whether the ensemble average meets a threshold condition including comparing the ensemble average to a template.

[0183] In Example 72, the subject matter of any one or more of Examples 70-71 optionally includes determining whether the ensemble average meets a threshold condition including comparing a magnitude characteristic of the ensemble average to a specified reference magnitude.

[0184] In Example 73, the subject matter of any one or more of Examples 67-72 optionally includes measuring the respective responses to the doses of the neurostimulation therapy including measuring respective portions of an acceleration signal from an accelerometer that is disposed in or coupled to an implantable housing, and wherein the implantable housing is coupled to the implantable lead.

[0185] Example 74 is at least one machine-readable medium including instructions that, when executed by processing circuitry, cause theprocessing circuitry to perform operations to implement of any of the methodologies described in Examples 1-73.

[0186] Example 75 is an apparatus comprising means to implement of any of Examples 1-73.

[0187] Example 76 is a system to implement of any of Examples 1-73.

[0188] Each of these non-limiting examples or embodiments can stand on its own or can be combined in various permutations or combinations with one or more of the other examples or embodiments.

[0189] This detailed description includes references to the accompanying drawings, which form a part of the detailed description. The drawings show, by way of illustration, specific embodiments in which the invention can be practiced. These embodiments are also referred to herein as“examples.” Such examples can include elements in addition to those shown or described. However, the present inventors also contemplate examples in which only those elements shown or described are provided. The present inventors contemplate examples using any combination or permutation of those elements shown or described (or one or more aspects thereof), either with respect to a particular example (or one or more aspects thereof), or with respect to other examples (or one or more aspects thereof) shown or described herein.

[0190] In this document, the terms “a” or “an” are used, as is common in patent documents, to include one or more than one, independent of any other instances or usages of “at least one” or “one or more.” In this document, the term “or” is used to refer to a nonexclusive or, such that “A or B” includes “A but not B,” “B but not A,” and “A and B,” unless otherwise indicated. In this document, the terms “including” and “in which” are used as the plain- English equivalents of the respective terms “comprising” and “wherein.”

[0191] In the following claims, the terms “including” and “comprising” are open-ended, that is, a system, device, article, composition, formulation, or process that includes elements in addition to those listed after such a term in a claim are still deemed to fall within the scope of that claim. Moreover, in the following claims, the terms “first,” “second,” and “third,” etc. are usedmerely as labels, and are not intended to impose numerical requirements on their objects.

[0192] Method examples described herein can be machine or computer- implemented at least in part. Some examples can include a computer- readable medium or machine-readable medium encoded with instructions operable to configure an electronic device to perform methods as described in the above examples. An implementation of such methods can include code, such as microcode, assembly language code, a higher-level language code, or the like. Such code can include computer readable instructions for performing various methods. The code may form portions of computer program products. Such instructions can be read and executed by one or more processors to enable performance of operations comprising a method, for example. The instructions are in any suitable form, such as but not limited to source code, compiled code, interpreted code, executable code, static code, dynamic code, and the like.

[0193] Further, in an example, the code can be tangibly stored on one or more volatile, non-transitory, or non-volatile tangible computer-readable media, such as during execution or at other times. Examples of these tangible computer-readable media can include, but are not limited to, hard disks, removable magnetic disks, removable optical disks (e.g., compact disks and digital video disks), magnetic cassettes, memory cards or sticks, random access memories (RAMs), read only memories (ROMs), and the like.

[0194] The above description is intended to be illustrative, and not restrictive. For example, the above-described examples (or one or more aspects thereof) may be used in combination with each other. Other embodiments can be used, such as by one of ordinary skill in the art upon reviewing the above description. Also, in the above Detailed Description, various features may be grouped together to streamline the disclosure. This should not be interpreted as intending that an unclaimed disclosed feature is essential to any claim. Rather, inventive subject matter may lie in less than all features of a particular disclosed embodiment. Thus, the followingstatements (aspects) are hereby incorporated into the Detailed Description as examples or embodiments, with each standing on its own as a separate embodiment, and it is contemplated that such embodiments can be combined with each other in various combinations or permutations.

Claims

What is claimed is:

1. A system comprising: an implantable lead assembly comprising: a flexible lead body configured to extend from a header of an implantable device housing to multiple distal electrodes; a plurality of conductors disposed within the lead body, the conductors configured to transmit respective electrical signals to the electrodes, wherein the conductors include at least one outer conductor positioned radially outermost relative to one or more inner conductors inside the lead body, wherein each of the conductors extends along an axis of the lead body; an insulator provided between the outer conductor and the one or more inner conductors; a first distal electrode of the multiple distal electrodes, wherein the first distal electrode is coupled to the at least one outer conductor; and a second distal electrode of the multiple distal electrodes, wherein the second distal electrode is coupled to one of the inner conductors; wherein a flexure resilience characteristic of the outer conductor is different than a flexure resilience characteristic of the one or more inner conductors.

2. The system of claim 1, wherein a flexure resilience characteristic of the one or more inner conductors exceeds a flexure resilience characteristic of the outer conductor.

3. The system of claim 1, comprising a processor circuit configured to: measure electrical characteristics of respective signal paths that include the first and second distal electrodes; and provide an indication of an integrity of the implantable lead assembly based on the measured electrical characteristics.

4. The system of claim 3, wherein the processor circuit is configured to provide an indication of lead failure for the implantable lead assembly when the measured electrical characteristic of the signal path that includes the first electrode deviates from a specified reference characteristic.

5. The system of claim 3, wherein the processor circuit is configured to measure impedance along the respective signal paths, and wherein the indication of integrity is based on changes in the measured impedance relative to a baseline impedance value.

6. The system of claim 3, wherein the processor circuit is configured to measure capacitance and / or inductance of the respective signal paths, and the indication of integrity is based on variations in capacitance and / or inductance that deviate from specified expected values.

7. The system of claim 3, comprising a memory storing a history of the electrical characteristics measured over time, and the processor circuit is configured to compare current measurements with the history of the electrical characteristics to detect changes in the electrical characteristics indicative of deterioration of the lead assembly.

8. The system of claim 1, comprising a processor circuit configured to execute a lead integrity assessment routine by measuring a first impedance characteristic at a first time using a first pair of electrodes comprising the first and second distal electrodes, measuring a second impedance characteristic at a second time using the same first pair of electrodes, and identifying a lead fault based on a relationship between a specified threshold impedance characteristic and the measured first and second impedance characteristics.

9. The system of claim 1, comprising a processor circuit configured to perform a series of at least three discrete impedance measurements for a first electrode pair comprising the first and second distal electrodes, wherein the processor circuit is configured to determine if each of the impedance measurements is outside of a specified impedance value range and, inresponse, provide an indication of a lead fault for the implantable lead assembly.

10. The system of claim 1, comprising a processor circuit configured to perform a series of at least two discrete, time-adjacent impedance measurements for a first electrode pair comprising the first and second distal electrodes, determine an impedance difference between impedance values of the first and subsequent second impedance measurements, and, in response to the impedance difference exceeding a specified threshold value, select a different second electrode pair from the multiple distal electrodes for use in neurostimulation therapy, wherein the different second electrode pair excludes the first distal electrode.

11. The system of claim 1, comprising an inner lumen, wherein the one or more inner conductors are disposed inside in the inner lumen.

12. The system of claim 11, wherein the inner lumen is configured to augment a flexure resilience of the one or more inner conductors in the lead assembly.

13. The system of claim 1, comprising a processor circuit configured to: coordinate delivery of a first neurostimulation therapy to a vagus nerve using a first electrode pair of the implantable lead assembly, wherein the first electrode pair comprises the first distal electrode; detect an error associated with the first distal electrode; and in response to detecting the error associated with the first distal electrode: provide an indication of a lead fault condition to a patient or clinician; and coordinate delivery of a second neurostimulation therapy to the vagus nerve using a second electrode pair of the implantable lead assembly, wherein the second electrode paircomprises the second distal electrode and excludes the first distal electrode.

14. An implantable lead assembly comprising: a lead body having a proximal end configured to be coupled with a header of an implantable device housing, and a distal portion comprising multiple electrodes; a first helical structure comprising a first electrode of the multiple electrodes; a second helical structure comprising a second electrode of the multiple electrodes; a third helical structure comprising a third electrode of the multiple electrodes, wherein the second helical structure is more proximal to the proximal end of the lead body than the third helical structure, and wherein the first helical structure is more proximal to the proximal end of the lead body than the second helical structure; wherein the lead body comprises: a first conductor extending axially along the lead from the proximal end and coupled to the first electrode; a second conductor extending axially along the lead from the proximal end and coupled to the second electrode; and a third conductor extending axially along the lead from the proximal end and coupled to the third electrode; wherein the second and third conductors are disposed radially nearer to a central axis of the lead body relative to the first conductor.

15. The implantable lead assembly of claim 14, wherein the first conductor has a different flexure resilience characteristic than the second and / or third conductors.

16. The implantable lead assembly of claim 14, wherein the second and third conductors comprise a twisted pair of conductors, and wherein the first conductor is radially spaced apart from the twisted pair of the second and third conductors by an insulator.

17. The implantable lead assembly of claim 16, wherein the first conductor extends along a helical path from the proximal end of the lead body to the first electrode.

18. The implantable lead assembly of claim 14, wherein the first conductor comprises a conductive sheath.

19. The implantable lead assembly of claim 14, wherein the second and third conductors are disposed within an inner lumen, and wherein the first conductor is outside of the inner lumen.

20. The implantable lead assembly of claim 14, wherein the first conductor comprises a twisted pair of conductors.

21. A system comprising: the implantable lead assembly of claim 14; and a controller circuit configured to: deliver a first neurostimulation therapy to a vagus nerve using a first electrode pair of the implantable lead assembly, wherein the first electrode pair comprises the first electrode; detect an error associated with the first electrode; and in response to detecting the error associated with the first electrode: provide an indication of a lead fault condition to a patient or clinician; and deliver a second neurostimulation therapy to the vagus nerve using a second electrode pair of the implantable lead assembly, wherein the second electrode pair comprises the second and third electrodes and excludes the first electrode.

22. A lead fault identification method for an implantable lead, the method comprising: using a lead integrity assessment routine initiated by a control circuit in an implantable medical device housing, measuring a first impedance characteristic at a first time using a first pair of electrodes of a firstimplantable lead, the first implantable lead comprising at least first, second, and third electrodes configured to be disposed at or around a nerve, wherein the first pair of electrodes comprises the first and second electrodes; measuring a second impedance characteristic at a second time, subsequent to the first time, using the first pair of electrodes of the first implantable lead; and identifying a lead fault for the first implantable lead based on a relationship between a specified threshold impedance characteristic and the measured first and second impedance characteristics.

23. The lead fault identification method of claim 22, comprising providing a neurostimulation therapy to the nerve using a second pair of electrodes that comprises the first and third electrodes of the first implantable lead.

24. The lead fault identification method of claim 23, wherein providing the neurostimulation therapy includes providing the neurostimulation therapy during an interval that follows the first impedance characteristic measurement at the first time and precedes the second impedance characteristic measurement at the second time.

25. The lead fault identification method of claim 22, comprising providing a neurostimulation therapy to the nerve using the first pair of electrodes, wherein providing the neurostimulation therapy includes providing the neurostimulation therapy during an interval that follows the first impedance characteristic measurement at the first time and precedes the second impedance characteristic measurement at the second time.

26. The lead fault identification method of claim 22, wherein relative to an implantable housing coupled to the implantable lead, the first electrode is a proximal electrode, the second electrode is an intermediate electrode, and the third electrode is a distal electrode.

27. The lead fault identification method of claim 26, wherein the electrodes are provided on respective helical supports configured to wrap around at least a portion of a target nerve.

28. The lead fault identification method of claim 22, wherein identifying the lead fault for the first implantable lead includes determining that each of the measured first and second impedance characteristics exceeds the specified threshold impedance characteristic.

29. The lead fault identification method of claim 22, wherein the specified threshold impedance characteristic is a specified impedance magnitude amount; and wherein identifying the lead fault includes determining whether a difference between the measured first and second impedance characteristics exceeds the specified impedance magnitude amount.

30. The lead fault identification method of claim 22, wherein identifying the lead fault is based on a trend of the measured first and second impedance characteristics.

31. The lead fault identification method of claim 22, wherein identifying the lead fault is based on a difference between the measured first and second impedance characteristics, and the specified threshold impedance characteristic is based on a duration of a time interval elapsed between the first and second impedance measurements.

32. The lead fault identification method of claim 22, comprising: in response to identifying the lead fault, selecting a different second pair of electrodes of the first implantable lead for impedance testing, wherein the different second pair of electrodes includes the third electrode and only one of the first and second electrodes.

33. The lead fault identification method of claim 22, comprising: in response to identifying the lead fault, selecting a different second pair of electrodes of the first implantable lead for therapy delivery.

34. The lead fault identification method of claim 22, comprising: in response to identifying the lead fault, providing a notification to a patient, caregiver, or clinician about the identified lead fault.

35. A system comprising: an implantable lead assembly including a flexible lead body configured to extend from a header of an implantable device housing to multiple distal electrodes, wherein the lead body includes at least first, second, and third electrodes configured to be disposed at or around a nerve; and a processor circuit configured to perform a lead integrity assessment routine, the assessment routine including measuring a first impedance characteristic at a first time using a first pair of electrodes comprising the first and second electrodes, measuring a second impedance characteristic at a second time using the same first pair of electrodes, and identifying a lead fault based on a relationship between a specified threshold impedance characteristic and the measured first and second impedance characteristics.

36. The system of claim 35, wherein the processor circuit is further configured to provide neurostimulation therapy to the nerve using a second pair of electrodes comprising the first and third electrodes of the implantable lead.

37. The system of claim 36, wherein the processor circuit is configured to provide the neurostimulation therapy during an interval that follows the first impedance characteristic measurement and precedes the second impedance characteristic measurement.

38. The system of claim 35, wherein the processor circuit is configured to provide neurostimulation therapy to the nerve using the first pair of electrodes during an interval that follows the first impedance characteristic measurement and precedes the second impedance characteristic measurement.

39. The system of claim 35, wherein the first electrode is a proximal electrode, the second electrode is an intermediate electrode, and the third electrode is a distal electrode, and wherein the electrodes are provided onrespective helical supports configured to wrap around at least a portion of a target nerve.

40. The system of claim 35, wherein the processor circuit is configured to identify the lead fault by determining that each of the measured first and second impedance characteristics exceeds the specified threshold impedance characteristic, and the specified threshold impedance characteristic is a specified impedance magnitude amount.

41. The system of claim 35, wherein the processor circuit is configured to, in response to identifying the lead fault, select a different second pair of electrodes of the implantable lead for impedance testing or therapy delivery, wherein the different second pair of electrodes includes the third electrode and only one of the first and second electrodes.

42. A lead fault identification method for an implantable lead, the method comprising: performing a series of at least three discrete impedance measurements for a first electrode pair of multiple electrode pairs, wherein the multiple electrode pairs comprise electrodes coupled to an electrostimulation circuit in an implantable device housing using a single implantable lead; and in response to each of the at least three impedance measurements being outside of a specified impedance value range, providing an indication of a lead fault for the single implantable lead.

43. The lead fault identification method of claim 42, wherein the impedance measurements are interleaved with therapy delivery events.

44. The lead fault identification method of claim 42, wherein the specified impedance value range is based on a baseline impedance measurement taken during an initial setup or calibration phase of the implantable device.

45. The lead fault identification method of claim 42, wherein in response to the indication of a lead fault, automatically adjusting one or more therapydelivery parameters to mitigate potential impacts on therapy effectiveness until the lead fault is resolved.

46. A lead fault identification method for an implantable lead, the method comprising: performing a series of at least first and subsequent second discrete impedance measurements for a first electrode pair of multiple electrode pairs, wherein the multiple electrode pairs comprise electrodes coupled to an electrostimulation circuit in an implantable device housing using a single implantable lead; determining an impedance difference between impedance values of the first and subsequent second impedance measurements; and in response to the impedance difference exceeding a specified threshold value, selecting a different second electrode pair, from the multiple electrode pairs, for use in a neurostimulation therapy.

47. The lead fault identification method of claim 46, further comprising determining whether one or both of the electrodes of the first electrode pair is faulty.

48. The lead fault identification method of claim 46, wherein the first discrete impedance measurement immediately precedes a blanking interval and the subsequent second discrete impedance measurement immediately follows the blanking interval.

49. The lead fault identification method of claim 46, wherein the first discrete impedance measurement immediately precedes a therapy delivery event and the subsequent second discrete impedance measurement immediately follows the same therapy delivery event.

50. The lead fault identification method of claim 46, wherein the specified threshold value is based on historical impedance measurements for the first electrode pair.

51. The lead fault identification method of claim 46, comprising, in response to the impedance difference exceeding the specified threshold value, notifying a healthcare provider via a connected health monitoring system that the implantable lead may be faulty.

52. A method comprising: delivering a first neurostimulation therapy to a nerve target using a first electrode pair, wherein the first electrode pair comprises one of multiple electrode pairs available on a lead that is coupled to a stimulation circuit in an implantable device housing; measuring a first portion of a sensor signal for a specified first duration following delivery of the first neurostimulation therapy; delivering a second neurostimulation therapy to the nerve target using the first electrode pair, wherein the first and second neurostimulation therapies have substantially the same first therapy signal parameters; measuring a second portion of a sensor signal for a specified second duration following delivery of the second neurostimulation therapy; and in response to determining each of the first and second portions of the sensor signal indicates an adverse effect, delivering a third neurostimulation therapy to the nerve target ( 1 ) using a second electrode pair, wherein the second electrode pair comprises a different one of the multiple electrode pairs available on the lead, or (2) using the first electrode pair and second therapy signal parameters that are different than the first therapy signal parameters.

53. The method of claim 52, comprising identifying an indication of autonomic engagement in the first and / or second portions of the sensor signal; and selecting for use in the third neurostimulation therapy the first or the second electrode pair based on the indication of autonomic engagement.

54. The method of claim 52, comprising determining an ensemble average of the first and second portions of the sensor signal;wherein determining the first and second portions of the sensor signal indicate an adverse effect includes determining the ensemble average indicates the adverse effect.

55. The method of claim 52, wherein the adverse effect is a laryngeal vibration or cough.

56. The method of claim 52, wherein measuring the first and second portions of the sensor signal comprise measuring acceleration information from an accelerometer.

57. The method of claim 52, wherein the first duration and the second duration are substantially the same length.

58. The method of claim 52, wherein the first duration and the second duration are each at least 5 seconds and less than 15 seconds.

59. The method of claim 52, wherein determining the first and second portions of the sensor signal each indicate an adverse effect includes determining the first and second portions of the sensor signal each indicate the same adverse effect.

60. The method of claim 52, wherein determining the first and second portions of the sensor signal each indicate an adverse effect includes determining the first and second portions of the sensor signal indicate respective different adverse effects.

61. The method of claim 52, wherein the therapy signal parameters comprise one or more of a pulse waveform parameter, a pulse magnitude parameter, and a pulse frequency.

62. A system comprising: an implantable lead assembly including a flexible lead body configured to extend from a header of an implantable device housing to multiple distal electrodes;a stimulation circuit configured to provide a neurostimulation therapy signal to a nerve target using a first electrode pair that comprises first and second electrodes of the multiple distal electrodes; a sensor configured to measure portions of a sensor signal for specified durations following delivery of the neurostimulation therapy signal; and a processor circuit configured to determine if each measured portion of the sensor signal indicates an adverse effect and, in response, to control the stimulation circuit to provide a subsequent neurostimulation therapy using either a different second electrode pair or the same first electrode pair with altered therapy signal parameters.

63. The system of claim 62, wherein the processor circuit is configured to identify indications of autonomic engagement in the sensor signal and, in response, select the first or second electrode pair for subsequent neurostimulation therapy based on the identified indication of autonomic engagement.

64. The system of claim 62, wherein the processor circuit is configured to calculate an ensemble average of the measured portions of the sensor signal and determine presence of an adverse effect based on the ensemble average.

65. The system of claim 62, wherein the sensor is an accelerometer configured to measure thoracic acceleration information.

66. The system of claim 62, wherein the sensor is an implantable sensor configured to monitor a physiologic status signal.

67. A method comprising: providing doses of a neurostimulation therapy to a portion of a vagus nerve, wherein the doses are separated in time by at least an inter-dose duration, and wherein the doses are delivered using a first electrode pair of multiple available electrode pairs on an implantable lead; using a first sensor, and during respective inter-dose durations, measuring respective responses to the doses of the neurostimulation therapy;determining whether each response indicates a presence or absence of an adverse effect; in response to identifying N consecutive responses that indicate an adverse effect, at least one of (1) changing a parameter of the neurostimulation therapy for a subsequent neurostimulation therapy, and (2) selecting a different second electrode pair of the multiple available electrode pairs for the subsequent neurostimulation therapy; and providing a dose of the subsequent neurostimulation therapy to the vagus nerve.

68. The method of claim 67, further comprising determining whether each response indicates a therapeutic effect.

69. The method of claim 67, wherein providing the doses of the neurostimulation therapy includes providing doses comprises pulses that progressively ramp up or ramp down in amplitude and / or frequency.

70. The method of claim 67, comprising determining an ensemble average of N or more consecutive responses that indicate the adverse effect; and in response to determining the ensemble average meets a threshold condition for the adverse effect, selecting the different second electrode pair for the subsequent neurostimulation therapy, and in response to determining the ensemble average fails to meet the threshold condition for the adverse effect, selecting the first electrode pair for the subsequent neurostimulation therapy.

71. The method of claim 70, wherein determining whether the ensemble average meets a threshold condition comprises comparing the ensemble average to a template.

72. The method of claim 70, wherein determining whether the ensemble average meets a threshold condition comprises comparing a magnitude characteristic of the ensemble average to a specified reference magnitude.

73. The method of claim 67, wherein measuring the respective responses to the doses of the neurostimulation therapy include measuring respective portions of an acceleration signal from an accelerometer that is disposed in or coupled to an implantable housing, and wherein the implantable housing is coupled to the implantable lead.

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