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WO2024184772A1 - Neurostimulation transœsophagienne - Google Patents

Neurostimulation transœsophagienne Download PDF

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Publication number
WO2024184772A1
WO2024184772A1 PCT/IB2024/052005 IB2024052005W WO2024184772A1 WO 2024184772 A1 WO2024184772 A1 WO 2024184772A1 IB 2024052005 W IB2024052005 W IB 2024052005W WO 2024184772 A1 WO2024184772 A1 WO 2024184772A1
Authority
WO
WIPO (PCT)
Prior art keywords
transesophageal
patient
stimulation
electrodes
expandable member
Prior art date
Application number
PCT/IB2024/052005
Other languages
English (en)
Inventor
David J. Miller
Original Assignee
Medtronic, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Medtronic, Inc. filed Critical Medtronic, Inc.
Publication of WO2024184772A1 publication Critical patent/WO2024184772A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0517—Esophageal electrodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36014—External stimulators, e.g. with patch electrodes
    • A61N1/36017—External stimulators, e.g. with patch electrodes with leads or electrodes penetrating the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00053—Mechanical features of the instrument of device
    • A61B2018/00214—Expandable means emitting energy, e.g. by elements carried thereon
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00053—Mechanical features of the instrument of device
    • A61B2018/00214—Expandable means emitting energy, e.g. by elements carried thereon
    • A61B2018/00267—Expandable means emitting energy, e.g. by elements carried thereon having a basket shaped structure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00053—Mechanical features of the instrument of device
    • A61B2018/00273—Anchoring means for temporary attachment of a device to tissue
    • A61B2018/00279—Anchoring means for temporary attachment of a device to tissue deployable
    • A61B2018/00285—Balloons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00315—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for treatment of particular body parts
    • A61B2018/00482—Digestive system
    • A61B2018/00488—Esophagus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0519—Endotracheal electrodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36014—External stimulators, e.g. with patch electrodes
    • A61N1/3603—Control systems
    • A61N1/36031—Control systems using physiological parameters for adjustment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36014—External stimulators, e.g. with patch electrodes
    • A61N1/3603—Control systems
    • A61N1/36034—Control systems specified by the stimulation parameters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36053—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for vagal stimulation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/36114—Cardiac control, e.g. by vagal stimulation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36128—Control systems
    • A61N1/36135—Control systems using physiological parameters

Definitions

  • the disclosure relates to devices and techniques for delivering neurostimulation to a patient transesophageally.
  • the disclosure is directed to devices, systems, and techniques for transesophageally stimulating a vagus nerve of a patient, for example, stimulating the vagus nerve of the patient from one or more electrodes disposed within the esophagus of the patient.
  • a vagus nerve may be challenging to stimulate without an invasive surgical procedure, which may be undesirable for situations including an acute illness, a short duration of stimulation, or when reduced time to stimulation is important to patient treatment.
  • the disclosure is directed to a device including: an elongated member defining a lumen configured for at least one of injection of a substance to a stomach of a patient or aspiration of a substance from the stomach of the patient; an expandable member disposed on or about the elongated member, the expandable member comprising a plurality of arms at respective locations around a perimeter of the elongated member, each of the plurality of arms comprising a portion configured to be disposed away from the elongated member in an expanded state; and a plurality of electrodes, wherein at least one electrode of the plurality of electrodes is disposed on a respective arm of the plurality of arms, wherein the plurality of electrodes disposed on the expandable member are configurable to deliver transesophageal neurostimulation to the patient.
  • this disclosure is directed to a method including expanding at least one expandable structure of a transesophageal neurostimulation device to an expanded state, the transesophageal neurostimulation device including: an elongated member defining a lumen configured for at least one of injection of a substance to a stomach of a patient or aspiration of a substance from the stomach of the patient; the at least one expandable member disposed on or about the elongated member, the at least one expandable member comprising a plurality of arms at respective locations around a perimeter of the elongated member, each of the plurality of arms comprising a portion configured to be disposed away from the elongated member in an expanded state; and a plurality of electrodes, wherein at least one electrode of the plurality of electrodes is disposed on a respective arm of the plurality of arms, wherein the plurality of electrodes disposed on the expandable member are configurable to deliver transesophageal neurostimulation to the patient; and applying
  • FIG. 1 is a conceptual diagram illustrating an example vagus nerve of a patient.
  • FIG. 2 is a conceptual diagram illustrating an example transesophageal neurostimulation system according to the techniques of this disclosure.
  • FIG. 3 is a conceptual diagram illustrating an example cross section of an elongated member of a transesophageal neurostimulation system according to the techniques of this disclosure.
  • FIG. 4 is a block diagram of an example transesophageal neurostimulation system that may be configured to perform techniques of this disclosure.
  • FIG. 5 is a block diagram illustrating an example configuration of a computing device.
  • FIG. 6 is a conceptual diagram of an example portion of a transesophageal neurostimulation system according to the techniques of this disclosure.
  • FIGS. 7A-7B are conceptual diagrams of an example expandable member according to the techniques of this disclosure.
  • FIGS. 8A-8C are conceptual diagrams of another example portion of a transesophageal neurostimulation system according to the techniques of this disclosure.
  • FIGS. 9A-9B are conceptual diagrams of another example portion of a transesophageal neurostimulation system according to the techniques of this disclosure.
  • FIGS. 10A-10B are conceptual diagrams of another example portion of a transesophageal neurostimulation system according to the techniques of this disclosure.
  • FIG. 11 is a conceptual diagram of another example portion of a transesophageal neurostimulation system according to the techniques of this disclosure.
  • FIG. 12 is a conceptual diagram illustrating another example of an expandable member according to the techniques of this disclosure.
  • FIG. 13 is a conceptual diagram illustrating a portion of an example arm and electrode of an expandable member according to the techniques of this disclosure.
  • FIG. 14 is a flow diagram illustrating example transesophageal neurostimulation techniques according to the present disclosure.
  • the present disclosure is directed to devices, systems, and techniques for transesophageal neurostimulation of a vagus nerve of a patient.
  • stimulation of a vagus nerve may include stimulation acting on the vagus nerve or other peripheral nerves.
  • the anatomical location of the vagus nerve makes the vagus nerve difficult to stimulate without an invasive surgical procedure.
  • an acute situation such as during other surgery or an abrupt illness, such as sepsis, stroke, myocardial infarction, traumatic brain injury, or when the required duration of stimulation is limited to short amount of time, it may be undesirable to undertake an invasive surgical procedure to implant a stimulation device.
  • transesophageal neurostimulation of the vagus nerve can be used prophylactically perioperatively to prevent acute kidney injury or postoperative ileus.
  • vagus nerve stimulation has uncovered the nervous system involvement and control of the body’s inflammatory response.
  • the nervous system senses inflammation, pathogens, and tissue damage, as well as, modulates the response.
  • One pathway of the nervous system is referred to as the cholinergic antiinflammatory pathway (CAP).
  • CAP cholinergic antiinflammatory pathway
  • Animal and humans studies have shown the stimulating certain nerves, usually branches of the vagus nerve, can dampen the inflammatory response and associated cytokines.
  • Stimulation has been investigated in the cervical vagus, the abdominal vagus, the auricular branch of the vagus in the ear, the sacral nerve, the tibial nerve, and others. Recent studies have shown that by varying the stimulation, inflammatory cytokines can be modulated up or down.
  • Implantable cervical vagus stimulators are commercially available for the treatment of epilepsy, but involve complex and invasive surgery to implant the stimulating electrode on the nerve. Other technologies attempt to stimulate the vagus transcutaneously with an external device, but those have shown limited success due to the distance from the skin surface to the vagus nerve.
  • a device configured to stimulate the vagus nerve without an invasive surgical procedure may be used to trigger the cholinergic anti-inflammatory pathway (CAP).
  • CAP has been shown to reduce excessive inflammation and would be useful for treating a variety of illness including, but not limited to: stroke; surgical or non-surgical acute kidney injury; postoperative ileus; postoperative cognitive decline or postoperative delirium; asthma; sepsis; bleeding control; myocardial infarction reduction; dysmotility and obesity; or the like. Treating any of these diseases or conditions may improve patient outcomes by shortening length of hospital stays and reducing medical costs.
  • IRI ischemia-reperfusion injury
  • the immune system reacts to the damaged or dead cells with an intense inflammatory response causing infarcted tissue and loss of long-term function. Reducing the inflammatory response during the ischemia or reperfusion can reduce the resulting infarct volume and improve function.
  • IRI acute kidney injury
  • AKI typically occurs in surgical patients and septic patients.
  • AKI is distinct from chronic kidney disease, which is the gradual loss of kidney function.
  • AKI can be caused by many things, but a common cause is reduced renal blood flow and/or renal blood oxygen extraction.
  • Vagus nerve stimulation may reduce inflammatory damage from IRI, return inflammation to a normal level and prevent the hyperinflammatory response, and/or restore a healthy, normal parasympathetic/sympathetic balance.
  • the inflammatory response of a patient to an acute health problem may be a major risk factor to complications during the acute health problem, such as surgery or an acute illness. It may not be desirable to engage in an invasive surgical procedure to implant a stimulation device during the time the patient is experiencing the acute health problem, as that may be a further risk factor to complications during the acute health problem. Therefore, there may be a need for devices, systems, and techniques for stimulating the cervical, thoracic, or abdominal vagus branches that is relatively easy and quick to use, such as a transesophageal stimulation system. Such devices or techniques may be used for short-term stimulation, such as during an acute health problem, such as surgery or during an abrupt illnesses, such as sepsis.
  • overstimulation of the vagus nerve may lower a heart rate of a patient, which may lead to arrhythmias, or lower a respiration rate of the patient. Therefore, it may be desirable to include closed-loop feedback techniques in any transesophageal neurostimulation system or device. This disclosure describes examples of such devices, systems, and techniques.
  • FIG. 1 is a conceptual diagram illustrating an example vagus nerve of a patient.
  • Patient 14 is depicted having stomach 25 and esophagus 24.
  • Mouth 12 and nasal cavity 16 are connected to esophagus 24 and may provide access to esophagus 24 for a transesophageal neurostimulation system (not shown).
  • Also depicted are representations of branches of the vagus nerve, namely anterior branch 26A of the vagus nerve or posterior branch 26B of the vagus nerve.
  • Transesophageal neurostimulation devices may deliver neurostimulation to one or more of anterior branch 26A of the vagus nerve or posterior branch 26B of the vagus nerve via one or more electrodes disposed within esophagus 24 of patient 14.
  • FIG. 2 is a conceptual diagram illustrating an example transesophageal neurostimulation system 10 according to the techniques of this disclosure.
  • a distal end of transesophageal neurostimulation system 10 may be introduced into esophagus 24 through either nasal cavity 16 (as shown) or mouth 12 and stimulate the vagus nerve through the wall of esophagus 24.
  • One possible location of the delivery of stimulus would be at or near where 24 esophagus passes through a diaphragm, or caudal from the diaphragm (not shown), of patient 14.
  • the vagus nerve is primarily organized into anterior branch 26A and posterior branch 26B (FIG. 1) that are both attached to the outer layer of esophagus 24.
  • Esophagus 24 may be thin, around only about 1 -3 mm thick, and even thinner if esophagus 24 is distended.
  • transesophageal neurostimulation system 10 may deliver electrical stimulation through the wall of esophagus 24 and to a portion of the vagus nerve.
  • transesophageal neurostimulation system 10 may be used to stimulate one or more of branches of the vagus nerve, roots of the vagus nerve, ganglia of the vagus nerve, or plexus of the vagus nerve.
  • Transesophageal neurostimulation system 10 includes controller 28, elongated member 30, and expandable member 32.
  • transesophageal neurostimulation system 10 may be biased, such as being bent or weighted, in such a manner as to position electrodes of transesophageal neurostimulation system 10 at locations more likely to be near the vagus nerve, such as anterior branch 26A and/or posterior branch 26B.
  • transesophageal neurostimulation system 10 may include a steerable or deflectable device configured to indent, appose, or penetrate electrodes of transesophageal neurostimulation system 10 into an inner wall of esophagus 24.
  • the steerable or deflectable device may be flexible for insertion into patient 14, but include a bias to a shaft of the device (such as elongated member 30) and/or a direction of deflection that facilitates the positioning of the electrodes at locations more likely to be near the vagus nerve.
  • a bigger and stiffer nasogastric tube may be relatively easier to insert and position within a patient than a smaller, more flexible nasogastric tube, which may be more difficult to insert and place as the smaller, more flexible nasogastric tube may be akin to “pushing a noodle.”
  • a smaller, more flexible elongated member 30 may be more comfortable for the patient. While this disclosure may include references to a nasogastric tube, any examples described are not intended to be limited to a nasogastric tube, and may be applicable to a transoral tube, for example.
  • a proximal portion of elongated member 30 may be smaller in diameter and more flexible than a distal portion of elongated member 30. Because the distal portion is bigger and stiffer, the distal portion may be is easier to introduce into patient 14. All or a portion of the distal portion, for example, the 5 centimeters (cm) to 20cm most distal portion of elongated member 30 may include a pre-bent curve to approximately match the curvature of the nasal passage and throat.
  • the proximal portion of elongated member 30 may be smaller in diameter and more flexible than the distal portion of elongated member 30. The smaller diameter and more flexible proximal portion of elongated member 30 may increase patient comfort when using the device.
  • a stiffer, larger diameter distal portion may be easier to introduce into the patient and a more flexible, smaller diameter proximal portion may be more comfortable when in the area of the nose or throat of the patient. If the entire elongated member 30 were stiffer and/or have the larger diameter, elongated member 30 may be uncomfortable to the patient. If the entire elongated member 30 were more flexible and/or have the smaller diameter, elongated member 30 may be difficult to introduce into the patient. As such, having an elongated member with a smaller diameter in a proximal portion and a larger diameter in a distal portion may be desirable.
  • the distal portion of elongated member 30 may be in the range of 10 to 20 French, such as 16 French, while the proximal portion may be in the range of 8 to 14 French, such as 10 or 11 French.
  • the differences in size and stiffness of elongated member 30 may increase the usability of the device for the clinician and the comfort for the patient.
  • the proximal portion of elongated member 30 may be constructed of different material(s) than the distal portion of elongated member 30.
  • the proximal portion may be constructed of softer (e.g., lower on a durometer scale) and/or more flexible material(s) than the distal potion, so as to be more flexible than the distal portion.
  • Elongated member 30 may include a lumen (not shown in FIG. 1) for injection into stomach 25 or aspiration from stomach 25. This lumen may be useful for delivering fluids or drugs to patient 14. The lumen may also be used by a clinician or transesophageal neurostimulation system 10 to confirm that elongated member 30 has been inserted towards the stomach and not the lungs. For example, the lumen may be used to confirm proper placement by aspirating fluid from patient 14 and testing the color or pH of the fluid to verify the fluid is from the digestive system of patient 14 rather than from the respiration system of patient 14.
  • the lumen may be used to inject air into patient 14 and a clinician may confirm proper placement by listening to a “gurgling” sound that may emanate from stomach 25 when air is injected into stomach 25.
  • a clinician may use the lumen to perform auscultation on patient 14 to evaluate the location of the device.
  • Esophagus 24 is located between the spinal column and the heart (neither shown in FIG. 2). The anterior of esophagus 24 is adjacent to the heart.
  • transesophageal neurostimulation system 10 may be configured to direct stimulation towards posterior branch 26B or posterior trunk of the vagus nerve.
  • transesophageal neurostimulation system 10 may include sensor 6 which may include an accelerometer which may be used to determine the posterior direction.
  • transesophageal neurostimulation system 10 can detect the movements due to each heartbeat and determine the posterior direction being away from the detected acceleration.
  • sensing electrodes of electrodes 34 or other electrodes may be used to sense an electrocardiogram (ECG or EKG) of patient 14 and controller 28 may determine the posterior direction based on the sensed EKG signal.
  • EKG signals sensed from electrodes facing the posterior of patient 14 may sense a lower amplitude EKG then electrodes facing the anterior of patient 14.
  • elongated member 30 and/or expandable member 32 may be shaped in such a manner as to automatically orient the stimulation electrode(s) posteriorly.
  • sensing electrodes of electrodes 34 or other electrodes may be used to sense an EKG of patient 14 to assist a clinician in otherwise positioning transesophageal neurostimulation system 10.
  • controller 28 may determine the position of electrodes within patient 14 based on the sensed amplitude of the EKG signals and may display a representation of the position of at least a portion of transesophageal neurostimulation system 10 with respect to patient anatomy which a clinician may use to guide transesophageal neurostimulation system 10 into a preferred position.
  • Controller 28 may be configured to control neurostimulation being delivered to the vagus nerve (not shown in FIG. 2) of patient 14.
  • controller 28 may include processing circuitry, telemetry circuitry, and memory.
  • the telemetry circuitry may be configured for wireless or wired communication.
  • controller 28 may also include stimulation circuitry configured to generate a stimulation signal.
  • the stimulation circuitry may be located in a portion of transesophageal neurostimulation system 10 that is internal to patient 14.
  • Controller 28 may be an example of a computing device.
  • external controller 28 may include a clinician programmer or patient programmer.
  • controller 28 may be a device for inputting stimulation programs or stimulation parameters into transesophageal neurostimulation system 10.
  • controller 28 may be a wearable communication device, with a therapy request input integrated into a key fob or a wristwatch, handheld computing device, smart phone, computer workstation, or networked computing device.
  • Controller 28 may include a user interface that is configured to receive input from a user (e.g., patient 14, a caretaker, or a clinician).
  • the user interface includes, for example, a keypad and a display, which may for example, be a liquid crystal display (LCD) or light emitting diode (LED) display.
  • the user interface may include a turnable knob or a representation of a turnable knob.
  • the keypad may take the form of an alphanumeric keypad or a reduced set of keys associated with particular functions.
  • Controller 28 may additionally or alternatively include a peripheral pointing device, such as a mouse, via which a user may interact with the user interface.
  • a display of controller 28 may include a touch screen display, and a user may interact with controller 28 via the display.
  • a user such as a clinician, a patient, or a caregiver, may also interact with controller 28 to communicate with transesophageal neurostimulation system 10.
  • controller 28 may interact with controller 28 to retrieve physiological or diagnostic information from one or more of a sensor, processing circuitry, or memory that may be located on or in a portion of transesophageal neurostimulation system 10 that is intended to be within patient 14 during stimulation.
  • the user may also interact with controller 28 to program transesophageal neurostimulation system 10, e.g., select values for the stimulation parameter with which transesophageal neurostimulation system 10 generates and delivers stimulation and/or the other operational parameters of transesophageal neurostimulation system 10, such as one or more stimulation parameters (e.g., pulse amplitude, pulse width, pulse frequency, pulse burst duration, electrode combination, etc.), user requested periods for stimulation or periods to prevent stimulation, or any other such user customization of therapy.
  • a clinician may use controller 28 to start stimulation with a relatively high intensity or start stimulation with a relatively low intensity and bring up the intensity until the patient indicates that the patient can feel the stimulation or the stimulation is painful or uncomfortable.
  • the clinician can then lower the intensity of the stimulation to be delivered as therapy to be within a therapeutic range, but lower than a perception threshold or a pain or discomfort threshold.
  • the perception threshold and pain threshold can also be used to determine the therapeutic intensity setting mathematically.
  • the therapeutic intensity setting may be set to be the average of the perception threshold and the discomfort threshold.
  • the therapeutic intensity setting may be set to a percentage of the perception threshold or the pain threshold, such as 80% of the perception threshold.
  • the user may use controller 28 to retrieve information from transesophageal neurostimulation system 10 relating to a heartrate of patient 14, a heart rate variability over time, respiration rate, vagus nerve sensed activity, temperature, or the like.
  • the user may use controller 28 to retrieve information from transesophageal neurostimulation system 10 relating to the performance or integrity of transesophageal neurostimulation system 10.
  • this information may be presented to the user as an alert if a system condition that may affect the efficacy of therapy is detected.
  • Patient 14 or a clinician may, for example, use a keypad or touch screen of controller 28 to request transesophageal neurostimulation system 10 to deliver or terminate the electrical stimulation.
  • patient 14 may use controller 28 to provide a therapy request to control the delivery of the electrical stimulation “on demand,” e.g., when patient 14 deems the second stimulation therapy desirable. This request may be a therapy trigger event used to terminate electrical stimulation.
  • Controller 28 may provide a notification to patient 14 or a clinician when the electrical stimulation is being delivered or notify patient 14 of the prospective termination of the electrical stimulation.
  • controller 28 may display a visible message, emit an audible alert signal or provide a somatosensory alert (e.g., by causing a housing of controller 28 to vibrate).
  • the notification may indicate when therapy is available (e.g., a countdown in minutes, or indication that therapy is ready).
  • controller 28 may be detachable or detached from elongated member 30 to facilitate the transportation of patient 14 to the device, insertion of patient 14 into the device, and operation of the device, if necessary.
  • controller 28 may be detachable or separate from elongated member 30.
  • the transesophageal neurostimulation system such as transesophageal neurostimulation system 10 may be MRI compatible such that the transesophageal neurostimulation system does not substantially interfere with the images taken by the MRI device.
  • elongated member 30 may include conductors configured to conduct the stimulation signal from the stimulation circuitry of controller 28 to electrodes 34A, 34B, and 34N (hereinafter referred to collectively as electrodes 34 which can include two or more electrodes).
  • electrodes 34 which can include two or more electrodes.
  • each of electrodes 34 may not form a closed loop so as reduce the risk of entanglement with another nasogastric tube, should another nasogastric tube be introduced or be already introduced into esophagus 24.
  • elongated member 30 may include conductors configured to conduct communication signals from telemetry circuitry of controller 28 to telemetry circuitry located in a portion of transesophageal neurostimulation system 10 designed to be internal to patient 14 when stimulation is delivered.
  • Elongated member 30 may also define a lumen configured to permit the removal or introduction of substances from patient 14.
  • the lumen may permit the introduction of food, drink, medication, or the like from external of the patient into esophagus 24 or stomach 25.
  • Expandable member 32 may be configured to expand from a non-expanded or collapsed state to a size approximately equal to the circumference of an internal wall of esophagus 24 thereby causing electrodes 34 to make physical contact with the internal wall of esophagus 24.
  • expandable member 32 may be configured to expand to distend the internal wall of esophagus 24.
  • expandable member 32 may include a basket-like structure or (which may be referred to herein as a basket or basket structure).
  • the basket may be a mechanically expandable structure that includes struts and/or linkages that enables expansion.
  • the basket may have an outer diameter of between 15 millimeters (mm) to 35mm.
  • the basket is constructed from a laser cut nitinol tube or polymer tube.
  • the basket is constructed from a relatively flat material (e.g., flex circuit) that is then rolled up to form a tube-like structure.
  • the basket includes an elastic material, superelastic material, elastomeric material, shape-memory material, or the like, having slits or etchings disposed thereupon to form the basket.
  • the basket may include individually constructed struts or arms that are assembled into the basket. In some examples, expansion of the basket may be variably controlled (e.g., mechanically controlled by a clinician) or may be spring loaded.
  • the clinician may control the expansion and/or contraction of the basket via a lever or dial which may be mechanically attached to an elongated member of the transesophageal neurostimulation system to control the basket to be in one of more than two different states of expansion.
  • the clinician may control the basket to be in one or more states of partial expansion (e.g., states between an expanded state and a collapsed or unexpanded state). Examples of baskets are set forth in FIGS. 6-12 hereinafter.
  • expandable member 32 may include a number of arms cut from a nitinol tube or polymer tube. Electrodes 34 may be disposed on the arms. In some examples, each arm of expandable member 32 includes one electrode. In some examples, each arm of expandable member 32 includes between one and four electrodes, inclusive. In some examples, electrodes 34 are flex circuit electrodes bonded to the arms (e.g., each bonded to a respective arm) of expandable member 32.
  • This disclosure describes several examples of expandable members which may take a basket-like shape when deployed in an expanded state and be referred to herein as a basket.
  • a basket may include a plurality of arms which may expand radially outward from an elongated member in an expanded state and collapse close to (or against) the elongated member in a collapsed or unexpanded state.
  • the basket may be configured to accommodate both: a) different esophagus sizes; and b) a changing esophagus diameter due to the swallowing peristalsis.
  • the basket may include one or more compliant member (e.g., biased member) applying an axial force that expands the basket.
  • one or more arms within the expandable structure may form the one or more compliant members.
  • the one or more compliant members may be compliant enough such that the one or more compliant members allow for some distortion and/or flexing. Such compliance may be tuned to allow for or permit peristaltic waves to pass by elongated member 30 without causing patient discomfort or dislodgement of elongated member 30.
  • the basket may be biased to be in an expanded state.
  • the basket may be biased to be in an unexpanded (e.g., collapsed) state.
  • the application of tension e.g., by a clinician, may change the basket from one state to another.
  • an additional expandable member 36 may be included in transesophageal neurostimulation system 10.
  • Expandable member 36 may be configured to expand in stomach 25 of patient 14, under the control of a clinician, in such a manner as to position electrodes 34 in a position to stimulate a target location in patient 14, such as one or more branches of the vagus nerve.
  • transesophageal neurostimulation system 10 may include a radio opaque marker band located on elongated member 30 which may serve as an indicator to a clinician that electrodes 34 may be in an appropriate location for stimulation when viewed with x-ray or fluoroscopy.
  • a clinician may desire to position electrodes 34 relative to a lower esophageal sphincter separating esophagus 24 from stomach 25.
  • esophagus 24 may be relatively thick and muscular at the lower esophageal sphincter, so it may be desirable to stimulate the vagus nerve cranially of the lower esophageal sphincter.
  • transesophageal neurostimulation system 10 may be configured such that a distance between a proximal shoulder of expandable member 36 to electrodes 34 is of such a size that electrodes 34 are positioned proximal of the lower esophageal sphincter.
  • the distance between the proximal shoulder of expandable member 36 to electrodes 34 may be in the range of 1 centimeter (cm) to 5cm, inclusive.
  • transesophageal neurostimulation system 10 may be configured such that electrodes 34 are located in the range of about 1 cm to about 12 cm from the z-line of patient 14.
  • the z-line is a term for a faint zig-zag impression at the gastro- esophageal junction. This impression demarcates the transition between the stratified squamous epithelium in the esophagus and the intestinal epithelium of the gastric cardia (e.g., the squamocolumnar junction).
  • expandable member 36 may include a balloon or other expandable structure, such as a mechanically expandable structure that includes struts and/or linkages that enables expansion (e.g., similar to a stent or cage).
  • the balloon may have a diameter, when in an expanded state, of in the range of 20mm to 60mm.
  • the diameter of the balloon in the expanded state may be approximately 35mm.
  • system 10 may include sensor 7 which may be positioned on expandable member 36, or in the example where system 10 does not include an expandable member 36, at or near a distal end of elongated member 30 (for example, distal to expandable member 32).
  • Sensor 7 may be configured to generate a signal indicative the entry of sensor 7 into stomach 25 or entry into the lower esophageal sphincter of patient 14.
  • electrodes 34 (or other stimulation device) may be placed at an appropriate location for stimulation within esophagus 24 of patient 14 without a need to use fluoroscopy.
  • sensor 7 may include a pressure sensor.
  • a pressure of esophagus 24, stomach 25, and the lower esophageal sphincter may be characteristically different.
  • controller 28 may determine when sensor 7 enters into stomach 25 or into the lower esophageal sphincter of patient 14.
  • Sensor 7 may include a pH sensor.
  • Sensor 7 may generate a signal indicative of a pH in patient 14.
  • the pH of esophagus 24 may typically be around 7.0, while a pH of stomach 25 may typically be in the range of 1.5 to 3.5.
  • controller 28 may determine when sensor 7, and the distal portion of elongated member 30, enters into stomach 25.
  • controller 28 may initiate stimulation and/or expansion of expandable member(s) 32 and/or 36.
  • Elongated member 30 and expandable members 32 and/or 36 may be sized in the range of from 8 to 18 French when expandable members 32 and/or 36 are in a non-expanded or collapsed state to enable relatively easy introduction of elongated member 30 and expandable members 32 and/or 36 within nasal cavity 16 or mouth 12 of patient 14.
  • elongated member 30, expandable member 32, and/or expandable member 36 may be lubricated.
  • the lubrication may be contained within packaging that encloses at least a portion of system 10, may be pre- lubricated, or, in some examples, system 10 may be configured to self-lubricate.
  • controller 28 may include a lubrication pump that pump lubricant onto an exterior surface of elongated member 30, expandable member 32, and/or expandable member 36.
  • elongated member 30, expandable member 32, and/or expandable member 36 may define a lubricating lumen which may carry lubricant from the lubrication pump to an exterior surface of elongated member 30, expandable member 32, and/or expandable member 36 via lubrication openings.
  • a lubrication lumen of elongated member 30, expandable member 32, and/or expandable member 36 may be prefilled with lubricant and the pressure exerted upon elongated member 30, expandable member 32, and/or expandable member 36 by esophagus 24 during insertion of elongated member 30 into esophagus 24 may cause the prefilled lubricant to be discharged via the lubrication openings to the exterior surface of elongated member 30.
  • a coating may be applied to elongated member 30, expandable member 32, and/or expandable member 36 which may become lubricious when in contact with saliva or mucus of patient 14.
  • elongated member 30, expandable member 32, and/or expandable member 36 may be pre-coated with a local anesthetic such as lidocaine.
  • the local anesthetic may be included in the packaging that encloses at least a portion of system 10.
  • the local anesthetic may be combined with a lubricant.
  • Transesophageal neurostimulation system 10 may deliver electrical stimulation to patient 14 by generating and delivering a programmable electrical stimulation signal (e.g., in the form of electrical pulses or an electrical waveform) to a target a therapy site near electrodes 34 disposed, in some examples, on an outer surface of expandable member 32.
  • a programmable electrical stimulation signal e.g., in the form of electrical pulses or an electrical waveform
  • the distal end of transesophageal neurostimulation system 10 may be inserted into patient 14 in such a manner as to locate electrodes 34 near the vagus nerve of patient 14.
  • Elongated member 30, expandable member 32, and expandable member 36 may be constructed of biocompatible materials.
  • Electrodes 34 may be configured to be circumferentially separated from each other on an outer surface of expandable member 32.
  • transesophageal neurostimulation system 10 may be configured to deliver a stimulation signal to the vagus nerve of patient 14 via electrodes 34 in a cycled manner.
  • the delivery of the stimulation signal may move over time between different electrode combinations of electrodes 34, such as delivering stimulation via electrode 34A and electrode 34B, then delivering stimulation via electrode 34B and another electrode, and so on. In this manner, a clinician may not need to circumferentially align any particular electrodes of electrodes 34 with branches of the vagus nerve.
  • electrodes 34 may operate in a bipolar or multi-polar configuration.
  • one or more electrodes of electrodes 34 may be configured as anodes and one or more of electrodes 34 may be configured as cathodes. Such a configuration is different than a unipolar configuration which would include an electrode located at a position relatively remote from the vagus nerve.
  • electrodes 34 may operate in unipolar configuration.
  • the return electrode(s) may be located on a portion of elongated member 30 in esophagus 24, distant from expandable member 32 (e.g., return electrode 37), or a return pad on the skin of the patient. The return pad on the skin may be placed on the abdomen near the lower esophagus to steer the current on a path the goes through the vagus nerve.
  • electrodes 34 are depicted arranged in an array circumferentially separated from each other, the illustrated numbers and configurations of electrodes 34 are merely exemplary. Other configurations, e.g., numbers and positions of electrodes, are also contemplated.
  • the electrodes may be used for delivering different stimulation therapies or other electrical stimulations to respective stimulation sites within patient 14 or for monitoring at least one physiological marker of patient 14. For example, a set of electrodes may deliver stimulation at a first frequency to a first branch of the vagus nerve while a different set of electrodes may deliver stimulation at a second frequency to a second branch of the vagus nerve.
  • a set of electrodes may deliver stimulation at a first frequency to a first location of first branch of the vagus nerve while a different set of electrodes may deliver stimulation at a second frequency to a second location of the first branch of the vagus nerve.
  • This may allow for directional stimulation, such as blocking in a distal direction and stimulating in a proximal direction for an afferent stimulation.
  • the first frequency may be on the order of 1 Hz to 200 Hz for delivery of therapy (e.g., about 20 Hz) and the second frequency may be on the order of 1 kHz to 50 kHz for creating a nerve block (e.g., between about 10 kHz to about 20 kHz).
  • there may be separate electrodes of electrodes 34 for delivering blocking and stimulating, and these separate electrodes may be arranged along a transesophageal neurostimulation device rather than, or in addition to, circumferentially around the device.
  • two or more of electrodes 34 may be used to measure an impedance of tissue to determine a location of a target stimulation location, such as branches of the vagus nerve and to indicate if the electrodes are in good contact with the tissue. For example, if impedance is too high (e.g., higher than a predetermined first impedance threshold), the electrodes may not be in physical contact with the tissue or may be insulated from physical contact with the tissue. Alternatively, if the impedance is too low (e.g., lower than a predetermined second impedance threshold), there may be a short circuit or other potential problem.
  • a target stimulation location such as branches of the vagus nerve
  • transesophageal neurostimulation system 10 may source an electrical signal, such as current, to one electrode of electrodes 34, while another electrode of electrodes 34 sinks the electrical signal. Transesophageal neurostimulation system 10 may then determine the voltage between these two electrodes. Transesophageal neurostimulation system 10 may then determine the impedance of the tissue between the electrodes using a known value of the electrical signal sourced the determined voltage.
  • transesophageal neurostimulation system 10 may be configured to detect branches of the vagus nerve, such as through the use of sensed impedances, and select the desired branch(es) to stimulate. Transesophageal neurostimulation system 10 may also be configured to select the appropriate electrode combination of electrodes 34 and/or other stimulation parameters to stimulate the desired branch(es).
  • the other stimulation parameters may include not stimulating via one or more of electrodes 34, for example, if a determined impedance is out of an acceptable range (e.g., higher than the first predetermined impedance threshold or lower than the second predetermined impedance threshold).
  • transesophageal neurostimulation system 10 may include sensors, such as sensor 6 shown disposed on the surface of expandable member 32, or be communicatively coupled to sensors, such as sensor 8, which may monitor one or more physiological parameters of patient 14.
  • sensor 6 and/or sensor 8 may be configured to monitor vital signs of patient 14 such as an EKG.
  • Controller 28 may monitor the vital signs of patient 14 based on signals from sensor 6 and/or sensor 8 and provide an alarm or alert based on such monitoring when the vital signs depart from a predetermined range by more than a predetermined amount.
  • Transesophageal neurostimulation system 10 may change stimulation parameters, terminate stimulation, or initiate stimulation, based on the sensed parameter(s). Such parameters may include heart rate, heart rate variability, respiration rate, vagus nerve sensed activity, temperature, electromyography (EMG), activity level of patient 14, pH of stomach 25 or esophagus 24, pressure in stomach 25 or esophagus 24, or other physiological parameters of patient 14. In this manner, transesophageal neurostimulation system 10 may be configured to operate as a closed-loop system using data from one or more sensors to adjust delivered electrical stimulation.
  • EMG electromyography
  • transesophageal neurostimulation system 10 may automatically begin to deliver stimulation with minimal user input. For example, transesophageal neurostimulation system 10 may start stimulation in response to determining that a measured impedance is below a predetermined threshold, when expandable member 32 or expandable member 36 is inflated or otherwise expanded, or when a signal from sensor 7 is indicative of sensor 7 being in stomach 25 of patient 14.
  • FIG. 3 is a conceptual diagram illustrating an example cross section of elongated member of a transesophageal neurostimulation system according to the techniques of this disclosure.
  • elongated member 30 includes an outer wall 86 and an inner wall 88 defining lumen 80.
  • Lumen 80 may be configured to facilitate the introduction or removal of substances, such as fluids, medication, air, or the like, from esophagus 24 or stomach 25 of patient 14.
  • a clinician may use lumen 80 to inject or aspirate substances into or from stomach 25.
  • Lumen 80 may be fluidically coupled to one or more fluid openings 83 near a distal end of elongated member 30 for injection or aspirating such substances.
  • Elongated member 30 may also include one or more electrical conductors, such as conductors 82A, 82B, 82N, etc. (referred to hereinafter collectively as conductors 82).
  • conductors 82 may include a conductor communicatively coupled to each of the electrodes disposed on expandable member 32 (FIG.
  • electrical conductors 82 may each be configured to conduct electrical signals, such as a stimulation signal or a sensed signal between controller 28 and an associated electrode.
  • Elongated member 30 may also define lumen 84A and/or lumen 84B.
  • Lumen 84A may be configured to carry a substance or to house a mechanism for expanding expandable member 32 or expandable member 42.
  • Lumen 84B may be configured to be coupled to an external inflation source and carry a substance, or to house a mechanism for expanding expandable member 36.
  • the substance may include air, saline, or any other gas or liquid which may be capable of inflating a balloon in examples where expandable members 32 or 36 include balloons and elongated member 30 may include at least one fluid opening for injecting or removing such substance which may be fluidically coupled to lumen 84A and/or lumen 84B.
  • lumen 84A and/or lumen 84B may be configured to receive a deployment mechanism (e.g., a pull wire or a push wire) for deploying an expandable structure.
  • elongated member 30 may include an access opening to provide the clinician with access to the deployment mechanism.
  • a distal portion of elongated member 30 and expandable members 32 or 36 may be configured to be contained within a removeable sheath that may be removed by a clinician after a portion of elongated member 30 is inserted into esophagus 24 which may cause any expandable members to expand.
  • FIG. 4 is a block diagram of an example transesophageal neurostimulation system that may be configured to perform techniques of this disclosure.
  • transesophageal neurostimulation system 210 of FIG. 4 may be one device.
  • transesophageal neurostimulation system 210 may represent more than one device or a collection of devices.
  • transesophageal neurostimulation system 210 may be an example of transesophageal neurostimulation system 10 of FIG. 2.
  • Transesophageal neurostimulation system 210 may include stimulation circuitry 52 configured to generate a stimulation signal, processing circuitry 53, telemetry circuitry 58, timing circuitry 55, memory 56, sensor(s) 22 (which may be an example any of sensors 6 - 8 (FIG. 2) and impedance circuitry 54. Transesophageal neurostimulation system 210 may also include one or more electrodes, such as electrodes 29A-29D (collectively referred to hereinafter as electrodes 29), electrodes 19A-19B, and electrodes 21A-21B. Electrodes 29, 19A-19B, and 21A-21B, may be examples of electrodes 34 (FIG. 2). In some examples, transesophageal neurostimulation system 210 may also include a user interface (UI 68) which may function similarly to user interface 94 of FIG. 5 described in more detail in the discussion of FIG. 5 below.
  • UI 68 user interface
  • Sensor(s) 22 may comprise a patient motion sensor that generates a signal indicative of patient posture state, orientation, or activity level.
  • transesophageal neurostimulation system 210 may use sensor(s) 22 (which may include an accelerometer) to identify posture states of patient 14.
  • Processing circuitry 53 may use the posture state to determine a position of one or more electrodes 29 and may use the position to determine which electrode combination or other stimulation parameters to use for stimulation.
  • stimulation programs 66 may include predetermined programs for supine, prone, lateral, or other common surgical positions.
  • Transesophageal neurostimulation system 210 may also operate in a closed-loop manner by controlling stimulation parameters and the delivery of stimulation is response to sensed physiologic parameters sensed by sensor(s) 22, such as heart rate, heart rate variability, respiration rate, vagus nerve sensed activity, temperature, EMG, activity level of patient 14, or other measures. These physiological parameters may be sensed by sensor(s) 22 and/or impedance circuitry 54.
  • processing circuitry 53 may control stimulation circuitry 52 to titrate and optimize the neurostimulation therapy based on the sensed physiological parameters.
  • processing circuitry 53 may monitor heart rate variability of patient 14 and, when the heart rate variability meets a heart rate variability threshold, terminate therapy.
  • sensor(s) 22 may include one or more temperature sensors which may be disposed one each arm of a basket of expandable member 32. Each temperature sensor may be located near one or more of electrodes 34 and sense a temperature of surrounding tissue.
  • Processing circuitry 53 may monitor the sensed temperatures and upon one or more of the sensed temperatures meeting a threshold temperature, automatically change or terminate stimulation so as to avoid or lower a risk of tissue damage due to the stimulation.
  • sensor(s) 22 may include one or more thermocouples. For example, after a stroke a body temperature of patient 14 may rise, peak, and then come back down.
  • processing circuitry 53 may monitor the sensed temperatures and, after the sensed temperatures (e.g., each of the sensed temperatures, an average of the sensed temperatures, or the like) peak and based on the sensed temperatures reaching a threshold temperature, automatically change or terminate stimulation.
  • sensor(s) 22 may include one or more pressure sensors, which may be located external to patient 14 or may be located along elongated member 30, on expandable member 32, and/or on expandable member 36. Such pressure sensor(s) may be used to monitor peristaltic pressure waves or gastric pressure.
  • the neurostimulation could be delivered to the vagus nerve (in neck, chest, or abdomen). While the target tissue for the delivery of stimulation is primarily discussed herein as being the vagus nerve, other potential locations of interest may include the sacral nerve, the pudendal nerve, the splenic nerve, the splanchnic nerve, tibial nerve, other peripheral nerves, or other cranial nerves.
  • the physiological parameters may be sensed by external devices, such as pulse oximetry sensors, Near Infrared Spectroscopy(NIRS), Bispectral Index processed electroencephalogram (EEG), EMG electrodes, EEG electrodes, wearable activity tracker, cameras, depth-sensing cameras, or other sensors.
  • physiological parameters may be measured by anesthesia equipment such as a multi-parameter monitor (MPM) or respirator.
  • MFM multi-parameter monitor
  • the physiological parameters may be sensed by an implantable sensor such as in a pacemaker or cardiac monitor.
  • processing circuitry 53 may maximize, optimize, or otherwise improve the stimulation of the cholinergic anti-inflammatory pathway (CAP).
  • CAP cholinergic anti-inflammatory pathway
  • CAP has been shown to reduce excessive inflammation and would be useful for treating a variety of illness including, but not limited to: surgical or non-surgical acute kidney injury, postoperative ileus, postoperative cognitive decline or Postoperative delirium; asthma; sepsis; bleeding control; myocardial infarction reduction; dysmotility and obesity. Treating any of these diseases may improve patient outcomes by shortening hospital length of stays and reducing costs.
  • processing circuitry 53 may utilize the sensed physiological parameters to provide feedback to a clinician indicative of whether the vagus nerve is actually being stimulated.
  • processing circuitry 53 identifies changes to the patient’s physiological state that are relevant to desired changes in neurostimulation.
  • processing circuitry 53 may control stimulation circuitry 52 to generate a stimulation signal that is gated to the respiratory cycle or heartbeat.
  • Vagus nerve stimulation may be more effective when gated to certain physiological activities. For example, it may enhance the potency of the vagus nerve stimulation if the stimulation is gated to be during a phase of respiration, such as the exhalation phase of respiration.
  • the respiration cycle of patient 14 may be accurately detected with pulse oximetry signal analysis or an accelerometer in the device.
  • processing circuitry 53 may use other physiologic activities to gate the stimulation. For example, processing circuitry 53 may determine heart rate or circadian rhythms and gate the stimulation signal based on the heart rate, phase of a cardiac cycle, or a phase of a circadian rhythm.
  • Monitoring other physiological parameters may also serve to enhance safety. For example, stimulating the cervical vagus may depress the heart rate of patient 14. Processing circuitry 53 may be configured to control stimulation circuitry 52 to stop stimulation or lower a stimulation intensity if the heart declined below a threshold. Similarly, processing circuitry 53 may monitor sensed vital signs to monitor pain in an unconscious person. Processing circuitry 53 may be configured to control stimulation circuitry 52 to stop stimulation or lower a stimulation intensity if processing circuitry 53 determines that increasing pain is not associated with surgery or changes in anesthesia. In some examples, processing circuitry 53 may use one or more of the sensed parameters to balance between a parasympathetic and sympathetic tone in patient 14.
  • transesophageal neurostimulation system 210 may comprise any suitable arrangement of hardware, alone or in combination with software and/or firmware, to perform the 1 techniques attributed to transesophageal neurostimulation system 210 and processing circuitry 53, stimulation circuitry 52, impedance circuitry 54, and telemetry circuitry 58 of transesophageal neurostimulation system 210.
  • transesophageal neurostimulation system 210 may include one or more processors, such as one or more microprocessors, digital signal processors (DSPs), application specific integrated circuits (ASICs), field programmable gate arrays (FPGAs), or any other equivalent integrated or discrete logic circuitry, as well as any combinations of such components.
  • DSPs digital signal processors
  • ASICs application specific integrated circuits
  • FPGAs field programmable gate arrays
  • Transesophageal neurostimulation system 210 also, in various examples, may include a memory 56, such as random access memory (RAM), read only memory (ROM), programmable read only memory (PROM), erasable programmable read only memory (EPROM), electronically erasable programmable read only memory (EEPROM), flash memory, comprising executable instructions for causing the one or more processors to perform the actions attributed to them.
  • a memory 56 such as random access memory (RAM), read only memory (ROM), programmable read only memory (PROM), erasable programmable read only memory (EPROM), electronically erasable programmable read only memory (EEPROM), flash memory, comprising executable instructions for causing the one or more processors to perform the actions attributed to them.
  • processing circuitry 53, stimulation circuitry 52, impedance circuitry 54, and telemetry circuitry 58 are described as separate circuitry, in some examples, processing circuitry 53, stimulation circuitry 52, impedance circuitry 54, and telemetry circuitry 58 are
  • processing circuitry 53, stimulation circuitry 52, impedance circuitry 54, and telemetry circuitry 58 correspond to individual hardware units, such as microprocessors, ASICs, DSPs, FPGAs, or other hardware units.
  • any of processing circuitry 53, stimulation circuitry 52, impedance circuitry 54, and telemetry circuitry 58 may correspond to multiple individual hardware units such as microprocessors, ASICs, DSPs, FPGAs, or other hardware units.
  • Memory 56 stores stimulation programs 66 that specify stimulation parameter values for the electrical stimulation provided by transesophageal neurostimulation system 210. Stimulation programs 66 may also store information relating to determining and using physiological parameters, such as threshold values. In some examples, transesophageal neurostimulation system 210 may deliver stimulation therapy based on one or more physiological markers. In other examples, transesophageal neurostimulation system 210 may deliver stimulation therapy that is not based on one or more physiological markers. In some examples, memory 56 also stores patient data 69 which may include sensed physiological parameters. Patient data 69 may also include timing information which may be associated with the sensed physiological parameters. [0077] Generally, stimulation circuitry 52 generates and delivers electrical stimulation under the control of processing circuitry 53.
  • processing circuitry 53 controls stimulation circuitry 52 by accessing memory 56 to selectively access and load at least one of stimulation programs 66 to stimulation circuitry 52.
  • processing circuitry 53 may access memory 56 to load one of stimulation programs 66 to stimulation circuitry 52.
  • stimulation circuitry 52 may access memory 56 and load one of the stimulation programs 66.
  • the electrical stimulation signal generated and delivered by stimulation circuitry 52 may be above around 10 Hz to avoid activating muscular contraction.
  • stimulation programs 66 may include stimulation programs that are configured to facilitate different effects.
  • stimulation circuitry may use different stimulation programs to generate different electrical stimulation signals to cause different effects.
  • stimulation circuitry 52 may generate an electrical stimulation signal in the range of about 1 to 200 Hz to reduce inflammation in patient 14 (e.g., around 20 Hz) or generate an electrical stimulation signal in the range of about 1 kHz to about 50 kHz to block and increase an inflammatory response (e.g., between about 10 kHz to about 20 kHz).
  • processing circuitry 53 may access memory 56 to load one of stimulation programs 66 to stimulation circuitry 52 for delivering the electrical stimulation to patient 14.
  • a clinician or patient 14 may select a particular one of stimulation programs 66 from a list using a programming device, such as controller 28 (FIG. 5).
  • Processing circuitry 53 may receive the selection via telemetry circuitry 58.
  • Stimulation circuitry 52 delivers the electrical stimulation to patient 14 according to the selected program for an extended period of time, such as minutes, hours, days, or until patient 14 or a clinician manually stops or changes the program.
  • Stimulation circuitry 52 delivers electrical stimulation according to stimulation parameters. In some examples, stimulation circuitry 52 delivers electrical stimulation in the form of electrical pulses.
  • relevant stimulation parameters may include a voltage amplitude, a current amplitude, a pulse rate, a pulse width, a duty cycle, a duty cycle of the stimulation ON/OFF periods, or the combination of electrodes 29 that stimulation circuitry 52 uses to deliver the stimulation signal.
  • stimulation circuitry 52 delivers electrical stimulation in the form of continuous waveforms.
  • relevant stimulation parameters may include a voltage or current amplitude, a frequency, a shape of the stimulation signal, a duty cycle of the stimulation signal, or the combination of electrodes 29 stimulation circuitry 52 uses to deliver the stimulation signal.
  • impedance circuitry 54 includes voltage measurement circuitry 72 and current source 64, and may include an oscillator (not shown) or the like for producing an alternating signal.
  • impedance circuitry 54 may use a four-wire, or Kelvin, arrangement.
  • processing circuitry 53 may periodically control current source 64 to, for example, source an electrical current signal through electrode 19A and sink the electrical current signal through electrode 21 A.
  • current source 64 may deliver electrical current signals that do not deliver stimulation therapy the vagus nerve, e.g., sub-threshold signals, due to, for example, the amplitudes or widths of such signals and/or the timing of delivery of such signals.
  • Impedance circuitry 54 may also include a switching circuitry (not shown) for selectively coupling electrodes 19 A, 19B, 21 A, and 21B to current source 64 and voltage measurement circuitry 72.
  • Voltage measurement circuitry 72 may measure the voltage between electrodes 19B and 21B.
  • Voltage measurement circuitry 72 may include sample and hold circuitry or other suitable circuitry for measuring voltage amplitudes.
  • Processing circuitry 53 may determine an impedance value from the measure voltage values received from voltage measurement circuitry 72.
  • processing circuitry 53 may control stimulation circuitry 52 to deliver or terminate the electrical stimulation based on patient or clinician input received via telemetry circuitry 58.
  • Telemetry circuitry 58 includes any suitable hardware, firmware, software or any combination thereof for communicating with another device, such as controller 28 (FIG. 5) or another device external to transesophageal neurostimulation system 210. Under the control of processing circuitry 53, telemetry circuitry 58 may receive communications, e.g., patient or clinician input, from and send communications, e.g., an alert, to controller 28.
  • transesophageal neurostimulation system 210 is representative of transesophageal neurostimulation system 10C
  • controller 28 may use an antenna (not shown) when communicating, which may be internal and/or external.
  • Processing circuitry 53 may provide the data to be sent to controller 28 and the control signals for the telemetry circuit within telemetry circuitry 58, and receive data from telemetry circuitry 58.
  • processing circuitry 53 may control telemetry circuitry 58 to exchange information with controller 28 or another device external to transesophageal neurostimulation system 210 wirelessly or wired.
  • Processing circuitry 53 may transmit operational information and patient data 69 and receive stimulation programs or stimulation parameter adjustments via telemetry circuitry 58.
  • transesophageal neurostimulation system 210 may communicate with other devices, such as stimulators, control devices, or sensors, via telemetry circuitry 58.
  • power source 70 delivers operating power to the components of transesophageal neurostimulation system 210.
  • power source 70 may include a battery and a power generation circuit to produce the operating power.
  • the battery may be rechargeable to allow extended operation. Recharging may be accomplished through proximal inductive interaction between an external charger and an inductive charging coil within transesophageal neurostimulation system 210.
  • an external inductive power supply may transcutaneously power transesophageal neurostimulation system 210 whenever electrical stimulation is to occur.
  • power source 70 may be coupled to an external power source, such as an outlet on a hospital wall.
  • a stimulation program of stimulation programs 66 may define various parameters of the stimulation waveform and electrode configuration which result in a predetermined stimulation intensity being delivered to the targeted vagus nerve.
  • the stimulation program defines parameters for at least one of a current or voltage amplitude of the stimulation signal, a frequency or pulse rate of the stimulation, the shape of the stimulation waveform, a duty cycle of the stimulation, a pulse width of the stimulation, a duty cycle of the stimulation ON/OFF periods, and/or the combination of electrodes 34 and respective polarities of the subset of electrodes 34 used to deliver the stimulation. Together, these stimulation parameter values may be used to define the stimulation intensity (also referred to herein as a stimulation intensity level).
  • a burst duty cycle also may contribute to stimulation intensity.
  • a particular pulse width and/or pulse rate may be selected from a range suitable for causing the desired therapeutic effect after stimulation is terminated and, optionally, during stimulation.
  • a period during which stimulation is delivered may include on and off periods (e.g., a duty cycle or bursts of pulses) where even the short inter-pulse durations of time when pulses are not delivered are still considered part of the delivery of stimulation.
  • a period during which transesophageal neurostimulation system 210 withholds stimulation delivery is a period in which no stimulation program is active and/or for which transesophageal neurostimulation system 210 is not tracking pulse durations or inter-pulse durations that occur as part of the electrical stimulation delivery scheme.
  • the stimulation may be defined by other characteristics, such as a time for which stimulation is delivered, a time for which stimulation is terminated, and times during which stimulation is withheld.
  • FIG. 5 is a block diagram illustrating an example configuration of a computing device.
  • Computing device 224 may be an example of controller 28.
  • Computing device 224 may include notebook computer, a smart phone, a workstation, a key fob, or a wearable device, for example.
  • computing device 224 may include a processing circuitry 90, memory 92, user interface 94, telemetry circuitry 96, and power source 98.
  • Memory 92 may store program instructions that, when executed by processing circuitry 90, cause processing circuitry 90 and computing device 224 to provide the functionality ascribed to controller 28 throughout this disclosure.
  • computing device 224 may include stimulation circuitry 91 which may function similarly to stimulation circuitry 52 of FIG. 4.
  • computing device 224 comprises any suitable arrangement of hardware, alone or in combination with software and/or firmware, to perform the techniques attributed to computing device 224, and processing circuitry 90, user interface 94, and telemetry circuitry 96 of computing device 224.
  • computing device 224 may include one or more processors, such as one or more microprocessors, DSPs, ASICs, FPGAs, or any other equivalent integrated or discrete logic circuitry, as well as any combinations of such components.
  • Computing device 224 also, in various examples, may include a memory 92, such as RAM, ROM, PROM, EPROM, EEPROM, flash memory, a hard disk, a CD-ROM, comprising executable instructions for causing the one or more processors to perform the actions attributed to them.
  • processing circuitry 90 and telemetry circuitry 96 are described as separate circuitry, in some examples, processing circuitry 90 and telemetry circuitry 96 are functionally integrated.
  • processing circuitry 90 and telemetry circuitry 96 and telemetry circuitry 58 correspond to individual hardware units, such as microprocessors, ASICs, DSPs, FPGAs, or other hardware units. In other examples, any of processing circuitry 90 and telemetry circuitry 96 and telemetry circuitry 58 may correspond to multiple individual hardware units, such as microprocessors, ASICs, DSPs, FPGAs, or other hardware units.
  • Memory 92 may store program instructions that, when executed by processing circuitry 90, cause processing circuitry 90 and computing device 224 to provide the functionality ascribed to computing device 224 throughout this disclosure.
  • memory 92 may further include program information, e.g., stimulation programs defining the neurostimulation, similar to those stored in memory 56 of transesophageal neurostimulation system 210.
  • the stimulation programs stored in memory 92 may be downloaded into memory 56 of transesophageal neurostimulation system 210.
  • computing device 224 includes a user interface 94 that allows the patient to provide input.
  • Patient 14 may, additionally or alternatively, request a change in stimulation program or settings through user interface 94.
  • patient 14 may use user interface 94 to enter a enter an indication of perceiving stimulation, feeling pain or discomfort from stimulation, or enter a level of perception, pain or discomfort caused by the stimulation (e.g., on a scale, such as from 1-10).
  • User interface 94 may include a button or keypad, lights, a speaker for voice commands, a turnable knob, a display, such as a liquid crystal (LCD), light-emitting diode (LED), or cathode ray tube (CRT).
  • a display such as a liquid crystal (LCD), light-emitting diode (LED), or cathode ray tube (CRT).
  • the display may be a touch screen.
  • the display may display a present measure of stimulation intensity, present duration of stimulation (e.g., a duration measured from when stimulation (e.g., therapeutic stimulation) began to a present time), and/or other information regarding the present therapy being delivered.
  • processing circuitry 90 may present and receive information relating to electrical stimulation and resulting therapeutic effects via user interface 94.
  • processing circuitry 90 may receive patient input via user interface 94.
  • the input may be, for example, in the form of pressing a button on a keypad or selecting an icon from a touch screen.
  • Processing circuitry 90 may also present information to the patient in the form of alerts related to delivery of the electrical stimulation to patient 14 or a caregiver via user interface 94.
  • computing device 224 may additionally or alternatively include a data or network interface to another computing device, to facilitate communication with the other device, and presentation of information relating to the electrical stimulation and therapeutic effects after termination of the electrical stimulation via the other device.
  • Telemetry circuitry 96 supports wireless or wired communication between transesophageal neurostimulation system 210 and computing device 224 under the control of processing circuitry 90. Telemetry circuitry 96 may also be configured to communicate with another computing device via wireless communication techniques, or direct communication through a wired connection. In some examples, telemetry circuitry 96 may be substantially similar to telemetry circuitry 58 of transesophageal neurostimulation system 210 described above, providing wireless communication via an RF or proximal inductive medium. In some examples, telemetry circuitry 96 may include an antenna, which may take on a variety of forms, such as an internal or external antenna.
  • Examples of local wireless communication techniques that may be employed to facilitate communication between computing device 224 and another computing device include RF communication according to the 802.11 or Bluetooth specification sets, infrared communication, e.g., according to the IrDA standard, or other standard or proprietary telemetry protocols. In this manner, other external devices may be capable of communicating with computing device 224 without needing to establish a secure wireless connection.
  • Power source 98 delivers operating power to the components of computing device 224.
  • Power source 98 may include a battery and a power generation circuit to produce the operating power.
  • the battery may be rechargeable to allow extended operation.
  • FIG. 6 is a conceptual diagram of an example portion of a transesophageal neurostimulation system according to the techniques of this disclosure.
  • Portion of transesophageal neurostimulation system 100 may include elongated member 130 may be an example of elongated member 30 (FIG. 2).
  • Elongated member 130 may include distal portion 130A and proximal portion 130B.
  • proximal portion 130B may extend to controller 28 or to another external device.
  • Distal portion 130A may be of a larger cross-sectional diameter (e.g., along line 150) than proximal portion 130B (e.g., along line 152).
  • distal portion 130A may be approximately 16 French, while proximal portion may be approximately 11 French.
  • Elongated member 130 may include one or more fluid openings 183 which may be examples of fluid openings 83 of FIG. 3, which may be used to inject or extract substances to/from stomach 25 of patient 14.
  • Elongated member 130 may also include one or more fluid openings 102 which may be fluidically coupled to an external inflation source to facilitate the inflation of expandable member 136 (which may be an example of expandable member 36 of FIG. 2) for example, via lumen 84B of FIG. 3.
  • expandable member 136 may be a balloon and may have a diameter between 20mm and 60mm when inflated.
  • an inflated expandable member 136 may have a diameter of approximately 35mm.
  • Transesophageal neurostimulation system 100 may include expandable member 132, which may be an example of expandable member 32 of FIG. 2. Expandable member 132 may take a basket-like shape when deployed in an expanded state and be referred to herein as a basket. As shown, expandable member 132 may include a plurality of arms 133. In some examples, each of arms 133 may include one or more electrodes (such as of electrodes 34 of FIG. 2), such as between one and four electrodes per arm. In some examples, each of arms 133 may include a temperature sensor as described above with respect to FIG. 4.
  • Expandable member 132 may be changed from the expanded state as shown in FIG. 6 to an unexpanded or collapsed state (or any number of partially expanded states therebetween) by moving section 140A of elongated member 130 distally to section 140B of elongated member 130 or by moving section 140B proximally to section 140A.
  • a mechanical mechanism for changing the expanded or unexpanded state of expandable member 132 may be carried in a lumen of elongated member 130, such as lumen 84 A of FIG. 3.
  • a clinician may use lever or dial 138, which may be mechanically coupled to section 140A and/or section 140B to change the expansion state of expandable member 132.
  • FIGS. 7A-7B are conceptual diagrams of an example expandable member according to the techniques of this disclosure.
  • FIG. 7A is an axial view of expandable member 132.
  • expandable member 132 includes a plurality of arms (e.g., twelve as shown, but may be any number greater than one), such as arm 133.
  • Each arm 133 may include an electrode 134 disposed generally at an outermost portion of arm 133 when expandable member 132 is in an expanded state. In this manner, when expandable member 132 is in an expanded state each electrode 134 may be more likely to be in physical contact with tissue of esophagus 24.
  • FIG. 7B is a different perspective view of expandable member 132. [0100] FIGS.
  • Elongated member 230 of transesophageal neurostimulation system 200 may be an example of elongated member 30 of FIG. 2.
  • Transesophageal neurostimulation system 200 may be similar to transesophageal neurostimulation system 100 of FIG. 6, however expandable member 232 may be different than expandable member 132 and/or the deployment mechanism for expandable member 232 may be different than for expandable member 132.
  • arms of expandable member 232 may be twisted when expandable member 232 is in the expandable mode such that electrodes disposed on the arms are not parallel to the axis 205 of elongated member 230.
  • elongated member 230 may be configured to twist one end of expandable member 232 relative to the other end of expandable member 232 when deploying expandable member 232 into an expanded state.
  • FIG. 8C shows a different perspective view of expandable member 232.
  • the deployment mechanism of expandable member 232 may include an inclined plane 250 of respective sections (which may correspond to sections 140A and 140B of elongated member 130 of FIG. 6) rather than an edge which is generally perpendicular to axis 205.
  • Inclined plane 250 may cause a twisting motion when expanding expandable member 232.
  • the twisting motion when expanding expandable member 232 may increase circumferential coverage within esophagus 24 of each electrode and may increase the chance of positioning one or more electrodes close to the vagus nerve fibers.
  • expandable member 232 includes a 60-degree twist of the basket when expandable member 232 is fully expanded.
  • FIGS. 9A-9B are conceptual diagrams of another example portion of a transesophageal neurostimulation system according to the techniques of this disclosure.
  • Elongated member 330 of FIG. 9A may be an example of elongated member 30 of FIG. 2.
  • Transesophageal neurostimulation system 300 may be similar to transesophageal neurostimulation system 100 100 of FIG. 6 and/or transesophageal neurostimulation system 200 of FIG. 8A, however expandable member 332 may be different than expandable member 132 and expandable member 232.
  • expandable member 332 may include a plurality of baskets.
  • expandable member 332 may include a first, outer basket structure 338 and a second, inner basket structure 340.
  • FIG. 9B shows a closer view of expandable member 332.
  • Inner basket structure 340 may be nested within outer basket structure 338.
  • expandable member 332 may include more arms and, potentially more electrodes, than expandable member 232 or expandable member 132.
  • expandable member 332 may provide greater electrode coverage for stimulation of the inner circumference of esophagus 24 than expandable member 232 or expandable member 132 as expandable member 332 may have more arms (and more electrodes) than expandable member 232 or expandable member 132.
  • outer basket structure 338 may substantially cover inner basket structure 340 which may be close to a center of axis 310 than outer basket structure 338.
  • FIGS. 10A-10B are conceptual diagrams of another example portion of a transesophageal neurostimulation system according to the techniques of this disclosure.
  • Elongated member 430 of FIG. 10A may be an example of elongated member 30 of FIG. 2.
  • Transesophageal neurostimulation system 400 may be similar to transesophageal neurostimulation system 100 of FIG. 6, transesophageal neurostimulation system 200 of FIG. 8A, and/or transesophageal neurostimulation system 300 of FIG. 9A, however expandable member 432 may be different than expandable member 132, expandable member 232, and expandable member 332.
  • expandable member 432 may include a plurality of expandable structures (e.g., basket 432A and basket 432B) separated from each other at different axial positions along a length of elongated member 430.
  • FIG. 10B shows a closer view of expandable member 432.
  • basket 432A may include a plurality of arms such as arm 433A.
  • Each arm of basket 432A may include one or more electrodes, such as electrode 434A.
  • Basket 432B may include a plurality of arms such as arm 433B.
  • Each arm of basket 432B may include one or more electrodes, such as electrode 434B.
  • Basket 432A may be separated from basket 432B axially along elongated member 430.
  • transesophageal neurostimulation system 400 may utilize bipolar stimulation from one basket to the other basket, which may create a field along a length of the vagus nerve for better stimulation efficiency. While baskets 432A and 432B are shown as being similar to the basket of expandable member 132 of FIGS 6-7B, baskets 432A and 432B may be implemented as any other basket-like structure described herein (e.g., nested or twisted). [0104] FIG. 11 is a conceptual diagram of another example portion of a transesophageal neurostimulation system according to the techniques of this disclosure. Elongated member 530 of FIG. 11 may be an example of elongated member 30 of FIG. 2.
  • Transesophageal neurostimulation system 500 may be similar to transesophageal neurostimulation system 100 of FIG. 6, transesophageal neurostimulation system 200 of FIG. 8 A, transesophageal neurostimulation system 300 of FIG. 9A, or transesophageal neurostimulation system 400 of FIG.
  • distal portion 502 of elongated member 530 may include a biased or pre-curved portion such that when distal portion 502 enters stomach 25 of patient 14, the biased or pre-curved portion may assume its natural shape (e.g., there is no longer a force being applied on the distal portion 502 by the inner wall of esophagus 24 to function to anchor transesophageal neurostimulation system 500.
  • distal portion 502 may include an actively steered shape that is larger than an opening of the esophagus (e.g., a lower esophageal sphincter).
  • a mechanism may be present (e.g., in or via lumen 84 A) in transesophageal neurostimulation system 500 to actively steer the shape of distal portion 502 which may curl distal portion 502 into a looped, pigtail, spiral, or helix shape.
  • the mechanism could include a pullwire biased to one side of elongated member 530 or another steering mechanism.
  • elongated member 530 may have a maximum diameter when any expandable members are in an unexpanded or collapsed state of between approximately 4 mm and 6 mm.
  • Distal portion 502 may be configured such that the force required to remove distal portion 502 from stomach 25 is greater than that which would be expected from natural movements of patient 14, esophagus 24, and/or stomach 25.
  • distal portion 502 may be between 5cm and 20cm in length.
  • the bias or pre-curve of distal portion 502 may approximately match a curvature of a nasal passage and/or throat.
  • FIG. 12 is a conceptual diagram illustrating another example of an expandable member according to the techniques of this disclosure.
  • Expandable member 632 may be an example of expandable member 32 of FIG. 2.
  • Expandable member 632 may be similar to expandable member 132 of FIGS. 6-7B, however, rather than the arms being generally curved when deployed in an expanded state, the arms (e.g., arm 633) may be biased to be bent such that electrode (e.g., electrode 634) of expandable member 632 may be relatively flat against and parallel to the inner wall of esophagus 24.
  • the arms of expandable member 632 may be biased such that when expandable member 632 is expanded into the expanded state, the arms do not present as curved, but rather in a plurality of relatively straight, or planar, sections, such as three sections (632A-632C) as shown.
  • Expandable member 632 may be generally more stable and less likely to buckle than other expandable members with curved arms as described herein when in an expanded state.
  • FIG. 13 is a conceptual diagram illustrating a portion of an example arm and electrode of an expandable member according to the techniques of this disclosure.
  • Arm 733 may be an example of any of arms 133, 233, 333, 433, 533, or 633 of FIGS. 7-12, respectively.
  • Arm 733 may have electrode 734 disposed thereon or therein.
  • Electrode 734 may be an example of any of electrodes 134, 234, 334, 434, 534, or 634 of FIGS. 7-12, respectively.
  • arm 733 may include an insulating material 735 which may be configured to prevent surface shorting of electrode 734.
  • arm 733 may itself be constructed from an insulating material, in which case, insulating material 735 may not be included in arm 733, as the insulative material of arm 733 may prevent such surface shorting.
  • FIG. 14 is a flow diagram illustrating example transesophageal neurostimulation techniques according to the present disclosure.
  • a clinician may insert a portion of transesophageal neurostimulation system 100 into esophagus 24 of patient 14 to a desired location.
  • the clinician may insert the portion of transesophageal neurostimulation system 100 into esophagus 24 of patient 14 to such that expandable member 132 may be proximate to a vagus nerve of patient 14.
  • Processing circuitry 53 or a clinician may expand an expandable structure of a transesophageal neurostimulation device to an expanded state (800).
  • processing circuitry 53 or the clinician may expand expandable member 132 to an expanded state.
  • the transesophageal neurostimulation device may include an elongated member defining a lumen configured for at least one of injection of a substance to a stomach of a patient or aspiration of a substance from the stomach of the patient; at least one expandable member disposed on or about the elongated member, the at least one expandable member comprising a basket structure having a plurality of arms; and at least electrode disposed on each arm of the plurality of arms.
  • the plurality of electrodes of the at least one expandable member may be configurable to deliver transesophageal neurostimulation to the patient.
  • processing circuitry 53 may control a motor or other mechanical device to expand expandable member 132 (or other expandable member disclosed herein) or a clinician may expand the expandable member 132, for example, by moving section 140A of elongated member 130 proximally to section 140B of elongated member 130 or by moving section 140B distally to section 140A.
  • Processing circuitry 53 may control stimulation circuitry 52 to apply transesophageal neurostimulation to the patient via the plurality of electrodes (802).
  • processing circuitry 53 may control stimulation circuitry 52 to generate a transesophageal neurostimulation signal and apply transesophageal neurostimulation utilizing the transesophageal neurostimulation signal to one or more of anterior branch 26A of the vagus nerve or posterior branch 26B of the vagus nerve via electrodes 134.
  • processing circuitry 53 may receive clinician input indicating one or more stimulation parameters to be used to generate a transesophageal neurostimulation signal.
  • a clinician may use controller 28 to start stimulation with a relatively high intensity or start stimulation with a relatively low intensity and bring up the intensity until patient 14 indicates that patient 14 can feel the stimulation or the stimulation is painful or uncomfortable.
  • patient 14 may so indicate by raising their hand, speaking, or providing some other visual (e.g., making a face indicative of pain), audible (e.g., saying “ow”), or tactile (e.g., squeezing a clinician’s hand) indication.
  • controller 28 also represents a patient programmer
  • patient 14 may, via user interface 94, enter an indication of perceiving the stimulation, feeling pain or discomfort from the stimulation, or enter a level of perception, pain or discomfort caused by the stimulation (e.g., on a scale, such as from 1-10).
  • the clinician can then program one or more stimulation parameters that may be used by stimulation circuitry 52 to generate the transesophageal neurostimulation signal which may be within a therapeutic range, but lower than a perception threshold or a pain or discomfort threshold of patient 14.
  • the transesophageal neurostimulation signal may be generated in accordance with the clinician input and may be based on patient-reported sensory information.
  • Processing circuitry 53 or the clinician may collapse expandable member 132 after the delivery of transesophageal neurostimulation.
  • processing circuitry 53 may control a motor or other mechanical device to collapse expandable member 132 (or other expandable member disclosed herein) or a clinician may collapse the expandable member 132, for example, by moving section 140A of elongated member 130 distally to section 140B of elongated member 130 or by moving section 140B proximally to section 140A.
  • the clinician may then remove transesophageal neurostimulation system 100 from esophagus 24 of patient 14.
  • the expandable member (e.g., expandable member 132) may be fabricated from at least one of a nitinol tube, a polymer tube, and/or a rolled material.
  • the expandable member may include at least one of an elastic material, a superelastic material, an elastomeric material, a shape-memory material.
  • the expandable member may include at least one of laser-cuts, slits, etchings, or individually constructed arms.
  • the plurality of electrodes include flex circuit electrodes, and the plurality of electrodes are bonded to the respective arms (e.g., of arms 133) of the expandable member.
  • the expandable member is configured to be variably controlled between a plurality of expanded states by a clinician or is spring-loaded between an unexpanded state and an expanded state.
  • the expandable member may be configurable to a plurality of expanded states, such that a first expanded state of the plurality of expanded states is different than a second expanded state of the plurality of expanded states.
  • the first expanded state may be less expanded (e.g., closer to an unexpanded or collapsed state) than the second expanded state.
  • the expandable member is spring-loaded.
  • the expandable member may be configured to spring loaded to automatically bias the expandable member against an internal wall of esophagus 24 when triggered.
  • expandable member 232 in an expanded state, expandable member 232 is configured such that each of the plurality of electrodes 234 are not parallel to an axis 205 of elongated member 230.
  • expandable member 332 includes a pair of nested expandable members, the pair of nested expandable members including two expandable members (e.g., basket structure 338 and basket structure 340) arrange axially along elongated member 300.
  • the expandable member 432 includes a plurality of expandable structures (e.g., 432Aand 432B), each respective expandable structure having a respective plurality of arms (e.g., 433A and 433B).
  • each of the plurality of arms 633 are biased to bend to form at least three sections (sections 633A-633C) when the expandable member 632 is in an expanded state.
  • each section of the three sections may be generally flat or planar, such as the end two sections extending away from the elongated member and the middle section generally parallel with the axis of the elongated member.
  • the expandable member includes a compliant member configured to apply an axial force to expand the expandable member.
  • one or more arms of the expandable member may be the compliant member.
  • the compliant member is configured to permit peristaltic waves to pass by the expandable member.
  • elongated member 130 includes a proximal portion 13 OB and a distal portion 130A.
  • Distal portion 130A may have a cross-sectional diameter that is less than a cross-sectional diameter of proximal portion 13 OB.
  • distal portion 502 includes a pre-bent section.
  • transesophageal neurostimulation system 10 includes a balloon (e.g., expandable member 36) configured to, when inflated in stomach 25 of patient 14, anchor the neurostimulation device.
  • transesophageal neurostimulation system 10 includes a balloon (e.g., expandable member 36) configured to, when inflated in stomach 25 of patient 14, position one or more of the plurality of electrodes (e.g., electrodes 34) in a lower portion of esophagus 24 (e.g., in a lower half of esophagus 24, iof the patient.
  • transesophageal neurostimulation system 10 includes at least one pressure sensor configured to sense at least one of a peristaltic wave pressure or a gastric pressure of the patient.
  • transesophageal neurostimulation system 10 includes at least one temperature sensor disposed on at least one arm of the expandable structure, the at least one temperature sensor being configured to sense a temperature of at least one or the patient or tissue being subjected to stimulation.
  • transesophageal neurostimulation system 10 includes a plurality of electrodes disposed on the elongated member, the plurality of electrodes being configured to sense an electrocardiogram of the patient.
  • transesophageal neurostimulation system 10 includes stimulation circuitry configured to generate a transesophageal stimulation signal; memory configured to store stimulation parameters that at least partially define the transesophageal stimulation signal; and processing circuitry communicatively coupled to the memory, and the stimulation circuitry, the processing circuitry being configured to: control the stimulation circuitry to generate the transesophageal stimulation signal based at least in part on at least one of the stimulation parameters.
  • transesophageal neurostimulation system 10 includes one or more sensors configured to sense at least one physiological parameter of the patient, and processing circuitry 53 is further configured to control the stimulation circuitry to change or terminate the transesophageal stimulation signal based on the at least one sensed physiological parameter.
  • the one or more sensors comprise at least one of a temperature sensor, a pressure sensor, or a plurality of electrodes.
  • the techniques of this disclosure may facilitate the stimulating the cervical, thoracic, or abdominal vagus branches in a manner that is relatively easy and quick to use, such as through transesophageal stimulation.
  • Such techniques may be used for short-term stimulation, such as during an acute health problem, such as surgery or during an abrupt illnesses, such as sepsis, without having to undertake an invasive surgical procedure to implant a vagus nerve stimulation device.
  • the techniques described herein may not be limited to treatment or monitoring of a human patient.
  • the techniques of this disclosure may be applied to non-human patients, e.g., primates, canines, equines, pigs, and felines. These other animals may undergo clinical or research therapies that my benefit from the subject matter of this disclosure.
  • stimulation devices may include features and functionality in addition to electrical stimulation. Many of these additional features are expressly discussed herein. A few example features include, but are not limited to, different types of sensing capabilities and different types of wireless communication capabilities. For ease of discussion, the present disclosure does not expressly recite every conceivable combination of the additional features, such as by repeating every feature each time different examples and uses of the stimulation devices are discussed.
  • the techniques of this disclosure may be implemented in a wide variety of computing devices, medical devices, or any combination thereof. Any of the described units, circuitry or components may be implemented together or separately as discrete but interoperable logic devices. Depiction of different features as circuitry or units is intended to highlight different functional aspects and does not necessarily imply that such circuitry or units must be realized by separate hardware or software components. Rather, functionality associated with one or more circuitry or units may be performed by separate hardware or software components, or integrated within common or separate hardware or software components. [0122] The disclosure contemplates computer-readable storage media comprising instructions to cause a processor to perform any of the functions and techniques described herein.
  • the computer-readable storage media may take the example form of any volatile, non-volatile, magnetic, optical, or electrical media, such as a RAM, ROM, NVRAM, EEPROM, or flash memory that is tangible.
  • the computer-readable storage media may be referred to as non- transitory.
  • a server, client computing device, or any other computing device may also contain a more portable removable memory type to enable easy data transfer or offline data analysis.
  • processors including one or more microprocessors, DSPs, ASICs, FPGAs, or any other equivalent integrated, discrete logic circuitry, or other processing circuitry, as well as any combinations of such components, remote servers, remote client devices, or other devices.
  • processors including one or more microprocessors, DSPs, ASICs, FPGAs, or any other equivalent integrated, discrete logic circuitry, or other processing circuitry, as well as any combinations of such components, remote servers, remote client devices, or other devices.
  • processing circuitry or “processing circuitry” may generally refer to any of the foregoing logic circuitry, alone or in combination with other logic circuitry, or any other equivalent circuitry.
  • Such hardware, software, firmware may be implemented within the same device or within separate devices to support the various operations and functions described in this disclosure.
  • any of the described units, circuitry or components may be implemented together or separately as discrete but interoperable logic devices. Depiction of different features as circuitry or units is intended to highlight different functional aspects and does not necessarily imply that such circuitry or units must be realized by separate hardware or software components. Rather, functionality associated with one or more circuitry or units may be performed by separate hardware or software components, or integrated within common or separate hardware or software components.
  • any circuitry described herein may include electrical circuitry configured to perform the features attributed to that particular circuitry, such as fixed function processing circuitry, programmable processing circuitry, or combinations thereof.
  • a computer-readable storage medium comprises non-transitory medium.
  • the term “non-transitory” may indicate that the storage medium is not embodied in a carrier wave or a propagated signal.
  • a non-transitory storage medium may store data that may, over time, change (e.g., in RAM or cache).
  • a transesophageal neurostimulation device comprising: an elongated member defining a lumen configured for at least one of injection of a substance to a stomach of a patient or aspiration of a substance from the stomach of the patient; an expandable member disposed on or about the elongated member, the expandable member comprising a plurality of arms at respective locations around a perimeter of the elongated member, each of the plurality of arms comprising a portion configured to be disposed away from the elongated member in an expanded state; and a plurality of electrodes, wherein at least one electrode of the plurality of electrodes is disposed on a respective arm of the plurality of arms, wherein the plurality of electrodes disposed on the expandable member are configurable to deliver transesophageal neurostimulation to the patient.
  • Example 2 The transesophageal neurostimulation device of example 1, wherein the plurality of electrodes comprise flex circuit electrodes, and wherein the plurality of electrodes are bonded to respective arms of the expandable member.
  • Example 3 The transesophageal neurostimulation device of example 1 or example 2, wherein the expandable member is configured to be variably controlled between a plurality of expanded states by a clinician or is spring-loaded between an unexpanded state and an expanded state.
  • Example 4 The transesophageal neurostimulation device of any of examples 1-3, wherein, in the expanded state, the expandable member is configured such that each of the plurality of electrodes are not parallel to an axis of the elongated member.
  • Example 5 The transesophageal neurostimulation device of any of examples 1-4, wherein the expandable member comprises a pair of nested expandable members, the pair of nested expandable members comprising two expandable members arranged axially along the elongated member.
  • Example 6 The transesophageal neurostimulation device of any of examples 1-5, wherein the expandable member comprises a plurality of expandable structures, each respective expandable structure having a respective plurality of arms.
  • Example 7 The transesophageal neurostimulation device of any of examples 1-6, wherein each of the plurality of arms are biased to bend to form at least three sections when the expandable member is in an expanded state.
  • Example 8 The transesophageal neurostimulation device of any of examples 1-7, wherein the expandable member comprises a compliant member configured to apply an axial force to expand the expandable member.
  • Example 9 The transesophageal neurostimulation device of any of example 8, wherein the compliant member is configured to permit peristaltic waves to pass by the expandable member.
  • Example 10 The transesophageal neurostimulation device of any of examples 1-9, wherein the elongated member comprises: a proximal portion; and a distal portion, the distal portion having a cross-sectional diameter that is less than a cross-sectional diameter of the proximal portion.
  • Example 11 The transesophageal neurostimulation device of example 10, wherein the distal portion comprises a pre-bent section.
  • Example 12 The transesophageal neurostimulation device of any of examples
  • a balloon configured to, when inflated in the stomach of the patient, anchor the neurostimulation device.
  • Example 13 The transesophageal neurostimulation device of any of examples 1-11, further comprising a balloon configured to, when inflated in the stomach of the patient, position one or more of the plurality of electrodes in a lower portion of an esophagus of the patient.
  • Example 14 The transesophageal neurostimulation device of any of examples 1-13, further comprising at least one pressure sensor configured to sense at least one of a peristaltic wave pressure or a gastric pressure of the patient.
  • Example 15 The transesophageal neurostimulation device of any of examples 1-14, further comprising at least one temperature sensor disposed on at least one arm of the expandable member, the at least one temperature sensor being configured to sense a temperature of at least one or the patient or tissue being subjected to stimulation.
  • Example 16 The transesophageal neurostimulation device of any of examples 1-15, further comprising a plurality of electrodes disposed on the elongated member, the plurality of electrodes being configured to sense an electrocardiogram of the patient.
  • Example 17 The transesophageal neurostimulation device of any of examples 1-16, further comprising: stimulation circuitry configured to generate a transesophageal stimulation signal; memory configured to store stimulation parameters that at least partially define the transesophageal stimulation signal; and processing circuitry communicatively coupled to the memory, and the stimulation circuitry, the processing circuitry being configured to control the stimulation circuitry to generate the transesophageal stimulation signal based at least in part on at least one of the stimulation parameters.
  • stimulation circuitry configured to generate a transesophageal stimulation signal
  • memory configured to store stimulation parameters that at least partially define the transesophageal stimulation signal
  • processing circuitry communicatively coupled to the memory, and the stimulation circuitry, the processing circuitry being configured to control the stimulation circuitry to generate the transesophageal stimulation signal based at least in part on at least one of the stimulation parameters.
  • Example 18 The neurostimulation device of example 17, further comprising one or more sensors configured to sense at least one physiological parameter of the patient, wherein the processing circuitry is further configured to control the stimulation circuitry to change or terminate the transesophageal stimulation signal based on the at least one sensed physiological parameter.
  • Example 19 The neurostimulation device of example 18, wherein the one or more sensors comprise at least one of a temperature sensor, a pressure sensor, or a plurality of electrodes.
  • Example 20 The transesophageal neurostimulation device of any of examples 1-19, wherein the expandable member comprises at least one of a nitinol tube, a polymer tube, or a rolled material.
  • Example 21 The transesophageal neurostimulation device of any of examples 1-20, wherein the expandable member comprises at least one of an elastic material, a superelastic material, an elastomeric material, a shape-memory material.
  • Example 22 The transesophageal neurostimulation device of any of examples 1-21, wherein the expandable member comprises at least one of laser-cuts, slits, etchings or individually constructed arms.
  • Example 23 A method comprising: expanding at least one expandable structure of a transesophageal neurostimulation device to an expanded state, the transesophageal neurostimulation device comprising: an elongated member defining a lumen configured for at least one of injection of a substance to a stomach of a patient or aspiration of a substance from the stomach of the patient; the at least one expandable member disposed on or about the elongated member, the at least one expandable member comprising a plurality of arms at respective locations around a perimeter of the elongated member, each of the plurality of arms comprising a portion configured to be disposed away from the elongated member in an expanded state; and a plurality of electrodes, wherein at least one electrode of the plurality of electrodes is disposed on a respective arm of the plurality of arms, wherein the plurality of electrodes disposed on the expandable member are configurable to deliver transesophageal neurostimulation to the patient; and applying transesoph
  • Example 24 The method of claim 23, further comprising: receiving, by the transesophageal neurostimulation device, clinician input indicating one or more stimulation parameters to be used to generate a transesophageal neurostimulation signal; andgenerating the transesophageal neurostimulation signal in accordance with the one or more stimulation parameters, wherein applying the transesophageal neurostimulation to the patient comprises delivering the transesophageal neurostimulation signal via one or more of the plurality of electrodes, and wherein the clinician input is based on patient-reported sensory information.

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Abstract

Des exemples de dispositifs et de techniques sont divulgués pour administrer une thérapie par neurostimulation transœsophagienne. Un dispositif comprend un élément allongé délimitant une lumière conçue pour l'injection d'une substance à l'estomac d'un patient et/ou l'aspiration d'une substance à partir de l'estomac du patient. Le dispositif comprend un élément extensible disposé sur l'élément allongé, ou autour de celui-ci, l'élément extensible comprenant une pluralité de bras à des emplacements respectifs autour d'un périmètre de l'élément allongé, chacun de la pluralité de bras comprenant une partie conçue pour être disposée à l'écart de l'élément allongé dans un état étendu. Le dispositif comprend une pluralité d'électrodes, au moins une électrode parmi la pluralité d'électrodes étant disposée sur un bras respectif parmi la pluralité de bras. La pluralité d'électrodes disposées sur l'élément extensible peut être conçue pour administrer une neurostimulation transœsophagienne au patient.
PCT/IB2024/052005 2023-03-09 2024-03-01 Neurostimulation transœsophagienne WO2024184772A1 (fr)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5117828A (en) * 1989-09-25 1992-06-02 Arzco Medical Electronics, Inc. Expandable esophageal catheter
US20030074039A1 (en) * 1999-06-25 2003-04-17 Puskas John D. Devices and methods for vagus nerve stimulation
US20150366508A1 (en) * 2013-02-08 2015-12-24 Acutus Medical., Inc. Expandable catheter assembly with flexible printed circuit board (pcb) electrical pathways
US20180055564A1 (en) * 2016-08-25 2018-03-01 Boston Scientific Scimed, Inc. Systems and methods for nerve denervation to relieve pulmonary disease symptoms
US20180311497A1 (en) * 2017-04-28 2018-11-01 Iowa Approach, Inc. Systems, devices, and methods for delivery of pulsed electric field ablative energy to esophageal tissue
US20230026849A1 (en) * 2021-07-22 2023-01-26 Medtronic, Inc. Transesophageal vagus nerve stimulation

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5117828A (en) * 1989-09-25 1992-06-02 Arzco Medical Electronics, Inc. Expandable esophageal catheter
US20030074039A1 (en) * 1999-06-25 2003-04-17 Puskas John D. Devices and methods for vagus nerve stimulation
US20150366508A1 (en) * 2013-02-08 2015-12-24 Acutus Medical., Inc. Expandable catheter assembly with flexible printed circuit board (pcb) electrical pathways
US20180055564A1 (en) * 2016-08-25 2018-03-01 Boston Scientific Scimed, Inc. Systems and methods for nerve denervation to relieve pulmonary disease symptoms
US20180311497A1 (en) * 2017-04-28 2018-11-01 Iowa Approach, Inc. Systems, devices, and methods for delivery of pulsed electric field ablative energy to esophageal tissue
US20230026849A1 (en) * 2021-07-22 2023-01-26 Medtronic, Inc. Transesophageal vagus nerve stimulation

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