US20220212001A1 - Systems and methods for establishing a nerve block - Google Patents
Systems and methods for establishing a nerve block Download PDFInfo
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- US20220212001A1 US20220212001A1 US17/700,415 US202217700415A US2022212001A1 US 20220212001 A1 US20220212001 A1 US 20220212001A1 US 202217700415 A US202217700415 A US 202217700415A US 2022212001 A1 US2022212001 A1 US 2022212001A1
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- A—HUMAN NECESSITIES
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- A61N1/02—Details
- A61N1/04—Electrodes
- A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
- A61N1/0551—Spinal or peripheral nerve electrodes
- A61N1/0556—Cuff electrodes
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- A61B5/316—Modalities, i.e. specific diagnostic methods
- A61B5/388—Nerve conduction study, e.g. detecting action potential of peripheral nerves
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- A61B5/4047—Evaluating nerves condition afferent nerves, i.e. nerves that relay impulses to the central nervous system
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- A61M5/142—Pressure infusion, e.g. using pumps
- A61M5/14212—Pumping with an aspiration and an expulsion action
- A61M5/14236—Screw, impeller or centrifugal type pumps
Definitions
- Embodiments of the invention relate generally to systems, devices, and methods of establishing a nerve block, and more specifically to systems, devices, and method of delivering a drug to establish a nerve block.
- a nerve block can be used to treat a variety of pain, such as chronic pain, acute pain, or the pain resulting from a surgical procedure.
- the nerve block can be established by delivering a local anesthetic to a nerve or ganglia to block a specific nerve distribution to reduce or eliminate pain in a specific portion of the anatomy.
- the anesthetic is typically delivered to the nerve by needle injection or catheter infusion.
- One drawback with this delivery method is that the anesthetic may diffuse rapidly into the surrounding tissue and into the vasculature, which can reduce the effectiveness of the anesthetic at the target site and cause adverse side effects.
- An alternative technique for establishing a nerve block is via electrical stimulation of the nerve or ganglia.
- electrical stimulation typically requires a relatively high level of power in order to block the nerve, which results in a rapid discharge of a battery powered device.
- any implanted device including circuitry it may be useful or necessary to include some form of time keeping or clocking function.
- a common example of such an implantable device is a pacemaker which must keep time for each beat of the patient's heart.
- Other examples include an implantable neuro stimulation device that periodically outputs some form of stimuli to address some underlying disorder (e.g. chronic pain).
- Nerve blocking implants are an example of such an implantable neurostimulation device.
- a clocking function may be necessary or helpful in these implantable devices because stimulating output from these devices may occur periodically and/or regularly over some period of time.
- these devices may utilize a clocking function to keep track of when a simulating session has occurred or will occur, and particularly clocks that are able to determine the time of day and/or date.
- the present invention may relate generally to systems, devices, and methods of establishing a nerve block, and more specifically to systems, devices, and method of delivering a drug to establish a nerve block.
- the apparatus for establishing a nerve block may include a nerve cuff.
- a nerve cuff can include a cuff body having a channel extending within the length of the cuff body for passage of a nerve; a reservoir within the cuff body, the reservoir configured to hold a drug, the reservoir in fluid communication with the channel; and an elongate opening slit extending the length of the cuff body configured to be opened to provide access to the channel, and configured to be closed around the channel and thereby enclose the cuff body around the nerve.
- the nerve cuff further includes a controller disposed within the cuff body; and an electrode in electrical communication with the controller, the electrode configured to be in electrical communication with the nerve when the nerve is enclosed in the channel.
- the controller and electrode are configured to sense electrical activity in the nerve enclosed in the channel.
- the nerve cuff further includes a pump, wherein the controller is configured to activate the pump to transfer drug from the reservoir to the channel based in part on the sensed electrical activity of the nerve.
- the pump is a screw pump.
- the electrode is in electrical communication with an electrical pulse generator and is configured to deliver electrical stimulation to the nerve enclosed in the channel.
- the electrode comprises a lumen in fluid communication with the reservoir and the channel, the lumen of the electrode configured to deliver drug from the reservoir to the channel.
- the controller is programmable.
- the controller is programmed to drive the pump at a constant rate.
- the controller is programmed to drive the pump at an intermittent rate.
- the nerve cuff further includes a drug disposed within the reservoir.
- the drug is disposed in a passive diffusion matrix and both the drug and passive diffusion matrix are disposed within the reservoir.
- the drug is an anesthetic or analgesic.
- the nerve cuff further includes a needle in fluid communication with the reservoir, the needle configured to deliver drug from the reservoir to the nerve.
- a system for establishing a nerve block on a nerve includes an implantable drug delivery device that includes a housing; a reservoir disposed within the housing, the reservoir configured to hold a drug; a pump disposed within the housing, the pump configured to meter the drug out of the reservoir; and a controller in communication with the pump, the controller configured to control the pump.
- the system further includes a sensor in communication with the controller, wherein the controller is configured to activate the pump when the sensor detects electrical activity from a nerve that meets or exceeds a predetermined threshold.
- the senor comprises a wireless transmitter configured to communicate wirelessly with the controller.
- the senor is configured to be remotely placed away from the implantable drug delivery device.
- the housing includes a channel extending within the length of the housing for passage of a nerve; and an elongate opening slit extending the length of the housing, the elongate slit configured to be opened to provide access to the channel, the elongate slit configured to be closed around the channel and thereby enclose the housing around the nerve.
- the system further includes a microstimulator that is removably disposed in a pocket within the housing, wherein the elongate opening slit is configured to be opened to provide access to the pocket, and configured to be closed around the pocket to secure the microstimulator within the pocket.
- a method of establishing a nerve block on a nerve includes implanting a drug delivery device proximate the nerve, the drug delivery device configured to deliver a drug to the nerve; sensing an electrical signal transmitted to or by the nerve; and delivering a drug from the drug delivery device to the nerve based at least in part on the step of sensing an electrical signal transmitted to or by the nerve.
- the drug delivery device includes an electrode configured to sense the electrical signal.
- the method further includes delivering an electrical stimulus to the nerve through the electrode.
- the method further includes implanting a remote sensor configured to sense the electrical signal.
- the remote sensor and the drug delivery device are in wireless communication.
- the method further includes placing the nerve within a channel that extends through the drug delivery device, wherein the drug is delivered to the channel.
- the method further includes opening a slit on the drug delivery device to provide access to the channel; and closing the slit to secure the nerve within the channel.
- the apparatuses described herein may be configured to include a nerve cuff and to apply electrical stimulation to induce a nerve block.
- apparatuses having a dual clocking system in which a generally less accurate, but lower power, clock may run continuously and be updated periodically with a more accurate secondary clock.
- a generally less accurate, but lower power, clock may run continuously and be updated periodically with a more accurate secondary clock.
- these apparatuses are described in the context of an apparatus configured for use in deploying a nerve block, this principle may be implemented in any implantable system.
- generally described herein are apparatuses and methods for calibrating a first clock within an implantable device with a more accurate secondary clock.
- the first (e.g., central) clock may be the primary time keeping mechanism within the implantable device. While not all implantable devices require a time-keeping unit, those that provide periodic outputs to the patient often require a method for keeping time that contribute to controlling when an output is given.
- implantable neuro stimulator device having a low-power clock calibration system.
- a device may include: a first clock configured to keep time within the implantable neurostimulator; a second clock having more accurate time-keeping capabilities than the first clock, wherein the second clock is in an off or idle mode while the first clocking is running; and control circuitry configured to be triggered by an event such that upon triggering, the control circuitry turns on the second clock, and uses the second clock to calibrate the the first clock, then turns the second clock back off.
- the first clock may count time based upon a reference voltage generated within a circuitry of the implantable device.
- the second clock may comprises a piezoelectric crystal oscillator.
- the control circuitry may be configured to be triggered by an event comprising a preset signal programmed into the control circuitry.
- the event or trigger is thermal, e.g., temperature change.
- the preset signal may be based on a set length of time, such as a few hours, a day, a few days, a week, a couple of weeks, a month, or a few months.
- the preset signal may be a voltage value above a certain threshold.
- a method of calibrating a clock within an implantable neurostimulator device may include: keeping time using a first clock of the implantable neurostimulator device, wherein the first clock runs continuously and is operating based upon a reference voltage generated within a circuitry of the implantable neurostimulator device; triggering a calibration protocol; turning on a reference clock within the implantable neurostimulator device; and calibrating the first clock based on the reference clock to correct for thermally-dependent time drift; and turning off the reference clock.
- the first clock may comprise a reference voltage associated with an RC circuit to produce a time reference.
- the event that triggers the calibration may be thermal or temporal.
- the event that triggers the calibration protocol may be a period of time (e.g., as determined by the first clock).
- the length of time may be a few hours, a day, a few days, a week, a couple of weeks, a month, a few months, and a year.
- the event that triggers the calibration protocol may be a change in the reference voltage above a threshold value.
- the second clock may comprise a piezoelectric clock.
- Such a device may include: a housing; at least two electrically conductive contacts disposed on the housing; a resonator within the sealed capsule body, the resonator comprising a coil and a capacitor configured to resonate at a predetermined frequency range; a battery within the housing; and an electronic assembly within the housing; wherein the electronic assembly comprises power management circuitry configured to receive power from the resonator to charge the battery, a microcontroller configured to control stimulation of the vagus nerve from the electrically conductive contacts, a first clock configured to keep time, a second clock having more accurate time-keeping capabilities than the first clock, wherein the second clocking is configured to periodically calibrate the first clock.
- the system includes a first clocking module configured to keep time within the implantable device for the majority of the time.
- the system also includes a second clocking module that possesses more accurate time-keeping capabilities that only turns on when a calibration routine is triggered. For the remainder of the time, the second clocking module is either in an OFF or idle mode.
- the triggering event may be the passage of a certain amount of time, or by a threshold parameter being met. In some instances, the triggering event may be a preset signal programmed into the control circuitry.
- the preset signal is based on a set length of time, such as a few hours, a day, a few days, a week, a couple of weeks, a month, or a few months.
- the preset signal may also be a voltage or current value above a certain threshold value.
- the system also includes control circuitry that is able to coordinate signals triggered by the event and signals sent to the central clocking module and the secondary clocking module.
- the system also may include a calibration module that corrects any time drifts within the first or central clocking module after the clocking calibration has been performed.
- the first clocking module are able to measure and count time based upon a reference voltage generated within general circuitry of the implantable device.
- the more accurate secondary time keeping module is a piezoelectric crystal oscillator.
- the method includes obtaining a clocking value associated with the central clocking module, where the clocking value is associated with how the central clocking module keeps time, establishing an event that will trigger a calibration protocol of the clocking module using a reference clocking module, activating the reference clocking module from an OFF mode to an active mode, calibrating the central clocking module based on the reference voltage, correcting any time drifts within the central clocking module, and turning off the reference clocking module.
- the clocking value is associated with a reference voltage associated with a reference voltage associated with the clocking module charges an RC circuit to produce a time reference.
- the events that trigger the calibration step may be the running of a set amount of time where at the end of such a period of time, a calibration routine is run.
- the length of time may be a few hours, a day, a few days, a week, a couple of weeks, a month, a few months, and a year.
- the event that triggers the calibration protocol may also be a change in the reference voltage above a threshold value.
- the implantable device may include a housing, at least two electrically conductive contacts disposed on the housing, a resonator within the sealed capsule body, where the resonator comprising a coil and a capacitor configured to resonate at a predetermined frequency range, a battery within the housing, and an electronic assembly within the housing.
- the electronic assembly may include a power management circuitry configured to receive power from the resonator to charge the battery, a microcontroller configured to control stimulation of the vagus nerve from the electrically conductive contacts, a first clocking module configured to keep time, a second clocking module having more accurate time-keeping capabilities than the first clocking module, and where the second clocking module is configured to periodically calibrate the first clocking module.
- FIG. 1A is a perspective view depicting a nerve cuff with an electrical (e.g., neurostimulation device) implanted proximate a nerve, according to an embodiment of the invention.
- This implant may also be configured to include a reservoir for delivery of a drug; alternatively or additionally, this implant may be configured to apply high-frequency nerve-block stimulation to the nerve from one or more electrodes (e.g., electrode pairs).
- FIG. 1B is a top view depicting an implanted nerve cuff with stimulation device of FIG. 1A .
- FIG. 1C is a top view of another variation of an implanted nerve cuff including a reservoir for delivery of a nerve blocking agent.
- FIG. 1D is a top view of another variation of an implanted nerve cuff including a reservoir for delivery of a nerve blocking agent, including a reservoir and one or more (one is shown) cannula for delivery of the active agent, which may be metered.
- FIG. 1E is another example of a nerve cuff apparatus adapted for delivery of a nerve blocking agent (such as a drug) including a connection to a remote depot for holding (and/or loading or reloading) agent into the apparatus.
- a nerve blocking agent such as a drug
- Either or both the nerve cuff and/or the implanted and tethered depot may include control circuitry for controlling delivery of the blocking agent.
- FIG. 2 is a front view depicting an implanted nerve cuff with strain relief according to an embodiment of the invention.
- FIG. 3 is a front view depicting an implanted nerve cuff with suture holes according to an embodiment of the invention.
- FIG. 4 is an open view depicting the nerve cuff with suture holes of FIG. 3 .
- FIG. 5 is a top view depicting a closing device for the implanted nerve cuff.
- FIG. 6 is a perspective view depicting marsupializaton of components such as electronic circuitry and/or a drug depot within a pocket of the nerve cuff of FIG. 1A ;
- FIG. 7A is a top view depicting a nerve cuff having a conforming shield according to an embodiment of the invention.
- FIG. 7B is a front view of the nerve cuff of FIG. 7A .
- FIG. 8A is a top view depicting another example of an open nerve cuff.
- FIG. 8B is a front view of the nerve cuff of FIG. 8A .
- FIG. 8C is a top view depicting the nerve cuff of FIG. 8A in a closed configuration.
- FIGS. 9A and 9B show side views through a section of the cuff body wall, indicating uniform and varying thicknesses, respectively.
- FIGS. 10A-10C illustrate one variation of a nerve cuff as described herein.
- FIG. 10A shows an end view
- FIG. 10B is a side perspective view
- FIG. 10C is a side view.
- FIGS. 11A-11H illustrate steps for inserting a nerve cuff such as the nerve cuffs described herein.
- FIG. 12A shows an embodiment of a nerve cuff having a drug reservoir for releasing drug to a nerve.
- FIG. 12B shows another embodiment of a nerve cuff having a drug reservoir.
- FIG. 12C shows yet another embodiment of a nerve cuff having a drug reservoir.
- FIG. 13 is a flowchart showing the steps of calibrating a first clocking module (“first clock”) with a second clocking module (“second clock”).
- FIG. 14 is a diagram showing calibration of a first clocking module by a second clocking module based on a change in voltage.
- FIG. 15 is a diagram showing calibration of a first clocking module by a second clocking module based on a pre-determined period of time.
- Described herein are apparatuses (devices, systems, including implants) configured to apply a nerve block. These devices may be part of or used in conjunction with a nerve stimulator that delivers electrical stimulation to a nerve.
- the nerve block may be part of a nerve sensing and/or stimulation apparatus that provides electrical stimulation to modulate the activity of the nerve and cause a wide variety of effects. For example, electrical stimulation of the vagus nerve can result in a reduction of inflammation through activation of the cholinergic anti-inflammatory pathway.
- Nerve blocking drugs and/or electrical stimulation can be delivered to a nerve.
- an anesthetic or analgesic can be delivered to the nerve to establish a nerve block or otherwise modulate the activity of the nerve, with or without electrical nerve stimulation.
- the nerve securing device described herein can also be used to deliver drugs to the nerve.
- Nerve 102 can comprise any nerve in the human body targeted for therapeutic treatment, such as, for example, the vagus nerve.
- Nerve cuff adapter 100 generally comprises an outer carrier or cuff 104 body that can comprise any of a variety of medical grade materials, such as, for example, SilasticTM brand silicone elastomers, or TecothaneTM polymer.
- a nerve cuff including a cuff 104 body having (or forming) one or more pouches or pockets 106 for removably receiving an active, implantable stimulation device 108 (e.g., including a stimulation device configured to apply a nerve block electrical signal) having one or more integrated, leadless electrodes 110 on a surface of stimulation device 108 proximate nerve 102 .
- the one or more pouches may include a depot holding an active agent and/or a controller (including circuitry and/or a valve for regulating flow of active agent from the depot). As illustrated in FIGS.
- a nerve cuff 100 may wrap around nerve 102 such that electrodes 110 and/or one or more outputs 133 for an active agent from the drug depot are positioned proximate nerve 102 .
- These outputs 133 may be regulated by including a valve, pump, or other fluid control to regulate when an active agent is delivered from the apparatus onto the nerve.
- the depot (which may be referred to as a reservoir) may be of any appropriate size.
- the depot may include between 0.1 and 10 mL of liquid drug solution (e.g., between 0.1 and 5 mL, etc.).
- the depot includes a solid drug formulation that is configured to be applied (and may include being mixed with fluid already present or surrounding the nerve).
- the depot may be refillable, as from an external port and/or from a second internal depot.
- Contacts or electrodes 110 can be positioned directly against nerve 102 , as illustrated in FIG. 1B , or in close proximity to nerve.
- the nerve cuff may include a pocket holding a depot 142 that includes a drug or other active agent (such as an anesthetic or any other compound for topically inhibiting nerve activity).
- Drug may be delivered from the depot onto the nerve and kept at a locally precise concentration for a a sustained period by holding it within the nerve cuff surrounding the nerve 102 , allowing lower amounts of active agent to be applied more precisely over all or just a portion of the nerve.
- additional depots or reservoirs may be included for adding additional agents to the nerve or other regions of the nerve within the cuff.
- a second reservoir may include a wash-out material (e.g., saline) for diluting or removing the drug or active agent.
- a controller for releasing or delivering the active agent/drug may be included.
- the controller may be included instead of or along with (e.g., integrated into) the electronics 108 of the stimulator.
- the depot holding the active agent/drug 142 ′ may be connected to the output 133 onto the nerve in the cuff by a channel 145 ; this channel may be regulated (opened/closed) by a drug delivery controller 147 that may include hardware, software and/or firmware for actively controlling the application of drug onto the nerve.
- the drug delivery controller may also include a valve for opening/closing the channel, such as a piezo valve, or a pump.
- the depot 142 may be pressurized so that drug is emitted when the channel 145 is opened by the drug delivery controller 147 .
- the controller may also regulate pressurizing of the depot.
- the depot may be located remotely from the nerve cuff, as illustrated in FIG. 1E .
- the nerve cuff 100 is configured to include one or more outputs for active agent/drug (not visible in FIG. 1E ), and may also include a drug delivery controller for regulating the delivery of drug onto the nerve.
- a second depot may be included within the cuff, which may be filled by the primary depot 142 ′.
- the remote depot 142 ′ may be connected by tubing 148
- a drug delivery controller may include control logic for controlling delivery of the active agent onto the nerve.
- the drug delivery controller may therefore include a timer (e.g., for delivering doses at a prescribed time) and/or may include wireless communication circuitry and/or antenna for transmitting and/or receiving control information from a remote source.
- the drug delivery controller may also include a power source/supply (e.g., battery and/or inductive loop(s), capacitive power source, etc.), and one or more pumps and/or valves.
- a micro pump for delivering small (e.g., less than a 1 ml, less than 0.5 ml, less than 0.1 ml, etc.) of drug per time period (e.g., min, second, etc.).
- any of the apparatuses described herein may be configured to apply drug based on activity on the nerve.
- the drug delivery controller may include input from one or more electrodes (or may be integrated with an electrical activity detector) receiving input from the electrodes on the nerve within the cuff or separate from the cuff. Electrical activity above a particular threshold may trigger release of drug.
- a pocket 106 for containing a drug delivery controller, stimulation device, and/or drug depot may be defined by the open space between the nerve 102 and the inner surface of the cuff body 104 .
- the sensing and/or stimulation device, drug depot and/or drug delivery controller (including any pump and/or valve components) can be passively retained within pocket by the cuff body, or can be actively retained on cuff body with fastening means, such as, for example, sutures.
- a pocket can comprise a pouch-like structure attached to cuff body into which sensing and/or stimulation device, drug depot and/or drug delivery controller can be inserted.
- the sensing and/or stimulation device, drug depot and/or drug delivery controller can be passively retained within a pouch-like pocket by simply inserting into the pocket or can be actively retained with fastening means.
- a pouch-like pocket can be positioned either in the interior or on the exterior of cuff body 104 .
- Pouch-like pocket and/or cuff body can include access openings to allow electrodes and/or drug outputs (including needles or cannula) to be positioned directly proximate or adjacent to nerve 102 .
- Cuff body 104 can have a constant thickness or a varying thickness as depicted in FIGS. 9A and 9B .
- the thickness of cuff body 104 can be determined to reduce the palpable profile of the device once the stimulation device is inserted. In one embodiment, the thickness of cuff body can range from about 1 to about 30 mils, or from about 5 to about 20 mils. In one embodiment shown in FIG. 9B , cuff 104 can have a greater thickness at a top and bottom portion of the cuff and a smaller thickness in a middle portion where the stimulation device is contained.
- a key obstacle to overcome with implanting stimulation devices proximate nerves or nerve bundles is attaching a rigid structure that makes up the stimulation device along a fragile nerve in soft tissue.
- this issue is resolved by encasing nerve 102 and device 108 in a cuff body 104 that comprises a low durometer material (e.g., SilasticTM or TecothaneTM) as described above, that conforms around nerve 102 .
- cuff body 104 can comprise strain reliefs 114 on its ends that reduce or prevent extreme torsional rotation and keep nerve 102 from kinking. Strain reliefs 114 can coil around nerve 102 , and are trimmable to a desired size, such as the size of nerve 102 .
- strain relief 114 can be tapered.
- the lateral ends of the nerve cuff, forming the channel into which the nerve may be place are tapered and have a tapering thickness, providing some amount of support for the nerve.
- the channel through the nerve cuff in which the nerve may sit is reinforced to prevent or limit axial loading (e.g., crushing) of the nerve or associated vascular structures when the nerve is within the cuff.
- any vertical movement of cuff body 104 on nerve 102 is not critical to electrical performance, but can result in friction between device 108 and nerve 102 that could potentially damage nerve 102 .
- device 108 should readily move up and down nerve 102 without significant friction while being sufficiently fixated to nerve 102 so that eventually connective tissue can form and aid in holding device 108 in place.
- the challenge is stabilizing device 108 so that it can be further biologically stabilized by connective tissue within several weeks.
- Nerve cuff 100 should not be stabilized to surrounding muscle or fascia that will shift relative to the nerve. Therefore, referring to FIGS. 3 and 4 , nerve cuff 100 can further comprise connection devices, such as suture holes or suture tabs, for coupling and stabilizing cuff body 104 with device 108 to at least one of the nerve bundle or nerve 102 , and the surrounding sheath that contains nerve 102 .
- connection devices such as suture holes or suture tabs, for coupling and stabilizing cuff body 104 with device 108 to at least one of the nerve bundle or nerve 102 , and the surrounding sheath that contains nerve 102 .
- cuff body 104 can comprise suture holes 116 that can be used with sutures to couple cuff 104 body with device 108 to the surrounding nerve sheath.
- suture tabs 118 with suture holes 116 extend from one or both sides of cuff body 104 .
- FIGS. 3 and 4 illustrates suture tabs and holes that can be fixed to the surrounding sheath with either absorbable sutures for soft tissue or sutures demanding rigid fixation.
- FIG. 5 illustrates sutures 120 that clamp or secure cuff body 104 with device 108 to a surgeon-elected tension.
- Sutures 120 can be tightened or loosened depending on the level of desired stability and anatomical concerns.
- a gap 122 can be present so long as cuff adapter 100 is sufficiently secured to nerve 102 , with a limit set to a nerve diameter to prevent compression of the vasculature within nerve 102 .
- Surgical adhesives (not shown) can be used in combination with sutures 120 on surrounding tissues that move in unison with the neural tissue.
- Muscle movement against cuff adapter 100 can also transfer undesired stresses on nerve 102 . Therefore, in an embodiment of the invention, low friction surfaces and/or hydrophilic coatings can be incorporated on one or more surfaces of cuff body 104 to provide further mechanisms reducing or preventing adjacent tissues from upsetting the stability of nerve cuff 100 .
- FIG. 6 illustrates a nerve cuff 100 with a sensing and/or stimulation device, drug depot and/or drug delivery controller device removably or marsupially secured within pocket or pouch 106 of cuff body 104 .
- active stimulator device 108 can be removed or replaced from cuff body 104 without threatening or endangering the surrounding anatomical structures and tissues.
- Device 108 can be secured within cuff body 104 by any of a variety of securing devices 124 , such as, for example, sutures, staples, ties, zippers, hook and loop fasteners, snaps, buttons, and combinations thereof. Sutures 124 are shown in FIG. 6 .
- Releasing sutures 124 allows access to pouch 106 for removal or replacement of device 108 .
- a capsule of connective tissue can naturally encapsulate nerve cuff 100 over time. Therefore, it will most likely be necessary to palpate device 108 to locate device 108 and cut through the connective tissue capsule to access sutures 124 and device.
- the removable/replaceable feature of nerve cuff 100 is advantageous over other cuff style leads because such leads cannot be removed due to entanglement with the target nerve and critical vasculature.
- compression of nerve 102 must be carefully controlled. Excess compression on nerve 102 can lead to devascularization and resulting death of the neural tissue. Compression can be controlled by over-sizing or rightsizing nerve cuff 100 , so that when pocket sutures 124 are maximally tightened, the nerve diameter is not reduced less that the measured diameter. Cuffs formed from SilasticTM or TecothaneTM materials are relatively low cost, and therefore several sizes can be provided to the surgeon performing the implantation of nerve cuff 100 to better avoid nerve compression.
- nerve cuff 100 can further comprise a protecting shield 126 conforming to the shape of the anatomical structures, such as in the carotid sheath.
- nerve cuff 100 is secured around the vagus nerve, while isolating device 108 from contact with both the internal jugular vein (IJV) 132 , and common carotid artery 134 . Shield 126 then further isolates device 108 from other surrounding tissues.
- IJV internal jugular vein
- protective shield 126 is formed from a PET material, such as Dacron®, optionally coated with SilasticTM or TecothaneTM forming a thin and compliant structure that will allow for tissue separation when required.
- FIG. 8A illustrates a variable size nerve cuff 100 with a wrappable retainer portion 128 extending from cuff body 104 .
- cuff body 104 is secured around nerve 102
- retainer portion 128 is secured around the sheath or other surrounding anatomical structures, such as the IJV 132 and/or carotid artery 134 .
- FIG. 8C illustrates a variable size nerve cuff 100 with a wrappable retainer portion 128 extending from cuff body 104 .
- retainer portion 128 is secured around the sheath or other surrounding anatomical structures, such as the IJV 132 and/or carotid artery 134 .
- wrappable retainer portion 128 can include securing devices 130 , such as suture holes, for securing the entire nerve cuff 100 around the desired anatomical structures.
- securing devices 130 such as suture holes
- This configuration allows for access to sensing and/or stimulation device, drug depot and/or drug delivery controller devices 108 through pocket 106 as in previous embodiments, while adapting to a multitude of anatomical variations to obtain the desired stability of nerve cuff 100 on nerve 102 .
- FIGS. 10A-10C illustrate a variation of a nerve cuff that includes a cuff body forming a channel (into which a nerve may be fitted) and an slit formed along the length of the nerve cuff body.
- the nerve cuff body also includes one or more pocket regions (not visible in FIGS. 10A-10C ) within the cuff body positioned above the nerve channel.
- the top of the body (opposite from the nerve channel) includes a long slit 1003 along its length forming on opening.
- the cuff body may be along the slit by pulling apart the edges, which may form one or more flaps.
- FIG. 10A-10C illustrate a variation of a nerve cuff that includes a cuff body forming a channel (into which a nerve may be fitted) and an slit formed along the length of the nerve cuff body.
- the nerve cuff body also includes one or more pocket regions (not visible in FIGS. 10A-10C ) within the cuff
- the slit may be split open to expose the inside of the nerve cuff and allow the nerve to be positioned within the internal channel, so that the cuff is positioned around the nerve.
- the same split may be used to insert the sensing and/or stimulation device, drug depot and/or drug delivery controller device as well.
- a separate opening slit or flap may be used to access the pocket or pouch for the sensing and/or stimulation device, drug depot and/or drug delivery controller.
- FIG. 10B shows a perspective view of the nerve cuff holding a sensing and/or stimulation device, drug depot and/or drug delivery controller after it has been inserted onto a nerve (e.g., the vagus nerve).
- FIG. 10C shows a side view of the same.
- the exemplary cuff shown in FIGS. 10A-10C has a conformal configuration, in which the wall thickness is relatively constant; in some variations of a nerve cuff, the wall thickness may vary along the perimeter. This non-uniform thickness may effectively cushion the device relative to the surrounding tissue, even as the patient moves or palpitates the region. This may have the added benefit of preventing impingement of the nerve. Similarly, the variable thickness may enable smooth transitions and help conform the cuff to the surrounding anatomy.
- the nerve cuff may be substantially rounded or conforming, and have non-traumatic (or atraumatic) outer surfaces. As mentioned, this relatively smooth outer surface may enhance comfort and limit encapsulation of the nerve cuff within the tissue.
- a nerve may sit within a supported channel through the nerve cuff.
- the channel may be formed having generally smooth sides, so as to prevent damage to the nerve and associated tissues.
- the nerve channel though the cuff is reinforced to prevent the cuff from pinching the device or from over-tightening the device when closed over the nerve.
- Supports may be formed of a different material forming the nerve cuff body, or from thickened regions of the same material.
- multiple sizes of nerve cuff may be used (e.g., small, medium, large), in some variations, an oversized nerve cuff may be used, because the insulated cuff body will prevent leak of current from the sensing and/or stimulation device, drug depot and/or drug delivery controller to surrounding tissues.
- any of the devices described herein may be positioned around the nerve, and the sensing and/or stimulation device, drug depot and/or drug delivery controller inserted into the nerve cuff, in any appropriate manner.
- FIGS. 11A-11H illustrate one variation of a method for applying the nerve cuff around the nerve and inserting a sensing and/or stimulation device, drug depot and/or drug delivery controller.
- the patient is prepared for application of the nerve cuff around the nerve to hold a sensing and/or stimulation device, drug depot and/or drug delivery controller device securely relative to the nerve ( FIG. 11A ).
- An incision is then made in the skin ( ⁇ 3 cm), e.g., when inserting onto the vagus nerve, along Lange's crease between the Facial Vein and the Omohyoid muscle ( FIG. 11B ), and the Sternocleidomastoid is retracted away to gain access to the carotid sheath ( FIG. 11C ).
- the IJV is then reflected and ⁇ 2 cm of the vagus is dissected from the carotid wall.
- a sizing tool may be used to measure the vagus (e.g., diameter) to select an appropriate sensing and/or stimulation device, drug depot and/or drug delivery controller and cuff (e.g., small, medium, large).
- an oversized cuff may be used.
- the nerve cuff is then placed under the nerve with the opening into the nerve cuff facing the surgeon ( FIG. 11D ), allowing access to the nerve and the pocket for holding the sensing and/or stimulation device, drug depot and/or drug delivery controller.
- the sensing and/or stimulation device, drug depot and/or drug delivery controller can then be inserted inside cuff ( FIG.
- the sensing and/or stimulation device, drug depot and/or drug delivery controller may then be tested ( FIG. 11G ) to confirm that the device is working and coupled to the nerve.
- a surgical tester device covered in a sterile plastic cover, may be used to activate the sensing and/or stimulation device, drug depot and/or drug delivery controller and perform system integrity and impedance checks, and shut the sensing and/or stimulation device, drug depot and/or drug delivery controller off. If necessary the procedure may be repeated to correctly position and connect the sensing and/or stimulation device, drug depot and/or drug delivery controller. Once this is completed and verified, the incision may be closed ( FIG. 11H ).
- Systems for electrically stimulating one or more nerves to treat chronic inflammation may include an implantable, wireless sensing and/or stimulation device, drug depot and/or drug delivery controller such as those described herein and an external charging device (which may be referred to as a charging wand, charger, or energizer).
- the system also includes a controller such as a “prescription pad” that helps control and regulate the dose delivered by the system.
- the sensing and/or stimulation device, drug depot and/or drug delivery controller may be secured in position using a securing device (which may be referred to as a “POD”) to hold the sensing and/or stimulation device, drug depot and/or drug delivery controller in position around or adjacent to a nerve.
- a securing device which may be referred to as a “POD”
- doses of active agent may be applied continuously, periodically or may the apparatus may be configured to apply a dose or additional dose upon triggering of an event such as an electrical activity on the never.
- a microliter and even picoliter doses of active agent may be delivered either continuously or periodically (e.g., at a frequency of x uL or pL per second, where x is between 0.001 and 10) or for a single dose (e.g. of x uL or pL, where x is between 0.001 and 10).
- a single dose may be delivered within the cuff, or multiple doses maybe delivered within the cuff.
- Doses may be separated by a dosage interval that may be predefined, regular, scheduled (based on time of day) and/or triggered (e.g., by nerve activity). Doses may be delivered on demand. For example, a doctor or patient may communicate wirelessly or via an input in the drug delivery control to trigger release of a dose.
- the nerve cuff 2800 can be modified to include a reservoir 2802 to hold an active agent/drug, such as an anesthetic like lidocaine.
- the nerve cuff 2800 can have one or more outputs/channels (ports 2804 ) for releasing the drug into the region surrounding the nerve 2806 within the cuff. Because the nerve cuff 2800 surrounds the portion of the nerve 2806 where the drug is being delivered, the diffusion of the drug away from the nerve is greatly reduced as compared to injection or infusion of the drug using a needle or catheter.
- the modified nerve cuff 2800 can be used with a microstimulator 2808 as described herein. In other embodiments, the modified nerve cuff can be used without a microstimulator to deliver drug to a nerve.
- the nerve cuff 2800 can have a refilling port 2810 in fluid communication with the reservoir 2802 .
- the refilling port 2810 can be used to refill the reservoir 2802 with drug (e.g., anesthetic).
- the refilling port 2810 can be located on the outer surface of the nerve cuff 2800 , and a needle or catheter can be used to access the refilling port and deliver drug to the reservoir (depot) while the nerve blocking device remains within the body around the nerve 2806 .
- drug e.g., anesthetic
- the refilling port 2810 can be located on the outer surface of the nerve cuff 2800 , and a needle or catheter can be used to access the refilling port and deliver drug to the reservoir (depot) while the nerve blocking device remains within the body around the nerve 2806 .
- the refilling port 2810 can be in fluid communication with a subcutaneous or subdermal access port 2812 , and a needle or catheter can be used to access the access port 2812 and deliver drug to the reservoir.
- the access port 2812 can be located at a subcutaneous location, and tubing 2814 can connect the access port 2812 with the drug refilling port 2810 on the nerve cuff 2800 .
- one or more of the electrodes 2816 can be modified to include a lumen 2818 or channel for drug delivery.
- the modified electrode 2816 can be a cuff type electrode, or a penetrating type electrode such as a needle electrode, or a combination of both.
- the modified electrode 2816 can deliver the drug from the reservoir to the nerve 2806 in a perifascicular or intrafascilular manner. Perifascicular delivery means delivery of the drug around a nerve or nerve bundle, while intrafascilular delivery means delivery of the drug into or inside the nerve or nerve bundle.
- a modified cuff electrode 2816 can be used for perifascicular drug delivery, while a modified penetrating electrode can be used for intrafascilular drug delivery.
- the device can have a dedicated drug delivery lumen or needle that is separate from the electrode.
- the drug can be delivered from the reservoir using a passive diffusion matrix drug delivery system.
- the drug can be incorporated into a polymer matrix and can diffuse out of the matrix and/or be release as the matrix erodes.
- the drug delivery system can use a pump 2820 , such as a screw pump or other small pump.
- the pump 2820 can deliver drug in a liquid form, a solid form such as a power, or a mixed form such as a paste or slurry, from the reservoir 2802 to the nerve 2806 .
- the modified electrodes can be electrically active and can be capable of delivering and/or detecting an electrical stimulus or signal to the nerve or other tissue. In other embodiments, the modified electrodes can be electrically inactive, and may only be used for drug delivery.
- a controller can be used to control the pump along with controlling the stimulation delivered by the electrodes and/or the signal detection and processing by the electrodes.
- the controller may be programmable and may drive the pump to deliver drug at a constant or intermittent rate.
- the controller may enable manual drug dosing, where the user can communicate with the controller using wireless communications.
- the controller may be programmed and/or communicate with a computing device, such as a tablet, smart phone, laptop, or desktop computer, using a wireless communication protocol, such as Bluetooth or WiFi.
- the controller provides closed loop control of the drug delivery.
- the controller can adjust the dosage of drug, i.e. the amount and/or the rate of drug delivered, based on feedback received from a sensor.
- the sensor can be the electrode described above used for local detection of action potential activity in a nerve.
- the sensor can be a remotely located sensor that detects a physiological aspect of the patient, such as inflammation or pain.
- one or more remote sensors can be placed at a different nerve that is remotely located from the nerve cuff but is part of the same sensory pathway. This allows the nerve cuff with drug delivery capabilities to be placed at an upstream, more central location that can potentially block pain signals from multiple nerves.
- this allows the sensors to be placed at upstream locations to improve detection of pain signals transmitted by the nerves while the drug delivery device is placed at one or more downstream locations to minimize or reduce the area affected by the drug.
- These remotely located sensors may communicate wirelessly with the controller in the nerve cuff, or the remote sensors may be directly connected to the nerve cuff using a wire. Local detection or remote detection of action potential activity in the any of the nerves in the pathway can trigger the delivery of drug from the reservoir.
- the senor can measure electrical activity from the heart and can be used to measure an ECG signal.
- the controller can be used to process and analyze the ECG signal to determine heart rate and heart rate variability.
- the drug dosage can be modified based on the heart rate and/or heart rate variability.
- the drug can be an anesthetic or analgesic or another type of painkiller
- One or more drugs can be used to provide a customizable dosing schedule tailored to the needs of the patient.
- the one or more drugs can be selected based in part on the desired wash out speed, volumetric optimization, and drug stability.
- the nerve cuff can include one or more reservoirs so that each drug can be contained in a separate reservoir, or the drugs can be mixed together and be placed into a single reservoir.
- drugs examples include ester based anesthetics such as procaine (novocaine), benzocaine, chloroprocaine cocaine, cyclomethycaine, dimethocaine, piperocaine, propoxycaine, proparacaine, and tetracaine; and amine based anesthetics such as lidocaine, bupivacaine (Marcaine), ropivacaine, cinchocaine, etidocaine, levobupivacaine, mepivacaine, articaine, prilocaine, and trimecaine.
- ester based anesthetics such as procaine (novocaine), benzocaine, chloroprocaine cocaine, cyclomethycaine, dimethocaine, piperocaine, propoxycaine, proparacaine, and tetracaine
- amine based anesthetics such as lidocaine, bupivacaine (Marcaine), ropivacaine, cinchocaine
- the drugs can be neurotrophic drugs with an effect on nerves.
- the pharmacokinetic profile of the drug or drug combination can be tailored to match the symptoms experienced by the patient, such as short term pain, chronic pain, or inflammation.
- lidocaine has a time constant of about 1 hour and Marcaine has a time constant of about 4 hrs. Therefore, to treat inflammation or pain lasting greater than 2 hours, it may be desirable to include Marcaine, which persists longer than lidocaine. In contrast, to treat inflammation or pain of shorter durations, for example, less than 2 hours, it may be desirable to include lidocaine.
- both a mixture of drugs having short and long time constants can be used.
- the device can be programmed to deliver drug at regular intervals, which can be determined based on the drug time constants and the degree of vascular profusion in the area, and/or in an on-demand fashion.
- the delivery of the drug can also be modified based on data received from a sensor, or in an on-demand fashion.
- the modified nerve cuff and electrode can be secured around the vagus nerve and both electrical stimulation and drug(s) can be delivered to the vagus nerve.
- the slit on the nerve cuff can be opened to allow access to a channel for receiving the nerve.
- the nerve can be placed within the channel, and the slit can then be closed to secure the nerve within the channel of the nerve cuff.
- the nerve cuff and electrode can be secured in a similar manner around a nerve responsible for generating the sensation of pain in the patient.
- one or more nerve cuffs and electrodes can be placed around or adjacent the interscalene nerve, supraclavicular nerve, infraclavicular nerve, and/or axillary nerve.
- An interscalene nerve block can be established for surgeries to the shoulder, clavicle, or upper arm; a supraclavicular nerve block can be established for surgeries to the upper arm to the hand; an infraclavicular nerve block can be established for surgeries to the elbow to the hand; and an axillary block can be established for surgeries to the elbow to the hand.
- one or more nerve cuffs and electrodes can be placed around or adjacent to the vertebral body in the paravertebral space and/or around or adjacent to nerves in the space between the internal oblique and the transversus abdominis muscles.
- one or more nerve cuffs and electrodes can be placed around or adjacent the lumbar plexus, the femoral nerve, and/or the sciatic nerve.
- the sensors can be positioned at or around the nerves listed above, and on other nerves or neural structures which receive signals from these nerves or are formed in part from these nerves, such as the brachial plexus and lumbar plexus, or on nerves that transmit signals to these nerves.
- the nerve cuff can include an electrode for sensing electrical signals, such as action potentials, to measure nerve activity of the nerve attached to the nerve cuff.
- remote sensors can be placed away from the nerve cuff at remote locations to sense electrical activity in nerves or nerve locations described herein. In some embodiments, the remote locations may be closer to the source of pain, such as near or at the extremities and joints.
- any of these apparatuses may be configured to provide an electrical nerve block using a microstimulator held within the cuff.
- Electrical nerve bock may involve reversibly blocking peripheral nerves by applying high frequency alternating current directly on a nerve trunk. For example, a current ranging from 5 kHz to 50 kHz may be applied (high frequency, compared to a current of less than 1 kHz for low frequency).
- a current ranging from 5 kHz to 50 kHz may be applied (high frequency, compared to a current of less than 1 kHz for low frequency).
- Efficacy of the high frequency alternating current therapy in acute non-human animal experiments has been reported, e.g., U.S. Pat. Nos. 7,389,145 and 8,060,208 describe this electrical stimulation.
- Reversibly blocking an action potential in a peripheral nerve having a diameter exceeding 3 mm and up to about 12 mm, e.g., a sciatic nerve, a tibial nerve, etc. may be applied by a neurostimulator held within any of the cuffs described herein, providing an electrical waveform for an interval of time sufficient to effect substantially immediate pain relief, defined generally as within about 10 min.
- a neurostimulator held within any of the cuffs described herein, providing an electrical waveform for an interval of time sufficient to effect substantially immediate pain relief, defined generally as within about 10 min.
- One embodiment uses a waveform ranging from 5 kHz to 50 kHz.
- One embodiment uses a 10 kHz sinusoidal waveform at a current ranging from 4 mA to 26 mA.
- the electrode can be retained in the cuff encircling the desired peripheral nerve in which the action potential is to be blocked.
- the time interval may be about 10 minutes, but an interval may be selected by a magnitude sufficient to effect pain relief in the patient.
- the electrical waveform to effect pain relief ranges from a voltage from 4 V to 20 V, or a current ranging from 4 mA to 26 mA.
- the time of increasing magnitude can range from about 10 seconds to about 60 seconds with a steady ramp up of voltage or current.
- the waveform may be provided by a waveform generator that is part of the apparatus.
- the application of the nerve block (including electrical nerve block) may be triggered by activity on the nerve to which the cuff is attached.
- a first or central clocking mechanism that uses a semiconductor junction to generate a reference voltage that in turn charges an RC circuit to produce a time reference. Because these voltage references have significant variations due to integrated circuit characteristics and parameters and temperature, they tend to be less accurate, though they may require lower power. Other, typically lower power and/or lower cost clocks may be used as the primary clock.
- a second more accurate clocking mechanism is employed.
- the second, more accurate clocking mechanism may be used to periodically recalibrate the first clocking mechanism.
- More accurate clocking mechanism include real time clocks.
- Real time clocks are a type of computer clock in the form of integrated circuits. Most real time clocks use a piezoelectric crystal oscillator, where the oscillator frequency is 32.768 kHz, the same frequency as in quartz clocks and watches.
- a time reference clocking module error in the RC circuit may be measured over fixed intervals or based on a change in a pre-determined parameter (e.g. voltage or current). Deviations may be measured against a more accurate real time crystal oscillator clocking mechanism. Based on the measured deviation and time elapsed since the last calibration, the amount of time deviation in the time reference clocking module may be calculated and corrected. Correction of any time deviation may be occur through correcting the central clocking module. Alternatively, the central clocking module may be temporarily replaced with the more accurate real time crystal oscillator clocking mechanism to bring the central clocking module back to a correct value.
- a pre-determined parameter e.g. voltage or current
- the implantable device will run the central clocking mechanism continuously while a second, more accurate clocking mechanism remains in an OFF or standby mode.
- the second, more accurate clocking mechanism may enter an active mode and re-calibrate the central clocking mechanism.
- the second, more accurate clocking mechanism will again revert to an OFF or standby mode until the next calibration is triggered.
- FIG. 13 shows a flowchart for visualizing the steps of implementing a clocking calibration routine 1300 .
- the clocking system for the implantable device such as a neurostimulator
- the systems clocking mechanism is running.
- the second, more accurate clocking mechanism is in a sleep or OFF mode ( 1308 ).
- an even triggers a signal being sent to the second clocking mechanism ( 1304 ).
- the trigger may correspond to the beginning of a new cycle in the implantable device.
- the trigger may be associated with the beginning of a stimulation session or a combination of features of the stimulation session (e.g.
- a trigger for calibration may also be a circuit parameter that has exceeded or dropped below a threshold value.
- a signal is sent to the second clocking module to turn from the OFF or standby mode to an active mode ( 1312 ). With the second clocking module in an active state, it will initiate the calibration routine ( 1310 ). Once the calibration routine ( 1310 ) has been performed, any deviation determined from running the calibration routine ( 1310 ) may be corrected in the following step ( 1314 ). Once the deviation has been corrected, a second signal may be sent to the second clocking module to return to an OFF or standby mode.
- a third signal may be sent to the central clocking module to switch it from an OFF or standby mode to an active mode.
- FIG. 14 a sample calibration routine based on some feature or characteristic of the implanted device output is shown.
- calibration of the central clocking system may be tied to when a stimulation session begins.
- a sensor may be incorporated to sense when a current or voltage has increased above a certain value and that a calibration routine should be initiated immediately or after a set amount of time.
- FIG. 14 shows stacked signals in order from top to bottom: a series of neurostimulation outputs for a neurostimulator 1430 , the functional state of the first or central clocking module 1440 , and the functional state of the second clocking module 1450 that is able to perform the calibration routine.
- the horizontal axis from left to right indicates the passage of time and may be in units of minutes, hours, days, weeks, months, and so forth.
- the diagram arbitrarily shows a snapshot of the output of an implanted device.
- the central clocking module 1440 is in an active mode 1441 and the second clocking module 1450 is in an OFF or standby mode ( 1451 ).
- the central clocking module 1440 will then continue to run for some period 1442 until a neurostimulation session begins ( 1432 ), at that point, signals are set to the both the central clocking module 1440 and the second clocking module 1450 when the neurostimulation output surpasses a certain threshold value.
- the central clocking module Upon reaching this state, the central clocking module will drop to an idle or OFF state 1442 while the second clocking module 1450 will switch from its OFF or standby mode 1451 to an active mode 1452 , where it will run a calibration routine 1453 either immediately or at a preset time in the future.
- a signal is sent to the central clocking module to coordinate switching it from the standby mode 1442 back to an active mode 1441 and for the second clocking module to return from an active mode 1452 to an OFF or standby mode 1451 in a coordinated fashion.
- the calibration routine may be tied to some other feature of the stimulating output and not necessarily correspond to the beginning of the stimulation output.
- FIG. 15 shows an alternative initiation of calibration routines in a system where a secondary, more accurate clocking module is used to calibrate and correct any deviations experienced by a less accurate central clocking module.
- the implanted device output will provide output periodically, where the time periods may be the same or different and may be set by the doctor or other user.
- a calibration routine may occur that aligns with a given time period t, that repeats.
- the central clocking module is in an active state 1541
- the second clocking module is in an OFF or inactive state 1551 .
- the central clocking module will switch to an idle or OFF mode 1542 while the second clocking module will turn to an active mode 1552 to calibrate the less accurate central clocking module 1540 and adjust for any deviations that is measured.
- the second clocking module 1550 will return to an OFF or standby mode 151 while the central clocking module 1540 will return to an active mode 1541 .
- These steps will repeat based on a pre-defined time interval. In some examples the time period will be the same, but in other examples the time period may be different or may be based on some algorithm or known relation between the length of time and the amount of deviation expected.
- the second clocking module may be linked to the calibration module that performs the actual calibration routine.
- the calibration module may be integrated into the circuitry of the implanted device.
- the systems clocking module is able to provide a central clocking signal that serves as a clock source.
- the systems clocking module is configured to provide a tick signal that acts as a time keeper. Periods between device outputs may be defined by the number of tick counts. While the tick counts accuracy is based upon characteristics of the circuit parameters, and may be not be as accurate as some other timing keeping mode, certain methods may be implemented to accommodate any inaccuracies.
- tick counts may be tied to the calibration module, which can be used to determine the duration of intervals between successive calibration routines. The start of a calibration routine is initialed by a signal which is configured to count the ticks from the central clocking module. The ticks may be counted until the calibration routine is complete and through a period where the central clocking module is keeping time. Tick counts may restart based upon the start of a new calibration routine.
- tick counts may be adjusted for accuracy using a more accurate time keeper located within the wireless transmitter unit.
- the tick counts may be matched with the more time keeping module within the wireless transmitter unit and any deviations may be corrected.
- the benefit of having a tick counting type time-keeping module is that a patient may move to different time zones without having to modify potentially salient circadian components of the stimulation output.
- the implanted device circuitry or controller will also be configured to detect a trigger or event that will commence a calibration routine.
- the trigger may be an increase in a threshold voltage or current value.
- the trigger may also be a combination or a pattern of changes in the voltage or current value in more complex arrangement of stimulating outputs.
- the implantable device will also be configured to provide a series of signals that will coordinate the switching of the central clocking module from an active mode to an OFF or standby mode, while signals are also sent for switching the second clocking module from an OFF mode to an active mode for the calibration routine.
- the implantable device may also include programs or algorithms that will be able to correct for any time drift that may be detected after the calibration routine is completed.
- the step of calibrating the central clocking module and accounting for any deviation may be performed in one step.
- the implantable neurostimulation device may be able to retain information on the calibration results such as the amount of drift that the central clocking module has experienced since the previous calibration routine. This information may be sent wirelessly to a telecommunication device or may be sent to the wireless transmitter module during recharging events.
- the clocking system described herein is directed to use within an implantable device, there is minimal temperature variations that may cause further drifts in the clocking system. Because the implant is in a temperature stable environment, there may be no need for temperature compensation.
- the circuit's wafer to wafer and die to die variations may be calibrated to a fixed temperature and scaled to 37° C. during manufacturing of the implantable device, may be calibrated during the programming of the implantable device, or during the wireless charging process.
- the calibration routine and subsequent correction steps may be in response to a received voltage or current signal from a sensor via some data communication link, and compares the received voltage or current signal against a set of pre-programmed or learned variables and values to determine if the central clocking module needs to be recalibrated. While the calibration routine may occur at any time, it may be beneficial to run the calibration routine when there is no stimulating output being provided. This would prevent overtaxing the overall circuitry of the implanted device.
- references to a structure or feature that is disposed “adjacent” another feature may have portions that overlap or underlie the adjacent feature.
- spatially relative terms such as “under”, “below”, “lower”, “over”, “upper” and the like, may be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if a device in the figures is inverted, elements described as “under” or “beneath” other elements or features would then be oriented “over” the other elements or features. Thus, the exemplary term “under” can encompass both an orientation of over and under.
- the device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly.
- the terms “upwardly”, “downwardly”, “vertical”, “horizontal” and the like are used herein for the purpose of explanation only unless specifically indicated otherwise.
- first and second may be used herein to describe various features/elements (including steps), these features/elements should not be limited by these terms, unless the context indicates otherwise. These terms may be used to distinguish one feature/element from another feature/element. Thus, a first feature/element discussed below could be termed a second feature/element, and similarly, a second feature/element discussed below could be termed a first feature/element without departing from the teachings of the present invention.
- any of the apparatuses and methods described herein should be understood to be inclusive, but all or a sub-set of the components and/or steps may alternatively be exclusive, and may be expressed as “consisting of” or alternatively “consisting essentially of” the various components, steps, sub-components or sub-steps.
- a numeric value may have a value that is +/ ⁇ 0.1% of the stated value (or range of values), +/ ⁇ 1% of the stated value (or range of values), +/ ⁇ 2% of the stated value (or range of values), +/ ⁇ 5% of the stated value (or range of values), +/ ⁇ 10% of the stated value (or range of values), etc.
- Any numerical values given herein should also be understood to include about or approximately that value, unless the context indicates otherwise. For example, if the value “10” is disclosed, then “about 10” is also disclosed. Any numerical range recited herein is intended to include all sub-ranges subsumed therein.
Abstract
A nerve cuff for establishing a nerve block on a nerve can have a cuff body with a channel for receiving a nerve, a reservoir for holding a drug, and an elongate opening slit extending the length of the cuff body that can be opened to provide access to the channel and can be closed to enclose the cuff body around the nerve. The nerve cuff can also include an electrode for detecting and measuring electrical signals generated by the nerve. A controller can be used to control delivery of the drug based on the electrical signals generated by the nerve.
Description
- This patent application is a continuation of U.S. patent application Ser. No. 16/785,400, filed Feb. 7, 2020, titled “SYSTEMS AND METHODS FOR ESTABLISHING A NERVE BLOCK,” now U.S. Pat. No. 11,278,718, which is a continuation of U.S. patent application Ser. No. 15/406,619, filed Jan. 13, 2017, titled “SYSTEMS AND METHODS FOR ESTABLISHING A NERVE BLOCK,” now U.S. Pat. No. 10,596,367, which claims the benefit under 35 U.S.C. § 119 of U.S. Provisional Patent Application No. 62/278,337, filed Jan. 13, 2016, titled “SYSTEMS AND METHODS FOR ESTABLISHING A NERVE BLOCK” and U.S. Provisional Patent Application No. 62/286,952, filed Jan. 25, 2016, titled “CALIBRATION OF CLOCK SIGNAL WITHIN AN IMPLANTABLE MICROSTIMULATOR,” each of which is herein incorporated by reference in its entirety.
- This patent application may be related to U.S. patent application Ser. No. 14/931,711, titled “NERVE CUFF WITH POCKET FOR LEADLESS STIMULATOR,” filed on Nov. 3, 2015, Publication No. US-2016-0051813-A1, which claims priority as a continuation of U.S. patent application Ser. No. 14/536,461, titled “NERVE CUFF WITH POCKET FOR LEADLESS STIMULATOR,” filed on Nov. 7, 2014, now U.S. Pat. No. 9,174,041, which is a divisional of U.S. patent application Ser. No. 12/797,452, titled “NERVE CUFF WITH POCKET FOR LEADLESS STIMULATOR”, filed on Jun. 9, 2010, now U.S. Pat. No. 8,886,339, which claims the benefit under 35 U.S.C. § 119 of U.S. Provisional Patent Application No. 61/185,494, titled “NERVE CUFF WITH POCKET FOR LEADLESS STIMULATOR”, filed on Jun. 9, 2009, each of which is herein incorporated by reference in its entirety.
- All publications and patent applications mentioned in this specification are herein incorporated by reference in their entirety to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.
- Embodiments of the invention relate generally to systems, devices, and methods of establishing a nerve block, and more specifically to systems, devices, and method of delivering a drug to establish a nerve block.
- A nerve block can be used to treat a variety of pain, such as chronic pain, acute pain, or the pain resulting from a surgical procedure. The nerve block can be established by delivering a local anesthetic to a nerve or ganglia to block a specific nerve distribution to reduce or eliminate pain in a specific portion of the anatomy. The anesthetic is typically delivered to the nerve by needle injection or catheter infusion. One drawback with this delivery method is that the anesthetic may diffuse rapidly into the surrounding tissue and into the vasculature, which can reduce the effectiveness of the anesthetic at the target site and cause adverse side effects.
- An alternative technique for establishing a nerve block is via electrical stimulation of the nerve or ganglia. However, such electrical stimulation typically requires a relatively high level of power in order to block the nerve, which results in a rapid discharge of a battery powered device.
- Accordingly, it would be desirable to provide a system and method for establishing a nerve block in an efficient and effective manner.
- Furthermore, in any implanted device including circuitry it may be useful or necessary to include some form of time keeping or clocking function. A common example of such an implantable device is a pacemaker which must keep time for each beat of the patient's heart. Other examples include an implantable neuro stimulation device that periodically outputs some form of stimuli to address some underlying disorder (e.g. chronic pain). Nerve blocking implants are an example of such an implantable neurostimulation device. A clocking function may be necessary or helpful in these implantable devices because stimulating output from these devices may occur periodically and/or regularly over some period of time. Thus, these devices may utilize a clocking function to keep track of when a simulating session has occurred or will occur, and particularly clocks that are able to determine the time of day and/or date.
- In designing the clocking function within implantable devices, certain considerations should be addressed. While a high level of accuracy is always desirable, there may be certain drawbacks associated with having a clocking assembly with high accuracy. While highly accurate main clocking systems are able to synchronize and coordinate various circuit and component operations, a major drawback is that they operate on a relatively large current and thus consume a lot of power. In addition, high accuracy clocking mechanism such as piezoelectric crystals are more expensive and more prone to damage. Because implantable devices are powered by batteries with a finite life and more recently through wireless charging, it is desirable to have a clocking mechanism for an implantable device that is able to maintain accuracy but does not draw a lot of power and is fairly inexpensive. Thus, it would be advantageous to have a clocking system that incorporated the low power consumption characteristics of a less accurate clocking module but still maintain a certain level of clocking accuracy.
- The present invention may relate generally to systems, devices, and methods of establishing a nerve block, and more specifically to systems, devices, and method of delivering a drug to establish a nerve block.
- In some embodiments, the apparatus for establishing a nerve block may include a nerve cuff. A nerve cuff can include a cuff body having a channel extending within the length of the cuff body for passage of a nerve; a reservoir within the cuff body, the reservoir configured to hold a drug, the reservoir in fluid communication with the channel; and an elongate opening slit extending the length of the cuff body configured to be opened to provide access to the channel, and configured to be closed around the channel and thereby enclose the cuff body around the nerve.
- In some embodiments, the nerve cuff further includes a controller disposed within the cuff body; and an electrode in electrical communication with the controller, the electrode configured to be in electrical communication with the nerve when the nerve is enclosed in the channel.
- In some embodiments, the controller and electrode are configured to sense electrical activity in the nerve enclosed in the channel.
- In some embodiments, the nerve cuff further includes a pump, wherein the controller is configured to activate the pump to transfer drug from the reservoir to the channel based in part on the sensed electrical activity of the nerve.
- In some embodiments, the pump is a screw pump.
- In some embodiments, the electrode is in electrical communication with an electrical pulse generator and is configured to deliver electrical stimulation to the nerve enclosed in the channel.
- In some embodiments, the electrode comprises a lumen in fluid communication with the reservoir and the channel, the lumen of the electrode configured to deliver drug from the reservoir to the channel.
- In some embodiments, the controller is programmable.
- In some embodiments, the controller is programmed to drive the pump at a constant rate.
- In some embodiments, the controller is programmed to drive the pump at an intermittent rate.
- In some embodiments, the nerve cuff further includes a drug disposed within the reservoir.
- In some embodiments, the drug is disposed in a passive diffusion matrix and both the drug and passive diffusion matrix are disposed within the reservoir.
- In some embodiments, the drug is an anesthetic or analgesic.
- In some embodiments, the nerve cuff further includes a needle in fluid communication with the reservoir, the needle configured to deliver drug from the reservoir to the nerve.
- In some embodiments, a system for establishing a nerve block on a nerve is provided. The system includes an implantable drug delivery device that includes a housing; a reservoir disposed within the housing, the reservoir configured to hold a drug; a pump disposed within the housing, the pump configured to meter the drug out of the reservoir; and a controller in communication with the pump, the controller configured to control the pump. The system further includes a sensor in communication with the controller, wherein the controller is configured to activate the pump when the sensor detects electrical activity from a nerve that meets or exceeds a predetermined threshold.
- In some embodiments, the sensor comprises a wireless transmitter configured to communicate wirelessly with the controller.
- In some embodiments, the sensor is configured to be remotely placed away from the implantable drug delivery device.
- In some embodiments, the housing includes a channel extending within the length of the housing for passage of a nerve; and an elongate opening slit extending the length of the housing, the elongate slit configured to be opened to provide access to the channel, the elongate slit configured to be closed around the channel and thereby enclose the housing around the nerve.
- In some embodiments, the system further includes a microstimulator that is removably disposed in a pocket within the housing, wherein the elongate opening slit is configured to be opened to provide access to the pocket, and configured to be closed around the pocket to secure the microstimulator within the pocket.
- In some embodiments, a method of establishing a nerve block on a nerve is provided. The method includes implanting a drug delivery device proximate the nerve, the drug delivery device configured to deliver a drug to the nerve; sensing an electrical signal transmitted to or by the nerve; and delivering a drug from the drug delivery device to the nerve based at least in part on the step of sensing an electrical signal transmitted to or by the nerve.
- In some embodiments, the drug delivery device includes an electrode configured to sense the electrical signal.
- In some embodiments, the method further includes delivering an electrical stimulus to the nerve through the electrode.
- In some embodiments, the method further includes implanting a remote sensor configured to sense the electrical signal.
- In some embodiments, the remote sensor and the drug delivery device are in wireless communication.
- In some embodiments, the method further includes placing the nerve within a channel that extends through the drug delivery device, wherein the drug is delivered to the channel.
- In some embodiments, the method further includes opening a slit on the drug delivery device to provide access to the channel; and closing the slit to secure the nerve within the channel.
- In any of the apparatuses described herein, the apparatuses described herein may be configured to include a nerve cuff and to apply electrical stimulation to induce a nerve block.
- Also described herein are apparatuses (systems and devices) having a dual clocking system in which a generally less accurate, but lower power, clock may run continuously and be updated periodically with a more accurate secondary clock. Although these apparatuses are described in the context of an apparatus configured for use in deploying a nerve block, this principle may be implemented in any implantable system. For example, generally described herein are apparatuses and methods for calibrating a first clock within an implantable device with a more accurate secondary clock. The first (e.g., central) clock may be the primary time keeping mechanism within the implantable device. While not all implantable devices require a time-keeping unit, those that provide periodic outputs to the patient often require a method for keeping time that contribute to controlling when an output is given.
- For example, described herein are implantable neuro stimulator device having a low-power clock calibration system. Such a device may include: a first clock configured to keep time within the implantable neurostimulator; a second clock having more accurate time-keeping capabilities than the first clock, wherein the second clock is in an off or idle mode while the first clocking is running; and control circuitry configured to be triggered by an event such that upon triggering, the control circuitry turns on the second clock, and uses the second clock to calibrate the the first clock, then turns the second clock back off.
- The first clock may count time based upon a reference voltage generated within a circuitry of the implantable device. The second clock may comprises a piezoelectric crystal oscillator. The control circuitry may be configured to be triggered by an event comprising a preset signal programmed into the control circuitry.
- In some variations, the event or trigger is thermal, e.g., temperature change.
- In some variations, the preset signal may be based on a set length of time, such as a few hours, a day, a few days, a week, a couple of weeks, a month, or a few months. The preset signal may be a voltage value above a certain threshold.
- Also described herein are methods of calibrating a neurostimulator. For example, a method of calibrating a clock within an implantable neurostimulator device may include: keeping time using a first clock of the implantable neurostimulator device, wherein the first clock runs continuously and is operating based upon a reference voltage generated within a circuitry of the implantable neurostimulator device; triggering a calibration protocol; turning on a reference clock within the implantable neurostimulator device; and calibrating the first clock based on the reference clock to correct for thermally-dependent time drift; and turning off the reference clock.
- The first clock may comprise a reference voltage associated with an RC circuit to produce a time reference.
- As mentioned above, the event that triggers the calibration may be thermal or temporal. For example, the event that triggers the calibration protocol may be a period of time (e.g., as determined by the first clock). The length of time may be a few hours, a day, a few days, a week, a couple of weeks, a month, a few months, and a year.
- In some variations, the event that triggers the calibration protocol may be a change in the reference voltage above a threshold value.
- As mentioned, the second clock may comprise a piezoelectric clock.
- Also described herein are neurostimulator devices including these self-calibrating clocks. For example, described herein are leadless, implantable microstimulator devices for treating chronic inflammation. Such a device may include: a housing; at least two electrically conductive contacts disposed on the housing; a resonator within the sealed capsule body, the resonator comprising a coil and a capacitor configured to resonate at a predetermined frequency range; a battery within the housing; and an electronic assembly within the housing; wherein the electronic assembly comprises power management circuitry configured to receive power from the resonator to charge the battery, a microcontroller configured to control stimulation of the vagus nerve from the electrically conductive contacts, a first clock configured to keep time, a second clock having more accurate time-keeping capabilities than the first clock, wherein the second clocking is configured to periodically calibrate the first clock.
- While having a central clocking module that is able to keep highly accurate time would be ideal, higher accuracy time-keeping modules are not only more expensive, but also require more power. Thus, it would be advantageous to have an internal clocking arrangement that is able to provide sufficient clocking accuracy for the lifetime of the implanted device but does not drain the power from the implanted device in an inordinately quick fashion.
- Described herein are clock calibration systems contained within an implantable device. The system includes a first clocking module configured to keep time within the implantable device for the majority of the time. The system also includes a second clocking module that possesses more accurate time-keeping capabilities that only turns on when a calibration routine is triggered. For the remainder of the time, the second clocking module is either in an OFF or idle mode. The triggering event may be the passage of a certain amount of time, or by a threshold parameter being met. In some instances, the triggering event may be a preset signal programmed into the control circuitry. the preset signal is based on a set length of time, such as a few hours, a day, a few days, a week, a couple of weeks, a month, or a few months. The preset signal may also be a voltage or current value above a certain threshold value.
- The system also includes control circuitry that is able to coordinate signals triggered by the event and signals sent to the central clocking module and the secondary clocking module. The system also may include a calibration module that corrects any time drifts within the first or central clocking module after the clocking calibration has been performed. In some examples, the first clocking module are able to measure and count time based upon a reference voltage generated within general circuitry of the implantable device. In some instances, the more accurate secondary time keeping module is a piezoelectric crystal oscillator.
- Also disclosed herein, is a method of calibrating a central clocking module within an implantable device. The method includes obtaining a clocking value associated with the central clocking module, where the clocking value is associated with how the central clocking module keeps time, establishing an event that will trigger a calibration protocol of the clocking module using a reference clocking module, activating the reference clocking module from an OFF mode to an active mode, calibrating the central clocking module based on the reference voltage, correcting any time drifts within the central clocking module, and turning off the reference clocking module. The clocking value is associated with a reference voltage associated with a reference voltage associated with the clocking module charges an RC circuit to produce a time reference. The events that trigger the calibration step may be the running of a set amount of time where at the end of such a period of time, a calibration routine is run. The length of time may be a few hours, a day, a few days, a week, a couple of weeks, a month, a few months, and a year. The event that triggers the calibration protocol may also be a change in the reference voltage above a threshold value.
- Also disclosed herein are implantable microstimulation devices for treating chronic inflammation. The implantable device may include a housing, at least two electrically conductive contacts disposed on the housing, a resonator within the sealed capsule body, where the resonator comprising a coil and a capacitor configured to resonate at a predetermined frequency range, a battery within the housing, and an electronic assembly within the housing. The electronic assembly may include a power management circuitry configured to receive power from the resonator to charge the battery, a microcontroller configured to control stimulation of the vagus nerve from the electrically conductive contacts, a first clocking module configured to keep time, a second clocking module having more accurate time-keeping capabilities than the first clocking module, and where the second clocking module is configured to periodically calibrate the first clocking module.
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FIG. 1A is a perspective view depicting a nerve cuff with an electrical (e.g., neurostimulation device) implanted proximate a nerve, according to an embodiment of the invention. This implant may also be configured to include a reservoir for delivery of a drug; alternatively or additionally, this implant may be configured to apply high-frequency nerve-block stimulation to the nerve from one or more electrodes (e.g., electrode pairs). -
FIG. 1B is a top view depicting an implanted nerve cuff with stimulation device ofFIG. 1A . -
FIG. 1C is a top view of another variation of an implanted nerve cuff including a reservoir for delivery of a nerve blocking agent. -
FIG. 1D is a top view of another variation of an implanted nerve cuff including a reservoir for delivery of a nerve blocking agent, including a reservoir and one or more (one is shown) cannula for delivery of the active agent, which may be metered. -
FIG. 1E is another example of a nerve cuff apparatus adapted for delivery of a nerve blocking agent (such as a drug) including a connection to a remote depot for holding (and/or loading or reloading) agent into the apparatus. Either or both the nerve cuff and/or the implanted and tethered depot may include control circuitry for controlling delivery of the blocking agent. -
FIG. 2 is a front view depicting an implanted nerve cuff with strain relief according to an embodiment of the invention. -
FIG. 3 is a front view depicting an implanted nerve cuff with suture holes according to an embodiment of the invention. -
FIG. 4 is an open view depicting the nerve cuff with suture holes ofFIG. 3 . -
FIG. 5 is a top view depicting a closing device for the implanted nerve cuff. -
FIG. 6 is a perspective view depicting marsupializaton of components such as electronic circuitry and/or a drug depot within a pocket of the nerve cuff ofFIG. 1A ; -
FIG. 7A is a top view depicting a nerve cuff having a conforming shield according to an embodiment of the invention. -
FIG. 7B is a front view of the nerve cuff ofFIG. 7A . -
FIG. 8A is a top view depicting another example of an open nerve cuff. -
FIG. 8B is a front view of the nerve cuff ofFIG. 8A . -
FIG. 8C is a top view depicting the nerve cuff ofFIG. 8A in a closed configuration. -
FIGS. 9A and 9B show side views through a section of the cuff body wall, indicating uniform and varying thicknesses, respectively. -
FIGS. 10A-10C illustrate one variation of a nerve cuff as described herein.FIG. 10A shows an end view,FIG. 10B is a side perspective view,FIG. 10C is a side view. -
FIGS. 11A-11H illustrate steps for inserting a nerve cuff such as the nerve cuffs described herein. -
FIG. 12A shows an embodiment of a nerve cuff having a drug reservoir for releasing drug to a nerve. -
FIG. 12B shows another embodiment of a nerve cuff having a drug reservoir. -
FIG. 12C shows yet another embodiment of a nerve cuff having a drug reservoir. -
FIG. 13 is a flowchart showing the steps of calibrating a first clocking module (“first clock”) with a second clocking module (“second clock”). -
FIG. 14 is a diagram showing calibration of a first clocking module by a second clocking module based on a change in voltage. -
FIG. 15 is a diagram showing calibration of a first clocking module by a second clocking module based on a pre-determined period of time. - Described herein are apparatuses (devices, systems, including implants) configured to apply a nerve block. These devices may be part of or used in conjunction with a nerve stimulator that delivers electrical stimulation to a nerve. In some variations, the nerve block may be part of a nerve sensing and/or stimulation apparatus that provides electrical stimulation to modulate the activity of the nerve and cause a wide variety of effects. For example, electrical stimulation of the vagus nerve can result in a reduction of inflammation through activation of the cholinergic anti-inflammatory pathway.
- Nerve blocking drugs and/or electrical stimulation can be delivered to a nerve. For example, an anesthetic or analgesic can be delivered to the nerve to establish a nerve block or otherwise modulate the activity of the nerve, with or without electrical nerve stimulation. In some embodiments, the nerve securing device described herein can also be used to deliver drugs to the nerve.
- Referring to
FIG. 1A , one example of anerve cuff 100 adapted for holding a device coupled to anerve 102 is shown.Nerve 102 can comprise any nerve in the human body targeted for therapeutic treatment, such as, for example, the vagus nerve.Nerve cuff adapter 100 generally comprises an outer carrier orcuff 104 body that can comprise any of a variety of medical grade materials, such as, for example, Silastic™ brand silicone elastomers, or Tecothane™ polymer. - In general, a nerve cuff including a
cuff 104 body having (or forming) one or more pouches orpockets 106 for removably receiving an active, implantable stimulation device 108 (e.g., including a stimulation device configured to apply a nerve block electrical signal) having one or more integrated,leadless electrodes 110 on a surface ofstimulation device 108proximate nerve 102. Alternatively or additionally, the one or more pouches may include a depot holding an active agent and/or a controller (including circuitry and/or a valve for regulating flow of active agent from the depot). As illustrated inFIGS. 1A and 1B , anerve cuff 100 may wrap aroundnerve 102 such thatelectrodes 110 and/or one ormore outputs 133 for an active agent from the drug depot are positionedproximate nerve 102. Theseoutputs 133 may be regulated by including a valve, pump, or other fluid control to regulate when an active agent is delivered from the apparatus onto the nerve. - The depot (which may be referred to as a reservoir) may be of any appropriate size. For example, the depot may include between 0.1 and 10 mL of liquid drug solution (e.g., between 0.1 and 5 mL, etc.). In some variations, the depot includes a solid drug formulation that is configured to be applied (and may include being mixed with fluid already present or surrounding the nerve). As mentioned, the depot may be refillable, as from an external port and/or from a second internal depot.
- Contacts or
electrodes 110 can be positioned directly againstnerve 102, as illustrated inFIG. 1B , or in close proximity to nerve. - Referring specifically to
FIG. 1C , in some variations the nerve cuff may include a pocket holding adepot 142 that includes a drug or other active agent (such as an anesthetic or any other compound for topically inhibiting nerve activity). Drug may be delivered from the depot onto the nerve and kept at a locally precise concentration for a a sustained period by holding it within the nerve cuff surrounding thenerve 102, allowing lower amounts of active agent to be applied more precisely over all or just a portion of the nerve. In some variations additional depots or reservoirs may be included for adding additional agents to the nerve or other regions of the nerve within the cuff. In some variations a second reservoir may include a wash-out material (e.g., saline) for diluting or removing the drug or active agent. In any of these variations, a controller (e.g., electronics board) for releasing or delivering the active agent/drug may be included. InFIG. 1A , the controller may be included instead of or along with (e.g., integrated into) theelectronics 108 of the stimulator. InFIG. 1D , for example, the depot holding the active agent/drug 142′ may be connected to theoutput 133 onto the nerve in the cuff by achannel 145; this channel may be regulated (opened/closed) by adrug delivery controller 147 that may include hardware, software and/or firmware for actively controlling the application of drug onto the nerve. The drug delivery controller may also include a valve for opening/closing the channel, such as a piezo valve, or a pump. Thedepot 142 may be pressurized so that drug is emitted when thechannel 145 is opened by thedrug delivery controller 147. The controller may also regulate pressurizing of the depot. - In some variations, the depot may be located remotely from the nerve cuff, as illustrated in
FIG. 1E . In this example, thenerve cuff 100 is configured to include one or more outputs for active agent/drug (not visible inFIG. 1E ), and may also include a drug delivery controller for regulating the delivery of drug onto the nerve. A second depot may be included within the cuff, which may be filled by theprimary depot 142′. Theremote depot 142′ may be connected bytubing 148 - In general, a drug delivery controller may include control logic for controlling delivery of the active agent onto the nerve. The drug delivery controller may therefore include a timer (e.g., for delivering doses at a prescribed time) and/or may include wireless communication circuitry and/or antenna for transmitting and/or receiving control information from a remote source. The drug delivery controller may also include a power source/supply (e.g., battery and/or inductive loop(s), capacitive power source, etc.), and one or more pumps and/or valves. In particular, a micro pump for delivering small (e.g., less than a 1 ml, less than 0.5 ml, less than 0.1 ml, etc.) of drug per time period (e.g., min, second, etc.). Any of the apparatuses described herein may be configured to apply drug based on activity on the nerve. For example the drug delivery controller may include input from one or more electrodes (or may be integrated with an electrical activity detector) receiving input from the electrodes on the nerve within the cuff or separate from the cuff. Electrical activity above a particular threshold may trigger release of drug.
- In one embodiment, a
pocket 106 for containing a drug delivery controller, stimulation device, and/or drug depot. One or more pockets may be defined by the open space between thenerve 102 and the inner surface of thecuff body 104. The sensing and/or stimulation device, drug depot and/or drug delivery controller (including any pump and/or valve components) can be passively retained within pocket by the cuff body, or can be actively retained on cuff body with fastening means, such as, for example, sutures. In other embodiments, a pocket can comprise a pouch-like structure attached to cuff body into which sensing and/or stimulation device, drug depot and/or drug delivery controller can be inserted. The sensing and/or stimulation device, drug depot and/or drug delivery controller can be passively retained within a pouch-like pocket by simply inserting into the pocket or can be actively retained with fastening means. A pouch-like pocket can be positioned either in the interior or on the exterior ofcuff body 104. Pouch-like pocket and/or cuff body can include access openings to allow electrodes and/or drug outputs (including needles or cannula) to be positioned directly proximate or adjacent tonerve 102. -
Cuff body 104 can have a constant thickness or a varying thickness as depicted inFIGS. 9A and 9B . The thickness ofcuff body 104 can be determined to reduce the palpable profile of the device once the stimulation device is inserted. In one embodiment, the thickness of cuff body can range from about 1 to about 30 mils, or from about 5 to about 20 mils. In one embodiment shown inFIG. 9B ,cuff 104 can have a greater thickness at a top and bottom portion of the cuff and a smaller thickness in a middle portion where the stimulation device is contained. - A key obstacle to overcome with implanting stimulation devices proximate nerves or nerve bundles is attaching a rigid structure that makes up the stimulation device along a fragile nerve in soft tissue. In one embodiment of the invention, this issue is resolved by encasing
nerve 102 anddevice 108 in acuff body 104 that comprises a low durometer material (e.g., Silastic™ or Tecothane™) as described above, that conforms aroundnerve 102. Further, as illustrated inFIG. 2 ,cuff body 104 can comprise strain reliefs 114 on its ends that reduce or prevent extreme torsional rotation and keepnerve 102 from kinking. Strain reliefs 114 can coil aroundnerve 102, and are trimmable to a desired size, such as the size ofnerve 102. Further, strain relief 114 can be tapered. In some variations, the lateral ends of the nerve cuff, forming the channel into which the nerve may be place, are tapered and have a tapering thickness, providing some amount of support for the nerve. In some variations, the channel through the nerve cuff in which the nerve may sit, is reinforced to prevent or limit axial loading (e.g., crushing) of the nerve or associated vascular structures when the nerve is within the cuff. - Given the design or architecture of
cuff body 104, any vertical movement ofcuff body 104 onnerve 102 is not critical to electrical performance, but can result in friction betweendevice 108 andnerve 102 that could potentially damagenerve 102. For that reason,device 108 should readily move up and downnerve 102 without significant friction while being sufficiently fixated tonerve 102 so that eventually connective tissue can form and aid in holdingdevice 108 in place. The challenge is stabilizingdevice 108 so that it can be further biologically stabilized by connective tissue within several weeks. -
Nerve cuff 100 should not be stabilized to surrounding muscle or fascia that will shift relative to the nerve. Therefore, referring toFIGS. 3 and 4 ,nerve cuff 100 can further comprise connection devices, such as suture holes or suture tabs, for coupling and stabilizingcuff body 104 withdevice 108 to at least one of the nerve bundle ornerve 102, and the surrounding sheath that containsnerve 102. In one embodiment of the invention, for example, as shown inFIG. 3 ,cuff body 104 can comprisesuture holes 116 that can be used with sutures tocouple cuff 104 body withdevice 108 to the surrounding nerve sheath. In an alternative embodiment of the invention, shown inFIG. 4 ,suture tabs 118 withsuture holes 116 extend from one or both sides ofcuff body 104. - Several stabilizing mechanisms can be used, including suture tabs and holes, staples, ties, surgical adhesives, bands, hook and loop fasteners, and any of a variety of coupling mechanisms.
FIGS. 3 and 4 , for example, illustrates suture tabs and holes that can be fixed to the surrounding sheath with either absorbable sutures for soft tissue or sutures demanding rigid fixation. -
FIG. 5 illustratessutures 120 that clamp orsecure cuff body 104 withdevice 108 to a surgeon-elected tension.Sutures 120 can be tightened or loosened depending on the level of desired stability and anatomical concerns. As shown inFIG. 5 , agap 122 can be present so long ascuff adapter 100 is sufficiently secured tonerve 102, with a limit set to a nerve diameter to prevent compression of the vasculature withinnerve 102. Surgical adhesives (not shown) can be used in combination withsutures 120 on surrounding tissues that move in unison with the neural tissue. - Muscle movement against
cuff adapter 100 can also transfer undesired stresses onnerve 102. Therefore, in an embodiment of the invention, low friction surfaces and/or hydrophilic coatings can be incorporated on one or more surfaces ofcuff body 104 to provide further mechanisms reducing or preventing adjacent tissues from upsetting the stability ofnerve cuff 100. -
FIG. 6 illustrates anerve cuff 100 with a sensing and/or stimulation device, drug depot and/or drug delivery controller device removably or marsupially secured within pocket orpouch 106 ofcuff body 104. By the use ofrecloseable pouch 106,active stimulator device 108 can be removed or replaced fromcuff body 104 without threatening or endangering the surrounding anatomical structures and tissues.Device 108 can be secured withincuff body 104 by any of a variety of securing devices 124, such as, for example, sutures, staples, ties, zippers, hook and loop fasteners, snaps, buttons, and combinations thereof. Sutures 124 are shown inFIG. 6 . Releasing sutures 124 allows access topouch 106 for removal or replacement ofdevice 108. Not unlike typical cuff style leads, a capsule of connective tissue can naturally encapsulatenerve cuff 100 over time. Therefore, it will most likely be necessary to palpatedevice 108 to locatedevice 108 and cut through the connective tissue capsule to access sutures 124 and device. The removable/replaceable feature ofnerve cuff 100 is advantageous over other cuff style leads because such leads cannot be removed due to entanglement with the target nerve and critical vasculature. - As discussed above, compression of
nerve 102 must be carefully controlled. Excess compression onnerve 102 can lead to devascularization and resulting death of the neural tissue. Compression can be controlled by over-sizing or rightsizingnerve cuff 100, so that when pocket sutures 124 are maximally tightened, the nerve diameter is not reduced less that the measured diameter. Cuffs formed from Silastic™ or Tecothane™ materials are relatively low cost, and therefore several sizes can be provided to the surgeon performing the implantation ofnerve cuff 100 to better avoid nerve compression. - Sensing and/or stimulation devices, drug depots and/or drug delivery controllers, may be large enough to be felt and palpated by patients. Referring to
FIG. 7A , to avoid such palpation,nerve cuff 100 can further comprise a protectingshield 126 conforming to the shape of the anatomical structures, such as in the carotid sheath. In this embodiment,nerve cuff 100 is secured around the vagus nerve, while isolatingdevice 108 from contact with both the internal jugular vein (IJV) 132, and commoncarotid artery 134.Shield 126 then further isolatesdevice 108 from other surrounding tissues. The profile of theentire cuff adapter 100 may be minimized while maintaining the compliance of such materials as Silastic™ or Tecothane™. In one embodiment of the invention,protective shield 126 is formed from a PET material, such as Dacron®, optionally coated with Silastic™ or Tecothane™ forming a thin and compliant structure that will allow for tissue separation when required. - When a nerve does not provide sufficient structural strength to support
nerve cuff adapter 100, collateral structures can be included in or oncuff body 104. Because of a high degree of anatomical variance such a scheme must demand the skill of the surgeon to utilize a highly customizable solution.FIG. 8A illustrates a variablesize nerve cuff 100 with awrappable retainer portion 128 extending fromcuff body 104. As shown inFIG. 8C ,cuff body 104 is secured aroundnerve 102, whileretainer portion 128 is secured around the sheath or other surrounding anatomical structures, such as theIJV 132 and/orcarotid artery 134. As shown inFIG. 8B ,wrappable retainer portion 128 can include securingdevices 130, such as suture holes, for securing theentire nerve cuff 100 around the desired anatomical structures. This configuration allows for access to sensing and/or stimulation device, drug depot and/or drugdelivery controller devices 108 throughpocket 106 as in previous embodiments, while adapting to a multitude of anatomical variations to obtain the desired stability ofnerve cuff 100 onnerve 102. -
FIGS. 10A-10C illustrate a variation of a nerve cuff that includes a cuff body forming a channel (into which a nerve may be fitted) and an slit formed along the length of the nerve cuff body. In this example, the nerve cuff body also includes one or more pocket regions (not visible inFIGS. 10A-10C ) within the cuff body positioned above the nerve channel. The top of the body (opposite from the nerve channel) includes along slit 1003 along its length forming on opening. The cuff body may be along the slit by pulling apart the edges, which may form one or more flaps. In the example shown inFIG. 10A , the slit may be split open to expose the inside of the nerve cuff and allow the nerve to be positioned within the internal channel, so that the cuff is positioned around the nerve. The same split may be used to insert the sensing and/or stimulation device, drug depot and/or drug delivery controller device as well. In some variations a separate opening (slit or flap) may be used to access the pocket or pouch for the sensing and/or stimulation device, drug depot and/or drug delivery controller. -
FIG. 10B shows a perspective view of the nerve cuff holding a sensing and/or stimulation device, drug depot and/or drug delivery controller after it has been inserted onto a nerve (e.g., the vagus nerve).FIG. 10C shows a side view of the same. - The exemplary cuff shown in
FIGS. 10A-10C has a conformal configuration, in which the wall thickness is relatively constant; in some variations of a nerve cuff, the wall thickness may vary along the perimeter. This non-uniform thickness may effectively cushion the device relative to the surrounding tissue, even as the patient moves or palpitates the region. This may have the added benefit of preventing impingement of the nerve. Similarly, the variable thickness may enable smooth transitions and help conform the cuff to the surrounding anatomy. - The nerve cuff may be substantially rounded or conforming, and have non-traumatic (or atraumatic) outer surfaces. As mentioned, this relatively smooth outer surface may enhance comfort and limit encapsulation of the nerve cuff within the tissue.
- A nerve may sit within a supported channel through the nerve cuff. The channel may be formed having generally smooth sides, so as to prevent damage to the nerve and associated tissues. In some variations the nerve channel though the cuff is reinforced to prevent the cuff from pinching the device or from over-tightening the device when closed over the nerve. Supports may be formed of a different material forming the nerve cuff body, or from thickened regions of the same material. Although multiple sizes of nerve cuff may be used (e.g., small, medium, large), in some variations, an oversized nerve cuff may be used, because the insulated cuff body will prevent leak of current from the sensing and/or stimulation device, drug depot and/or drug delivery controller to surrounding tissues.
- In operation, any of the devices described herein may be positioned around the nerve, and the sensing and/or stimulation device, drug depot and/or drug delivery controller inserted into the nerve cuff, in any appropriate manner.
FIGS. 11A-11H illustrate one variation of a method for applying the nerve cuff around the nerve and inserting a sensing and/or stimulation device, drug depot and/or drug delivery controller. In this example, the patient is prepared for application of the nerve cuff around the nerve to hold a sensing and/or stimulation device, drug depot and/or drug delivery controller device securely relative to the nerve (FIG. 11A ). An incision is then made in the skin (≈3 cm), e.g., when inserting onto the vagus nerve, along Lange's crease between the Facial Vein and the Omohyoid muscle (FIG. 11B ), and the Sternocleidomastoid is retracted away to gain access to the carotid sheath (FIG. 11C ). The IJV is then reflected and ≤2 cm of the vagus is dissected from the carotid wall. - In some variations, a sizing tool may be used to measure the vagus (e.g., diameter) to select an appropriate sensing and/or stimulation device, drug depot and/or drug delivery controller and cuff (e.g., small, medium, large). In some variations of the method, as described above, an oversized cuff may be used. The nerve cuff is then placed under the nerve with the opening into the nerve cuff facing the surgeon (
FIG. 11D ), allowing access to the nerve and the pocket for holding the sensing and/or stimulation device, drug depot and/or drug delivery controller. The sensing and/or stimulation device, drug depot and/or drug delivery controller can then be inserted inside cuff (FIG. 11E ) while assuring that the sensing and/or stimulation device, drug depot and/or drug delivery controller contacts capture the nerve, or communicate with any internal contacts/leads. The nerve cuff may then be sutured shut (FIG. 11F ). In some variations, the sensing and/or stimulation device, drug depot and/or drug delivery controller may then be tested (FIG. 11G ) to confirm that the device is working and coupled to the nerve. For example, a surgical tester device, covered in a sterile plastic cover, may be used to activate the sensing and/or stimulation device, drug depot and/or drug delivery controller and perform system integrity and impedance checks, and shut the sensing and/or stimulation device, drug depot and/or drug delivery controller off. If necessary the procedure may be repeated to correctly position and connect the sensing and/or stimulation device, drug depot and/or drug delivery controller. Once this is completed and verified, the incision may be closed (FIG. 11H ). - Systems for electrically stimulating one or more nerves to treat chronic inflammation may include an implantable, wireless sensing and/or stimulation device, drug depot and/or drug delivery controller such as those described herein and an external charging device (which may be referred to as a charging wand, charger, or energizer). In some variations the system also includes a controller such as a “prescription pad” that helps control and regulate the dose delivered by the system. The sensing and/or stimulation device, drug depot and/or drug delivery controller may be secured in position using a securing device (which may be referred to as a “POD”) to hold the sensing and/or stimulation device, drug depot and/or drug delivery controller in position around or adjacent to a nerve.
- In any of the apparatuses described herein, doses of active agent (e.g., nerve block agent) may be applied continuously, periodically or may the apparatus may be configured to apply a dose or additional dose upon triggering of an event such as an electrical activity on the never. For example, a microliter and even picoliter doses of active agent may be delivered either continuously or periodically (e.g., at a frequency of x uL or pL per second, where x is between 0.001 and 10) or for a single dose (e.g. of x uL or pL, where x is between 0.001 and 10). A single dose may be delivered within the cuff, or multiple doses maybe delivered within the cuff. Doses may be separated by a dosage interval that may be predefined, regular, scheduled (based on time of day) and/or triggered (e.g., by nerve activity). Doses may be delivered on demand. For example, a doctor or patient may communicate wirelessly or via an input in the drug delivery control to trigger release of a dose.
- As described above, and as shown in
FIG. 12A , thenerve cuff 2800 can be modified to include areservoir 2802 to hold an active agent/drug, such as an anesthetic like lidocaine. Thenerve cuff 2800 can have one or more outputs/channels (ports 2804) for releasing the drug into the region surrounding thenerve 2806 within the cuff. Because thenerve cuff 2800 surrounds the portion of thenerve 2806 where the drug is being delivered, the diffusion of the drug away from the nerve is greatly reduced as compared to injection or infusion of the drug using a needle or catheter. Consequently, a low volume, low diffusion system for delivering the drug to the nerve can be sufficient to establish an effective nerve block over a long period of time, such as days, weeks, or months. In some embodiments, the modifiednerve cuff 2800 can be used with amicrostimulator 2808 as described herein. In other embodiments, the modified nerve cuff can be used without a microstimulator to deliver drug to a nerve. - In some embodiments, as shown in
FIG. 12A , thenerve cuff 2800 can have a refillingport 2810 in fluid communication with thereservoir 2802. The refillingport 2810 can be used to refill thereservoir 2802 with drug (e.g., anesthetic). In some embodiments as shown inFIG. 12A , the refillingport 2810 can be located on the outer surface of thenerve cuff 2800, and a needle or catheter can be used to access the refilling port and deliver drug to the reservoir (depot) while the nerve blocking device remains within the body around thenerve 2806. In some embodiments as shown inFIG. 12B , the refillingport 2810 can be in fluid communication with a subcutaneous orsubdermal access port 2812, and a needle or catheter can be used to access theaccess port 2812 and deliver drug to the reservoir. For example, theaccess port 2812 can be located at a subcutaneous location, andtubing 2814 can connect theaccess port 2812 with thedrug refilling port 2810 on thenerve cuff 2800. - In some embodiments as shown in
FIG. 12C , one or more of theelectrodes 2816 can be modified to include alumen 2818 or channel for drug delivery. For example, the modifiedelectrode 2816 can be a cuff type electrode, or a penetrating type electrode such as a needle electrode, or a combination of both. The modifiedelectrode 2816 can deliver the drug from the reservoir to thenerve 2806 in a perifascicular or intrafascilular manner. Perifascicular delivery means delivery of the drug around a nerve or nerve bundle, while intrafascilular delivery means delivery of the drug into or inside the nerve or nerve bundle. In some embodiments, a modifiedcuff electrode 2816 can be used for perifascicular drug delivery, while a modified penetrating electrode can be used for intrafascilular drug delivery. In other embodiments, the device can have a dedicated drug delivery lumen or needle that is separate from the electrode. - In some embodiments, the drug can be delivered from the reservoir using a passive diffusion matrix drug delivery system. For example, the drug can be incorporated into a polymer matrix and can diffuse out of the matrix and/or be release as the matrix erodes.
- In other embodiments as shown in
FIGS. 12A and 12B , the drug delivery system can use apump 2820, such as a screw pump or other small pump. Thepump 2820 can deliver drug in a liquid form, a solid form such as a power, or a mixed form such as a paste or slurry, from thereservoir 2802 to thenerve 2806. - In some embodiments, the modified electrodes can be electrically active and can be capable of delivering and/or detecting an electrical stimulus or signal to the nerve or other tissue. In other embodiments, the modified electrodes can be electrically inactive, and may only be used for drug delivery.
- In some embodiments, a controller can be used to control the pump along with controlling the stimulation delivered by the electrodes and/or the signal detection and processing by the electrodes. The controller may be programmable and may drive the pump to deliver drug at a constant or intermittent rate. In some embodiments, the controller may enable manual drug dosing, where the user can communicate with the controller using wireless communications. In some embodiments, the controller may be programmed and/or communicate with a computing device, such as a tablet, smart phone, laptop, or desktop computer, using a wireless communication protocol, such as Bluetooth or WiFi.
- In some embodiments, the controller provides closed loop control of the drug delivery. In some embodiments, the controller can adjust the dosage of drug, i.e. the amount and/or the rate of drug delivered, based on feedback received from a sensor. The sensor can be the electrode described above used for local detection of action potential activity in a nerve. Alternatively or additionally, the sensor can be a remotely located sensor that detects a physiological aspect of the patient, such as inflammation or pain. For example, one or more remote sensors can be placed at a different nerve that is remotely located from the nerve cuff but is part of the same sensory pathway. This allows the nerve cuff with drug delivery capabilities to be placed at an upstream, more central location that can potentially block pain signals from multiple nerves. Alternatively, this allows the sensors to be placed at upstream locations to improve detection of pain signals transmitted by the nerves while the drug delivery device is placed at one or more downstream locations to minimize or reduce the area affected by the drug. These remotely located sensors may communicate wirelessly with the controller in the nerve cuff, or the remote sensors may be directly connected to the nerve cuff using a wire. Local detection or remote detection of action potential activity in the any of the nerves in the pathway can trigger the delivery of drug from the reservoir.
- In some embodiments, the sensor can measure electrical activity from the heart and can be used to measure an ECG signal. The controller can be used to process and analyze the ECG signal to determine heart rate and heart rate variability. In some embodiments, the drug dosage can be modified based on the heart rate and/or heart rate variability.
- In some embodiments, the drug can be an anesthetic or analgesic or another type of painkiller One or more drugs can be used to provide a customizable dosing schedule tailored to the needs of the patient. The one or more drugs can be selected based in part on the desired wash out speed, volumetric optimization, and drug stability. The nerve cuff can include one or more reservoirs so that each drug can be contained in a separate reservoir, or the drugs can be mixed together and be placed into a single reservoir. Examples of drugs include ester based anesthetics such as procaine (novocaine), benzocaine, chloroprocaine cocaine, cyclomethycaine, dimethocaine, piperocaine, propoxycaine, proparacaine, and tetracaine; and amine based anesthetics such as lidocaine, bupivacaine (Marcaine), ropivacaine, cinchocaine, etidocaine, levobupivacaine, mepivacaine, articaine, prilocaine, and trimecaine.
- In some embodiments, the drugs can be neurotrophic drugs with an effect on nerves.
- Since the drugs may have different time constants, the pharmacokinetic profile of the drug or drug combination can be tailored to match the symptoms experienced by the patient, such as short term pain, chronic pain, or inflammation. For example, lidocaine has a time constant of about 1 hour and Marcaine has a time constant of about 4 hrs. Therefore, to treat inflammation or pain lasting greater than 2 hours, it may be desirable to include Marcaine, which persists longer than lidocaine. In contrast, to treat inflammation or pain of shorter durations, for example, less than 2 hours, it may be desirable to include lidocaine. In some embodiments, both a mixture of drugs having short and long time constants can be used. In addition, the device can be programmed to deliver drug at regular intervals, which can be determined based on the drug time constants and the degree of vascular profusion in the area, and/or in an on-demand fashion. In addition, as described above, the delivery of the drug can also be modified based on data received from a sensor, or in an on-demand fashion.
- In some embodiments, the modified nerve cuff and electrode can be secured around the vagus nerve and both electrical stimulation and drug(s) can be delivered to the vagus nerve. For example, when using the nerve cuffs described herein, the slit on the nerve cuff can be opened to allow access to a channel for receiving the nerve. The nerve can be placed within the channel, and the slit can then be closed to secure the nerve within the channel of the nerve cuff.
- In some embodiments, the nerve cuff and electrode can be secured in a similar manner around a nerve responsible for generating the sensation of pain in the patient. For example, to establish a nerve block in the upper extremities, one or more nerve cuffs and electrodes can be placed around or adjacent the interscalene nerve, supraclavicular nerve, infraclavicular nerve, and/or axillary nerve. An interscalene nerve block can be established for surgeries to the shoulder, clavicle, or upper arm; a supraclavicular nerve block can be established for surgeries to the upper arm to the hand; an infraclavicular nerve block can be established for surgeries to the elbow to the hand; and an axillary block can be established for surgeries to the elbow to the hand. To establish a nerve block in the chest and abdomen, one or more nerve cuffs and electrodes can be placed around or adjacent to the vertebral body in the paravertebral space and/or around or adjacent to nerves in the space between the internal oblique and the transversus abdominis muscles. To establish a nerve block in the lower extremities, one or more nerve cuffs and electrodes can be placed around or adjacent the lumbar plexus, the femoral nerve, and/or the sciatic nerve.
- The sensors can be positioned at or around the nerves listed above, and on other nerves or neural structures which receive signals from these nerves or are formed in part from these nerves, such as the brachial plexus and lumbar plexus, or on nerves that transmit signals to these nerves. For example, as described herein, the nerve cuff can include an electrode for sensing electrical signals, such as action potentials, to measure nerve activity of the nerve attached to the nerve cuff. Alternatively or additionally, as described above, remote sensors can be placed away from the nerve cuff at remote locations to sense electrical activity in nerves or nerve locations described herein. In some embodiments, the remote locations may be closer to the source of pain, such as near or at the extremities and joints.
- In addition or alternative to the use of drug agents as described above, any of these apparatuses may be configured to provide an electrical nerve block using a microstimulator held within the cuff. Electrical nerve bock may involve reversibly blocking peripheral nerves by applying high frequency alternating current directly on a nerve trunk. For example, a current ranging from 5 kHz to 50 kHz may be applied (high frequency, compared to a current of less than 1 kHz for low frequency). Efficacy of the high frequency alternating current therapy in acute non-human animal experiments (frog, cat) has been reported, e.g., U.S. Pat. Nos. 7,389,145 and 8,060,208 describe this electrical stimulation.
- Reversibly blocking an action potential in a peripheral nerve having a diameter exceeding 3 mm and up to about 12 mm, e.g., a sciatic nerve, a tibial nerve, etc., may be applied by a neurostimulator held within any of the cuffs described herein, providing an electrical waveform for an interval of time sufficient to effect substantially immediate pain relief, defined generally as within about 10 min. One embodiment uses a waveform ranging from 5 kHz to 50 kHz. One embodiment uses a 10 kHz sinusoidal waveform at a current ranging from 4 mA to 26 mA. The electrode can be retained in the cuff encircling the desired peripheral nerve in which the action potential is to be blocked. The time interval may be about 10 minutes, but an interval may be selected by a magnitude sufficient to effect pain relief in the patient. In one embodiment, the electrical waveform to effect pain relief ranges from a voltage from 4 V to 20 V, or a current ranging from 4 mA to 26 mA. The time of increasing magnitude can range from about 10 seconds to about 60 seconds with a steady ramp up of voltage or current. The waveform may be provided by a waveform generator that is part of the apparatus. As mentioned above, the application of the nerve block (including electrical nerve block) may be triggered by activity on the nerve to which the cuff is attached.
- As mentioned above, also described herein are methods and apparatuses for keeping highly accurate time in a implant (including, but not limited to the nerve block apparatuses described above) using very low power. In particular, described herein are methods and apparatuses for calibration of a first (e.g., low power) clock/clocking mechanism, where the calibration occurs periodically or based upon some event or signal being detected and through use of a second, more accurate clock/clocking mechanism.
- In implantable devices, and many other electrical devices in general, there is great demand for having systems with lower power consumption as well as lower cost. Lower power expenditure may be achieved through having a process that does not draw as much power, but often this is at the expense of having less accurate outputs. In the case with a clocking system, the use of a less accurate clock signal may lead to lower power consumption compared to a more accurate clocking mechanism, but a less accurate clock having lower power consumption may result in providing output at imprecise or unpredictable times.
- One way to compensate for having a systems clocking mechanism that is a less accurate clocking mechanism that will be periodically calibrated with a more accurate clocking system, including one which is present on/in the implant, but which may be deactivated or inactive until triggered. For example, disclosed herein is a first or central clocking mechanism that uses a semiconductor junction to generate a reference voltage that in turn charges an RC circuit to produce a time reference. Because these voltage references have significant variations due to integrated circuit characteristics and parameters and temperature, they tend to be less accurate, though they may require lower power. Other, typically lower power and/or lower cost clocks may be used as the primary clock.
- To compensate for the lack in accuracy of the first clocking mechanism, a second more accurate clocking mechanism is employed. The second, more accurate clocking mechanism may be used to periodically recalibrate the first clocking mechanism.
- More accurate clocking mechanism include real time clocks. Real time clocks are a type of computer clock in the form of integrated circuits. Most real time clocks use a piezoelectric crystal oscillator, where the oscillator frequency is 32.768 kHz, the same frequency as in quartz clocks and watches.
- In one non-limiting example, a time reference clocking module error in the RC circuit may be measured over fixed intervals or based on a change in a pre-determined parameter (e.g. voltage or current). Deviations may be measured against a more accurate real time crystal oscillator clocking mechanism. Based on the measured deviation and time elapsed since the last calibration, the amount of time deviation in the time reference clocking module may be calculated and corrected. Correction of any time deviation may be occur through correcting the central clocking module. Alternatively, the central clocking module may be temporarily replaced with the more accurate real time crystal oscillator clocking mechanism to bring the central clocking module back to a correct value.
- In another non-limiting example, the implantable device will run the central clocking mechanism continuously while a second, more accurate clocking mechanism remains in an OFF or standby mode. Upon the occurrence of a pre-determine event or time interval, the second, more accurate clocking mechanism may enter an active mode and re-calibrate the central clocking mechanism. Upon completion of the calibration routine, the second, more accurate clocking mechanism will again revert to an OFF or standby mode until the next calibration is triggered.
-
FIG. 13 shows a flowchart for visualizing the steps of implementing aclocking calibration routine 1300. Presumably the clocking system for the implantable device, such as a neurostimulator, will be activated once the device is implanted in the patient. At 1302, the systems clocking mechanism is running. At this point, the second, more accurate clocking mechanism is in a sleep or OFF mode (1308). At some point in time later, an even triggers a signal being sent to the second clocking mechanism (1304). The trigger may correspond to the beginning of a new cycle in the implantable device. In the case of an implantable neurostimulator, the trigger may be associated with the beginning of a stimulation session or a combination of features of the stimulation session (e.g. a time interval after the start of the stimulation session). A trigger for calibration may also be a circuit parameter that has exceeded or dropped below a threshold value. Once the trigger event has occurred (1304), a signal is sent to the second clocking module to turn from the OFF or standby mode to an active mode (1312). With the second clocking module in an active state, it will initiate the calibration routine (1310). Once the calibration routine (1310) has been performed, any deviation determined from running the calibration routine (1310) may be corrected in the following step (1314). Once the deviation has been corrected, a second signal may be sent to the second clocking module to return to an OFF or standby mode. In the final step, a third signal may be sent to the central clocking module to switch it from an OFF or standby mode to an active mode. These steps may be repeated based on a condition being satisfied, an event occurring, or a pre-determined period of time. Also, it may be possible to delay calibration to sometime past the triggering event. - Turning to
FIG. 14 , a sample calibration routine based on some feature or characteristic of the implanted device output is shown. In the case of an implantable neurostimulation device, calibration of the central clocking system may be tied to when a stimulation session begins. In this scenario, a sensor may be incorporated to sense when a current or voltage has increased above a certain value and that a calibration routine should be initiated immediately or after a set amount of time. To better visualize each component status,FIG. 14 shows stacked signals in order from top to bottom: a series of neurostimulation outputs for aneurostimulator 1430, the functional state of the first orcentral clocking module 1440, and the functional state of thesecond clocking module 1450 that is able to perform the calibration routine. The horizontal axis from left to right indicates the passage of time and may be in units of minutes, hours, days, weeks, months, and so forth. - As the diagram arbitrarily shows a snapshot of the output of an implanted device. Initially, when the neurostimulation device is in an idle state (1431), the
central clocking module 1440 is in anactive mode 1441 and thesecond clocking module 1450 is in an OFF or standby mode (1451). Thecentral clocking module 1440 will then continue to run for someperiod 1442 until a neurostimulation session begins (1432), at that point, signals are set to the both thecentral clocking module 1440 and thesecond clocking module 1450 when the neurostimulation output surpasses a certain threshold value. Upon reaching this state, the central clocking module will drop to an idle orOFF state 1442 while thesecond clocking module 1450 will switch from its OFF orstandby mode 1451 to anactive mode 1452, where it will run a calibration routine 1453 either immediately or at a preset time in the future. Upon completion of the calibration routine 1453, a signal is sent to the central clocking module to coordinate switching it from thestandby mode 1442 back to anactive mode 1441 and for the second clocking module to return from anactive mode 1452 to an OFF orstandby mode 1451 in a coordinated fashion. These steps will repeat based on some feature of the stimulating output from the implanted device. In some other variations, the calibration routine may be tied to some other feature of the stimulating output and not necessarily correspond to the beginning of the stimulation output. -
FIG. 15 shows an alternative initiation of calibration routines in a system where a secondary, more accurate clocking module is used to calibrate and correct any deviations experienced by a less accurate central clocking module. In this arrangement, the implanted device output will provide output periodically, where the time periods may be the same or different and may be set by the doctor or other user. A calibration routine may occur that aligns with a given time period t, that repeats. As the diagram shows, during the evolution of time period t, the central clocking module is in anactive state 1541, while the second clocking module is in an OFF orinactive state 1551. At the end of the time period t, the central clocking module will switch to an idle orOFF mode 1542 while the second clocking module will turn to anactive mode 1552 to calibrate the less accuratecentral clocking module 1540 and adjust for any deviations that is measured. Upon completion of the calibration routine thesecond clocking module 1550 will return to an OFF or standby mode 151 while thecentral clocking module 1540 will return to anactive mode 1541. These steps will repeat based on a pre-defined time interval. In some examples the time period will be the same, but in other examples the time period may be different or may be based on some algorithm or known relation between the length of time and the amount of deviation expected. - The second clocking module may be linked to the calibration module that performs the actual calibration routine. The calibration module may be integrated into the circuitry of the implanted device. The systems clocking module is able to provide a central clocking signal that serves as a clock source.
- In some other examples, the systems clocking module is configured to provide a tick signal that acts as a time keeper. Periods between device outputs may be defined by the number of tick counts. While the tick counts accuracy is based upon characteristics of the circuit parameters, and may be not be as accurate as some other timing keeping mode, certain methods may be implemented to accommodate any inaccuracies. For example, tick counts may be tied to the calibration module, which can be used to determine the duration of intervals between successive calibration routines. The start of a calibration routine is initialed by a signal which is configured to count the ticks from the central clocking module. The ticks may be counted until the calibration routine is complete and through a period where the central clocking module is keeping time. Tick counts may restart based upon the start of a new calibration routine. Every time the calibration routine is run, any deviations resulting from the tick counts may be corrected. In the example of an implantable neurostimulation device that has wireless recharging capabilities, the tick counts may be adjusted for accuracy using a more accurate time keeper located within the wireless transmitter unit. Thus, whenever the implanted neurostimulation device is being recharged, the tick counts may be matched with the more time keeping module within the wireless transmitter unit and any deviations may be corrected. The benefit of having a tick counting type time-keeping module is that a patient may move to different time zones without having to modify potentially salient circadian components of the stimulation output.
- As alluded to above, the implanted device circuitry or controller will also be configured to detect a trigger or event that will commence a calibration routine. The trigger may be an increase in a threshold voltage or current value. The trigger may also be a combination or a pattern of changes in the voltage or current value in more complex arrangement of stimulating outputs.
- The implantable device will also be configured to provide a series of signals that will coordinate the switching of the central clocking module from an active mode to an OFF or standby mode, while signals are also sent for switching the second clocking module from an OFF mode to an active mode for the calibration routine.
- The implantable device may also include programs or algorithms that will be able to correct for any time drift that may be detected after the calibration routine is completed. In another variation, the step of calibrating the central clocking module and accounting for any deviation may be performed in one step.
- In some non-limiting variations of the clocking calibration systems and methods, the implantable neurostimulation device may be able to retain information on the calibration results such as the amount of drift that the central clocking module has experienced since the previous calibration routine. This information may be sent wirelessly to a telecommunication device or may be sent to the wireless transmitter module during recharging events.
- It should be noted that because the clocking system described herein is directed to use within an implantable device, there is minimal temperature variations that may cause further drifts in the clocking system. Because the implant is in a temperature stable environment, there may be no need for temperature compensation. The circuit's wafer to wafer and die to die variations may be calibrated to a fixed temperature and scaled to 37° C. during manufacturing of the implantable device, may be calibrated during the programming of the implantable device, or during the wireless charging process.
- In yet other variations, the calibration routine and subsequent correction steps may be in response to a received voltage or current signal from a sensor via some data communication link, and compares the received voltage or current signal against a set of pre-programmed or learned variables and values to determine if the central clocking module needs to be recalibrated. While the calibration routine may occur at any time, it may be beneficial to run the calibration routine when there is no stimulating output being provided. This would prevent overtaxing the overall circuitry of the implanted device.
- When a feature or element is herein referred to as being “on” another feature or element, it can be directly on the other feature or element or intervening features and/or elements may also be present. In contrast, when a feature or element is referred to as being “directly on” another feature or element, there are no intervening features or elements present. It will also be understood that, when a feature or element is referred to as being “connected”, “attached” or “coupled” to another feature or element, it can be directly connected, attached or coupled to the other feature or element or intervening features or elements may be present. In contrast, when a feature or element is referred to as being “directly connected”, “directly attached” or “directly coupled” to another feature or element, there are no intervening features or elements present. Although described or shown with respect to one embodiment, the features and elements so described or shown can apply to other embodiments. It will also be appreciated by those of skill in the art that references to a structure or feature that is disposed “adjacent” another feature may have portions that overlap or underlie the adjacent feature.
- Terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. For example, as used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and/or “comprising,” when used in this specification, specify the presence of stated features, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and/or groups thereof. As used herein, the term “and/or” includes any and all combinations of one or more of the associated listed items and may be abbreviated as “/”.
- Spatially relative terms, such as “under”, “below”, “lower”, “over”, “upper” and the like, may be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if a device in the figures is inverted, elements described as “under” or “beneath” other elements or features would then be oriented “over” the other elements or features. Thus, the exemplary term “under” can encompass both an orientation of over and under. The device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly. Similarly, the terms “upwardly”, “downwardly”, “vertical”, “horizontal” and the like are used herein for the purpose of explanation only unless specifically indicated otherwise.
- Although the terms “first” and “second” may be used herein to describe various features/elements (including steps), these features/elements should not be limited by these terms, unless the context indicates otherwise. These terms may be used to distinguish one feature/element from another feature/element. Thus, a first feature/element discussed below could be termed a second feature/element, and similarly, a second feature/element discussed below could be termed a first feature/element without departing from the teachings of the present invention.
- Throughout this specification and the claims which follow, unless the context requires otherwise, the word “comprise”, and variations such as “comprises” and “comprising” means various components can be co-jointly employed in the methods and articles (e.g., compositions and apparatuses including device and methods). For example, the term “comprising” will be understood to imply the inclusion of any stated elements or steps but not the exclusion of any other elements or steps.
- In general, any of the apparatuses and methods described herein should be understood to be inclusive, but all or a sub-set of the components and/or steps may alternatively be exclusive, and may be expressed as “consisting of” or alternatively “consisting essentially of” the various components, steps, sub-components or sub-steps.
- As used herein in the specification and claims, including as used in the examples and unless otherwise expressly specified, all numbers may be read as if prefaced by the word “about” or “approximately,” even if the term does not expressly appear. The phrase “about” or “approximately” may be used when describing magnitude and/or position to indicate that the value and/or position described is within a reasonable expected range of values and/or positions. For example, a numeric value may have a value that is +/−0.1% of the stated value (or range of values), +/−1% of the stated value (or range of values), +/−2% of the stated value (or range of values), +/−5% of the stated value (or range of values), +/−10% of the stated value (or range of values), etc. Any numerical values given herein should also be understood to include about or approximately that value, unless the context indicates otherwise. For example, if the value “10” is disclosed, then “about 10” is also disclosed. Any numerical range recited herein is intended to include all sub-ranges subsumed therein. It is also understood that when a value is disclosed that “less than or equal to” the value, “greater than or equal to the value” and possible ranges between values are also disclosed, as appropriately understood by the skilled artisan. For example, if the value “X” is disclosed the “less than or equal to X” as well as “greater than or equal to X” (e.g., where X is a numerical value) is also disclosed. It is also understood that the throughout the application, data is provided in a number of different formats, and that this data, represents endpoints and starting points, and ranges for any combination of the data points. For example, if a particular data point “10” and a particular data point “15” are disclosed, it is understood that greater than, greater than or equal to, less than, less than or equal to, and equal to 10 and 15 are considered disclosed as well as between 10 and 15. It is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.
- Although various illustrative embodiments are described above, any of a number of changes may be made to various embodiments without departing from the scope of the invention as described by the claims. For example, the order in which various described method steps are performed may often be changed in alternative embodiments, and in other alternative embodiments one or more method steps may be skipped altogether. Optional features of various device and system embodiments may be included in some embodiments and not in others. Therefore, the foregoing description is provided primarily for exemplary purposes and should not be interpreted to limit the scope of the invention as it is set forth in the claims.
- The examples and illustrations included herein show, by way of illustration and not of limitation, specific embodiments in which the subject matter may be practiced. As mentioned, other embodiments may be utilized and derived there from, such that structural and logical substitutions and changes may be made without departing from the scope of this disclosure. Such embodiments of the inventive subject matter may be referred to herein individually or collectively by the term “invention” merely for convenience and without intending to voluntarily limit the scope of this application to any single invention or inventive concept, if more than one is, in fact, disclosed. Thus, although specific embodiments have been illustrated and described herein, any arrangement calculated to achieve the same purpose may be substituted for the specific embodiments shown. This disclosure is intended to cover any and all adaptations or variations of various embodiments. Combinations of the above embodiments, and other embodiments not specifically described herein, will be apparent to those of skill in the art upon reviewing the above description.
Claims (20)
1. A method of calibrating a clock of an implantable neurostimulator device, the method comprising:
keeping time using a first clock of the implantable neurostimulator device, wherein the first clock runs continuously and is operating based upon a reference voltage generated within a circuitry of the implantable neurostimulator device;
triggering a calibration protocol;
turning on a second clock within the implantable neurostimulator device;
calibrating the first clock based on the second clock to correct for thermally dependent time drift; and
turning off the second clock.
2. The method of claim 1 , wherein the reference voltage is associated with an RC circuit to produce a time reference.
3. The method of claim 1 , wherein an event triggers the calibration protocol, wherein the event is a period of time determined by the first clock.
4. The method of claim 3 , wherein the period of time is few hours, a day, a few days, a week, a couple of weeks, a month, a few months, or a year.
5. The method of claim 1 , wherein an event triggers the calibration protocol, wherein the event is a change in the reference voltage above a threshold value.
6. The method of claim 1 , wherein the second clock comprises a piezoelectric clock.
7. An implantable neurostimulator device comprising:
a first clock configured to keep time within the implantable neurostimulator device; and
a second clock having more accurate time-keeping capabilities than the first clock, wherein the second clock is configured to be in an off or idle mode while the first clocking is running; and
a control circuitry configured to be triggered by an event such that upon triggering, the control circuitry turns the second clock on, uses the second clock to calibrate the first clock, and then turns the second clock off.
8. The implantable neurostimulator device of claim 7 , wherein the first clock is configured to count time based upon a reference voltage generated by the control circuitry.
9. The implantable neurostimulator device of claim 7 , wherein the second clock comprises a piezoelectric crystal oscillator.
10. The implantable neurostimulator device of claim 7 , wherein the event comprises a preset signal programmed into the control circuitry.
11. The implantable neurostimulator device of claim 10 , wherein the event is a temperature change.
12. The implantable neurostimulator device of claim 10 , wherein the preset signal is based on a set length of time.
13. The implantable neurostimulator device of claim 10 , wherein the preset signal is a voltage value above a certain threshold.
14. A leadless, implantable microstimulator device comprising:
a housing;
at least two electrically conductive contacts disposed on the housing;
a microcontroller configured to control stimulation of a vagus nerve from the electrically conductive contacts;
a first clock configured to keep time; and
a second clock having more accurate time-keeping capabilities than the first clock, wherein the second clocking is configured to periodically calibrate the first clock.
15. The leadless, implantable microstimulator device of claim 14 , wherein the second clocking module is configured to be in an idle mode when not calibrating the first clock.
16. The leadless, implantable microstimulator device of claim 14 , further comprising:
a resonator comprising a coil and a capacitor configured to resonate at a predetermined frequency range, wherein an electronic assembly is configured to receive power from the resonator to charge a battery.
17. The leadless, implantable microstimulator device of claim 14 , wherein a control circuitry is configured to be triggered by an event such that upon triggering, the control circuitry turns the second clock on, uses the second clock to calibrate the first clock, and then turns the second clock off.
18. The leadless, implantable microstimulator device of claim 17 , wherein the control circuitry is configured to correct a time drift of the first clock after a calibration is performed.
19. The leadless, implantable microstimulator device of claim 17 , wherein the event comprises a preset signal programmed into the control circuitry.
20. The leadless, implantable microstimulator device of claim 19 , wherein the preset signal is based on a set length of time, a voltage value threshold, or a current value threshold.
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Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11857788B2 (en) | 2018-09-25 | 2024-01-02 | The Feinstein Institutes For Medical Research | Methods and apparatuses for reducing bleeding via coordinated trigeminal and vagal nerve stimulation |
US11890471B2 (en) | 2017-08-14 | 2024-02-06 | Setpoint Medical Corporation | Vagus nerve stimulation pre-screening test |
US11938324B2 (en) | 2020-05-21 | 2024-03-26 | The Feinstein Institutes For Medical Research | Systems and methods for vagus nerve stimulation |
US11964150B2 (en) | 2016-01-20 | 2024-04-23 | Setpoint Medical Corporation | Batteryless implantable microstimulators |
US11969253B2 (en) | 2021-06-02 | 2024-04-30 | Setpoint Medical Corporation | Closed-loop vagus nerve stimulation |
Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8914114B2 (en) | 2000-05-23 | 2014-12-16 | The Feinstein Institute For Medical Research | Inhibition of inflammatory cytokine production by cholinergic agonists and vagus nerve stimulation |
US10912712B2 (en) | 2004-03-25 | 2021-02-09 | The Feinstein Institutes For Medical Research | Treatment of bleeding by non-invasive stimulation |
EP2298410B1 (en) | 2004-12-27 | 2013-10-09 | The Feinstein Institute for Medical Research | Treating inflammatory disorders by electrical vagus nerve stimulation |
US11207518B2 (en) | 2004-12-27 | 2021-12-28 | The Feinstein Institutes For Medical Research | Treating inflammatory disorders by stimulation of the cholinergic anti-inflammatory pathway |
AU2010258792B2 (en) | 2009-06-09 | 2015-07-02 | Setpoint Medical Corporation | Nerve cuff with pocket for leadless stimulator |
AU2010336337B2 (en) | 2009-12-23 | 2016-02-04 | Setpoint Medical Corporation | Neural stimulation devices and systems for treatment of chronic inflammation |
US11406833B2 (en) | 2015-02-03 | 2022-08-09 | Setpoint Medical Corporation | Apparatus and method for reminding, prompting, or alerting a patient with an implanted stimulator |
US10596367B2 (en) | 2016-01-13 | 2020-03-24 | Setpoint Medical Corporation | Systems and methods for establishing a nerve block |
CN108882885A (en) | 2016-01-20 | 2018-11-23 | 赛博恩特医疗器械公司 | The control of vagal stimulation |
US10583304B2 (en) | 2016-01-25 | 2020-03-10 | Setpoint Medical Corporation | Implantable neurostimulator having power control and thermal regulation and methods of use |
KR101917500B1 (en) * | 2017-03-08 | 2018-11-09 | 재단법인대구경북과학기술원 | Neural electrode device comprsing neural electrode array and micro fluidic channel for deliverying drug |
US10751469B2 (en) * | 2017-04-07 | 2020-08-25 | Northwesten University | Computer controlled pediatric regional anesthesia |
CA3073215A1 (en) | 2017-10-06 | 2019-04-11 | Medtronic Xomed, Inc. | Pledget stimulation and recording electrode assemblies |
KR102648346B1 (en) | 2017-12-13 | 2024-03-15 | 뉴로스 메디컬 인코포레이티드 | Nerve Cuff Placement Device |
US10729342B2 (en) * | 2018-02-28 | 2020-08-04 | Medtronic Xomed, Inc. | Nerve monitoring and/or stimulation electrode assemblies |
EP3773876B1 (en) | 2018-04-09 | 2024-04-17 | Neuros Medical, Inc. | Apparatuses for setting an electrical dose |
US11167130B2 (en) * | 2018-06-26 | 2021-11-09 | Microtransponder, Inc. | Manipulation member for nerve cuff |
US20210170083A1 (en) * | 2019-12-04 | 2021-06-10 | Medtronic, Inc. | Implantable medical device including cable fastener |
WO2021163308A1 (en) | 2020-02-11 | 2021-08-19 | Neuros Medical, Inc. | System and method for quantifying qualitative patient-reported data sets |
Family Cites Families (585)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB191404133A (en) | 1914-02-17 | 1915-01-07 | British Thomson Houston Co Ltd | Improvements in and relating to Protective Devices for Electric Distribution Systems. |
US2164121A (en) | 1938-05-04 | 1939-06-27 | Pescador Hector | Electric hearing apparatus for the deaf |
US3363623A (en) | 1965-07-28 | 1968-01-16 | Charles F. Atwell | Hand-held double-acting nerve reflex massager |
US3631534A (en) | 1969-09-05 | 1971-12-28 | Matsushita Electric Ind Co Ltd | Variable inductance device |
FR2315274A1 (en) | 1975-06-27 | 1977-01-21 | Parcor | NEW DERIVATIVES OF THIENO (2,3-C) PYRIDINE, THEIR PREPARATION AND THEIR APPLICATIONS |
US4073296A (en) | 1976-01-02 | 1978-02-14 | Mccall Francis J | Apparatus for acupressure treatment |
US4098277A (en) | 1977-01-28 | 1978-07-04 | Sherwin Mendell | Fitted, integrally molded device for stimulating auricular acupuncture points and method of making the device |
US4503863A (en) | 1979-06-29 | 1985-03-12 | Katims Jefferson J | Method and apparatus for transcutaneous electrical stimulation |
US4305402A (en) | 1979-06-29 | 1981-12-15 | Katims Jefferson J | Method for transcutaneous electrical stimulation |
US4702254A (en) | 1983-09-14 | 1987-10-27 | Jacob Zabara | Neurocybernetic prosthesis |
US5025807A (en) | 1983-09-14 | 1991-06-25 | Jacob Zabara | Neurocybernetic prosthesis |
US4867164A (en) | 1983-09-14 | 1989-09-19 | Jacob Zabara | Neurocybernetic prosthesis |
US4590946A (en) | 1984-06-14 | 1986-05-27 | Biomed Concepts, Inc. | Surgically implantable electrode for nerve bundles |
US4573481A (en) | 1984-06-25 | 1986-03-04 | Huntington Institute Of Applied Research | Implantable electrode array |
US4649936A (en) | 1984-10-11 | 1987-03-17 | Case Western Reserve University | Asymmetric single electrode cuff for generation of unidirectionally propagating action potentials for collision blocking |
US4632095A (en) | 1984-11-05 | 1986-12-30 | Tamiko Inc. | Pressure-point attachment for use with electrical hand-held massagers |
US4930516B1 (en) | 1985-11-13 | 1998-08-04 | Laser Diagnostic Instr Inc | Method for detecting cancerous tissue using visible native luminescence |
US4929734A (en) | 1987-03-31 | 1990-05-29 | Warner-Lambert Company | Tetrahydropyridine oxime compounds |
US4935234A (en) | 1987-06-11 | 1990-06-19 | Dana-Farber Cancer Institute | Method of reducing tissue damage at an inflammatory site using a monoclonal antibody |
US4840793A (en) | 1987-06-11 | 1989-06-20 | Dana-Farber Cancer Institute | Method of reducing tissue damage at an inflammatory site using a monoclonal antibody |
US5019648A (en) | 1987-07-06 | 1991-05-28 | Dana-Farber Cancer Institute | Monoclonal antibody specific for the adhesion function domain of a phagocyte cell surface protein |
DE3736664A1 (en) | 1987-10-29 | 1989-05-11 | Boehringer Ingelheim Kg | TETRAHYDRO-FURO- AND -THIENO (2,3-C) PYRIDINE, THEIR USE AS A MEDICAMENT AND METHOD FOR THE PRODUCTION THEREOF |
US5038781A (en) | 1988-01-21 | 1991-08-13 | Hassan Hamedi | Multi-electrode neurological stimulation apparatus |
US5049659A (en) | 1988-02-09 | 1991-09-17 | Dana Farber Cancer Institute | Proteins which induce immunological effector cell activation and chemattraction |
US4920979A (en) | 1988-10-12 | 1990-05-01 | Huntington Medical Research Institute | Bidirectional helical electrode for nerve stimulation |
US4991578A (en) | 1989-04-04 | 1991-02-12 | Siemens-Pacesetter, Inc. | Method and system for implanting self-anchoring epicardial defibrillation electrodes |
US5106853A (en) | 1989-05-15 | 1992-04-21 | Merck Sharp & Dohme, Ltd. | Oxadiazole and its salts, their use in treating dementia |
US4979511A (en) | 1989-11-03 | 1990-12-25 | Cyberonics, Inc. | Strain relief tether for implantable electrode |
US5235980A (en) | 1989-11-13 | 1993-08-17 | Cyberonics, Inc. | Implanted apparatus disabling switching regulator operation to allow radio frequency signal reception |
US5154172A (en) | 1989-11-13 | 1992-10-13 | Cyberonics, Inc. | Constant current sources with programmable voltage source |
US5179950A (en) | 1989-11-13 | 1993-01-19 | Cyberonics, Inc. | Implanted apparatus having micro processor controlled current and voltage sources with reduced voltage levels when not providing stimulation |
US5186170A (en) | 1989-11-13 | 1993-02-16 | Cyberonics, Inc. | Simultaneous radio frequency and magnetic field microprocessor reset circuit |
US6140490A (en) | 1996-02-01 | 2000-10-31 | Nexstar Pharmaceuticals, Inc. | High affinity nucleic acid ligands of complement system proteins |
CA2084987C (en) | 1990-06-11 | 2007-02-13 | Larry Gold | Nucleic acid ligands |
US6127119A (en) | 1990-06-11 | 2000-10-03 | Nexstar Pharmaceuticals, Inc. | Nucleic acid ligands of tissue target |
US5712375A (en) | 1990-06-11 | 1998-01-27 | Nexstar Pharmaceuticals, Inc. | Systematic evolution of ligands by exponential enrichment: tissue selex |
US5726017A (en) | 1990-06-11 | 1998-03-10 | Nexstar Pharmaceuticals, Inc. | High affinity HIV-1 gag nucleic acid ligands |
US6168778B1 (en) | 1990-06-11 | 2001-01-02 | Nexstar Pharmaceuticals, Inc. | Vascular endothelial growth factor (VEGF) Nucleic Acid Ligand Complexes |
US5654151A (en) | 1990-06-11 | 1997-08-05 | Nexstar Pharmaceuticals, Inc. | High affinity HIV Nucleocapsid nucleic acid ligands |
US5503978A (en) | 1990-06-11 | 1996-04-02 | University Research Corporation | Method for identification of high affinity DNA ligands of HIV-1 reverse transcriptase |
US6147204A (en) | 1990-06-11 | 2000-11-14 | Nexstar Pharmaceuticals, Inc. | Nucleic acid ligand complexes |
US5637459A (en) | 1990-06-11 | 1997-06-10 | Nexstar Pharmaceuticals, Inc. | Systematic evolution of ligands by exponential enrichment: chimeric selex |
US5683867A (en) | 1990-06-11 | 1997-11-04 | Nexstar Pharmaceuticals, Inc. | Systematic evolution of ligands by exponential enrichment: blended SELEX |
US5472841A (en) | 1990-06-11 | 1995-12-05 | Nexstar Pharmaceuticals, Inc. | Methods for identifying nucleic acid ligands of human neutrophil elastase |
US5496938A (en) | 1990-06-11 | 1996-03-05 | Nexstar Pharmaceuticals, Inc. | Nucleic acid ligands to HIV-RT and HIV-1 rev |
US5580737A (en) | 1990-06-11 | 1996-12-03 | Nexstar Pharmaceuticals, Inc. | High-affinity nucleic acid ligands that discriminate between theophylline and caffeine |
US6083696A (en) | 1990-06-11 | 2000-07-04 | Nexstar Pharmaceuticals, Inc. | Systematic evolution of ligands exponential enrichment: blended selex |
US6124449A (en) | 1990-06-11 | 2000-09-26 | Nexstar Pharmaceuticals, Inc. | High affinity TGFβ nucleic acid ligands and inhibitors |
US5705337A (en) | 1990-06-11 | 1998-01-06 | Nexstar Pharmaceuticals, Inc. | Systematic evolution of ligands by exponential enrichment: chemi-SELEX |
US5567588A (en) | 1990-06-11 | 1996-10-22 | University Research Corporation | Systematic evolution of ligands by exponential enrichment: Solution SELEX |
US5073560A (en) | 1990-07-20 | 1991-12-17 | Fisons Corporation | Spiro-isoxazolidine derivatives as cholinergic agents |
US5111815A (en) | 1990-10-15 | 1992-05-12 | Cardiac Pacemakers, Inc. | Method and apparatus for cardioverter/pacer utilizing neurosensing |
US5188104A (en) | 1991-02-01 | 1993-02-23 | Cyberonics, Inc. | Treatment of eating disorders by nerve stimulation |
US5263480A (en) | 1991-02-01 | 1993-11-23 | Cyberonics, Inc. | Treatment of eating disorders by nerve stimulation |
US5269303A (en) | 1991-02-22 | 1993-12-14 | Cyberonics, Inc. | Treatment of dementia by nerve stimulation |
US5251634A (en) | 1991-05-03 | 1993-10-12 | Cyberonics, Inc. | Helical nerve electrode |
US5215086A (en) | 1991-05-03 | 1993-06-01 | Cyberonics, Inc. | Therapeutic treatment of migraine symptoms by stimulation |
US5299569A (en) | 1991-05-03 | 1994-04-05 | Cyberonics, Inc. | Treatment of neuropsychiatric disorders by nerve stimulation |
US5335657A (en) | 1991-05-03 | 1994-08-09 | Cyberonics, Inc. | Therapeutic treatment of sleep disorder by nerve stimulation |
US6028186A (en) | 1991-06-10 | 2000-02-22 | Nexstar Pharmaceuticals, Inc. | High affinity nucleic acid ligands of cytokines |
US5205285A (en) | 1991-06-14 | 1993-04-27 | Cyberonics, Inc. | Voice suppression of vagal stimulation |
WO1993001862A1 (en) | 1991-07-22 | 1993-02-04 | Cyberonics, Inc. | Treatment of respiratory disorders by nerve stimulation |
US5222494A (en) | 1991-07-31 | 1993-06-29 | Cyberonics, Inc. | Implantable tissue stimulator output stabilization system |
US5231988A (en) | 1991-08-09 | 1993-08-03 | Cyberonics, Inc. | Treatment of endocrine disorders by nerve stimulation |
US5582981A (en) | 1991-08-14 | 1996-12-10 | Gilead Sciences, Inc. | Method for identifying an oligonucleotide aptamer specific for a target |
US5175166A (en) | 1991-08-27 | 1992-12-29 | The University Of Toledo | Muscarinic agonists |
US5215089A (en) | 1991-10-21 | 1993-06-01 | Cyberonics, Inc. | Electrode assembly for nerve stimulation |
US5304206A (en) | 1991-11-18 | 1994-04-19 | Cyberonics, Inc. | Activation techniques for implantable medical device |
US5237991A (en) | 1991-11-19 | 1993-08-24 | Cyberonics, Inc. | Implantable medical device with dummy load for pre-implant testing in sterile package and facilitating electrical lead connection |
US5203326A (en) | 1991-12-18 | 1993-04-20 | Telectronics Pacing Systems, Inc. | Antiarrhythmia pacer using antiarrhythmia pacing and autonomic nerve stimulation therapy |
US5330507A (en) | 1992-04-24 | 1994-07-19 | Medtronic, Inc. | Implantable electrical vagal stimulation for prevention or interruption of life threatening arrhythmias |
US5330515A (en) | 1992-06-17 | 1994-07-19 | Cyberonics, Inc. | Treatment of pain by vagal afferent stimulation |
US5977144A (en) | 1992-08-31 | 1999-11-02 | University Of Florida | Methods of use and compositions for benzylidene- and cinnamylidene-anabaseines |
JP3034953B2 (en) | 1992-08-31 | 2000-04-17 | ユニバーシティー オブ フロリダ リサーチ ファンデーション,インコーポレーテッド | Anabaseine derivatives useful for the treatment of degenerative diseases of the nervous system |
DE4404140B4 (en) | 1993-02-10 | 2005-11-10 | Siemens Ag | Use of a pressure pulse source pulse-like shock waves and provided for such use pressure pulse source |
US5344438A (en) | 1993-04-16 | 1994-09-06 | Medtronic, Inc. | Cuff electrode |
JPH08511005A (en) | 1993-06-01 | 1996-11-19 | コーテックス ファーマシューティカルズ インコーポレイテッド | Alkaline or acid phosphatase inhibitors in the treatment of neurological disorders |
DE4324152A1 (en) | 1993-07-19 | 1995-01-26 | Bayer Ag | Compositions for the removal of additives containing silicone oil, aqueous dispersions prepared therefrom and their use |
US5594106A (en) | 1993-08-23 | 1997-01-14 | Immunex Corporation | Inhibitors of TNF-α secretion |
US5599984A (en) | 1994-01-21 | 1997-02-04 | The Picower Institute For Medical Research | Guanylhydrazones and their use to treat inflammatory conditions |
JP3269125B2 (en) | 1994-01-28 | 2002-03-25 | 東レ株式会社 | Atopic dermatitis drug |
ES2157326T3 (en) | 1994-04-22 | 2001-08-16 | Sanquin Bloedvoorziening | SYSTEM FOR THE TREATMENT OF ANOMALIES IN THE CASCADA DE COAGULACION SANGUINEA. |
US5458625A (en) | 1994-05-04 | 1995-10-17 | Kendall; Donald E. | Transcutaneous nerve stimulation device and method for using same |
US6017891A (en) | 1994-05-06 | 2000-01-25 | Baxter Aktiengesellschaft | Stable preparation for the treatment of blood coagulation disorders |
US6405732B1 (en) | 1994-06-24 | 2002-06-18 | Curon Medical, Inc. | Method to treat gastric reflux via the detection and ablation of gastro-esophageal nerves and receptors |
CN1056846C (en) | 1994-08-24 | 2000-09-27 | 阿斯特拉公司 | Spiro-azabicyclic compounds useful in therapy |
US5531778A (en) | 1994-09-20 | 1996-07-02 | Cyberonics, Inc. | Circumneural electrode assembly |
US5540734A (en) | 1994-09-28 | 1996-07-30 | Zabara; Jacob | Cranial nerve stimulation treatments using neurocybernetic prosthesis |
US5571150A (en) | 1994-12-19 | 1996-11-05 | Cyberonics, Inc. | Treatment of patients in coma by nerve stimulation |
US5487756A (en) | 1994-12-23 | 1996-01-30 | Simon Fraser University | Implantable cuff having improved closure |
US5604231A (en) | 1995-01-06 | 1997-02-18 | Smith; Carr J. | Pharmaceutical compositions for prevention and treatment of ulcerative colitis |
US5540730A (en) | 1995-06-06 | 1996-07-30 | Cyberonics, Inc. | Treatment of motility disorders by nerve stimulation |
US5707400A (en) | 1995-09-19 | 1998-01-13 | Cyberonics, Inc. | Treating refractory hypertension by nerve stimulation |
US5700282A (en) | 1995-10-13 | 1997-12-23 | Zabara; Jacob | Heart rhythm stabilization using a neurocybernetic prosthesis |
WO1997014473A1 (en) | 1995-10-18 | 1997-04-24 | Novartis Ag | Thermopile powered transdermal drug delivery device |
US5607459A (en) | 1995-10-27 | 1997-03-04 | Intermedics, Inc. | Implantable cardiac stimulation device with time-of-day selectable warning system |
US5611350A (en) | 1996-02-08 | 1997-03-18 | John; Michael S. | Method and apparatus for facilitating recovery of patients in deep coma |
US6096728A (en) | 1996-02-09 | 2000-08-01 | Amgen Inc. | Composition and method for treating inflammatory diseases |
US5913876A (en) | 1996-02-20 | 1999-06-22 | Cardiothoracic Systems, Inc. | Method and apparatus for using vagus nerve stimulation in surgery |
US5651378A (en) | 1996-02-20 | 1997-07-29 | Cardiothoracic Systems, Inc. | Method of using vagal nerve stimulation in surgery |
WO1997029802A2 (en) | 1996-02-20 | 1997-08-21 | Advanced Bionics Corporation | Improved implantable microstimulator and systems employing the same |
SE9600683D0 (en) | 1996-02-23 | 1996-02-23 | Astra Ab | Azabicyclic esters of carbamic acids useful in therapy |
CZ81997A3 (en) | 1996-03-20 | 1997-10-15 | Immuno Ag | Pharmaceutical preparation for treating disorders connected with blood clotting, process of its preparation and use |
US5618818A (en) | 1996-03-20 | 1997-04-08 | The University Of Toledo | Muscarinic agonist compounds |
EP0796634B1 (en) | 1996-03-21 | 2005-11-16 | BIOTRONIK Mess- und Therapiegeräte GmbH & Co Ingenieurbüro Berlin | Implantable stimulation electrode |
US5690681A (en) | 1996-03-29 | 1997-11-25 | Purdue Research Foundation | Method and apparatus using vagal stimulation for control of ventricular rate during atrial fibrillation |
US5726179A (en) | 1996-04-01 | 1998-03-10 | The University Of Toledo | Muscarinic agonists |
US6166048A (en) | 1999-04-20 | 2000-12-26 | Targacept, Inc. | Pharmaceutical compositions for inhibition of cytokine production and secretion |
US6735471B2 (en) | 1996-04-30 | 2004-05-11 | Medtronic, Inc. | Method and system for endotracheal/esophageal stimulation prior to and during a medical procedure |
US7269457B2 (en) | 1996-04-30 | 2007-09-11 | Medtronic, Inc. | Method and system for vagal nerve stimulation with multi-site cardiac pacing |
US7225019B2 (en) | 1996-04-30 | 2007-05-29 | Medtronic, Inc. | Method and system for nerve stimulation and cardiac sensing prior to and during a medical procedure |
US6006134A (en) | 1998-04-30 | 1999-12-21 | Medtronic, Inc. | Method and device for electronically controlling the beating of a heart using venous electrical stimulation of nerve fibers |
US6628987B1 (en) | 2000-09-26 | 2003-09-30 | Medtronic, Inc. | Method and system for sensing cardiac contractions during vagal stimulation-induced cardiopalegia |
US6532388B1 (en) | 1996-04-30 | 2003-03-11 | Medtronic, Inc. | Method and system for endotracheal/esophageal stimulation prior to and during a medical procedure |
USRE38705E1 (en) | 1996-04-30 | 2005-02-22 | Medtronic, Inc. | Method and device for electronically controlling the beating of a heart using venous electrical stimulation of nerve fibers |
US6449507B1 (en) | 1996-04-30 | 2002-09-10 | Medtronic, Inc. | Method and system for nerve stimulation prior to and during a medical procedure |
US20040199209A1 (en) | 2003-04-07 | 2004-10-07 | Hill Michael R.S. | Method and system for delivery of vasoactive drugs to the heart prior to and during a medical procedure |
US6904318B2 (en) | 2000-09-26 | 2005-06-07 | Medtronic, Inc. | Method and system for monitoring and controlling systemic and pulmonary circulation during a medical procedure |
US5853005A (en) | 1996-05-02 | 1998-12-29 | The United States Of America As Represented By The Secretary Of The Army | Acoustic monitoring system |
WO1997045160A1 (en) | 1996-05-31 | 1997-12-04 | Southern Illinois University | Methods of modulating aspects of brain neural plasticity by vagus nerve stimulation |
US5792210A (en) | 1996-06-10 | 1998-08-11 | Environmental Behavior Modification Inc. | Electrical tongue stimulator and method for addiction treatment |
JPH1094613A (en) | 1996-08-02 | 1998-04-14 | Mieko Sato | Appetite adjusting implement |
US5718912A (en) | 1996-10-28 | 1998-02-17 | Merck & Co., Inc. | Muscarine agonists |
US20050191661A1 (en) | 1996-11-06 | 2005-09-01 | Tetsuya Gatanaga | Treatment of inflammatory disease by cleaving TNF receptors |
CA2271693C (en) | 1996-11-15 | 2009-01-20 | The Picower Institute For Medical Research | Guanylhydrazones useful for treating diseases associated with t cell activation |
US6208894B1 (en) | 1997-02-26 | 2001-03-27 | Alfred E. Mann Foundation For Scientific Research And Advanced Bionics | System of implantable devices for monitoring and/or affecting body parameters |
US6164284A (en) | 1997-02-26 | 2000-12-26 | Schulman; Joseph H. | System of implantable devices for monitoring and/or affecting body parameters |
US5788656A (en) | 1997-02-28 | 1998-08-04 | Mino; Alfonso Di | Electronic stimulation system for treating tinnitus disorders |
US5919216A (en) | 1997-06-16 | 1999-07-06 | Medtronic, Inc. | System and method for enhancement of glucose production by stimulation of pancreatic beta cells |
AR013184A1 (en) | 1997-07-18 | 2000-12-13 | Astrazeneca Ab | SPYROZOBICYCLIC HETERO CYCLIC AMINES, PHARMACEUTICAL COMPOSITION, USE OF SUCH AMINES TO PREPARE MEDICINES AND METHOD OF TREATMENT OR PROPHYLAXIS |
US5824027A (en) | 1997-08-14 | 1998-10-20 | Simon Fraser University | Nerve cuff having one or more isolated chambers |
US6479523B1 (en) | 1997-08-26 | 2002-11-12 | Emory University | Pharmacologic drug combination in vagal-induced asystole |
US6011005A (en) | 1997-09-18 | 2000-01-04 | The Picower Institute For Medical Research | Prevention of pregnancy miscarriages |
US6141590A (en) | 1997-09-25 | 2000-10-31 | Medtronic, Inc. | System and method for respiration-modulated pacing |
US6528529B1 (en) | 1998-03-31 | 2003-03-04 | Acadia Pharmaceuticals Inc. | Compounds with activity on muscarinic receptors |
US6018682A (en) | 1998-04-30 | 2000-01-25 | Medtronic, Inc. | Implantable seizure warning system |
US5928272A (en) | 1998-05-02 | 1999-07-27 | Cyberonics, Inc. | Automatic activation of a neurostimulator device using a detection algorithm based on cardiac activity |
US6002964A (en) | 1998-07-15 | 1999-12-14 | Feler; Claudio A. | Epidural nerve root stimulation |
US7209787B2 (en) | 1998-08-05 | 2007-04-24 | Bioneuronics Corporation | Apparatus and method for closed-loop intracranial stimulation for optimal control of neurological disease |
US7242984B2 (en) | 1998-08-05 | 2007-07-10 | Neurovista Corporation | Apparatus and method for closed-loop intracranial stimulation for optimal control of neurological disease |
US8762065B2 (en) | 1998-08-05 | 2014-06-24 | Cyberonics, Inc. | Closed-loop feedback-driven neuromodulation |
US7599736B2 (en) | 2001-07-23 | 2009-10-06 | Dilorenzo Biomedical, Llc | Method and apparatus for neuromodulation and physiologic modulation for the treatment of metabolic and neuropsychiatric disease |
US7231254B2 (en) | 1998-08-05 | 2007-06-12 | Bioneuronics Corporation | Closed-loop feedback-driven neuromodulation |
US6564102B1 (en) | 1998-10-26 | 2003-05-13 | Birinder R. Boveja | Apparatus and method for adjunct (add-on) treatment of coma and traumatic brain injury with neuromodulation using an external stimulator |
US6611715B1 (en) | 1998-10-26 | 2003-08-26 | Birinder R. Boveja | Apparatus and method for neuromodulation therapy for obesity and compulsive eating disorders using an implantable lead-receiver and an external stimulator |
US6505074B2 (en) | 1998-10-26 | 2003-01-07 | Birinder R. Boveja | Method and apparatus for electrical stimulation adjunct (add-on) treatment of urinary incontinence and urological disorders using an external stimulator |
US20050137644A1 (en) | 1998-10-26 | 2005-06-23 | Boveja Birinder R. | Method and system for vagal blocking and/or vagal stimulation to provide therapy for obesity and other gastrointestinal disorders |
US6208902B1 (en) | 1998-10-26 | 2001-03-27 | Birinder Bob Boveja | Apparatus and method for adjunct (add-on) therapy for pain syndromes utilizing an implantable lead and an external stimulator |
US6615081B1 (en) | 1998-10-26 | 2003-09-02 | Birinder R. Boveja | Apparatus and method for adjunct (add-on) treatment of diabetes by neuromodulation with an external stimulator |
US6366814B1 (en) | 1998-10-26 | 2002-04-02 | Birinder R. Boveja | External stimulator for adjunct (add-on) treatment for neurological, neuropsychiatric, and urological disorders |
US6205359B1 (en) | 1998-10-26 | 2001-03-20 | Birinder Bob Boveja | Apparatus and method for adjunct (add-on) therapy of partial complex epilepsy, generalized epilepsy and involuntary movement disorders utilizing an external stimulator |
US6668191B1 (en) | 1998-10-26 | 2003-12-23 | Birinder R. Boveja | Apparatus and method for electrical stimulation adjunct (add-on) therapy of atrial fibrillation, inappropriate sinus tachycardia, and refractory hypertension with an external stimulator |
US6269270B1 (en) | 1998-10-26 | 2001-07-31 | Birinder Bob Boveja | Apparatus and method for adjunct (add-on) therapy of Dementia and Alzheimer's disease utilizing an implantable lead and external stimulator |
US20030212440A1 (en) | 2002-05-09 | 2003-11-13 | Boveja Birinder R. | Method and system for modulating the vagus nerve (10th cranial nerve) using modulated electrical pulses with an inductively coupled stimulation system |
US7076307B2 (en) | 2002-05-09 | 2006-07-11 | Boveja Birinder R | Method and system for modulating the vagus nerve (10th cranial nerve) with electrical pulses using implanted and external components, to provide therapy neurological and neuropsychiatric disorders |
US6356788B2 (en) | 1998-10-26 | 2002-03-12 | Birinder Bob Boveja | Apparatus and method for adjunct (add-on) therapy for depression, migraine, neuropsychiatric disorders, partial complex epilepsy, generalized epilepsy and involuntary movement disorders utilizing an external stimulator |
FR2785287B1 (en) | 1998-10-30 | 2000-12-29 | De Chily Pierre Charlier | PROCESS FOR THE POLYMERIZATION BY DIELECTRIC HEATING OF UNSATURATED FATTY ACIDS, UNSATURATED FATTY ACID ESTERS, UNSATURATED HYDROCARBONS, OR UNSATURATED DERIVATIVES THEREOF |
US5994330A (en) | 1998-11-09 | 1999-11-30 | El Khoury; Georges F. | Topical application of muscarinic agents such as neostigmine for treatment of acne and other inflammatory conditions |
US6138302A (en) | 1998-11-10 | 2000-10-31 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Apparatus and method for positioning patient |
FR2786770B1 (en) | 1998-12-04 | 2001-01-19 | Synthelabo | NONANE 1,4-DIAZABICYCLO [3.2.2.] DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION |
US6376675B2 (en) | 1999-01-22 | 2002-04-23 | The University Of Toledo | Muscarinic receptor agonists |
US6303321B1 (en) | 1999-02-11 | 2001-10-16 | North Shore-Long Island Jewish Research Institute | Methods for diagnosing sepsis |
US6341236B1 (en) | 1999-04-30 | 2002-01-22 | Ivan Osorio | Vagal nerve stimulation techniques for treatment of epileptic seizures |
CA2376903A1 (en) | 1999-06-25 | 2001-01-04 | Emory University | Devices and methods for vagus nerve stimulation |
US6233488B1 (en) | 1999-06-25 | 2001-05-15 | Carl A. Hess | Spinal cord stimulation as a treatment for addiction to nicotine and other chemical substances |
US6587719B1 (en) | 1999-07-01 | 2003-07-01 | Cyberonics, Inc. | Treatment of obesity by bilateral vagus nerve stimulation |
US6804558B2 (en) | 1999-07-07 | 2004-10-12 | Medtronic, Inc. | System and method of communicating between an implantable medical device and a remote computer system or health care provider |
US6210321B1 (en) | 1999-07-29 | 2001-04-03 | Adm Tronics Unlimited, Inc. | Electronic stimulation system for treating tinnitus disorders |
US6171795B1 (en) | 1999-07-29 | 2001-01-09 | Nexstar Pharmaceuticals, Inc. | Nucleic acid ligands to CD40ligand |
US6304775B1 (en) | 1999-09-22 | 2001-10-16 | Leonidas D. Iasemidis | Seizure warning and prediction |
US6636767B1 (en) | 1999-09-29 | 2003-10-21 | Restore Medical, Inc. | Implanatable stimulation device for snoring treatment |
US6473644B1 (en) | 1999-10-13 | 2002-10-29 | Cyberonics, Inc. | Method to enhance cardiac capillary growth in heart failure patients |
US20020026141A1 (en) | 1999-11-04 | 2002-02-28 | Medtronic, Inc. | System for pancreatic stimulation and glucose measurement |
CA2397607A1 (en) | 1999-12-17 | 2001-06-21 | Carla M. Mann | Magnitude programming for implantable electrical stimulator |
FR2803186B1 (en) | 2000-01-05 | 2002-08-09 | Guy Charvin | METHOD AND APPARATUS FOR COLLECTING HEARING MESSAGE POTENTIALS |
US6447443B1 (en) | 2001-01-13 | 2002-09-10 | Medtronic, Inc. | Method for organ positioning and stabilization |
US6885888B2 (en) | 2000-01-20 | 2005-04-26 | The Cleveland Clinic Foundation | Electrical stimulation of the sympathetic nerve chain |
US6356787B1 (en) | 2000-02-24 | 2002-03-12 | Electro Core Techniques, Llc | Method of treating facial blushing by electrical stimulation of the sympathetic nerve chain |
US20060085046A1 (en) | 2000-01-20 | 2006-04-20 | Ali Rezai | Methods of treating medical conditions by transvascular neuromodulation of the autonomic nervous system |
JP2003530169A (en) | 2000-04-11 | 2003-10-14 | ザ・ボード・オブ・リージェンツ・オブ・ザ・ユニバーシティ・オブ・テキサス・システム | Electrical stimulation of the gastrointestinal tract |
US6826428B1 (en) | 2000-04-11 | 2004-11-30 | The Board Of Regents Of The University Of Texas System | Gastrointestinal electrical stimulation |
US6610713B2 (en) | 2000-05-23 | 2003-08-26 | North Shore - Long Island Jewish Research Institute | Inhibition of inflammatory cytokine production by cholinergic agonists and vagus nerve stimulation |
US8914114B2 (en) | 2000-05-23 | 2014-12-16 | The Feinstein Institute For Medical Research | Inhibition of inflammatory cytokine production by cholinergic agonists and vagus nerve stimulation |
US6511500B1 (en) | 2000-06-06 | 2003-01-28 | Marc Mounir Rahme | Use of autonomic nervous system neurotransmitters inhibition and atrial parasympathetic fibers ablation for the treatment of atrial arrhythmias and to preserve drug effects |
AU2001282873A1 (en) | 2000-08-18 | 2002-03-04 | Pharmacia And Upjohn Company | Quinuclidine-substituted aryl compounds for treatment of disease |
ATE332668T1 (en) | 2000-09-26 | 2006-08-15 | Medtronic Inc | MEDICAL DEVICE FOR BLOOD FLOW CONTROL |
US6487446B1 (en) | 2000-09-26 | 2002-11-26 | Medtronic, Inc. | Method and system for spinal cord stimulation prior to and during a medical procedure |
US20020077675A1 (en) | 2000-09-26 | 2002-06-20 | Transneuronix, Inc. | Minimally invasive surgery placement of stimulation leads in mediastinal structures |
AU2002210378A1 (en) | 2000-10-11 | 2002-04-22 | Ronald R. Riso | Nerve cuff electrode |
US7011638B2 (en) | 2000-11-14 | 2006-03-14 | Science Medicus, Inc. | Device and procedure to treat cardiac atrial arrhythmias |
US6832114B1 (en) | 2000-11-21 | 2004-12-14 | Advanced Bionics Corporation | Systems and methods for modulation of pancreatic endocrine secretion and treatment of diabetes |
US6633779B1 (en) | 2000-11-27 | 2003-10-14 | Science Medicus, Inc. | Treatment of asthma and respiratory disease by means of electrical neuro-receptive waveforms |
US6884807B2 (en) | 2000-12-01 | 2005-04-26 | Neurosearch, A/S | 3-substituted quinuclidines and their use as nicotinic agonists |
US20020086871A1 (en) | 2000-12-29 | 2002-07-04 | O'neill Brian Thomas | Pharmaceutical composition for the treatment of CNS and other disorders |
US6609025B2 (en) | 2001-01-02 | 2003-08-19 | Cyberonics, Inc. | Treatment of obesity by bilateral sub-diaphragmatic nerve stimulation |
US7519421B2 (en) | 2001-01-16 | 2009-04-14 | Kenergy, Inc. | Vagal nerve stimulation using vascular implanted devices for treatment of atrial fibrillation |
WO2002057275A1 (en) | 2001-01-17 | 2002-07-25 | University Of Kentucky Research Foundation | Boron-containing nicotine analogs for use in the treatment of cns pathologies |
US6735475B1 (en) | 2001-01-30 | 2004-05-11 | Advanced Bionics Corporation | Fully implantable miniature neurostimulator for stimulation as a therapy for headache and/or facial pain |
US7389145B2 (en) | 2001-02-20 | 2008-06-17 | Case Western Reserve University | Systems and methods for reversibly blocking nerve activity |
US8060208B2 (en) | 2001-02-20 | 2011-11-15 | Case Western Reserve University | Action potential conduction prevention |
US7167751B1 (en) | 2001-03-01 | 2007-01-23 | Advanced Bionics Corporation | Method of using a fully implantable miniature neurostimulator for vagus nerve stimulation |
JP2004524125A (en) | 2001-04-05 | 2004-08-12 | メド−エル・エレクトロメディツィニシェ・ゲラーテ・ゲーエムベーハー | Pacemaker for bilateral autonomic palsy |
US7369897B2 (en) | 2001-04-19 | 2008-05-06 | Neuro And Cardiac Technologies, Llc | Method and system of remotely controlling electrical pulses provided to nerve tissue(s) by an implanted stimulator system for neuromodulation therapies |
US6684105B2 (en) | 2001-08-31 | 2004-01-27 | Biocontrol Medical, Ltd. | Treatment of disorders by unidirectional nerve stimulation |
US6901294B1 (en) | 2001-05-25 | 2005-05-31 | Advanced Bionics Corporation | Methods and systems for direct electrical current stimulation as a therapy for prostatic hypertrophy |
US20050240229A1 (en) | 2001-04-26 | 2005-10-27 | Whitehurst Tood K | Methods and systems for stimulation as a therapy for erectile dysfunction |
US6928320B2 (en) | 2001-05-17 | 2005-08-09 | Medtronic, Inc. | Apparatus for blocking activation of tissue or conduction of action potentials while other tissue is being therapeutically activated |
US6947782B2 (en) | 2001-06-18 | 2005-09-20 | Alfred E. Mann Foundation For Scientific Research | Miniature implantable connectors |
US7054692B1 (en) | 2001-06-22 | 2006-05-30 | Advanced Bionics Corporation | Fixation device for implantable microdevices |
US20060167498A1 (en) | 2001-07-23 | 2006-07-27 | Dilorenzo Daniel J | Method, apparatus, and surgical technique for autonomic neuromodulation for the treatment of disease |
US20060116736A1 (en) | 2001-07-23 | 2006-06-01 | Dilorenzo Daniel J | Method, apparatus, and surgical technique for autonomic neuromodulation for the treatment of obesity |
US6622047B2 (en) | 2001-07-28 | 2003-09-16 | Cyberonics, Inc. | Treatment of neuropsychiatric disorders by near-diaphragmatic nerve stimulation |
US6622038B2 (en) | 2001-07-28 | 2003-09-16 | Cyberonics, Inc. | Treatment of movement disorders by near-diaphragmatic nerve stimulation |
WO2003015863A2 (en) | 2001-08-17 | 2003-02-27 | Advanced Bionics Corporation | Gradual recruitment of muscle/neural excitable tissue using high-rate electrical stimulation parameters |
US6600956B2 (en) | 2001-08-21 | 2003-07-29 | Cyberonics, Inc. | Circumneural electrode assembly |
US6622041B2 (en) | 2001-08-21 | 2003-09-16 | Cyberonics, Inc. | Treatment of congestive heart failure and autonomic cardiovascular drive disorders |
US6760626B1 (en) | 2001-08-29 | 2004-07-06 | Birinder R. Boveja | Apparatus and method for treatment of neurological and neuropsychiatric disorders using programmerless implantable pulse generator system |
US7054686B2 (en) | 2001-08-30 | 2006-05-30 | Biophan Technologies, Inc. | Pulsewidth electrical stimulation |
US20140046407A1 (en) | 2001-08-31 | 2014-02-13 | Bio Control Medical (B.C.M.) Ltd. | Nerve stimulation techniques |
US8571653B2 (en) | 2001-08-31 | 2013-10-29 | Bio Control Medical (B.C.M.) Ltd. | Nerve stimulation techniques |
US7974693B2 (en) | 2001-08-31 | 2011-07-05 | Bio Control Medical (B.C.M.) Ltd. | Techniques for applying, configuring, and coordinating nerve fiber stimulation |
US7885709B2 (en) | 2001-08-31 | 2011-02-08 | Bio Control Medical (B.C.M.) Ltd. | Nerve stimulation for treating disorders |
US7778711B2 (en) | 2001-08-31 | 2010-08-17 | Bio Control Medical (B.C.M.) Ltd. | Reduction of heart rate variability by parasympathetic stimulation |
US8615294B2 (en) | 2008-08-13 | 2013-12-24 | Bio Control Medical (B.C.M.) Ltd. | Electrode devices for nerve stimulation and cardiac sensing |
US7778703B2 (en) | 2001-08-31 | 2010-08-17 | Bio Control Medical (B.C.M.) Ltd. | Selective nerve fiber stimulation for treating heart conditions |
US7734355B2 (en) | 2001-08-31 | 2010-06-08 | Bio Control Medical (B.C.M.) Ltd. | Treatment of disorders by unidirectional nerve stimulation |
US20040002546A1 (en) | 2001-09-15 | 2004-01-01 | Eric Altschuler | Methods for treating crohn's and other TNF associated diseases |
US6934583B2 (en) | 2001-10-22 | 2005-08-23 | Pacesetter, Inc. | Implantable lead and method for stimulating the vagus nerve |
US6745079B2 (en) | 2001-11-07 | 2004-06-01 | Medtronic, Inc. | Electrical tissue stimulation apparatus and method |
US7155284B1 (en) | 2002-01-24 | 2006-12-26 | Advanced Bionics Corporation | Treatment of hypertension |
US6721603B2 (en) | 2002-01-25 | 2004-04-13 | Cyberonics, Inc. | Nerve stimulation as a treatment for pain |
US20040048795A1 (en) | 2002-02-26 | 2004-03-11 | North Shore-Long Island Jewish Research Institute | Inhibition of inflammatory cytokine production by stimulation of brain muscarinic receptors |
US7689276B2 (en) | 2002-09-13 | 2010-03-30 | Leptos Biomedical, Inc. | Dynamic nerve stimulation for treatment of disorders |
US7937145B2 (en) | 2002-03-22 | 2011-05-03 | Advanced Neuromodulation Systems, Inc. | Dynamic nerve stimulation employing frequency modulation |
US7465555B2 (en) | 2002-04-02 | 2008-12-16 | Becton, Dickinson And Company | Early detection of sepsis |
US6978787B1 (en) | 2002-04-03 | 2005-12-27 | Michael Broniatowski | Method and system for dynamic vocal fold closure with neuro-electrical stimulation |
US20080213331A1 (en) * | 2002-04-08 | 2008-09-04 | Ardian, Inc. | Methods and devices for renal nerve blocking |
US20030191404A1 (en) | 2002-04-08 | 2003-10-09 | Klein George J. | Method and apparatus for providing arrhythmia discrimination |
US6990372B2 (en) | 2002-04-11 | 2006-01-24 | Alfred E. Mann Foundation For Scientific Research | Programmable signal analysis device for detecting neurological signals in an implantable device |
WO2003092796A1 (en) | 2002-05-03 | 2003-11-13 | Musc Foundation For Research Development | Method, apparatus and system for determining effects and optimizing parameters of vagus nerve stimulation |
US20050165458A1 (en) | 2002-05-09 | 2005-07-28 | Boveja Birinder R. | Method and system to provide therapy for depression using electroconvulsive therapy(ECT) and pulsed electrical stimulation to vagus nerve(s) |
US20060079936A1 (en) | 2003-05-11 | 2006-04-13 | Boveja Birinder R | Method and system for altering regional cerebral blood flow (rCBF) by providing complex and/or rectangular electrical pulses to vagus nerve(s), to provide therapy for depression and other medical disorders |
US7191012B2 (en) | 2003-05-11 | 2007-03-13 | Boveja Birinder R | Method and system for providing pulsed electrical stimulation to a craniel nerve of a patient to provide therapy for neurological and neuropsychiatric disorders |
US20050216070A1 (en) | 2002-05-09 | 2005-09-29 | Boveja Birinder R | Method and system for providing therapy for migraine/chronic headache by providing electrical pulses to vagus nerve(s) |
US20070067004A1 (en) | 2002-05-09 | 2007-03-22 | Boveja Birinder R | Methods and systems for modulating the vagus nerve (10th cranial nerve) to provide therapy for neurological, and neuropsychiatric disorders |
US20050154426A1 (en) | 2002-05-09 | 2005-07-14 | Boveja Birinder R. | Method and system for providing therapy for neuropsychiatric and neurological disorders utilizing transcranical magnetic stimulation and pulsed electrical vagus nerve(s) stimulation |
US20060009815A1 (en) | 2002-05-09 | 2006-01-12 | Boveja Birinder R | Method and system to provide therapy or alleviate symptoms of involuntary movement disorders by providing complex and/or rectangular electrical pulses to vagus nerve(s) |
US20050209654A1 (en) | 2002-05-09 | 2005-09-22 | Boveja Birinder R | Method and system for providing adjunct (add-on) therapy for depression, anxiety and obsessive-compulsive disorders by providing electrical pulses to vagus nerve(s) |
US7561922B2 (en) | 2004-12-22 | 2009-07-14 | Biocontrol Medical Ltd. | Construction of electrode assembly for nerve control |
US20050065553A1 (en) | 2003-06-13 | 2005-03-24 | Omry Ben Ezra | Applications of vagal stimulation |
US8036745B2 (en) | 2004-06-10 | 2011-10-11 | Bio Control Medical (B.C.M.) Ltd. | Parasympathetic pacing therapy during and following a medical procedure, clinical trauma or pathology |
US7885711B2 (en) | 2003-06-13 | 2011-02-08 | Bio Control Medical (B.C.M.) Ltd. | Vagal stimulation for anti-embolic therapy |
US7321793B2 (en) | 2003-06-13 | 2008-01-22 | Biocontrol Medical Ltd. | Vagal stimulation for atrial fibrillation therapy |
US20060116739A1 (en) | 2002-05-23 | 2006-06-01 | Nir Betser | Electrode assembly for nerve control |
US7277761B2 (en) | 2002-06-12 | 2007-10-02 | Pacesetter, Inc. | Vagal stimulation for improving cardiac function in heart failure or CHF patients |
US20040015202A1 (en) | 2002-06-14 | 2004-01-22 | Chandler Gilbert S. | Combination epidural infusion/stimulation method and system |
US7292890B2 (en) | 2002-06-20 | 2007-11-06 | Advanced Bionics Corporation | Vagus nerve stimulation via unidirectional propagation of action potentials |
US7203548B2 (en) | 2002-06-20 | 2007-04-10 | Advanced Bionics Corporation | Cavernous nerve stimulation via unidirectional propagation of action potentials |
US20040015205A1 (en) | 2002-06-20 | 2004-01-22 | Whitehurst Todd K. | Implantable microstimulators with programmable multielectrode configuration and uses thereof |
US7860570B2 (en) | 2002-06-20 | 2010-12-28 | Boston Scientific Neuromodulation Corporation | Implantable microstimulators and methods for unidirectional propagation of action potentials |
KR100553516B1 (en) | 2002-06-24 | 2006-02-20 | 정종필 | Apparatus for inducing alpha -wave by electrical stimulation |
US20040049240A1 (en) | 2002-09-06 | 2004-03-11 | Martin Gerber | Electrical and/or magnetic stimulation therapy for the treatment of prostatitis and prostatodynia |
US20040049121A1 (en) | 2002-09-06 | 2004-03-11 | Uri Yaron | Positioning system for neurological procedures in the brain |
US7209790B2 (en) | 2002-09-30 | 2007-04-24 | Medtronic, Inc. | Multi-mode programmer for medical device communication |
EP1558131A4 (en) | 2002-10-15 | 2008-05-28 | Medtronic Inc | Timed delay for redelivery of treatment therapy for a medical device system |
WO2004036376A2 (en) | 2002-10-15 | 2004-04-29 | Medtronic Inc. | Multi-modal operation of a medical device system |
WO2004034997A2 (en) | 2002-10-15 | 2004-04-29 | Medtronic Inc. | Medical device system with relaying module for treatment of nervous system disorders |
EP1565102A4 (en) | 2002-10-15 | 2008-05-28 | Medtronic Inc | Synchronization and calibration of clocks for a medical device and calibrated clock |
AU2003301255A1 (en) | 2002-10-15 | 2004-05-04 | Medtronic Inc. | Screening techniques for management of a nervous system disorder |
WO2004037204A2 (en) | 2002-10-25 | 2004-05-06 | University Of South Florida | Methods and compounds for disruption of cd40r/cd40l signaling in the treatment of alzheimer's disease |
US20030229380A1 (en) | 2002-10-31 | 2003-12-11 | Adams John M. | Heart failure therapy device and method |
US7305265B2 (en) | 2002-11-25 | 2007-12-04 | Terumo Kabushiki Kaisha | Heart treatment equipment for treating heart failure |
EP1426078A1 (en) | 2002-12-04 | 2004-06-09 | Terumo Kabushiki Kaisha | Heart treatment equipment for preventing fatal arrhythmia |
US7273872B2 (en) | 2002-12-06 | 2007-09-25 | The Feinstein Institute For Medical Research | Inhibition of inflammation using α 7 receptor-binding cholinergic agonists |
US7238715B2 (en) | 2002-12-06 | 2007-07-03 | The Feinstein Institute For Medical Research | Treatment of pancreatitis using alpha 7 receptor-binding cholinergic agonists |
US20040111139A1 (en) | 2002-12-10 | 2004-06-10 | Mccreery Douglas B. | Apparatus and methods for differential stimulation of nerve fibers |
TR200202651A2 (en) | 2002-12-12 | 2004-07-21 | Met�N�Tulgar | the vücutádışındanádirekátedaviásinyaliátransferliáábeyinápil |
JP2004201901A (en) | 2002-12-25 | 2004-07-22 | Yoshimi Kurokawa | Stomach electrostimulator |
WO2004064918A1 (en) | 2003-01-14 | 2004-08-05 | Department Of Veterans Affairs, Office Of General Counsel | Cervical wagal stimulation induced weight loss |
EP1596805A2 (en) | 2003-01-15 | 2005-11-23 | Alfred E. Mann Institute for Biomedical Engineering at the University of Southern California | Treatments for snoring using injectable neuromuscular stimulators |
US20050143781A1 (en) | 2003-01-31 | 2005-06-30 | Rafael Carbunaru | Methods and systems for patient adjustment of parameters for an implanted stimulator |
US7167750B2 (en) | 2003-02-03 | 2007-01-23 | Enteromedics, Inc. | Obesity treatment with electrically induced vagal down regulation |
US20040172084A1 (en) | 2003-02-03 | 2004-09-02 | Knudson Mark B. | Method and apparatus for treatment of gastro-esophageal reflux disease (GERD) |
JP2006519229A (en) | 2003-02-13 | 2006-08-24 | アルバート・アインシュタイン・カレッジ・オヴ・メディシン・オヴ・イェシヴァ・ユニヴァーシティ | Regulation of food intake and glucose production by modulation of long-chain fatty acyl-CoA levels in the hypothalamus |
US7269455B2 (en) | 2003-02-26 | 2007-09-11 | Pineda Jaime A | Method and system for predicting and preventing seizures |
US20060015151A1 (en) | 2003-03-14 | 2006-01-19 | Aldrich William N | Method of using endoscopic truncal vagoscopy with gastric bypass, gastric banding and other procedures |
US7430449B2 (en) | 2003-03-14 | 2008-09-30 | Endovx, Inc. | Methods and apparatus for testing disruption of a vagal nerve |
US6814418B2 (en) | 2003-03-14 | 2004-11-09 | D'orso Ronald | Locker organizer |
US7783358B2 (en) | 2003-03-14 | 2010-08-24 | Endovx, Inc. | Methods and apparatus for treatment of obesity with an ultrasound device movable in two or three axes |
JP4252830B2 (en) | 2003-03-24 | 2009-04-08 | テルモ株式会社 | Heart treatment equipment |
US7155279B2 (en) | 2003-03-28 | 2006-12-26 | Advanced Bionics Corporation | Treatment of movement disorders with drug therapy |
US7228167B2 (en) | 2003-04-10 | 2007-06-05 | Mayo Foundation For Medical Education | Method and apparatus for detecting vagus nerve stimulation |
US7065412B2 (en) | 2003-04-25 | 2006-06-20 | Medtronic, Inc. | Implantable trial neurostimulation device |
US7187979B2 (en) | 2003-04-25 | 2007-03-06 | Medtronic, Inc. | Medical device synchronization |
US7706871B2 (en) | 2003-05-06 | 2010-04-27 | Nellcor Puritan Bennett Llc | System and method of prediction of response to neurological treatment using the electroencephalogram |
WO2004100765A2 (en) | 2003-05-06 | 2004-11-25 | Aspect Medical Systems, Inc. | System and method of assessment of the efficacy of treatment of neurological disorders using the electroencephalogram |
DE10320863B3 (en) | 2003-05-09 | 2004-11-11 | Siemens Audiologische Technik Gmbh | Attaching a hearing aid or earmold in the ear |
US20050187590A1 (en) | 2003-05-11 | 2005-08-25 | Boveja Birinder R. | Method and system for providing therapy for autism by providing electrical pulses to the vagus nerve(s) |
US7444184B2 (en) | 2003-05-11 | 2008-10-28 | Neuro And Cardial Technologies, Llc | Method and system for providing therapy for bulimia/eating disorders by providing electrical pulses to vagus nerve(s) |
US20060074450A1 (en) | 2003-05-11 | 2006-04-06 | Boveja Birinder R | System for providing electrical pulses to nerve and/or muscle using an implanted stimulator |
US20050197678A1 (en) | 2003-05-11 | 2005-09-08 | Boveja Birinder R. | Method and system for providing therapy for Alzheimer's disease and dementia by providing electrical pulses to vagus nerve(s) |
US20060173508A1 (en) | 2003-05-16 | 2006-08-03 | Stone Robert T | Method and system for treatment of eating disorders by means of neuro-electrical coded signals |
US20060287679A1 (en) | 2003-05-16 | 2006-12-21 | Stone Robert T | Method and system to control respiration by means of confounding neuro-electrical signals |
US20060111755A1 (en) | 2003-05-16 | 2006-05-25 | Stone Robert T | Method and system to control respiration by means of neuro-electrical coded signals |
US6937903B2 (en) | 2003-05-16 | 2005-08-30 | Science Medicus, Inc. | Respiratory control by means of neuro-electrical coded signals |
US20060064137A1 (en) | 2003-05-16 | 2006-03-23 | Stone Robert T | Method and system to control respiration by means of simulated action potential signals |
US7620454B2 (en) | 2003-05-19 | 2009-11-17 | Medtronic, Inc. | Gastro-electric stimulation for reducing the acidity of gastric secretions or reducing the amounts thereof |
US7742818B2 (en) | 2003-05-19 | 2010-06-22 | Medtronic, Inc. | Gastro-electric stimulation for increasing the acidity of gastric secretions or increasing the amounts thereof |
US20100010603A1 (en) | 2008-07-09 | 2010-01-14 | Tamir Ben-David | Electrode cuffs |
JP4213522B2 (en) | 2003-05-30 | 2009-01-21 | テルモ株式会社 | Heart treatment equipment |
US7738952B2 (en) | 2003-06-09 | 2010-06-15 | Palo Alto Investors | Treatment of conditions through modulation of the autonomic nervous system |
US7149574B2 (en) | 2003-06-09 | 2006-12-12 | Palo Alto Investors | Treatment of conditions through electrical modulation of the autonomic nervous system |
DE10328816A1 (en) | 2003-06-21 | 2005-01-05 | Biotronik Meß- und Therapiegeräte GmbH & Co. Ingenieurbüro Berlin | Implantable stimulation electrode with a coating to increase tissue compatibility |
WO2005002672A2 (en) | 2003-07-01 | 2005-01-13 | President And Fellows Of Harvard College | Sirt1 modulators for manipulating cells/organism lifespan/stress response |
WO2005007223A2 (en) * | 2003-07-16 | 2005-01-27 | Sasha John | Programmable medical drug delivery systems and methods for delivery of multiple fluids and concentrations |
US10322284B2 (en) | 2003-07-18 | 2019-06-18 | The John Hopkins University | Method for treating nausea and vomiting by vagus nerve stimulation with selectable stimulation modes |
US7174218B1 (en) | 2003-08-12 | 2007-02-06 | Advanced Bionics Corporation | Lead extension system for use with a microstimulator |
JP4439215B2 (en) | 2003-08-26 | 2010-03-24 | テルモ株式会社 | Heart treatment equipment |
US7263405B2 (en) | 2003-08-27 | 2007-08-28 | Neuro And Cardiac Technologies Llc | System and method for providing electrical pulses to the vagus nerve(s) to provide therapy for obesity, eating disorders, neurological and neuropsychiatric disorders with a stimulator, comprising bi-directional communication and network capabilities |
US7797058B2 (en) | 2004-08-04 | 2010-09-14 | Ndi Medical, Llc | Devices, systems, and methods employing a molded nerve cuff electrode |
US20050070970A1 (en) | 2003-09-29 | 2005-03-31 | Knudson Mark B. | Movement disorder stimulation with neural block |
US20050070974A1 (en) | 2003-09-29 | 2005-03-31 | Knudson Mark B. | Obesity and eating disorder stimulation treatment with neural block |
US20050075702A1 (en) | 2003-10-01 | 2005-04-07 | Medtronic, Inc. | Device and method for inhibiting release of pro-inflammatory mediator |
US7418292B2 (en) | 2003-10-01 | 2008-08-26 | Medtronic, Inc. | Device and method for attenuating an immune response |
US20050153885A1 (en) | 2003-10-08 | 2005-07-14 | Yun Anthony J. | Treatment of conditions through modulation of the autonomic nervous system |
US7062320B2 (en) | 2003-10-14 | 2006-06-13 | Ehlinger Jr Philip Charles | Device for the treatment of hiccups |
EP1677667A2 (en) | 2003-10-24 | 2006-07-12 | Medtronic, Inc. | Techniques to treat neurological disorders by attenuating the production of pro-inflammatory mediators |
KR20050039445A (en) | 2003-10-25 | 2005-04-29 | 대한민국(경북대학교 총장) | Wireless power transmission equipment for totally middle ear implant |
DE20316509U1 (en) | 2003-10-27 | 2004-03-11 | Lukl, Alfred | Ear acupressure and massage unit covers whole ear and applies sprung pins from commercial massage unit |
US20050131467A1 (en) | 2003-11-02 | 2005-06-16 | Boveja Birinder R. | Method and apparatus for electrical stimulation therapy for at least one of atrial fibrillation, congestive heart failure, inappropriate sinus tachycardia, and refractory hypertension |
US7317941B2 (en) | 2003-11-13 | 2008-01-08 | Medtronic, Inc. | Time syncrhonization of data |
CA2536188A1 (en) | 2003-11-20 | 2005-06-09 | Angiotech International Ag | Electrical devices and anti-scarring agents |
US7450998B2 (en) | 2003-11-21 | 2008-11-11 | Alfred E. Mann Foundation For Scientific Research | Method of placing an implantable device proximate to neural/muscular tissue |
US20090312817A1 (en) | 2003-11-26 | 2009-12-17 | Wicab, Inc. | Systems and methods for altering brain and body functions and for treating conditions and diseases of the same |
US20050137645A1 (en) | 2003-12-05 | 2005-06-23 | Juha Voipio | Novel method for the adjustment of human and animal vagus nerve stimulation |
US7769461B2 (en) | 2003-12-19 | 2010-08-03 | Boston Scientific Neuromodulation Corporation | Skull-mounted electrical stimulation system and method for treating patients |
US7460906B2 (en) | 2003-12-24 | 2008-12-02 | Cardiac Pacemakers, Inc. | Baroreflex stimulation to treat acute myocardial infarction |
US20080015659A1 (en) | 2003-12-24 | 2008-01-17 | Yi Zhang | Neurostimulation systems and methods for cardiac conditions |
US7486991B2 (en) | 2003-12-24 | 2009-02-03 | Cardiac Pacemakers, Inc. | Baroreflex modulation to gradually decrease blood pressure |
US20050149129A1 (en) | 2003-12-24 | 2005-07-07 | Imad Libbus | Baropacing and cardiac pacing to control output |
US7422555B2 (en) | 2003-12-30 | 2008-09-09 | Jacob Zabara | Systems and methods for therapeutically treating neuro-psychiatric disorders and other illnesses |
US20050177290A1 (en) | 2004-02-11 | 2005-08-11 | Farmer Michael E. | System or method for classifying target information captured by a sensor |
US8147561B2 (en) | 2004-02-26 | 2012-04-03 | Endosphere, Inc. | Methods and devices to curb appetite and/or reduce food intake |
WO2005089646A1 (en) | 2004-03-16 | 2005-09-29 | Medtronic, Inc. | Sensitivity analysis for selecting therapy parameter sets |
US7255675B2 (en) | 2004-03-23 | 2007-08-14 | Michael Gertner | Devices and methods to treat a patient |
US7361813B2 (en) | 2004-03-25 | 2008-04-22 | Syngenta Participations Ag | Corn event MIR604 |
JP2007530586A (en) | 2004-03-25 | 2007-11-01 | ザ ファインスタイン インスティテュート フォー メディカル リサーチ | Nervous hemostasis |
US10912712B2 (en) | 2004-03-25 | 2021-02-09 | The Feinstein Institutes For Medical Research | Treatment of bleeding by non-invasive stimulation |
WO2006007048A2 (en) | 2004-05-04 | 2006-01-19 | The Cleveland Clinic Foundation | Methods of treating medical conditions by neuromodulation of the sympathetic nervous system |
US20060111644A1 (en) | 2004-05-27 | 2006-05-25 | Children's Medical Center Corporation | Patient-specific seizure onset detection system |
WO2006001982A2 (en) | 2004-06-04 | 2006-01-05 | Washington University | Methods and compositions for treating neuropathies |
DE112005001299B4 (en) | 2004-06-07 | 2016-09-29 | Ulvac, Inc. | Magnetron sputtering method and magnetron sputtering apparatus |
US7565197B2 (en) | 2004-06-18 | 2009-07-21 | Medtronic, Inc. | Conditional requirements for remote medical device programming |
US7664551B2 (en) | 2004-07-07 | 2010-02-16 | Medtronic Transneuronix, Inc. | Treatment of the autonomic nervous system |
US7711432B2 (en) | 2004-07-26 | 2010-05-04 | Advanced Neuromodulation Systems, Inc. | Stimulation system and method for treating a neurological disorder |
US20060025828A1 (en) | 2004-07-28 | 2006-02-02 | Armstrong Randolph K | Impedance measurement for an implantable device |
US7204815B2 (en) | 2004-08-11 | 2007-04-17 | Georgia K. Connor | Mastoid ear cuff and system |
US8452407B2 (en) | 2004-08-16 | 2013-05-28 | Boston Scientific Neuromodulation Corporation | Methods for treating gastrointestinal disorders |
US20050154425A1 (en) | 2004-08-19 | 2005-07-14 | Boveja Birinder R. | Method and system to provide therapy for neuropsychiatric disorders and cognitive impairments using gradient magnetic pulses to the brain and pulsed electrical stimulation to vagus nerve(s) |
US7373204B2 (en) | 2004-08-19 | 2008-05-13 | Lifestim, Inc. | Implantable device and method for treatment of hypertension |
US8082039B2 (en) | 2004-09-08 | 2011-12-20 | Spinal Modulation, Inc. | Stimulation systems |
WO2006045054A2 (en) | 2004-10-18 | 2006-04-27 | E-Soc | Device for neuromusclar, peripheral body stimulation and electrical stimulation (es) for wound healing using rf energy harvesting |
WO2006047264A1 (en) | 2004-10-21 | 2006-05-04 | Advanced Neuromodulation Systems, Inc. | Peripheral nerve stimulation to treat auditory dysfunction |
US7672733B2 (en) | 2004-10-29 | 2010-03-02 | Medtronic, Inc. | Methods and apparatus for sensing cardiac activity via neurological stimulation therapy system or medical electrical lead |
US7818342B2 (en) | 2004-11-12 | 2010-10-19 | Sap Ag | Tracking usage of data elements in electronic business communications |
US8332047B2 (en) | 2004-11-18 | 2012-12-11 | Cardiac Pacemakers, Inc. | System and method for closed-loop neural stimulation |
JP5060304B2 (en) | 2004-11-18 | 2012-10-31 | カーディアック ペースメイカーズ, インコーポレイテッド | System for closed-loop nerve stimulation |
US9089691B2 (en) | 2004-12-07 | 2015-07-28 | Cardiac Pacemakers, Inc. | Stimulator for auricular branch of vagus nerve |
US7366571B2 (en) | 2004-12-10 | 2008-04-29 | Cyberonics, Inc. | Neurostimulator with activation based on changes in body temperature |
US7123976B2 (en) | 2004-12-13 | 2006-10-17 | Taiwan Semiconductor Manufacturing Co., Ltd. | Capacity management system and method |
US20060161217A1 (en) | 2004-12-21 | 2006-07-20 | Jaax Kristen N | Methods and systems for treating obesity |
US11207518B2 (en) | 2004-12-27 | 2021-12-28 | The Feinstein Institutes For Medical Research | Treating inflammatory disorders by stimulation of the cholinergic anti-inflammatory pathway |
EP2298410B1 (en) | 2004-12-27 | 2013-10-09 | The Feinstein Institute for Medical Research | Treating inflammatory disorders by electrical vagus nerve stimulation |
JP2008527002A (en) | 2005-01-13 | 2008-07-24 | サートリス ファーマシューティカルズ, インコーポレイテッド | Novel composition for preventing and treating neurodegenerative disorders and blood coagulation disorders |
US8788044B2 (en) | 2005-01-21 | 2014-07-22 | Michael Sasha John | Systems and methods for tissue stimulation in medical treatment |
US8825166B2 (en) | 2005-01-21 | 2014-09-02 | John Sasha John | Multiple-symptom medical treatment with roving-based neurostimulation |
US8609082B2 (en) | 2005-01-25 | 2013-12-17 | Bio Control Medical Ltd. | Administering bone marrow progenitor cells or myoblasts followed by application of an electrical current for cardiac repair, increasing blood supply or enhancing angiogenesis |
DE102005003735B4 (en) | 2005-01-26 | 2008-04-03 | Cerbomed Gmbh | Device for transcutaneous stimulation of a nerve of the human body |
US8600521B2 (en) | 2005-01-27 | 2013-12-03 | Cyberonics, Inc. | Implantable medical device having multiple electrode/sensor capability and stimulation based on sensed intrinsic activity |
US7454245B2 (en) | 2005-01-28 | 2008-11-18 | Cyberonics, Inc. | Trained and adaptive response in a neurostimulator |
US20060173493A1 (en) | 2005-01-28 | 2006-08-03 | Cyberonics, Inc. | Multi-phasic signal for stimulation by an implantable device |
US7561918B2 (en) | 2005-01-28 | 2009-07-14 | Cyberonics, Inc. | Autocapture in a neurostimulator |
WO2006084193A2 (en) | 2005-02-02 | 2006-08-10 | Nuvasive, Inc. | System and methods for performing neurophysiologic assessments during spine surgery |
US20090048194A1 (en) | 2005-02-08 | 2009-02-19 | Janssen Pharmaceutica N.V. | Vagal Afferent Neurons as Targets for Treatment |
US8185199B2 (en) | 2005-02-10 | 2012-05-22 | Zoll Medical Corporation | Monitoring physiological signals during external electrical stimulation |
US7548780B2 (en) | 2005-02-22 | 2009-06-16 | Cardiac Pacemakers, Inc. | Cell therapy and neural stimulation for cardiac repair |
US20060200219A1 (en) | 2005-03-01 | 2006-09-07 | Ndi Medical, Llc | Systems and methods for differentiating and/or identifying tissue regions innervated by targeted nerves for diagnostic and/or therapeutic purposes |
US8700163B2 (en) | 2005-03-04 | 2014-04-15 | Cyberonics, Inc. | Cranial nerve stimulation for treatment of substance addiction |
US7613511B2 (en) | 2005-03-09 | 2009-11-03 | Cardiac Pacemakers, Inc. | Implantable vagal stimulator for treating cardiac ischemia |
US7702385B2 (en) | 2005-11-16 | 2010-04-20 | Boston Scientific Neuromodulation Corporation | Electrode contact configurations for an implantable stimulator |
KR100667337B1 (en) | 2005-03-15 | 2007-01-12 | 삼성전자주식회사 | On screen display apparatus and method for displaying menu |
US20060229681A1 (en) | 2005-04-11 | 2006-10-12 | Fischell Robert E | Implantable system for the treatment of atrial fibrillation |
US7499748B2 (en) | 2005-04-11 | 2009-03-03 | Cardiac Pacemakers, Inc. | Transvascular neural stimulation device |
US7881782B2 (en) | 2005-04-20 | 2011-02-01 | Cardiac Pacemakers, Inc. | Neural stimulation system to prevent simultaneous energy discharges |
US20060282121A1 (en) | 2005-04-25 | 2006-12-14 | Payne Bryan R | Vagus nerve stimulation for chronic intractable hiccups |
US7640057B2 (en) | 2005-04-25 | 2009-12-29 | Cardiac Pacemakers, Inc. | Methods of providing neural markers for sensed autonomic nervous system activity |
US7899540B2 (en) | 2005-04-29 | 2011-03-01 | Cyberonics, Inc. | Noninvasively adjustable gastric band |
US7835796B2 (en) | 2005-04-29 | 2010-11-16 | Cyberonics, Inc. | Weight loss method and device |
US7310557B2 (en) | 2005-04-29 | 2007-12-18 | Maschino Steven E | Identification of electrodes for nerve stimulation in the treatment of eating disorders |
EP1896127B1 (en) | 2005-05-04 | 2013-05-29 | St. Jude Medical AB | Synchronization of implantable medical devices |
US7765000B2 (en) | 2005-05-10 | 2010-07-27 | Cardiac Pacemakers, Inc. | Neural stimulation system with pulmonary artery lead |
US7734348B2 (en) | 2005-05-10 | 2010-06-08 | Cardiac Pacemakers, Inc. | System with left/right pulmonary artery electrodes |
US7617003B2 (en) | 2005-05-16 | 2009-11-10 | Cardiac Pacemakers, Inc. | System for selective activation of a nerve trunk using a transvascular reshaping lead |
US20060292099A1 (en) | 2005-05-25 | 2006-12-28 | Michael Milburn | Treatment of eye disorders with sirtuin modulators |
US8036750B2 (en) | 2005-06-13 | 2011-10-11 | Cardiac Pacemakers, Inc. | System for neural control of respiration |
US7584004B2 (en) | 2005-06-13 | 2009-09-01 | Cardiac Pacemakers, Inc. | Vascularly stabilized peripheral nerve cuff assembly |
DE102005028872B3 (en) | 2005-06-22 | 2006-08-03 | Siemens Ag | Production machine tool with linear drive unit on traverse, permits selective relative movements between supports, traverse and measurement component |
US20060293721A1 (en) | 2005-06-28 | 2006-12-28 | Cyberonics, Inc. | Vagus nerve stimulation for treatment of depression with therapeutically beneficial parameter settings |
US20070016262A1 (en) | 2005-07-13 | 2007-01-18 | Betastim, Ltd. | Gi and pancreatic device for treating obesity and diabetes |
US7711419B2 (en) | 2005-07-13 | 2010-05-04 | Cyberonics, Inc. | Neurostimulator with reduced size |
US8165693B2 (en) | 2005-07-21 | 2012-04-24 | Cyberonics, Inc. | Safe-mode implantable medical devices |
US20070021786A1 (en) | 2005-07-25 | 2007-01-25 | Cyberonics, Inc. | Selective nerve stimulation for the treatment of angina pectoris |
US20070027497A1 (en) | 2005-07-27 | 2007-02-01 | Cyberonics, Inc. | Nerve stimulation for treatment of syncope |
US20070027504A1 (en) | 2005-07-27 | 2007-02-01 | Cyberonics, Inc. | Cranial nerve stimulation to treat a hearing disorder |
US7840280B2 (en) | 2005-07-27 | 2010-11-23 | Cyberonics, Inc. | Cranial nerve stimulation to treat a vocal cord disorder |
US7706874B2 (en) | 2005-07-28 | 2010-04-27 | Cyberonics, Inc. | Stimulating cranial nerve to treat disorders associated with the thyroid gland |
US7856273B2 (en) | 2005-07-28 | 2010-12-21 | Cyberonics, Inc. | Autonomic nerve stimulation to treat a gastrointestinal disorder |
US8660647B2 (en) | 2005-07-28 | 2014-02-25 | Cyberonics, Inc. | Stimulating cranial nerve to treat pulmonary disorder |
US20070027484A1 (en) | 2005-07-28 | 2007-02-01 | Cyberonics, Inc. | Autonomic nerve stimulation to treat a pancreatic disorder |
US20070027486A1 (en) | 2005-07-29 | 2007-02-01 | Cyberonics, Inc. | Medical devices for enhancing intrinsic neural activity |
US20070027499A1 (en) | 2005-07-29 | 2007-02-01 | Cyberonics, Inc. | Neurostimulation device for treating mood disorders |
US7499752B2 (en) | 2005-07-29 | 2009-03-03 | Cyberonics, Inc. | Selective nerve stimulation for the treatment of eating disorders |
US7532935B2 (en) | 2005-07-29 | 2009-05-12 | Cyberonics, Inc. | Selective neurostimulation for treating mood disorders |
CA2617557A1 (en) | 2005-08-04 | 2007-02-15 | Sirtris Pharmaceuticals, Inc. | Benzimidazole derivatives as sirtuin modulators |
US7822486B2 (en) | 2005-08-17 | 2010-10-26 | Enteromedics Inc. | Custom sized neural electrodes |
US7672727B2 (en) | 2005-08-17 | 2010-03-02 | Enteromedics Inc. | Neural electrode treatment |
US20070198063A1 (en) | 2005-10-03 | 2007-08-23 | Hunter William L | Electrical devices and anti-scarring drug combinations |
US7860566B2 (en) | 2005-10-06 | 2010-12-28 | The Cleveland Clinic Foundation | System and method for achieving regular slow ventricular rhythm in response to atrial fibrillation |
EP2471448A1 (en) | 2005-10-14 | 2012-07-04 | Nanostim, Inc. | Leadless cardiac pacemaker and system |
US7856264B2 (en) | 2005-10-19 | 2010-12-21 | Advanced Neuromodulation Systems, Inc. | Systems and methods for patient interactive neural stimulation and/or chemical substance delivery |
US7616990B2 (en) | 2005-10-24 | 2009-11-10 | Cardiac Pacemakers, Inc. | Implantable and rechargeable neural stimulator |
US7620455B2 (en) | 2005-10-25 | 2009-11-17 | Cyberonics, Inc. | Cranial nerve stimulation to treat eating disorders |
US20070100263A1 (en) | 2005-10-27 | 2007-05-03 | Merfeld Daniel M | Mechanical actuator for a vestibular stimulator |
US7555344B2 (en) | 2005-10-28 | 2009-06-30 | Cyberonics, Inc. | Selective neurostimulation for treating epilepsy |
US7957796B2 (en) | 2005-10-28 | 2011-06-07 | Cyberonics, Inc. | Using physiological sensor data with an implantable medical device |
US20070100377A1 (en) | 2005-10-28 | 2007-05-03 | Cyberonics, Inc. | Providing multiple signal modes for a medical device |
US10537728B2 (en) | 2005-11-10 | 2020-01-21 | ElectroCore, LLC | Vagal nerve stimulation to avert or treat stroke or transient ischemic attack |
US8812112B2 (en) | 2005-11-10 | 2014-08-19 | ElectroCore, LLC | Electrical treatment of bronchial constriction |
US8983628B2 (en) | 2009-03-20 | 2015-03-17 | ElectroCore, LLC | Non-invasive vagal nerve stimulation to treat disorders |
EP1948301B8 (en) | 2005-11-10 | 2014-03-12 | ElectroCore LLC | Electrical stimulation treatment of bronchial constriction |
US7630760B2 (en) | 2005-11-21 | 2009-12-08 | Cardiac Pacemakers, Inc. | Neural stimulation therapy system for atherosclerotic plaques |
US7650192B2 (en) | 2005-12-02 | 2010-01-19 | Medtronic, Inc. | Passive charge of implantable medical device utilizing external power source and method |
US7596414B2 (en) | 2005-12-05 | 2009-09-29 | Boston Scientific Neuromodulation Corporation | Cuff electrode arrangement for nerve stimulation and methods of treating disorders |
US7570999B2 (en) | 2005-12-20 | 2009-08-04 | Cardiac Pacemakers, Inc. | Implantable device for treating epilepsy and cardiac rhythm disorders |
US20070150027A1 (en) | 2005-12-22 | 2007-06-28 | Rogers Lesco L | Non-invasive device and method for electrical stimulation of neural tissue |
US7672728B2 (en) | 2005-12-28 | 2010-03-02 | Cardiac Pacemakers, Inc. | Neural stimulator to treat sleep disordered breathing |
US9566447B2 (en) | 2005-12-28 | 2017-02-14 | Cardiac Pacemakers, Inc. | Neural stimulation system for reducing atrial proarrhythmia |
US7610100B2 (en) | 2005-12-30 | 2009-10-27 | Boston Scientific Neuromodulation Corporation | Methods and systems for treating osteoarthritis |
WO2007087875A1 (en) | 2006-01-13 | 2007-08-09 | Universität Duisburg-Essen | Stimulation system, in particular a cardiac pacemaker |
US20080051852A1 (en) | 2006-01-21 | 2008-02-28 | Cerbomed Gmbh | Device and method for the transdermal stimulation of a nerve of the human body |
US7467016B2 (en) | 2006-01-27 | 2008-12-16 | Cyberonics, Inc. | Multipolar stimulation electrode with mating structures for gripping targeted tissue |
US20090105782A1 (en) | 2006-03-15 | 2009-04-23 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Vagus nerve stimulation apparatus, and associated methods |
ES2573323T3 (en) | 2006-03-29 | 2016-06-07 | Dignity Health | Electrical stimulation of cranial nerve microburst for the treatment of medical conditions |
US7974706B2 (en) | 2006-03-30 | 2011-07-05 | Boston Scientific Neuromodulation Corporation | Electrode contact configurations for cuff leads |
US20070255333A1 (en) | 2006-04-28 | 2007-11-01 | Medtronic, Inc. | Neuromodulation therapy for perineal or dorsal branch of pudendal nerve |
US20070255320A1 (en) | 2006-04-28 | 2007-11-01 | Cyberonics, Inc. | Method and apparatus for forming insulated implantable electrodes |
US7962220B2 (en) | 2006-04-28 | 2011-06-14 | Cyberonics, Inc. | Compensation reduction in tissue stimulation therapy |
US7774056B2 (en) | 2006-04-28 | 2010-08-10 | Medtronic, Inc. | Device site stimulation for notification |
US7869885B2 (en) | 2006-04-28 | 2011-01-11 | Cyberonics, Inc | Threshold optimization for tissue stimulation therapy |
WO2007133718A2 (en) | 2006-05-11 | 2007-11-22 | Neurometrix, Inc | Non-invasive acquisition of large nerve action potentials (naps) with closely spaced surface electrodes and reduced stimulus artifacts |
WO2007140597A1 (en) | 2006-06-02 | 2007-12-13 | Victhom Human Bionics Inc. | Nerve cuff, method and apparatus for manufacturing same |
US9913976B2 (en) | 2006-06-19 | 2018-03-13 | Highland Instruments, Inc. | Systems and methods for stimulating and monitoring biological tissue |
DE102006036069B4 (en) | 2006-07-18 | 2008-09-04 | Cerbomed Gmbh | Audiological transmission system |
DE102006033623B4 (en) | 2006-07-18 | 2010-04-08 | Cerbomed Gmbh | System for transcutaneous stimulation of a nerve of the human body |
US7996088B2 (en) | 2006-07-26 | 2011-08-09 | Cyberonics, Inc. | Vagus nerve stimulation by electrical signals for controlling cerebellar tremor |
US20100241207A1 (en) | 2006-08-14 | 2010-09-23 | Henry Bluger | Implantable Medical Cuff with Electrode Array |
US8868211B2 (en) | 2006-08-15 | 2014-10-21 | Case Western Reserve University | Nerve cuff for implantable electrode |
US8457734B2 (en) | 2006-08-29 | 2013-06-04 | Cardiac Pacemakers, Inc. | System and method for neural stimulation |
US7738961B2 (en) | 2006-10-09 | 2010-06-15 | Endostim, Inc. | Method and apparatus for treatment of the gastrointestinal tract |
US7797041B2 (en) | 2006-10-11 | 2010-09-14 | Cardiac Pacemakers, Inc. | Transcutaneous neurostimulator for modulating cardiovascular function |
US7809442B2 (en) | 2006-10-13 | 2010-10-05 | Apnex Medical, Inc. | Obstructive sleep apnea treatment devices, systems and methods |
US7729760B2 (en) | 2006-10-27 | 2010-06-01 | Cyberonics, Inc. | Patient management system for providing parameter data for an implantable medical device |
US7981150B2 (en) | 2006-11-09 | 2011-07-19 | Boston Scientific Scimed, Inc. | Endoprosthesis with coatings |
WO2008070996A1 (en) | 2006-12-13 | 2008-06-19 | Angiotech Pharmaceuticals Inc. | Medical implants with a combination of compounds |
US7996092B2 (en) | 2007-01-16 | 2011-08-09 | Ndi Medical, Inc. | Devices, systems, and methods employing a molded nerve cuff electrode |
US7706875B2 (en) | 2007-01-25 | 2010-04-27 | Cyberonics, Inc. | Modulation of drug effects by vagus nerve stimulation |
US7974707B2 (en) | 2007-01-26 | 2011-07-05 | Cyberonics, Inc. | Electrode assembly with fibers for a medical device |
US20080183246A1 (en) | 2007-01-26 | 2008-07-31 | Cyberonics, Inc. | Method, apparatus and system for guiding a procedure relating to an implantable medical device |
WO2008100974A2 (en) | 2007-02-13 | 2008-08-21 | Sharma Virender K | Method and apparatus for electrical stimulation of the pancreatico-biliary system |
US8233982B2 (en) | 2007-02-21 | 2012-07-31 | Cardiac Pacemakers, Inc. | Systems and methods for treating supraventricular arrhythmias |
US8068918B2 (en) | 2007-03-09 | 2011-11-29 | Enteromedics Inc. | Remote monitoring and control of implantable devices |
EP2129352B1 (en) | 2007-03-13 | 2016-03-09 | The Feinstein Institute for Medical Research | Treatment of inflammation by non-invasive stimulation |
US7819883B2 (en) | 2007-03-13 | 2010-10-26 | Cardiac Pacemakers, Inc. | Method and apparatus for endoscopic access to the vagus nerve |
CA2680823A1 (en) | 2007-03-19 | 2008-09-25 | Sirtris Pharmaceuticals, Inc. | Biomarkers of sirtuin activity and methods of use thereof |
US7974701B2 (en) | 2007-04-27 | 2011-07-05 | Cyberonics, Inc. | Dosing limitation for an implantable medical device |
US20080281372A1 (en) | 2007-05-09 | 2008-11-13 | Cardiac Pacemakers, Inc. | Neural stimulation system analyzer |
US20080281365A1 (en) | 2007-05-09 | 2008-11-13 | Tweden Katherine S | Neural signal duty cycle |
TW200918542A (en) | 2007-06-20 | 2009-05-01 | Sirtris Pharmaceuticals Inc | Sirtuin modulating compounds |
US9795836B2 (en) | 2007-07-03 | 2017-10-24 | Acushnet Company | Golf balls comprising medium hardness gradient core |
US20090012590A1 (en) | 2007-07-03 | 2009-01-08 | Cyberonics, Inc. | Neural Conductor |
US8391970B2 (en) | 2007-08-27 | 2013-03-05 | The Feinstein Institute For Medical Research | Devices and methods for inhibiting granulocyte activation by neural stimulation |
WO2009027755A1 (en) | 2007-08-28 | 2009-03-05 | Institut National De La Recherche Agronomique (Inra) | Device and method for reducing weight |
US20090082832A1 (en) | 2007-09-25 | 2009-03-26 | Boston Scientific Neuromodulation Corporation | Thermal Management of Implantable Medical Devices |
US8019419B1 (en) | 2007-09-25 | 2011-09-13 | Dorin Panescu | Methods and apparatus for leadless, battery-less, wireless stimulation of tissue |
US8942798B2 (en) | 2007-10-26 | 2015-01-27 | Cyberonics, Inc. | Alternative operation mode for an implantable medical device based upon lead condition |
US8244367B2 (en) | 2007-10-26 | 2012-08-14 | Medtronic, Inc. | Closed loop long range recharging |
US9089707B2 (en) | 2008-07-02 | 2015-07-28 | The Board Of Regents, The University Of Texas System | Systems, methods and devices for paired plasticity |
US20150233904A1 (en) | 2009-11-27 | 2015-08-20 | Msdx, Inc. | Detection of neurological diseases via measurement of neuromelanin in recirculating phagocytes |
US8180446B2 (en) | 2007-12-05 | 2012-05-15 | The Invention Science Fund I, Llc | Method and system for cyclical neural modulation based on activity state |
US8195287B2 (en) | 2007-12-05 | 2012-06-05 | The Invention Science Fund I, Llc | Method for electrical modulation of neural conduction |
US8165668B2 (en) | 2007-12-05 | 2012-04-24 | The Invention Science Fund I, Llc | Method for magnetic modulation of neural conduction |
US8180447B2 (en) * | 2007-12-05 | 2012-05-15 | The Invention Science Fund I, Llc | Method for reversible chemical modulation of neural activity |
CN201230913Y (en) | 2007-12-06 | 2009-05-06 | 崔树森 | Human nerve conduit with amplified self-functionality |
WO2009097542A2 (en) | 2008-01-30 | 2009-08-06 | Board Of Regents Of The University Of Texas System | Ileal electrical stimulation |
CA2715543C (en) | 2008-02-15 | 2017-02-14 | Angeltear Solutions Inc. | Adjustable tissue or nerve cuff and method of use |
US9014801B2 (en) | 2008-03-19 | 2015-04-21 | The Board Of Trustees Of The University Of Illinois | Electromagnetic field therapy delays cellular senescence and death by enhancement of the heat shock response |
US9662490B2 (en) | 2008-03-31 | 2017-05-30 | The Feinstein Institute For Medical Research | Methods and systems for reducing inflammation by neuromodulation and administration of an anti-inflammatory drug |
WO2009146030A1 (en) | 2008-03-31 | 2009-12-03 | The Feinstein Institute For Medical Research | Methods and systems for reducing inflammation by neuromodulation of t-cell activity |
JP5486588B2 (en) | 2008-04-04 | 2014-05-07 | エンテロメディクス インコーポレイテッド | Methods and systems for sugar regulation |
US20090275997A1 (en) | 2008-05-01 | 2009-11-05 | Michael Allen Faltys | Vagus nerve stimulation electrodes and methods of use |
WO2010005482A1 (en) | 2008-07-08 | 2010-01-14 | Cardiac Pacemakers, Inc. | Systems for delivering vagal nerve stimulation |
US8583252B2 (en) | 2008-07-11 | 2013-11-12 | Medtronic, Inc. | Patient interaction with posture-responsive therapy |
WO2010009032A1 (en) | 2008-07-14 | 2010-01-21 | Medtronic, Inc. | Method for clock management for an implantable medical device |
US20100016746A1 (en) | 2008-07-15 | 2010-01-21 | Hampton David R | Personal alerting device for use with diagnostic device |
EP2355893B1 (en) | 2008-11-18 | 2013-12-25 | Setpoint Medical Corporation | Devices for optimizing electrode placement for anti-inflamatory stimulation |
EP2376189B1 (en) | 2008-12-09 | 2018-02-07 | Nephera Ltd. | Stimulation of the urinary system |
US20100191304A1 (en) | 2009-01-23 | 2010-07-29 | Scott Timothy L | Implantable Medical Device for Providing Chronic Condition Therapy and Acute Condition Therapy Using Vagus Nerve Stimulation |
US10232178B2 (en) | 2009-03-20 | 2019-03-19 | Electrocore, Inc. | Non-invasive magnetic or electrical nerve stimulation to treat or prevent dementia |
US10252074B2 (en) | 2009-03-20 | 2019-04-09 | ElectroCore, LLC | Nerve stimulation methods for averting imminent onset or episode of a disease |
US10286212B2 (en) | 2009-03-20 | 2019-05-14 | Electrocore, Inc. | Nerve stimulation methods for averting imminent onset or episode of a disease |
US8918178B2 (en) | 2009-03-20 | 2014-12-23 | ElectroCore, LLC | Non-invasive vagal nerve stimulation to treat disorders |
US9254383B2 (en) | 2009-03-20 | 2016-02-09 | ElectroCore, LLC | Devices and methods for monitoring non-invasive vagus nerve stimulation |
US9403001B2 (en) | 2009-03-20 | 2016-08-02 | ElectroCore, LLC | Non-invasive magnetic or electrical nerve stimulation to treat gastroparesis, functional dyspepsia, and other functional gastrointestinal disorders |
US8843210B2 (en) | 2009-03-20 | 2014-09-23 | ElectroCore, LLC | Non-invasive vagal nerve stimulation to treat disorders |
US10220207B2 (en) | 2009-03-20 | 2019-03-05 | Electrocore, Inc. | Nerve stimulation methods for averting imminent onset or episode of a disease |
US8983629B2 (en) | 2009-03-20 | 2015-03-17 | ElectroCore, LLC | Non-invasive vagal nerve stimulation to treat disorders |
CN102460153A (en) | 2009-04-06 | 2012-05-16 | 里奇诊断学股份有限公司 | Biomarkers for monitoring treatment of neuropsychiatric diseases |
US9211410B2 (en) | 2009-05-01 | 2015-12-15 | Setpoint Medical Corporation | Extremely low duty-cycle activation of the cholinergic anti-inflammatory pathway to treat chronic inflammation |
US8996116B2 (en) | 2009-10-30 | 2015-03-31 | Setpoint Medical Corporation | Modulation of the cholinergic anti-inflammatory pathway to treat pain or addiction |
US20110054569A1 (en) | 2009-09-01 | 2011-03-03 | Zitnik Ralph J | Prescription pad for treatment of inflammatory disorders |
AU2010258792B2 (en) | 2009-06-09 | 2015-07-02 | Setpoint Medical Corporation | Nerve cuff with pocket for leadless stimulator |
US11051744B2 (en) | 2009-11-17 | 2021-07-06 | Setpoint Medical Corporation | Closed-loop vagus nerve stimulation |
US9833621B2 (en) | 2011-09-23 | 2017-12-05 | Setpoint Medical Corporation | Modulation of sirtuins by vagus nerve stimulation |
US20160331952A1 (en) | 2009-11-17 | 2016-11-17 | Michael A. Faltys | External programmer |
US20110144717A1 (en) | 2009-12-10 | 2011-06-16 | Paunceforte Technologies, LLC | Implantable neurostimulation system and methods of using the system for appetite control and pain control |
AU2010336337B2 (en) | 2009-12-23 | 2016-02-04 | Setpoint Medical Corporation | Neural stimulation devices and systems for treatment of chronic inflammation |
DE212011100038U1 (en) | 2010-03-05 | 2012-07-17 | Endostim, Inc. | Device and implantation system for electrical stimulation of biological systems |
WO2011127314A2 (en) * | 2010-04-07 | 2011-10-13 | Chart Sequal Technologies Inc. | Portable oxygen delivery device |
US9358381B2 (en) | 2011-03-10 | 2016-06-07 | ElectroCore, LLC | Non-invasive vagal nerve stimulation to treat disorders |
US20120053657A1 (en) | 2010-08-31 | 2012-03-01 | John Parker | Implant recharging |
US8725259B2 (en) | 2011-01-19 | 2014-05-13 | Medtronic, Inc. | Vagal stimulation |
US9399134B2 (en) | 2011-03-10 | 2016-07-26 | ElectroCore, LLC | Non-invasive vagal nerve stimulation to treat disorders |
WO2012154865A2 (en) | 2011-05-09 | 2012-11-15 | Setpoint Medical Corporation | Single-pulse activation of the cholinergic anti-inflammatory pathway to treat chronic inflammation |
US20220072309A9 (en) | 2011-05-09 | 2022-03-10 | Setpoint Medical Corporation | Vagus nerve stimulation to treat neurodegenerative disorders |
EP2543411A1 (en) | 2011-07-06 | 2013-01-09 | BIOTRONIK SE & Co. KG | Medical implant and method for secure implant communication |
US8577458B1 (en) | 2011-12-07 | 2013-11-05 | Cyberonics, Inc. | Implantable device for providing electrical stimulation of cervical vagus nerves for treatment of chronic cardiac dysfunction with leadless heart rate monitoring |
US8630709B2 (en) | 2011-12-07 | 2014-01-14 | Cyberonics, Inc. | Computer-implemented system and method for selecting therapy profiles of electrical stimulation of cervical vagus nerves for treatment of chronic cardiac dysfunction |
US8918190B2 (en) | 2011-12-07 | 2014-12-23 | Cyberonics, Inc. | Implantable device for evaluating autonomic cardiovascular drive in a patient suffering from chronic cardiac dysfunction |
US8918191B2 (en) | 2011-12-07 | 2014-12-23 | Cyberonics, Inc. | Implantable device for providing electrical stimulation of cervical vagus nerves for treatment of chronic cardiac dysfunction with bounded titration |
US8600505B2 (en) | 2011-12-07 | 2013-12-03 | Cyberonics, Inc. | Implantable device for facilitating control of electrical stimulation of cervical vagus nerves for treatment of chronic cardiac dysfunction |
US8700150B2 (en) | 2012-01-17 | 2014-04-15 | Cyberonics, Inc. | Implantable neurostimulator for providing electrical stimulation of cervical vagus nerves for treatment of chronic cardiac dysfunction with bounded titration |
US8571654B2 (en) | 2012-01-17 | 2013-10-29 | Cyberonics, Inc. | Vagus nerve neurostimulator with multiple patient-selectable modes for treating chronic cardiac dysfunction |
US20150018728A1 (en) | 2012-01-26 | 2015-01-15 | Bluewind Medical Ltd. | Wireless neurostimulators |
WO2013119732A1 (en) | 2012-02-07 | 2013-08-15 | Cardiac Pacemakers, Inc. | Neural modulation therapy control using cervical impedance |
US8965521B2 (en) | 2012-03-19 | 2015-02-24 | Cardiac Pacemakers, Inc. | Systems and methods for monitoring neurostimulation dosing |
US9572983B2 (en) | 2012-03-26 | 2017-02-21 | Setpoint Medical Corporation | Devices and methods for modulation of bone erosion |
US8688212B2 (en) | 2012-07-20 | 2014-04-01 | Cyberonics, Inc. | Implantable neurostimulator-implemented method for managing bradycardia through vagus nerve stimulation |
US8923964B2 (en) | 2012-11-09 | 2014-12-30 | Cyberonics, Inc. | Implantable neurostimulator-implemented method for enhancing heart failure patient awakening through vagus nerve stimulation |
US9452290B2 (en) | 2012-11-09 | 2016-09-27 | Cyberonics, Inc. | Implantable neurostimulator-implemented method for managing tachyarrhythmia through vagus nerve stimulation |
US10293160B2 (en) | 2013-01-15 | 2019-05-21 | Electrocore, Inc. | Mobile phone for treating a patient with dementia |
US10220211B2 (en) | 2013-01-22 | 2019-03-05 | Livanova Usa, Inc. | Methods and systems to diagnose depression |
US9101770B2 (en) | 2013-03-07 | 2015-08-11 | Cardiac Pacemakers, Inc. | Hypertension therapy device with longevity management |
US9610444B2 (en) | 2013-03-15 | 2017-04-04 | Pacesetter, Inc. | Erythropoeitin production by electrical stimulation |
US9999773B2 (en) | 2013-10-30 | 2018-06-19 | Cyberonics, Inc. | Implantable neurostimulator-implemented method utilizing multi-modal stimulation parameters |
US9511228B2 (en) | 2014-01-14 | 2016-12-06 | Cyberonics, Inc. | Implantable neurostimulator-implemented method for managing hypertension through renal denervation and vagus nerve stimulation |
WO2015127476A1 (en) | 2014-02-24 | 2015-08-27 | Setpoint Medial Corporation | Vagus nerve stimulation screening test |
US9272143B2 (en) | 2014-05-07 | 2016-03-01 | Cyberonics, Inc. | Responsive neurostimulation for the treatment of chronic cardiac dysfunction |
US9415224B2 (en) | 2014-04-25 | 2016-08-16 | Cyberonics, Inc. | Neurostimulation and recording of physiological response for the treatment of chronic cardiac dysfunction |
US9409024B2 (en) | 2014-03-25 | 2016-08-09 | Cyberonics, Inc. | Neurostimulation in a neural fulcrum zone for the treatment of chronic cardiac dysfunction |
US9533153B2 (en) | 2014-08-12 | 2017-01-03 | Cyberonics, Inc. | Neurostimulation titration process |
US11311725B2 (en) | 2014-10-24 | 2022-04-26 | Setpoint Medical Corporation | Systems and methods for stimulating and/or monitoring loci in the brain to treat inflammation and to enhance vagus nerve stimulation |
US9504832B2 (en) | 2014-11-12 | 2016-11-29 | Cyberonics, Inc. | Neurostimulation titration process via adaptive parametric modification |
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2017
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2020
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US11890471B2 (en) | 2017-08-14 | 2024-02-06 | Setpoint Medical Corporation | Vagus nerve stimulation pre-screening test |
US11857788B2 (en) | 2018-09-25 | 2024-01-02 | The Feinstein Institutes For Medical Research | Methods and apparatuses for reducing bleeding via coordinated trigeminal and vagal nerve stimulation |
US11938324B2 (en) | 2020-05-21 | 2024-03-26 | The Feinstein Institutes For Medical Research | Systems and methods for vagus nerve stimulation |
US11969253B2 (en) | 2021-06-02 | 2024-04-30 | Setpoint Medical Corporation | Closed-loop vagus nerve stimulation |
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US20200238078A1 (en) | 2020-07-30 |
US11278718B2 (en) | 2022-03-22 |
US20170197076A1 (en) | 2017-07-13 |
US10596367B2 (en) | 2020-03-24 |
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