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Número de publicaciónUS20040015205 A1
Tipo de publicaciónSolicitud
Número de solicitudUS 10/178,011
Fecha de publicación22 Ene 2004
Fecha de presentación20 Jun 2002
Fecha de prioridad20 Jun 2002
También publicado comoUS9409028, US20120316622
Número de publicación10178011, 178011, US 2004/0015205 A1, US 2004/015205 A1, US 20040015205 A1, US 20040015205A1, US 2004015205 A1, US 2004015205A1, US-A1-20040015205, US-A1-2004015205, US2004/0015205A1, US2004/015205A1, US20040015205 A1, US20040015205A1, US2004015205 A1, US2004015205A1
InventoresTodd Whitehurst, Rafael Carbunaru, Kerry Bradley, James McGivern, Matthew Haller, Tom He, Janusz Kuzma
Cesionario originalWhitehurst Todd K., Rafael Carbunaru, Kerry Bradley, Mcgivern James P., Haller Matthew I., He Tom Xiaohai, Kuzma Janusz A.
Exportar citaBiBTeX, EndNote, RefMan
Enlaces externos: USPTO, Cesión de USPTO, Espacenet
Implantable microstimulators with programmable multielectrode configuration and uses thereof
US 20040015205 A1
Resumen
Miniature implantable stimulators (i.e., microstimulators) with programmably configurable electrodes allow, among other things, steering of the electric fields created. In addition, the microstimulators are capable of producing unidirectionally propagating action potentials (UPAPs).
Imágenes(14)
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Reclamaciones(38)
What is claimed is:
1. A microstimulator capable of being electrically positioned, comprising:
at least two programmably configurable electrodes for applying steerable electric fields;
electrical circuitry electrically connected to the at least two electrodes, wherein the electrical circuitry generates stimulation pulses applied by the electrodes, which stimulation pulses are variable to create steerable electric fields;
programmable memory connected to the electrical circuitry, which programmable memory stores stimulation parameters determining the activated electrodes and the stimulation pulses generated by the electrical circuitry and applied by the activated electrodes; and
a power source connected to the electrical circuitry, which power source provides operating power to the microstimulator.
2. The microstimulator of claim 1 further comprising a multiplicity of programmably configurable electrodes for applying steerable electric fields.
3. The microstimulator of claim 2 wherein the electrodes are positioned along and around the microstimulator.
4. The microstimulator of claim 3 wherein the electric fields are steerable radially around the microstimulator and longitudinally along the microstimulator.
5. The microstimulator of claim 1 wherein the electrodes are programmably configurable prior to implantation and after implantation.
6. The microstimulator of claim 1 further comprising at least one hard-wired electrode.
7. The microstimulator of claim 1 further comprising a lead, wherein at least one of the electrodes is positioned on the lead.
8. The microstimulator of claim 7 wherein the lead is no longer than about 150 mm in length.
9. The microstimulator of claim 1 wherein each activated electrode is configured as one of an anode, cathode, and an open circuit.
10. The microstimulator of claim 9 further comprising at least one configurable group of electrodes comprising at least two activated electrodes.
11. The microstimulator of claim 9 wherein the stimulation parameters include controlling the amount of current flowing from at least one of the electrodes that is activated.
12. The microstimulator of claim 1 further comprising an external programmer that adjusts the stimulation parameters.
13. The microstimulator of claim 1 wherein the stimulation parameters are fixed.
14. The microstimulator of claim 1 further comprising at least one sensor that senses a physical condition of a patient.
15. The microstimulator of claim 14 wherein the sensed physical condition is used to adjust the stimulation parameters.
16. The microstimulator of claim 15 wherein the stimulation parameters are automatically adjusted.
17. The microstimulator of claim 1 wherein the stimulation parameters include controlling the amount of current flowing from at least one of the electrodes that is activated.
18. The microstimulator of claim 1 wherein the electrodes are programmed to unidirectionally propagate action potentials.
19. The microstimulator of claim 18 further comprising at least one lead and wherein at least one electrode is positioned on the at least one lead.
20. The microstimulator of claim 18 further comprising at least one cuff electrode wherein at least one electrode is positioned on the at least one cuff and the at least one cuff is attached to the microstimulator via a lead.
21. The microstimulator of claim 18 further comprising at least one cuff electrode wherein the at least one cuff electrode is incorporated into the microstimulator.
22. The microstimulator of claim 18 wherein the microstimulator is programmed to create a stimulation pulse with a plateau pulsewidth of about 10 μsec to about 5 msec and a decaying trailing phase with a fall time of about 50 μsec to about 5 msec and a charge recovery pulse with a plateau pulsewidth of about 50 μsec to about 10 msec and a decaying trailing phase with a fall time of about 50 μsec to about 5 msec.
23. A microstimulator, comprising:
at least two programmably configurable electrodes for applying steerable electric fields;
means for generating stimulation pulses applied by the electrodes, which stimulation pulses are variable to create steerable electric fields, and which generating means are connected to the at least two electrodes;
means for storing stimulation parameters, which stimulation parameters determine the activated electrodes and the stimulation pulses applied by the activated electrodes, which storing means are connected to the means for generating stimulation pulses; and
means for providing operating power to the microstimulator, which power means are connected to the means for generating stimulation pulses.
24. The microstimulator of claim 23 wherein each activated electrode is configurable as one of an anode, cathode, and an open circuit.
25. The microstimulator of claim 24 further comprising at least one configurable group of electrodes comprising at least two activated electrodes.
26. The microstimulator of claim 24 wherein the stimulation parameters control the amount of current flowing from at least one of the activated electrodes.
27. The microstimulator of claim 23 further comprising means for adjusting the stimulation parameters.
28. The microstimulator of claim 23 further comprising means for sensing a physical condition of a patient.
29. The microstimulator of claim 28 wherein the sensed physical condition is used to adjust the stimulation parameters.
30. The microstimulator of claim 23 further including means for providing unidirectional propagation of action potentials.
31. A method of electrically positioning a microstimulator, wherein the microstimulator comprises:
at least two programmably configurable electrodes for applying steerable electric fields,
electrical circuitry electrically connected to the electrodes, which electrical circuitry generates stimulation pulses applied by the electrodes,
programmable memory electrically connected to the electrical circuitry, which programmable memory stores stimulation parameters, and
a power source connected to the electrical circuitry, which power source provides operating power to the microstimulator;
said method comprising:
determining the electrodes to activate and the stimulation pulses to apply with the activated electrodes using the stimulation parameters stored in the programmable memory; and
generating the stimulation pulses using the electrical circuitry and based on the stimulation parameters, which stimulation pulses are variable to create steerable electric fields that electrically position the microstimulator.
32. The method of claim 31 further comprising adjusting the stimulation parameters to configure each activated electrode as one of an anode, cathode, and an open circuit.
33. The method of claim 32 further comprising adjusting the stimulation parameters to configure at least two activated electrodes into at least one configurable group of electrodes.
34. The method of claim 31 further comprising adjusting the stimulation parameters to steer the electric fields at least one of radially around the microstimulator and longitudinally along the microstimulator.
35. The method of claim 31 further comprising adjusting the stimulation parameters to control the amount of current flowing from at least one of the electrodes that is activated.
36. The method of claim 31 wherein the microstimulator further comprises at least one sensor for sensing at least one physical condition of a patient and the method further comprises sensing at least one physical condition of the patient.
37. The method of claim 36 further comprising using the sensed physical condition to adjust the stimulation parameters.
38. The method of claim 31 further comprising configuring the electrodes to provide unidirectional propagation of action potentials.
Descripción
    FIELD OF THE INVENTION
  • [0001]
    The present invention generally relates to implantable medical systems and methods, and more particularly relates to implantable microstimulator systems with programmable multielectrode configuration and uses therefor.
  • BACKGROUND OF THE INVENTION
  • [0002]
    Implantable electrical stimulation devices have proven therapeutic in a wide variety of diseases and disorders. Pacemakers and implantable cardiac defibrillators (ICDs) have proven highly effective in the treatment of a number of cardiac conditions (e.g., arrhythmias). Spinal cord stimulation (SCS) systems have long been accepted as a therapeutic modality for the treatment of chronic pain syndromes. Deep brain stimulation has also been applied therapeutically for well over a decade for the treatment of refractory chronic pain syndromes, and it has also recently been applied in additional areas such as movement disorders. In recent investigations, peripheral nerve stimulation (PNS) systems have demonstrated efficacy in the treatment of chronic pain syndromes, and a number of additional applications are currently under investigation. Finally, functional electrical stimulation (FES) systems such as the Freehand™ system by NeuroControl™ Corporation of Cleveland, Ohio have been applied to restore some functionality to paralyzed extremities in spinal cord injury patients.
  • [0003]
    Current implantable electrical stimulation systems typically consist of a system with electrodes on a lead, separate from but connected to an implantable pulse generator (IPG) that contains the power source and the stimulation circuitry. A number of these systems have multiple programmable electrodes, allowing each electrode to be configured as an anode, a cathode, or as an open circuit (i.e., electrically disconnected). However, these types of leaded systems have several disadvantages. The implantation procedure may be rather difficult and time-consuming, as the electrodes and the IPG must usually be implanted in separate areas and the lead must be tunneled through body tissue to connect to the IPG. Also, the leads are typically thin and rather long and are thus prone to mechanical damage over time. Additionally, many conventional systems typically consist of a relatively large IPG, which can have a negative cosmetic appearance if positioned subcutaneously.
  • [0004]
    Neurons typically propagate signals in one direction. Peripheral nerve fibers that propagate signals away from the central nervous system (CNS, i.e., the brain and the spinal cord) and towards the periphery and viscera are referred to as efferent nerve fibers. Peripheral nerve fibers that propagate signals away from the periphery and viscera and towards the CNS are referred to as afferent nerve fibers.
  • [0005]
    Efferent impulses may initiate a variety of actions, from movement of a muscle to initiation of changes in the heart rate or force of contraction or in the level of constriction of the vascular smooth muscle in arterioles. Through increasing or decreasing the activity of efferent fibers, the CNS can, for example, alter the blood pressure by changing the characteristics of the cardiovascular system.
  • [0006]
    Afferent impulses from specialized nerve endings or receptors inform the controlling neurons in the CNS about characteristics of the system, e.g., if a limb is feeling pain or if blood pressure is high or low. Most peripheral nerves contain both afferent and efferent nerve fibers.
  • [0007]
    A typical individual neuron consists of a soma (i.e., cell body), which contains the nucleus of the cell; dendrites, which receive input from pre-synaptic neurons; and an axon, which send signals via axon terminals (i.e., the distal portion of the axon) to post-synaptic neurons (or to effector cells, e.g., muscle fibers). An action potential is initiated at the initial segment of the axon (i.e., the proximal portion of the axon) when triggered by input from the dendrites. An action potential is an electrochemical signal that propagates from the initial segment down the axon to the axon terminals. Such propagation is referred to as orthodromic. (Orthodromic is defined as “of, relating to, or inducing nerve impulses along an axon in the normal direction.”) Action potential propagation in the opposite direction is referred to as antidromic. (Antidromic is defined as “proceeding or conducting in a direction opposite to the usual one—used especially of a nerve impulse or fiber.”)
  • [0008]
    In a neuron at rest, i.e., that is not propagating an action potential, the inside of the axon is negatively charged relative to the outside of the neuron, i.e., the membrane of the axon is at a negative resting potential.
  • [0009]
    When the soma receives sufficient stimulation at its associated dendrites, it initiates an action potential at the initial segment, which travels orthodromically down the axon. An action potential is initiated and propagated by opening channels in the axon membrane to allow positive charge (e.g., sodium ions) to enter the axon. This causes the voltage of the inside of the axon to become positive, i.e., it depolarizes a segment of the axon. Depolarization of one part of the axon causes depolarization of an adjacent patch of axon; this mechanism allows a wave of depolarization to sweep down the axon. After a brief period of depolarization (e.g., approximately 1 msec), the axon membrane automatically repolarizes to return to a resting state.
  • [0010]
    Electrical stimulation causes depolarization of the local axon membrane and may be used to initiate action potentials. For instance, electrical activation of an axon performed near the middle of an axon (i.e., not at the initial segment) produces two action potentials. One action potential propagates orthodromically, while the other propagates antidromically.
  • SUMMARY OF THE INVENTION
  • [0011]
    The invention disclosed and claimed herein addresses problems noted above and others by providing miniature implantable stimulators (i.e., microstimulators) with programmably configurable electrodes. In addition, to further address the above and other problems, the invention disclosed and claimed herein provides miniature implantable stimulators capable of unidirectional propagation of action potentials (UPAPs). Further, the instant disclosure teaches and claims methods of using UPAPs in certain locations and for certain disorders.
  • [0012]
    A microstimulator may be implanted via a small incision and/or via endoscopic means. A more complicated surgical procedure may be required for sufficient access to the nerve or portion of the nerve (e.g., nerve fibers surrounded by scar tissue) or for purposes of fixing the neurostimulator in place. A single microstimulator may be implanted, or two or more microstimulators may be implanted to achieve greater stimulation of the neural fibers.
  • [0013]
    The microstimulators used with the present invention possesses one or more of the following properties, among others:
  • [0014]
    at least two electrodes (e.g., one active electrode and one reference electrode) for applying stimulating current to surrounding tissue;
  • [0015]
    electrical and/or mechanical components encapsulated in a hermetic package made from biocompatible material(s);
  • [0016]
    an electrical coil or other means of receiving energy and/or information inside the package, which receives power and/or data by inductive or radio-frequency (RF) coupling to a transmitting coil placed outside the body;
  • [0017]
    means for receiving and/or transmitting signals via telemetry;
  • [0018]
    means for receiving and/or storing electrical power within the microstimulator; and
  • [0019]
    a form factor making the microstimulator implantable via a minimal surgical procedure.
  • [0020]
    In some configurations, the microstimulator has at least three electrodes. In certain configurations, the microstimulator is leadless, while in others it may include electrodes on a relatively short lead. Additional microstimulator configurations are discussed in the detailed description of the invention.
  • [0021]
    Each electrode or section of a partitioned electrode may be configured via programming of stimulation parameters (i.e., programmably configured) as a cathode, an anode, or an open circuit with different current outputs. This allows the microstimulator to be “electrically positioned” once it has been implanted or otherwise fixed in place. This also allows the stimulation electrodes to be redefined via reprogramming of the stimulation parameters should the microstimulator migrate slightly. In turn, this allows stimulation to be directed to the appropriate site without needing to physically manipulate the microstimulator. Additionally, the use of the proper set(s) of electrodes allows more localized and selective stimulation of the target structures and reduces the magnitude of the injected electric current required to achieve neural stimulation, which results in less power consumed by the microstimulator.
  • [0022]
    A microstimulator may operate independently, or in a coordinated manner with other implanted devices, or with external devices. For instance, a microstimulator may incorporate means for sensing a patient's condition, which it may then use to control stimulation parameters in a closed loop manner. The sensing and stimulating means may be incorporated into a single microstimulator, or a sensing means may communicate sensed information to at least one microstimulator with stimulating means.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • [0023]
    The above and other aspects of the present invention will be more apparent from the following more particular description thereof, presented in conjunction with the following drawings wherein:
  • [0024]
    [0024]FIG. 1A is a section view through an exemplary, two-electrode microstimulator that may be used with certain embodiments of the present invention;
  • [0025]
    [0025]FIG. 1B is an isometric view of an exemplary, two-electrode microstimulator that may be used with certain embodiments of the present invention;
  • [0026]
    [0026]FIG. 1C is an isometric view of an exemplary, two or more electrode microstimulator that may be used with certain embodiments of the present invention;
  • [0027]
    [0027]FIG. 2A is an isometric view of an exemplary microstimulator of the present invention, including a plurality of electrodes;
  • [0028]
    [0028]FIG. 2B is an isometric view of an exemplary microstimulator of the present invention, including one or more cuff electrodes;
  • [0029]
    [0029]FIG. 2C is a section view taken through 2C-2C of FIG. 2B;
  • [0030]
    [0030]FIG. 2D is a section view taken through 2D-2D of FIG. 2B;
  • [0031]
    [0031]FIG. 2E is an isometric view of an exemplary microstimulator of the present invention, including a plurality of partitioned electrodes;
  • [0032]
    [0032]FIGS. 3A and 3B show isometric views of microstimulators with fixation devices;
  • [0033]
    [0033]FIG. 3C depicts a microstimulator with a fixation device that includes helices that wrap around a nerve or other body tissue;
  • [0034]
    [0034]FIG. 4 illustrates possible external components of the invention;
  • [0035]
    [0035]FIG. 5 depicts a system of implantable devices that communicate with each other and/or with external control/programming devices;
  • [0036]
    [0036]FIG. 6A illustrates various autonomic nerves in the head, neck, and thorax;
  • [0037]
    [0037]FIG. 6B is a cross-section through the neck, at the level of cervical vertebra C7;
  • [0038]
    [0038]FIG. 6C illustrates various autonomic nerves in the abdomen;
  • [0039]
    [0039]FIG. 7A depicts the nerves of the male pelvic viscera and surrounding anatomy, where a stimulation system of the present invention may be implanted; and
  • [0040]
    [0040]FIG. 7B is a section view through the body of a penis.
  • [0041]
    Corresponding reference characters indicate corresponding components throughout the several views of the drawings.
  • DETAILED DESCRIPTION OF THE INVENTION
  • [0042]
    The following description is of the best mode presently contemplated for carrying out the invention. This description is not to be taken in a limiting sense, but is made merely for the purpose of describing the general principles of the invention. The scope of the invention should be determined with reference to the claims.
  • [0043]
    Unidirectionally Propagating Action Potentials (UPAPS)
  • [0044]
    As mentioned earlier, electrical activation of an axon usually produces action potentials that propagate in both the orthodromic and antidromic directions. Generation of a unidirectionally propagating action potential (UPAP) requires three essential components:
  • [0045]
    (1) Anodic Block in One Direction: Depolarization of an axon membrane leads to two action potentials traveling in opposite directions. In order to generate a UPAP, the propagation of one of the action potentials is blocked (i.e., arrested or inhibited), while the other is allowed to propagate. To block or arrest an action potential, a section of an axon membrane along the path of the undesired action potential is kept hyperpolarized during the time (or part of the time) the action potential would have traveled through that segment. To hyperpolarize the membrane, an electrode with anodic current is used. Therefore, to create a UPAP, the membrane must be depolarized at one electrode and hyperpolarized at another electrode. For instance, a cathodic current depolarizes the local axon membrane and initiates action potentials in opposing directions. A high anodic current may be used to hyperpolarize a section of axon membrane, thereby arresting action potential propagation in that direction.
  • [0046]
    Due to properties of the neurons, significantly less current is required to depolarize an axon enough to initiate an action potential than the current that is required to hyperpolarize an axon enough to arrest an action potential. Thus, the current that must be applied at the anode to arrest an action potential is typically higher in amplitude and of longer duration than that required for neurostimulation. Since the current flows between the cathode and the anode, this results in a relatively large cathodic current as well. This additional current requirement is not damaging to the cell or difficult to achieve. However, the generation of such high currents requires more energy from the neurostimulator and also requires electrodes with a relatively large surface area, so as to maintain safe levels of charge density and current density.
  • [0047]
    (2) Rebound Depolarization Control: Experimentally, if the very high anodic current used for hyperpolarization of the axon is discontinued abruptly, then the portion of the axon that was hyperpolarized suddenly depolarizes due to the non-linear properties of the axon membrane. In other words, if the hyperpolarizing anodic pulse is suddenly discontinued, the axon membrane can undergo a rebound depolarization (also known as anodic break) which may result in the generation of action potentials. Thus, to avoid rebound depolarization, the anodic current may be discontinued gradually, i.e., tapered off.
  • [0048]
    (3) Virtual Cathode Elimination: A nerve cuff is typically used for generation of UPAPs, as explained further presently. When a nerve cuff is used, it is desired that the current that flows between the anode and the cathode stay within the nerve cuff. However, some of the current inevitably flows from the anode, out of the nerve cuff, around the outside of the nerve cuff, and back in the other end, to the cathode. Since the hyperpolarizing current must be relatively large in magnitude, this “leakage” current is relatively high in magnitude as well. As this leakage current leaves the cuff at the end proximal to the anode, it effectively behaves as a “virtual cathode.” (Under normal bidirectional stimulation conditions, the virtual cathode current is relatively low in amplitude, so it may not create sufficient depolarization to fire an action potential. Even if it does, with bidirectional stimulation the effect is likely to be indistinguishable from stimulation at the actual cathode.) In this case, the virtual cathode current is relatively high in amplitude, and thus can initiate an action potential. This is unwelcome, since the purpose of the nearby anode is to hyperpolarize the nerve and prevent action potential propagation in the direction of the anode. Different techniques have been used to eliminate the virtual cathode effect, including the introduction of an additional anode at the other end of the nerve cuff, as described in more detail presently.
  • [0049]
    Anodic Block in One Direction
  • [0050]
    Generating a UPAP requires that an unwanted propagating action potential be arrested (in one direction). A nerve containing nerve fibers of differing diameters and with differing conduction velocities may respond well to stimulation when the site of action potential initiation and site of arrest are closely spaced to minimize stimulus pulsewidth (and consequent charge injection). Such an arrangement may take the form of a conventional bipolar electrode configuration in a nerve cuff with the anode located at one end of the nerve cuff and the cathode located closer to the other end of the cuff.
  • [0051]
    Since the hyperpolarizing anodic current pulse is applied when the action potential is expected to reach the anode (or before), it is helpful if the spacing between the electrodes is known. Assuming a known velocity of action potential propagation in given nerve fibers, the time at which an action potential arrives at the anode may thus be predicted. Precise timing of the anodic pulse is also aided by known spacing between the electrodes and the nerve. Minimizing the spacing between the electrodes and the nerve reduces the current required for stimulation. In addition, fully enclosed cuffs concentrate the current near the nerve, reducing the amplitude of the required (cathodic and anodic) currents. In order to ensure that spacing is both controlled and minimized, a nerve cuff is typically used for UPAP; however, any arrangement in which the electrodes are closely apposed to the nerve, which also allows stimulation with less current, may be used for UPAP.
  • [0052]
    Virtual Cathode Elimination
  • [0053]
    UPAPs have been demonstrated in several experimental systems. In 1979, van den Honert and Mortimer demonstrated that single, unidirectionally propagated action potentials could be elicited in peripheral nerves by electrical stimuli of short duration. (See Van den Honert C; Mortimer J T “Generation of unidirectionally propagated action potentials in a peripheral nerve by brief stimuli” Science Dec. 14, 1979; 206(4424):1311-2.) They reduced the depolarizing effects of the virtual cathode using a tripolar electrode configuration; the center electrode was the cathode, and the two outside electrodes were anodes. The second anode created an additional electric field that opposed the flow of current from the first anode to the cathode through the path outside the cuff. Arresting (i.e., blocking or inhibiting) propagation of action potentials from both anodes was avoided by injecting a smaller current through the “escape” end anode than through the “arrest” end anode. This method required coordinated control of two stimulators. The stimulation pulse for UPAP was quasitrapezoidal in shape with a plateau pulsewidth of 350 μsec and an exponential trailing phase having a fall time of 350 μsec. The plateau amplitude necessary for UPAPs was 5-6 mA.
  • [0054]
    Other Methods of Generation of UPAP
  • [0055]
    In 1986, Ungar, et al. described a system for generation of UPAPs via a “collision block” in a cat myelinated peripheral nerve. (See Ungar I J; Mortimer J T; Sweeney J D “Generation of unidirectionally propagating action potentials using a monopolar electrode cuff.” Annals of Biomedical Engineering 1986; 14(5):437-50.) This system used a monopolar electrode cuff with the conductor positioned closest to the “arrest” end of the cuff. A single cathode located at least 5 mm from the arrest end resulted in unidirectional propagation with minimal current and charge injection. The range of stimulus current values that produced unidirectional propagation increased with increases in longitudinal asymmetry of cathode placement over the range of asymmetries tested. The stimulus current pulse that minimized charge injection was quasitrapezoidal in shape with a plateau pulsewidth of approximately 350 μsec and an exponential trailing phase having a fall time of approximately 600 μsec. These stimulation parameters were found to be independent of cuff geometry. Arrest efficiency was not degraded using a cuff of sufficient internal diameter to prevent nerve compression in chronic implantation. The critical current density within the extracellular space of the electrode cuff required to produce conduction failure at the arrest end was estimated to be 0.47±0.08 mA/mm2. The necessary total cuff length for effective unidirectional stimulation was from 32-48 mm.
  • [0056]
    Also in 1986, Sweeney, at al. described a system for generation of UPAPs using an asymmetric two-electrode cuff (ATEC). (See Sweeney J D; Mortimer J T “An asymmetric two electrode cuff for generation of unidirectionally propagated action potentials” IEEE Transactions on Biomedical Engineering 1986 June; 33(6):541-9.) This configuration differs from a standard bipolar cuff electrode in that the anode is enclosed by an insulating sheath of larger diameter than the cathode and the electrodes are asymmetrically placed within the cuff. The diameter of the cathode portion of the cuff was 16 mm and the diameter of the anode portion was as large as 26 mm. These electrodes were used to perform acute experiments in 13 adult cats. The stimulation pulse for UPAP was quasitrapezoidal in shape with a plateau pulsewidth of 200-500 μsec and an exponential trailing phase having a fall time of 400-1200 μsec. The plateau amplitude averaged 0.5 mA, and it varied from 0.1-2.3 mA. From the related dimensions specified in the article, it seems likely that the necessary total cuff length for effective unidirectional stimulation was less than 3 cm.
  • [0057]
    In the above studies, only cuff electrodes were used. In addition, the pulse generators used in these studies were not implantable, and as such, leads were used to enter the body and travel to the stimulation site(s). Use of the implantable systems and methods disclosed herein results in improved generation and delivery of UPAPs, among other improvements that will be evident to those of skill in the art upon review of the present disclosure.
  • [0058]
    The body reacts properly to orthodromic stimulation. Antidromic stimulation has a less significant physiological effect. UPAPs allow a system to effectively select afferent or efferent stimulation. For instance, when stimulating a nerve, if an action potential is allowed to escape in the direction of signals traveling away from the viscera and periphery and towards the CNS, both afferent and efferent fibers will transport the action potentials, but only the afferent fibers (with signals traveling orthodromically) will have an important physiological effect. Antidromic pulses on the efferent fibers will have a less significant physiological effect. This is referred to herein as “effective selection of afferent fibers.” Correspondingly, “effective selection of efferent fibers” is performed via stimulation with UPAPs in the direction of signals traveling away from the CNS and toward the viscera and periphery, resulting in physiological effects via orthodromic pulses on the efferent fibers, while the antidromic pulses on the afferent fibers have a less significant physiological effect. Several applications of neuromodulation would benefit from neurostimulation applied to effectively select just the afferent or just the efferent nerves. Systems and methods described herein provide this ability.
  • [0059]
    For example, the vagus nerve provides the primary parasympathetic nerve to the thoracic organs (e.g., the lungs and heart) and most of the abdominal organs (e.g., the stomach and small intestine). It originates in the brainstem and runs in the neck through the carotid sheath with the jugular vein and the common carotid artery, and then adjacent to the esophagus to the thoracic and abdominal viscera. Through stimulation to effectively select afferent fibers (via UPAP stimulation traveling away from the viscera and the periphery and towards the CNS), unidirectional stimulation of the vagus nerve may be an effective treatment for a variety of disorders, including epilepsy and depression. Through stimulation to effectively select efferent fibers (via UPAP stimulation traveling away from the CNS and towards the viscera and the periphery), unidirectional stimulation of the vagus nerve may be an effective treatment for, e.g., tachycardia.
  • [0060]
    As yet another example, electrical stimulation of the cavernous nerve in the pelvis has been demonstrated to produce and sustain erection, and as such, is likely to prove an effective therapy for erectile dysfunction. The therapeutic effect is mediated by the efferent fibers, which stimulate structures in the corpora cavernosa and spongiosum of the penis. Stimulation of the afferent fibers of the cavernous nerve is likely to produce sensations that may be distracting, painful, or the like. Effectively selecting the efferent fibers of the cavernous nerve(s) as a therapy for erectile dysfunction could allow relatively higher levels of stimulation, which might provide more effective therapy for erectile dysfunction. This would also mitigate side effects such as pain at relatively high levels of stimulation.
  • [0061]
    The present invention provides, inter alia, microstimulator systems for stimulation of a nerve with unidirectionally propagating action potentials. In addition, the present invention provides programmably configurable multielectrode microstimulator systems. The present invention also provides improved treatments for various medical conditions, as mentioned above and described in more detail presently.
  • [0062]
    A microminiature implantable electrical stimulator, referred to herein as a microstimulator, and known as the BION® microstimulator, has been developed (by Advanced Bionics of Sylmar, Calif.) to overcome some of the disadvantages of traditional leaded systems. The standard BION is a leadless microstimulator, as the IPG and the electrodes have been combined into a single microminiature package. A standard configuration of the BION is a cylinder that is about 3 mm in diameter and between about 2 and 3 cm in length. This form factor allows the BION to be implanted with relative ease and rapidity, e.g., via endoscopic or laparoscopic techniques. With this configuration, the BION consists of only two electrodes: a reference, or indifferent, electrode at one end and an active electrode at the other end. In addition, with this configuration, electrical signals delivered to nerves travel away from the stimulation location along the nerve fibers in both directions.
  • [0063]
    The microstimulators of the present invention may be similar to or of the type referred to as BION devices. The following documents describe various features and details associated with the manufacture, operation, and use of BION implantable microstimulators, and are all incorporated herein by reference:
    Application/Patent/ Filing/Publication
    Publication No. Date Title
    U.S. Pat. No. Issued Implantable Microstimulator
    5,193,539 Mar. 16, 1993
    U.S. Pat. No. Issued Structure and Method of
    5,193,540 Mar. 16, 1993 Manufacture of an
    Implantable Microstimulator
    U.S. Pat. No. Issued Implantable Device Having
    5,312,439 May 17, 1994 an Electrolytic Storage
    Electrode
    U.S. Pat. No. Issued Implantable Microstimulator
    5,324,316 Jun. 28, 1994
    U.S. Pat. No. Issued Structure and Method of
    5,405,367 Apr. 11, 1995 Manufacture of an
    Implantable Microstimulator
    U.S. Pat. No. Issued Improved Implantable
    6,051,017 Apr. 18, 2000 Microstimulator and Systems
    Employing Same
    PCT Publication Published Battery-Powered Patient
    WO 98/37926 Sep. 3, 1998 Implantable Device
    PCT Publication Published System of Implantable
    WO 98/43700 Oct. 8, 1998 Devices For Monitoring and/
    or Affecting Body Parameters
    PCT Publication Published System of Implantable
    WO 98/43701 Oct. 8, 1998 Devices For Monitoring and/
    or Affecting Body Parameters
    Published Micromodular Implants to
    September, 1997 Provide Electrical Stimulation
    of Paralyzed Muscles and
    Limbs, by Cameron, et al.,
    published in IEEE
    Transactions on
    Biomedical Engineering,
    Vol. 44, No. 9,
    pages 781-790.
  • [0064]
    As shown, for instance, in FIGS. 1A, 1B, and 1C, microstimulator device 100 may include a narrow, elongated capsule 102 containing electrical circuitry 104 connected to electrodes 110, which may pass through or comprise a part of the walls of the capsule, as in FIG. 1A. Alternatively, electrodes 110 may be built into the capsule (FIG. 1B) or arranged along a lead(s) 112 (FIG. 1C), as described below. As detailed in the referenced patent publications, electrodes 110 generally comprise a stimulating electrode, or cathode (to be placed close to the target tissue) and an indifferent electrode, or anode (for completing the circuit). Other configurations of microstimulator device 100 are possible, as is evident from the above-referenced publications, and as described in more detail herein.
  • [0065]
    Microstimulator 100 may be implanted via a minimal surgical procedure. Microstimulator 100 may be implanted with a surgical insertion tool specifically designed for the purpose, or may be placed, for instance, via a small incision and through an insertion cannula. Alternatively, microstimulator 100 may be implanted via conventional surgical methods, or may be inserted using other endoscopic or laparoscopic techniques. A more complicated surgical procedure may be required for sufficient access to a nerve or a portion of a nerve (e.g., nerve fibers surrounded by scar tissue, or more distal portions of the nerve) and/or for fixing the neurostimulator in place.
  • [0066]
    The external surfaces of microstimulator 100 may advantageously be composed of biocompatible materials. Capsule 102 may be made of, for instance, glass, ceramic, or other material that provides a hermetic package that will exclude water vapor but permit passage of electromagnetic fields used to transmit data and/or power. Electrodes 110 may be made of a noble or refractory metal or compound, such as platinum, iridium, tantalum, titanium, titanium nitride, niobium, or alloys of any of these, in order to avoid corrosion, electrolysis, or other electrochemical reactions which could damage the surrounding tissues and the device.
  • [0067]
    Microstimulator 100 contains, when necessary and/or desired, electrical circuitry 104 for receiving data and/or power from outside the body by inductive, radio-frequency (RF), or other electromagnetic coupling. In some embodiments, electrical circuitry 104 includes an inductive coil for receiving and transmitting RF data and/or power, an integrated circuit (IC) chip(s) for decoding and storing stimulation parameters and generating stimulation pulses (either intermittent or continuous), and additional discrete electrical components required to complete the electrical circuit functions, e.g. capacitor(s), resistor(s), coil(s), diode(s), and the like.
  • [0068]
    Microstimulator 100 includes, when necessary and/or desired, a programmable memory 114 (which may be a part of the electrical circuitry 104) for storing a set(s) of data, stimulation, and/or control parameters. Among other things, memory 114 may allow stimulation and control parameters to be adjusted to settings that are safe and efficacious with minimal discomfort for each individual. In addition, this allows the parameters to be adjusted to ensure that the stimulation favors unidirectional propagation, when desired. The device(s) may be implanted to deliver electrical stimulation to any location that is likely to be therapeutic, and the stimulation parameters may be adjusted to any set of parameters that prove efficacious, as described herein. Specific stimulation sites and parameters may provide therapeutic advantages for various medical conditions, their forms, and/or severity. For instance, some patients may respond favorably to intermittent stimulation, while others may require continuous stimulation to alleviate their symptoms. Therefore, various embodiments of the invention include means for providing stimulation intermittently and/or continuously.
  • [0069]
    The present invention provides means of maintaining the advantages of earlier BION microstimulator systems while extending their functionality to enable, inter alia, programmably configurable multielectrode systems that allow current to be more effectively directed towards a target stimulation site. For instance, possible microstimulator configurations have one or more programmably configurable electrodes 110 arranged along the stimulator outer capsule, as shown in FIG. 2A. Thus, a microstimulator 100 may have a combination of programmably configurable and hard-wired electrodes, or may have only programmably configurable electrodes, or may have only a plurality of hard-wired electrodes.
  • [0070]
    The configuration of microstimulator 100 may be determined by the structure of the desired target, the surrounding area, and the method of implantation. The size and the shape of the microstimulator may be varied in order to deliver more effective treatment. A thin, elongated cylinder with electrodes at the ends and/or along the cylindrical case are possible configurations, but other shapes, such as disks, spheres, helical structures, and others are possible. Additional alterations in configuration, such as the number, orientation, and shape of electrodes (which may be programmably configurable), may be varied in order to deliver more effective treatment. For instance, the electrodes may be rectangular, semi-spherical, arcs, bands/rings, or any other useful shape, and may be distributed along and/or around the surface of the microstimulator.
  • [0071]
    Implantable microstimulator 100 is sufficiently small to permit its placement in or near the structures to be stimulated. For instance, capsule 102 may have a diameter of about 4-5 mm, or only about 3 mm, or even less than 3 mm. Capsule 102 length may be about 25-40 mm, or only about 20-25 mm, or even less than 20 mm. In some configurations and for some stimulation sites, it may be useful for microstimulator 100 to be larger, to be of a different shape, or to include a lead(s) 112, as described in more detail below.
  • [0072]
    In some embodiments of the instant invention, microstimulator 100 comprises two or more leadless electrodes. However, one or more electrodes 110 may alternatively be located along short, flexible leads 112 (FIG. 1C) as described in U.S. patent application Ser. No. 09/624,130, filed Jul. 24, 2000, which is incorporated herein by reference in its entirety. The use of such leads permits, among other things, electrical stimulation to be directed more locally to targeted tissue(s) a short distance from the surgical fixation of the bulk of the implantable microstimulator 100, while allowing most elements of the microstimulator to be located in a more surgically convenient site and/or in a position making telemetry with and/or powering and/or replacing or removing the device simpler. This minimizes the distance traversed and the surgical planes crossed by the device and any lead(s). Other uses of such configurations will be apparent presently. For instance, the electrodes may be positioned on a cuff(s) attached to the microstimulator via a lead(s), as described below. In most uses of this invention, the leads are no longer than about 150 mm.
  • [0073]
    A microstimulator including a cuff electrode, as shown in FIGS. 2B, 2C, and 2D, may be a tripolar cuff electrode 116, possibly with an asymmetric placement of the center electrode. The electrodes may substantially form a ring, or the electrodes may be partitioned. Other cuff electrode configurations, as known to those of skill in the art, may alternatively or additionally be used. Such a cuff electrode may be a bipolar cuff electrode 118 with the anode placed farther from the nerve than the cathode via the use of an insulating sheath of larger diameter for the anode than the cathode.
  • [0074]
    According to one embodiment of the invention, a microstimulator is attached to the cuff electrode via a lead 112. According to another embodiment of the invention, the cuff electrode is incorporated into the microstimulator package, e.g., a microstimulator with a cuff electrode attachment or other microstimulator fixation device 130, as in U.S. patent application Ser. No. 10/146,332 (the '332 application), which application is incorporated herein by reference in its entirety. As discussed in the '332 application, fixation device 130 may include one or more electrodes 110. Examples of microstimulator cuff electrode attachments/fixation devices 130 that may be used with the present invention are shown in, but not limited to, FIGS. 2B, 2C, 2D, 3A, 3B, and 3C.
  • [0075]
    In some applications, a microstimulator having a single cathode may be sufficient. For instance, in some applications, such as pudendal nerve stimulation for urge incontinence, the target may be rather large in at least one dimension, allowing for some positioning error. However, for some applications, a single cathode microstimulator may prove insufficient or imperfect. For instance, if a target site is very small in all dimensions, the microstimulator may be difficult to place precisely. For example, in deep brain stimulation for Parkinson's disease, the subthalamic nucleus has a maximum dimension of only 4-7 mm. Precisely placing the microstimulator at this target is likely to be difficult, and even slight migration of the microstimulator over time may reduce its efficacy. Other stimulation target sites may be physically constrained, so that the microstimulator cannot be or is difficult to position ideally in relation to the stimulation target. For example, the trigeminal ganglion, which receives sensation from all of the sensory nerves of the face, sits in a dural compartment known as the trigeminal (Meckel's) cave, which lies in a depression on the anterior slope of the petrous portion of the temporal bone. The trigeminal cave is a rather confined space that is surrounded by bone, and a solid device, even a microstimulator, may not be easy to manipulate and precisely position in such a space.
  • [0076]
    In addition, in configurations where the microstimulator electrodes are cylindrical (either on a lead or on the case of a cylindrical microstimulator), the stimulation current is generally directed 360 degrees radially outward. However, the target neurons may be located only to one side of the electrode(s). Such a situation can result in higher thresholds (due to wasted current directed away from the neural targets) as well as undesired stimulation of neurons that are not the desired targets of stimulation. Solutions to this problem may involve locating the electrodes to one side of the array. However, lead or microstimulator migration or rotation can make such designs ineffective or cumbersome to deploy and maintain.
  • [0077]
    The programmably configurable multielectrode microstimulators of the present invention, which can be “electrically positioned” as described herein, address these and other problems. In certain embodiments, such as shown in FIG. 2A, the microstimulator has a cylindrical shape, with electrodes 110 configured as a plurality of anodes, cathodes, and/or open circuit electrodes distributed along its surface. One or both ends may be capped with an electrode 110, and one or more electrodes may be arranged along the microstimulator outer case.
  • [0078]
    In various embodiments, the end cap electrode(s) and/or those along the length of the microstimulator and/or those on a lead attached to a microstimulator can be further divided as shown in FIG. 2E into “partitioned” electrodes. Thus, individual electrodes, rather than extending completely around the microstimulator, are partitioned into short arcs. In between each of the partitioned electrodes 110 is an insulating material 120 to provide some electrical isolation. In an extreme alternative, the microstimulator could be covered with small arcs of electrodes along its entire surface. The size of the electrodes 110 and the insulating areas 120 may be uniform or may be independent and varied.
  • [0079]
    Electrodes configured along and/or around the microstimulator can be individually programmed via stimulation parameters into various configurations to “steer” the electric field radially around the microstimulator (e.g., activating cathode(s) and anode(s) positioned substantially radially around the microstimulator) and/or longitudinally along the microstimulator (e.g., activating cathode(s) and anode(s) positioned substantially linearly along the microstimulator); such a microstimulator can be “electrically positioned.” A relatively large number of small independent electrodes allows the electric field to be programmed in many configurations, such as very wide fields (e.g., multiple grouped cathodes and anodes) or very narrow fields (e.g., single electrodes for one cathode and one anode, using adjacent electrodes). Such electrode array designs can mimic the electrode design of FIGS. 1A, 1B, and/or 2A, for instance, while still allowing the more focal stimulation from choosing individual electrodes.
  • [0080]
    Steering of the electric field (a.k.a., electrically positioning the stimulator) can be achieved by programming the stimulation parameters to activate different electrodes and program each activated electrode as a cathode, an anode, or an open circuit, as well as by controlling the current flowing from each electrode that is activated. Such steering capability allows the electric field to be located more precisely to target desired neurons, minimizing stimulation thresholds needed to capture the desired neural targets, thus minimizing power consumption of the stimulator. Also, if microstimulator 100 or lead 112 happens to rotate or migrate, some designs allow the electric field to be reprogrammed by adjusting the stimulation parameters, thus allowing the microstimulator to be electrically positioned without having to physically manipulate and reposition the microstimulator or electrodes.
  • [0081]
    All or some cathodes may be electrically connected, or some or all of the cathodes may be independently driven individually or in configurable groups, i.e., the stimulator may have multiple stimulation channels. Similarly, all or some anodes may be electrically connected, or some or all of the anodes may be independently driven individually or in configurable groups. In some embodiments, at least one electrode is a dedicated anode, and in various embodiments, at least one electrode is a dedicated cathode.
  • [0082]
    In certain embodiments, microstimulator 100 is capable of producing waveforms that can cause electrical stimulation and activation of neural fibers. Such a waveform includes a periodic asymmetric square wave pulse that consists of an initial cathodic pulse followed by a programmable delay with minimal or no current and ending with an anodic charge recovery pulse. Between stimulation pulses, the output of a given electrode consists of minimal and ideally no current. Other waveforms, including but not limited to trapezoidal and exponential, may be used. In some such nerve stimulation embodiments, the stimulator produces pulses in the range from about 10 μA to about 15 mA, with a compliance voltage from about 0.05 volts to about 20 volts, a pulsewidth range from about 10 μsec to about 4.0 msec, and a stimulation frequency range from about 1 pulse per second (pps) to about 10,000 pps.
  • [0083]
    Certain embodiments include means for producing a biphasic stimulation periodic pulse waveform with a programmable stimulation phase pulsewidth in the range of about 50 μsec to about 5 msec and a charge recovery phase having a programmable pulsewidth in the range of about 50 μsec to about 5 msec. The biphasic stimulation periodic pulse waveform may be symmetric or asymmetric. The shapes of these waveforms may be any of those known to those of skill in the art. For example, the stimulation pulse may be a square pulse, and the charge recovery pulse may be a square pulse, or it may be a trapezoidal or quasitrapezoidal pulse.
  • [0084]
    Some embodiments of the present invention, such as those producing UPAPs, include means for producing a stimulation pulse with, e.g., a quasitrapezoidal shape, with a programmable plateau pulsewidth in the range of about 10 μsec to about 5 msec, and a decaying trailing phase (e.g., an exponentially decaying trailing phase) having a programmable fall time in the range of about 50 μsec to about 5 msec. The stimulation pulse may be a square pulse, a trapezoidal or triangular pulse, or any other shape known to those of skill in the art. The charge recovery pulse may be a square pulse, a trapezoidal or quasitrapezoidal pulse, or any other shape known to those of skill in the art, with, e.g., a plateau pulse width of about 50 μsec to about 10 msec. As described earlier, this anodic charge recovery pulse may be tapered to avoid rebound depolarization and generation of additional action potentials. As such, the anodic pulse with, for instance, a trapezoidal or quasitrapezoidal pulse, may have a decaying trailing phase (e.g., an exponentially decaying trailing phase) with a programmable fall time in the range of about 50 μsec to about 5 msec.
  • [0085]
    In some embodiments, part or all of the charge recovery pulse may precede the stimulation pulse. In certain embodiments, the charge recovery pulse entirely precedes the stimulation pulse. In various embodiments, a charge recovery pulse precedes the stimulation pulse and an additional charge recovery pulse follows the stimulation pulse.
  • [0086]
    If a tripolar or other multipolar electrode configuration is used (e.g., a tripolar nerve cuff), then means for distributing the current asymmetrically between the electrodes may be included, i.e., the polarities and currents of the electrodes may be independently programmable. For example, in a nerve cuff with one cathode and two anodes, the anodic currents may be independently programmed to be of different amplitudes.
  • [0087]
    The BION microstimulators described in the earlier referenced patents and publications require some architectural modifications in order to provide UPAP. The microstimulators 100 of the present invention configured to provide UPAP include, in some embodiments, at least three electrodes 110, and more specifically, at least one cathode and at least two anodes (which may be configured as such by the programmable stimulation parameters). The electrodes may be distributed collinearly along the long axis of the microstimulator, with the at least one cathode in between the at least two anodes. In some embodiments, the electrodes surround the microstimulator radially. In alternative embodiments, the electrodes may be segmented such that an individual electrode extends part way around the microstimulator; this should provide more focal application of cathodic and/or anodic currents.
  • [0088]
    In various embodiments, one or more of the electrodes may be a “virtual” electrode, for instance, when a microstimulator with a fixation device such as a nerve cuff is used. A nerve cuff is typically used to maintain the electrodes in close proximity to a specific target tissue and to maintain a larger density of injected charge in the target area within the cuff. However, some of the current inevitably flows around the outside the cuff. When this happens, the edges of the cuff behave as “virtual” electrodes. The virtual electrodes typically have a polarity opposite that of the “real” electrodes that create the current flowing around the edge of the cuff. These virtual electrodes can stimulate tissue, as do real electrodes.
  • [0089]
    For example, a single real anode inside a nerve cuff with a reference electrode outside the cuff will behave similar to a tripolar cuff electrode with real cathodes on either side of a real anode. As injected electric current from the anode flows towards the reference electrode (which is located external and typically relatively distant from the cuff), the current is forced to leave the cuff at the edges since the cuff is less electrically conducting than the tissue. As perceived by the tissue inside the cuff, the edges of the cuff appear to behave as sinks of current, thus creating virtual cathodes at the edges of the cuff. Similarly, if the single electrode in the cuff is a cathode, the edges of the cuff will behave as anodes.
  • [0090]
    The amount of current and current density that flows through the edges of the cuff will determine the relative strength of the virtual electrodes. Different means can be used to control the relative strength of the virtual electrodes. For instance, by placing a single electrode asymmetrically within the cuff and a reference electrode symmetrically outside the cuff, a stronger virtual electrode (more current) will typically be created on the edge of the cuff that is closer to the real electrode. As another example, by placing the reference electrode asymmetrically outside the cuff and the real electrode symmetrically within the cuff, a stronger virtual electrode (more current) will be created on the edge of the cuff that is closer to the reference electrode. As yet another example, by increasing the diameter of one side of the cuff, the virtual electrode on that side can be made relatively weaker. Similarly, by decreasing the diameter of one side of the cuff, the virtual electrode on that side can be made relatively stronger. These and other means to control the relative strength of virtual electrodes can be combined to allow for further control of the relative strength of the virtual electrodes.
  • [0091]
    As described above, due to the presence of virtual electrodes, systems with a given number of real electrodes can behave like systems with a greater number of electrodes. For instance, a system with a single real electrode, such as a single real cathode placed asymmetrically within a nerve cuff or a single real cathode placed asymmetrically on a microstimulator with a fixation device, can be used to generate UPAPs. The edge of the cuff/fixation device closer to the real electrode will be a stronger virtual anode than the edge of the cuff/fixation device further from the real electrode. Therefore, propagation of action potentials created by the cathode can be arrested by the stronger virtual anode but allowed to propagate past the weaker virtual anode. Previously described methods for controlling the relative strength of the virtual anodes can also be used in single real electrode UPAP generating systems. For purposes of this description and the claims defining the scope of the invention, virtual and real electrodes are both encompassed by the term “electrodes”. Therefore, for instance, this single real electrode UPAP generating system comprises at least three electrodes: the “real” cathode and two “virtual” anodes. Similarly, where herein reference is made to “a cathode” or “an anode” the cathode and/or anode may be “real” or “virtual”.
  • [0092]
    UPAPs can also be produced with systems containing only two real electrodes. For instance, the asymmetric two-electrode cuff (ATEC) system described earlier used a larger cuff diameter at the anode side of the cuff and asymmetrically placed the anode and cathode within the cuff. This configuration reduced the relative strength of the virtual cathode, thereby reducing the depolarizing effects of the virtual cathode. Similarly, a microstimulator with a fixation device, even one with only two electrodes, can be configured to produce UPAPs. In configurations where the anode and cathode share a power source, the current that depolarizes the nerve at the cathode hyperpolarizes the nerve fibers at the anode. In configurations including, e.g., a reference electrode, an anode, a cathode, and more than one power source, the hyperpolarizing current may be, for instance, of longer duration and/or higher in amplitude than the depolarizing current. These anodes and cathodes may be real or virtual. Methods described above for reducing the relative strength of a virtual cathode can also be used in UPAP systems with two real electrodes.
  • [0093]
    Virtual electrodes can also be used to reduce the effect of other virtual electrodes. A virtual cathode may be eliminated with the addition of an anode on the opposite side of the cuff from the virtual cathode. This extra anode can also be a virtual anode. Additionally or alternatively, the virtual cathode can be addressed with the methods described above for controlling the relative strength of virtual electrodes. For instance, in a two “real” electrode cuff system, a virtual cathode appears on the edge of the cuff near the real anode, while a virtual anode appears on the side near the real cathode. By placing the real electrodes asymmetrically within the cuff, in such a way that the real anode is further from the edge of the cuff than the real cathode, the relative strength of the virtual anode will increase and the relative strength of the virtual cathode will diminish. This system with two real electrodes will effectively produce UPAPs in the direction of the real cathode, while arresting propagation in the direction of the real anode.
  • [0094]
    As mentioned earlier, a microstimulator may include or be attached to a fixation device that holds the microstimulator and/or electrodes in close apposition to the nerve. Among other things, this may help control the spacing desired between the electrodes and target nerve. For example, the microstimulator might include or be integrated as part of a nerve cuff. Various embodiments of this invention include a cuff electrode assembly that allows UPAPs. Such a device may be a tripolar cuff electrode 116 (FIG. 2B), possibly with an asymmetric placement of the center (cathodic) electrode. Other cuff electrodes can be as described above, where one or more of the electrodes is a virtual electrode. According to some embodiments of the invention, a microstimulator as in the '332 application, with examples shown in FIGS. 3A-3C, includes a fixation device 130. Once again, one or more of the electrodes may be a virtual electrode. According to other embodiments, a microstimulator is attached to one or more cuff electrodes via a lead, as in FIG. 2B.
  • [0095]
    The microstimulator may also include means for simultaneously providing anodic current of different amplitude through two or more different anodes. For example, when a microstimulator with a nerve cuff or the like is used, this allows one anode to be used to produce a relatively high amplitude hyperpolarizing anodic current, while another anode may be used to produce a relatively low amplitude anodic current to shunt some of the current that leaks outside the nerve cuff, thereby preventing depolarization and stimulation by a virtual cathode. In some such embodiments, the means includes two different current sources with a common cathode and different anodes. In some embodiments, the means includes programmable stimulation parameters. In some embodiments, the means includes two or more microstimulators.
  • [0096]
    The present invention also provides means for unidirectional propagation of action potentials in a selected subset(s) of neurons by taking advantage of the fact that the speed of an action potential depends on the diameter of a neuron. For instance, as is known in the art, the relatively large diameter A-α fibers (up to about 22 micron diameter) conduct action potentials at up to about 120 m/sec, while the relatively small diameter C fibers (up to about 1 micron diameter) conduct action potentials at up to about 2 m/sec. As used herein, large diameter fibers means relatively large diameter nerve fibers, and includes A-α, A-β, and A-γ fibers, while small diameter fibers means relatively small diameter nerve fibers, and includes A-δ, B, and C fibers. Through appropriate timing, an action potential may be passed along one size fiber and may be arrested in another.
  • [0097]
    For example, action potentials in large diameter afferent fibers travel relatively faster than in small diameter afferent fibers. A relatively high-amplitude depolarizing current is applied to the nerve to initiate bidirectional action potentials in both small and large diameter nerve fibers. To arrest afferent propagation of action potentials in small diameter fibers, relatively high-amplitude hyperpolarizing anodic current is applied at the anode after the large diameter action potentials has passed (or has at least been initiated) and before the action potentials in the small diameter fibers has been initiated (or at least before it has passed). Thus, some or all of the action potentials in the small diameter afferent fibers would be arrested. To do this would likely require the electrodes to be spaced relatively far apart, for instance, with one or more microstimulators or with electrodes on leads attached to a microstimulator(s).
  • [0098]
    Similarly, action potentials in large diameter efferent fibers travel relatively faster than in small diameter efferent fibers. Again, a relatively high-amplitude depolarizing current is applied to the nerve to initiate bidirectional action potentials in both small and large diameter nerve fibers. To arrest efferent propagation of action potentials in small diameter fibers, once again, relatively high-amplitude hyperpolarizing anodic current is applied at the anode after the large diameter action potentials has passed (or has at least been initiated) and before the action potentials in the small diameter fibers has been initiated (or at least before it has passed). Thus, some or all of the action potentials in the small diameter efferent fibers would be arrested. As above, electrodes spaced relatively far apart, such as electrodes on leads attached to one or more microstimulators, would likely be required.
  • [0099]
    In another example, the present invention provides means for arresting propagation of action potentials in small and large diameter fibers in one direction along a nerve. As in the examples above, a relatively high-amplitude depolarizing current is applied to the nerve to initiate bidirectional action potentials in both small and large diameter nerve fibers. As used herein, a relatively high-amplitude depolarizing current is applied at an amplitude of about 0.01 mA to about 15 mA, with a pulse width of about 0.01 msec to about 5.0 msec. To arrest propagation of action potentials in small and large diameter fibers, a hyperpolarizing anodic current(s), which is of relatively high-amplitude, is applied at the anode before the action potentials in the small and large diameters fibers has passed. As used herein, relatively high-amplitude hyperpolarizing anodic current is applied at an amplitude of about 0.1 mA to about 15 mA, with a pulse width of about 0.1 msec to about 10.0 msec. In this and the examples above, the anodic current may be tapered at the end in order to reduce the likelihood of a rebound stimulation of an action potential, as described earlier. Apply additional anodic current(s) as needed to prevent stimulation at a virtual cathode.
  • [0100]
    As yet another example, the present invention provides means for arresting propagation of action potentials in large diameter fibers. A relatively large cathodic current can initiate a bi-directional action potential in both small diameter and large diameter fibers. However, a relatively low-amplitude hyperpolarizing anodic current is more likely to hyperpolarize a large diameter fiber than a small diameter fiber and is thus more likely to cause anodic block and arrest of action potential propagation in a large fiber. Thus, in order to selectively arrest action potentials in large diameter fibers while allowing propagation of action potentials in small diameter fibers, the following steps may be followed:
  • [0101]
    1) Apply a relatively high-amplitude depolarizing cathodic current to the nerve. This will depolarize axons of all sizes and will thus initiate bi-directional action potentials in both small and large nerve fibers.
  • [0102]
    2) On the side(s) of the cathode on which arrest is desired, apply a relatively low-amplitude hyperpolarizing anodic current to the nerve. As used herein, relatively low-amplitude hyperpolarizing anodic current is applied at an amplitude of about 0.01 mA to about 10 mA, with a pulse width of about 0.01 msec to about 5.0 msec. This current should be sufficient to hyperpolarize and arrest action potentials in large fibers but not in small fibers, as large fibers are more easily hyperpolarized than small fibers. Once again, the anodic current may be tapered at the end to reduce the likelihood of rebound stimulation.
  • [0103]
    3) Apply additional anodic current(s) simultaneously with the steps above as needed to prevent stimulation at a virtual cathode.
  • [0104]
    Stimulation parameters may have different effects on different neural tissue, and parameters may be chosen to target specific neural populations and to exclude others, or to increase neural activity in specific neural populations and to decrease neural activity in others. As an example, relatively low frequency stimulation (i.e., less than about 50-100 Hz) typically has an excitatory effect on surrounding neural tissue, leading to increased neural activity, whereas relatively high frequency stimulation (i.e., greater than about 50-100 Hz) may have an inhibitory effect, leading to decreased neural activity. Therefore, low frequency electrical stimulation may be used to increase electrical activity of a nerve by increasing the number of action potentials per second in either one direction or in both directions. As yet another example, a relatively low-amplitude stimulation current is more likely to initiate an action potential in large diameter fibers, while a relatively high-amplitude stimulation current is more likely to initiate an action potential in both large and small diameter fibers.
  • [0105]
    Some embodiments of implantable microstimulator 100 include a power source and/or power storage device 126. Possible power options for a microstimulator of the present invention include, but are not limited to, an external power source coupled to the stimulation device, e.g., via an RF link, a self-contained power source utilizing any suitable means of generation or storage of energy (e.g., a primary battery, a replenishable or rechargeable battery such as a lithium ion battery, an electrolytic capacitor, a super- or ultra-capacitor, or the like), and if the self-contained power source is replenishable or rechargeable, means of replenishing or recharging the power source (e.g., an RF link, an optical link, a thermal link, or other energy-coupling link).
  • [0106]
    According to certain embodiments of the invention, a microstimulator operates independently. According to various embodiments of the invention, a microstimulator operates in a coordinated manner with other microstimulator(s), other implanted device(s), or other device(s) external to the patient's body. For instance, a microstimulator may control or operate under the control of another implanted microstimulator(s), other implanted device(s), or other device(s) external to the patient's body. A microstimulator may communicate with other implanted microstimulators, other implanted devices, and/or devices external to a patient's body via, e.g., an RF link, an ultrasonic link, a thermal link, an optical link, or the like. Specifically, a microstimulator may communicate with an external remote control (e.g., patient and/or physician programmer) that is capable of sending commands and/or data to a microstimulator and that may also be capable of receiving commands and/or data from a microstimulator.
  • [0107]
    In certain embodiments, and as illustrated in FIG. 4, the patient 170 switches microstimulator 100 on and off by use of controller 180, which may be hand held. Microstimulator 100 is operated by controller 180 by any of various means, including sensing the proximity of a permanent magnet located in controller 180, sensing RF transmissions from controller 180, or the like.
  • [0108]
    External components for programming and/or providing power to various embodiments of microstimulator 100 are also illustrated in FIG. 4. When communication with microstimulator 100 is desired, patient 170 is positioned on or near external communications appliance 190, which appliance contains one or more inductive coils 192 or other means of communication (e.g., RF transmitter and receiver). External communications appliance 190 is connected to or is a part of external programmer 200 which may receive power 202 from a conventional power source. External programmer 200 contains manual input means 208, e.g., a keypad, whereby the patient 170 or a caregiver 212 can request changes in the stimulation parameters produced during the normal operation of microstimulator 100. In these embodiments, manual input means 208 includes various electromechanical switches and/or visual display devices or the like that provide the patient and/or caregiver with information about the status and prior programming of microstimulator 100.
  • [0109]
    Alternatively or additionally, external programmer 200 is provided with an interface means 216 for interacting with other computing means 218, such as by a serial interface cable or infrared link to a personal computer or to a telephone modem or the like. Such interface means 216 may permit a clinician to monitor the status of the implant and prescribe new stimulation parameters from a remote location.
  • [0110]
    The external appliance(s) may be embedded in a cushion, pillow, mattress cover, or garment. Other possibilities exist, including a belt, scarf, patch, or other structure(s) that may be affixed to the patient's body or clothing. External appliances may include a package that can be, e.g., worn on the belt, may include an extension to a transmission coil affixed, e.g., with a velcro band or adhesive, or may be combinations of these or other structures able to perform the functions described herein.
  • [0111]
    In order to help determine the strength and/or duration of electrical stimulation required to produce the desired effect, in some embodiments, a patient's response to and/or need for treatment is sensed. For example, muscle activity (e.g., limb EMG), electrical activity of a nerve (e.g., ENG), and/or electrical activity of the brain (e.g., EEG) may be sensed. Other measures of the state of the patient may additionally or alternatively be sensed. For instance, medication, neurotransmitter, hormone, interleukin, cytokine, lymphokine, chemokine, growth factor, and/or enzyme levels or their changes, and/or levels or changes in other substance(s) borne in the blood and/or in the cerebrospinal fluid (CSF) may be sensed, using, e.g., one or more Chemically Sensitive Field-Effect Transistors (CHEMFETs) such as Enzyme-Selective Field-Effect Transistors (ENFETs) or Ion-Sensitive Field-Effect Transistors (ISFETs, as are available from Sentron CMT of Enschede, The Netherlands). For instance, the level or changes in level of neuron-specific enolase, a key glycolytic enzyme, in either or both the blood serum or CSF may be sensed. As another example, to sense erectile dysfunction, a penile tumescence sensor, penile arteriole pressure sensor, and/or nitric oxide sensor may be used.
  • [0112]
    As another example, when electrodes of implantable stimulator 100 are implanted on or near the vagus nerve, a sensor or stimulating electrode (or other electrode) of microstimulator 100 may be used to sense changes in EEG resulting from the stimulation applied to the nerve. Alternatively, a “microstimulator” dedicated to sensory processes communicates with a microstimulator that provides the stimulation pulses. The implant circuitry 104 may, if necessary, amplify and transmit these sensed signals, which may be analog or digital. Other methods of determining the required stimulation include sensing impedance, pressure, acceleration, mechanical stress, and capacitance, as well as other methods mentioned herein, and yet others that will be evident to those of skill in the art upon review of the present disclosure. The sensed information may be used to control stimulation parameters in a closed-loop manner.
  • [0113]
    As mentioned earlier, use of, for instance, a multi-electrode cuff, where electrodes are present on the inner surface of the cuff, may be used to create UPAPs. In this example of sensing a physical condition of a patient, sense amplifiers may be employed to sense the propagating action potentials that result from the cathodic stimulus from the cuff's stimulating electrode. For instance, a technique (such as described herein) to implement the UPAP is employed, and the signal at each end of the cuff, or at a more remote location(s) on the nerve, is measured. If the UPAP generation is successful, then an action potential will be sensed traveling only in the desired direction, for instance, at only one end of the cuff.
  • [0114]
    If the UPAP technique is unsuccessful, it may be because (1) no action potential was generated by the stimulus, (2) bidirectional action potentials were generated, (3) a UPAP was generated in the wrong direction. In the case of such a failure, an algorithm can be employed to generate the correct UPAP. For instance, if no action potentials were produced, the cathodic stimulus may be increased until bi-directional action potentials are generated. If bi-directional action potentials were produced or a UPAP was generated in the wrong direction, one of the techniques discussed herein for creating UPAPs may be implemented and adjusted until the UPAP in the appropriate direction results. When using virtual and real electrodes, the configuration and/or stimulus strengths may be adjusted to create the effect. Or, if stimulus waveform characteristics are employed (trapezoidal pulses with an exponential trailing edge), the parameters of the waveforms may be adjusted until the proper UPAPs are generated.
  • [0115]
    In some instances, the time(s) of arrival of the sensed action potentials and/or evoked potentials at the electrodes may be used to adjust the UPAP-generating mechanisms. Since various nerve fiber types have different conduction velocities, the arrival time of an action potential (as defined by a waveform morphological feature, such as an upstroke, maximum rate of change of sensed amplitude, peak value, zero crossing, or the like) at an electrode some distance from the stimulation site may be used to determine if the UPAP generation was successful, i.e., whether the fiber type to be inhibited is no longer generating action potentials in the direction to be blocked.
  • [0116]
    In certain instances, the morphology of the sensed action potentials and/or evoked potentials may be used to determine the effectiveness of UPAP generation. At an electrode close to the stimulating electrode, the difference in propagation velocity between fibers is often not great enough to create differences in arrival times between sensed propagating action potentials; that is, the sensed signal at a nearby electrode will be a spatial- and time-averaged waveform that is made up of the traveling action potentials of different fiber types. Techniques for decomposing the waveform into the constituent action potentials from the different fiber types have been proposed. (See, for instance, Barker, et al., “Determination of the Distribution of Conduction Velocities in Human Nerve Trunks” Biomedical Engineering 26(2):76-81,1979 and Schoonhoven, et al., “The Inverse Problem in Electroneurography-I: Conceptual Basis and Mathematical Formulation” Biomedical Engineering 35(10):769-777, 1988.) An algorithm incorporating waveform analysis can be utilized to decompose the sensed signal to determine if the UPAP is successfully arresting the propagation of an action potential from a specific fiber type(s).
  • [0117]
    As an example, the sensed waveform may be characterized during a calibration routine. A sensed signal may be obtained from the desired UPAP configuration/parameters and compared to a sensed signal obtained from bi-directional propagation configuration/parameters. The state of bidirectional versus unidirectional propagation may be verified by either or both sensed signals and/or by clinical symptoms. The differences in the unidirectional and bidirectional waveforms could be characterized by a feature or suite of features indicating the differences.
  • [0118]
    For instance, if it is reliably determined that the peak value of the sensed action potential from a fiber is related to the square of the conduction velocity of that fiber, then, given a known or assumed distribution of fibers within the cuff electrode, the fibers which are propagating action potentials may be inferred from the amplitude of the compound action potential (CAP) waveshape. As an example, if larger fibers (which have higher conduction velocities) are to be blocked by UPAP techniques, then, during bidirectional propagation (e.g., for calibration), large sensed CAP waveforms would be detected on the electrode in the direction to be blocked. When the UPAP technique is successful, a dramatic reduction in sensed signal amplitude will result, due to blocked propagation of the larger fibers. There may still be a propagated CAP of lower amplitude sensed by the electrode due to some smaller fibers being activated by the cathodic stimulus, but a sense threshold can be established, where signals that exceed this threshold indicate propagation by larger fibers and failure of the UPAP method.
  • [0119]
    In an alternative example, if sense electrodes are placed at each end of a nerve cuff, a differential comparison can be made. After timing and gain adjustments are made, a large difference in signal amplitude between the two electrodes would indicate UPAP success, where a small difference in signals would indicate either loss of nerve capture or bilateral propagation.
  • [0120]
    Again, the stimulator may sense a physical condition of a patient by monitoring the sensed signal(s) for the characteristic feature(s) to determine if the UPAP generation was successful. If the UPAP succeeded, no changes need be made to the stimulator parameters or configuration. If the UPAP failed, stimulator parameter(s) and/or configuration may be modified until the desired UPAP is recreated, as indicated by the sensed, characteristic waveform that indicates the UPAP. This system may be periodically recalibrated, either automatically or during follow-up sessions with a clinician.
  • [0121]
    While a microstimulator may also incorporate means of sensing one or more conditions of the patient, it may alternatively or additionally be desirable to use a separate or specialized implantable device to sense and telemeter physiological conditions/responses in order to adjust stimulation parameters. This information may be transmitted to an external device, such as external appliance 190, or may be transmitted directly to implanted stimulator(s) 100. However, in some cases, it may not be necessary or desired to include a sensing function or device, in which case stimulation parameters are fixed and/or determined and refined, for instance, by patient feedback, or the like.
  • [0122]
    Thus, it is seen that in accordance with the present invention, one or more external appliances may be provided to interact with microstimulator 100, and may be used to accomplish, potentially among other things, one or more of the following functions:
  • [0123]
    Function 1: If necessary, transmit electrical power from external programmer 200 via appliance 190 to microstimulator 100 in order to power the device and/or recharge power source/storage device 126. External programmer 200 may include an algorithm that adjusts stimulation parameters automatically whenever microstimulator(s) 100 is/are recharged, whenever communication is established between them, and/or when instructed to do so.
  • [0124]
    Function 2: Transmit data from external programmer 200 via external appliance 190 to implantable stimulator 100 in order to change the operational parameters (e.g., electrical stimulation parameters) used by stimulator 100.
  • [0125]
    Function 3: Transmit sensed data indicating a need for treatment or in response to stimulation from neurostimulator 100 (e.g., EEG, change in neurotransmitter or medication level, or other activity) to external programmer 200 via external appliance 190.
  • [0126]
    Function 4: Transmit data indicating state, address and/or type of implantable stimulator 100 (e.g., battery level, stimulation settings, etc.) to external programmer 200 via external appliance 190.
  • [0127]
    For the treatment of various types and degrees of medical conditions, it may be desirable to modify or adjust the algorithmic functions performed by the implanted and/or external components, as well as the surgical approaches, in ways that would be obvious to skilled practitioners of these arts. For example, in some situations, it may be desirable to employ more than one implantable stimulator 100, each of which could be separately controlled by means of a digital address. Multiple channels and/or multiple patterns of stimulation might thereby be programmed by the clinician and controlled by the patient in order to, for instance, stimulate larger areas of neural tissue in order to maximize therapeutic efficacy.
  • [0128]
    In some embodiments discussed earlier, microstimulator 100, or a group of two or more microstimulators, is controlled via closed-loop operation. A need for and/or response to stimulation is sensed via microstimulator 100, or by an additional microstimulator (which may or may not be dedicated to the sensing function), or by another implanted or external device. If necessary, the sensed information is transmitted to microstimulator 100. In some embodiments, the stimulation parameters used by microstimulator 100 are automatically adjusted based on the sensed information. Thus, the stimulation parameters are adjusted in a closed-loop manner to provide stimulation tailored to the need for and/or response to stimulation.
  • [0129]
    For instance, in some embodiments of the present invention, a first and second “stimulator” are provided. The second “stimulator” periodically (e.g. once per minute) records e.g., nerve activity (or medication, etc.), which it transmits to the first stimulator. The first stimulator uses the sensed information to adjust stimulation parameters according to an algorithm programmed, e.g., by a clinician. For example, stimulation may be activated (or stimulation current amplitude may be increased) in response to EEG changes indicative of an impending or an actual seizure. As another example, when the microstimulator is used to stimulate the cavernous nerve to produce an erection, stimulation current amplitude may be increased in response to a decrease in intracavernosal pressure. Alternatively, one “microstimulator” performs both the sensing and stimulating functions.
  • [0130]
    For example, as shown in the example of FIG. 5, a first microstimulator 100, implanted beneath the skin of patient 170, provides electrical stimulation via electrodes 110 to a first location; a second microstimulator 100′ provides electrical stimulation to a second location; and a third microstimulator 100″ provides electrical stimulation to a third location. As mentioned earlier, the implanted devices may operate independently or may operate in a coordinated manner with other similar implanted devices, other implanted devices, or other devices external to the patient's body, as shown by the control lines 222, 223 and 224 in FIG. 5. That is, in accordance with certain embodiments of the invention, external controller 220 controls the operation of each of the implanted microstimulators 100, 100′ and 100″. According to various embodiments of the invention, an implanted device, e.g. microstimulator 100, may control or operate under the control of another implanted device(s), e.g., microstimulator 100′ and/or microstimulator 100″. That is, a device made in accordance with the invention may communicate with other implanted stimulators, other implanted devices, and/or devices external to a patient's body, e.g., via an RF link, an ultrasonic link, a thermal link, an optical link, or other communications link. Specifically, as illustrated in FIG. 5, microstimulator 100, 100′, and/or 100″, made in accordance with the invention, may communicate with an external remote control (e.g., patient and/or physician programmer 220) that is capable of sending commands and/or data to implanted devices and that may also be capable of receiving commands and/or data from implanted devices.
  • [0131]
    For instance, two or more stimulators may be used in a UPAP system. One stimulator may depolarize the nerve, inducing bidirectional propagation of action potentials. One or more additional stimulators may be responsible for hyperpolarizing the nerve, or certain fiber types within the nerve. The stimulators may communicate with each other to coordinate these activities, or they may communicate with and/or receive communications from an external controller. The stimulation parameters and/or timing may be fixed, adjusted manually, and/or automatically updated based on sensed physical condition(s) of the patient. One or more microstimulators included in the system may include a fixation device, such as a nerve cuff. For instance, in certain embodiments, the stimulator(s) used for hyperpolarizing include a nerve cuff, while the stimulator(s) for depolarizing do not.
  • [0132]
    A microstimulator made in accordance with the invention may incorporate, in some embodiments, first sensing means 228 for sensing therapeutic effects, clinical variables, or other indicators of the state of the patient, such as EEG, ENG, and/or EMG. The stimulator additionally or alternatively incorporates second means 229 for sensing levels or changes in one or more medications, neurotransmitters, hormones, interleukins, cytokines, lymphokines, chemokines, growth factors, enzymes, and/or other substances in the blood plasma, in the cerebrospinal fluid, or in the local interstitial fluid. The stimulator additionally or alternatively incorporates third means 230 for sensing electrical current levels and/or waveforms. Sensed information may be used to control the parameters of the stimulator(s) in a closed loop manner, as shown by control lines 225, 226, and 227. Thus, the sensing means may be incorporated into a device that also includes electrical stimulation means, or the sensing means (that may or may not have stimulating means) may communicate the sensed information to another device(s) with stimulating means, or to another device capable of commanding other devices to stimulate. For instance, a “central” device can analyze the sensed data and command other devices to stimulate appropriately. This central device may or may not be implanted.
  • [0133]
    As described earlier, the present invention teaches a microstimulator system for stimulation of a nerve with unidirectionally propagating action potentials that may effectively select the efferent fibers or the afferent fibers propagating more towards the periphery and viscera or more towards the CNS. Such selective stimulation may be an effective treatment for a variety of disorders. For instance, and as discussed in more detail below, stimulation of the vagus nerve with unidirectionally propagating action potentials that effectively select and stimulate the therapeutic afferent fibers of the vagus nerve may be an effective treatment for a variety of disorders, including epilepsy and/or depression.
  • [0134]
    A commercially available vagus nerve stimulation (VNS) system is currently used as a therapy for refractory epilepsy. Epilepsy afflicts one to two percent of the population in the developed world, and an estimated 25-33% of these are refractory to medication and conventional surgery. The currently available VNS system produces a significant number of side effects due to recruitment of efferent fibers.
  • [0135]
    The vagus nerve 250 (see FIGS. 6A, 6B, and 6C) provides the primary parasympathetic nerve to the thoracic organs and most of the abdominal organs. It originates in the brainstem and runs in the neck through the carotid sheath 252 (FIG. 6B) with jugular vein 256 and common carotid artery 258, and then adjacent to the esophagus to the thoracic and abdominal viscera. As seen in FIGS. 6A and 6C, vagus nerve 250 has many branches, including pharyngeal and laryngeal branches 260, cardiac branches 264, gastric branches 266, and pancreaticoduodenal branches 268. Because the vagus nerve innervates the pharynx, the most common side effect associated with VNS therapy is a hoarse voice during stimulation. Some patients also experience a mild cough, tickling in the back of the pharynx, or increased hoarseness. Stimulation of the vagus nerve may also lead to a decreased opening of the vocal cords, which results in shortness of breath during exertion.
  • [0136]
    The vagus nerve provides parasympathetic innervation to the heart, and stimulation of the vagus nerve has been demonstrated to cause bradycardia and arrhythmias. Stimulation of the left vagus nerve distal to the cardiac branch of the vagus nerve has not resulted in significantly increased cardiac side effects; however, the stimulating electrodes may only be safely placed on this distal portion of the left vagus nerve. Bilateral stimulation is not allowed, as stimulation of the right vagus nerve produces significant cardiac side effects. Finally, the vagus nerve provides parasympathetic innervation to the lungs and most of the abdominal organs (e.g., the stomach and small intestine), and improper stimulation of the vagus nerve may impair proper functioning of these organs.
  • [0137]
    Some embodiments of this invention include a microstimulator that generates UPAPs of the vagus nerve (which, as used herein, includes branches of the vagus nerve). A microstimulator may be implanted on or near the vagus nerve in the neck region, e.g., by dissecting down to the carotid sheath. A microstimulator may also/instead be surgically implanted on or near a more proximal or distal portion of the vagus nerve. Various stimulator configurations may be used. For instance, a cuff electrode, which may be part of a microstimulator, attached to a microstimulator via a short lead, or attached to an IPG, may be implanted around the vagus nerve.
  • [0138]
    A single microstimulator may be implanted, or two or more microstimulators may be implanted to achieve greater stimulation of the vagus nerve. According to some embodiments of the invention, a single microstimulator is implanted for stimulation of the left vagus nerve. According to various embodiments of the invention, one microstimulator is implanted for stimulation of the left vagus nerve and another is implanted for stimulation of the right vagus nerve. Bilateral stimulation may be effected with two separate microstimulators or by a microstimulator with multiple leads. Vagus nerve stimulation with UPAPs may alternatively or additionally be provided by one or more IPGs attached to one or more leads with, for instance, electrodes in a nerve cuff.
  • [0139]
    For instance, a UPAP system (e.g., a microstimulator with a fixation device, a nerve cuff attached to an IPG implanted in a subclavicular location, or the like) may be provided on the vagus nerve in the carotid sheath (unilaterally or bilaterally). Stimulation parameters may comprise, for instance, a stimulation pulse with a quasitrapezoidal shape, with a plateau pulse width in the range of about 10 μsec to about 5 msec and/or an exponentially decaying trailing phase having a fall time in the range of about 50 μsec to about 5 msec. A charge recovery pulse, may comprise, for instance, a quasitrapezoidal shape with a plateau pulsewidth of about 50 μsec to about 10 msec and/or a decaying trailing phase with a fall time of about 50 μsec to about 5 msec. Other possible UPAP parameters are taught herein. In some electrode configurations, for instance tripolar or other multipolar configurations, means for distributing the current asymmetrically between the electrodes may be included, i.e., the polarities and currents of the electrodes are independently programmable.
  • [0140]
    According to such an embodiment of the invention, the stimulation can increase excitement of afferent fibers of the vagus nerve(s), thereby treating epilepsy and/or depression, while limiting side effects typically caused by bidirectional stimulation that activates efferent fibers with orthodromically propagating action potentials. Low-frequency electrical stimulation (i.e., less than about 50-100 Hz) is likely to produce the therapeutic activation. To determine the need for and/or response to such treatment, EEG of the cortex, thalamus, a region adjacent to a scarred region of the brain, or any area of the brain known to give rise to a seizure in a particular patient, may be sensed. Alternatively or additionally, limb EMG and/or other conditions, as known to those of skill in the art, may be sensed.
  • [0141]
    Additional uses include the application to tachycardia via effective selection and stimulation of the efferent fibers of the vagus nerve, such as one or more superior and/or inferior cardiac branches. Electrodes capable of UPAP may be provided on the right and/or left vagus nerve(s) in, for instance, the neck, the thorax, and/or adjacent to the esophagus. Excitatory stimulation (i.e., less than about 50-100 Hz) should be used to stimulate vagal parasympathetic activity to the heart to promote a decrease in heart rate and thereby treat tachycardia. To determine the need for and/or response to such treatment, ECG, heart rate, blood pressure, blood flow, cardiac output, acceleration, and/or breathing, for instance, may be sensed.
  • [0142]
    As another example, stimulation of the cavernous nerve(s) with unidirectionally propagating action potentials that effectively select the therapeutic parasympathetic efferent fibers of the cavernous nerve(s) may be an effective treatment for erectile dysfunction and may minimize distracting, unpleasant, or uncomfortable sensation that may be associated with electrical stimulation of the cavernous nerve(s).
  • [0143]
    Recent estimates suggest that the number of men in the U.S. with erectile dysfunction may be 10-20 million, and inclusion of men with partial erectile dysfunction increases the estimate to about 30 million. Erectile dysfunction has a number of causes, both physiological and psychological, and in many patients the disorder is multifactorial. The causes include several that are essentially neurologic in origin. Damage to the autonomic pathways innervating the penis may eliminate “psychogenic” erection initiated by the central nervous system. Lesions of the somatic nervous pathways may impair reflexogenic erections and may interrupt tactile sensation needed to maintain psychogenic erections. Spinal cord lesions may produce varying degrees of erectile failure depending on the location and completeness of the lesions. Not only do traumatic lesions affect erectile ability, but disorders leading to peripheral neuropathy may impair neuronal innervation of the penis or of the sensory afferents.
  • [0144]
    A well-publicized medication is available for erectile dysfunction, but it requires an hour to exert its full effects, and it may have significant side effects such as abnormal vision, flushing, headache, and diarrhea. Intracavernosal injection therapy, in which a patient injects vasodilator substances (e.g., papaverine) into the corpora of the penis, suffers a high rate of patient dropout, as do vacuum constriction devices. Several forms of penile prostheses are available, including semirigid, malleable, and inflatable, but these have significant problems with mechanical failure, infection, and erosions.
  • [0145]
    The male erectile response is a vascular event initiated by neuronal action and maintained by a complex interplay between vascular and neurological events. The pelvic splanchnic nerve plexus 280, the nerve fibers of which originate in the sacral spinal cord (S2, S3, S4, respectively) and intertwine with the inferior hypogastric plexus 284, provides the primary parasympathetic input to the penis, i.e., the corpus cavernosa 286 and the corpus spongiosum 288, via the greater cavernous nerve 290 and lesser cavernous nerve 292. This parasympathetic input allows erection by relaxation of the smooth muscle and dilation of the helicine arteries of the penis. The cavernous nerves 290, 292 pass bilaterally near the apex, mid, and base of prostate 294 and then near the posterolateral urethra (not shown). The nerves then run underneath the pubic symphysis 296 and into the penis. Conversely, sympathetic innervation from the hypogastric nerves, specifically from the interior hypogastric plexus 284, makes the penis flaccid due to constriction of the smooth muscle and helicine arteries of the penis.
  • [0146]
    One or more stimulators may be implanted to stimulate cavernous nerve(s) 290, 292, branches thereof, and/or nerves that give rise to a cavernous nerve(s) (collectively referred to herein simply as cavernous nerves) in any of the aforementioned regions by dissecting down to the nerve(s). Such dissection may usually be performed through any incision allowing access to the prostate and/or the posterolateral urethra. For example, an incision could be made above the pubic symphysis 296, and the tissues between the incision and at least one of the cavernous nerves could be dissected away. Alternatively, an incision may be made immediately below the pubic symphysis 296, or an incision may be made through the perineum. As another alternative, an incision may be made in the dorsolateral penis 298.
  • [0147]
    Some embodiments of this invention include a stimulator that allows UPAPs of the cavernous nerve(s). Such a stimulator (for instance, a microstimulator of the present invention) allows the effective selection of efferent fibers. Via stimulation of primarily efferent fibers, unidirectional stimulation of the cavernous nerve(s) may be an effective treatment for erectile dysfunction. By effectively avoiding the production of orthodromic action potentials on the afferent fibers, such stimulation may minimize distracting, unpleasant, or uncomfortable sensation that may be associated with electrical stimulation of the cavernous nerve(s) or other associated nerve fibers, as mentioned above.
  • [0148]
    According to such an embodiment of the invention, a UPAP system (e.g., a microstimulator with a fixation device or a nerve cuff attached to an IPG implanted in the abdomen or the like) may be provided on one or more cavernous nerves or neurovascular bundles containing a cavernous nerve. Stimulation parameters may comprise, for instance, a stimulation pulse with a quasitrapezoidal shape, with a plateau pulse width in the range of about 10 μsec to about 5 msec and an exponentially decaying trailing phase having a fall time in the range of about 50 μsec to about 5 msec. A charge recovery pulse, may comprise, for instance, a quasitrapezoidal shape with a plateau pulsewidth of about 50 μsec to about 10 msec and a decaying trailing phase with a fall time of about 50 μsec to about 5 msec. Again, other possible UPAP parameters are taught herein. In some electrode configurations, for instance, tripolar or other multipolar configurations, means for distributing the current asymmetrically between the electrodes may be included, i.e., the polarities and currents of the electrodes are independently programmable.
  • [0149]
    The stimulation can increase excitement of a nerve(s), such as a cavernous nerve(s), thereby treating erectile dysfunction. Low-frequency electrical stimulation (i.e., less than about 50-100 Hz) is likely to produce such activation. To determine the need for and/or response to such treatment, a penile tumescence sensor, penile arteriole pressure sensor, and/or nitric oxide sensor, for instance, may be used.
  • [0150]
    A single microstimulator may be implanted, or two or more systems may be implanted to achieve greater stimulation of a cavernous nerve(s). According to one embodiment of the invention, a single microstimulator is implanted for stimulation of a single cavernous nerve. According to another embodiment of the invention, one microstimulator is implanted for stimulation of one of the left cavernous nerves and another is implanted for stimulation of one of the right cavernous nerves. According to other embodiments, several microstimulators are used: one for each nerve to be stimulated, or even multiple for each nerve to be stimulated. Bilateral stimulation and other multiple stimulation site treatments may be effected with two separate microstimulators or by a microstimulator with multiple leads. Cavernous nerve stimulation with UPAPs may alternatively or additionally be provided by one or more IPGs attached to one or more leads with, for instance, electrodes in a nerve cuff.
  • [0151]
    Additionally, sensing means described earlier may be used to orchestrate first the activation of microstimulator(s)/electrode(s) targeting one area of a nerve, and then, when appropriate, the microstimulator(s)/electrode(s) targeting the same or another area of the nerve, in order to, for instance, implement UPAPs. Alternatively, this orchestration may be programmed, and not based on a sensed condition.
  • [0152]
    While the invention herein disclosed has been described by means of specific embodiments and applications thereof, numerous modifications and variations could be made thereto by those skilled in the art without departing from the scope of the invention set forth in the claims.
Citas de patentes
Patente citada Fecha de presentación Fecha de publicación Solicitante Título
US3850161 *9 Abr 197326 Nov 1974Liss SMethod and apparatus for monitoring and counteracting excess brain electrical energy to prevent epileptic seizures and the like
US3881495 *8 Ago 19736 May 1975Anthony N PannozzoMethod of nerve therapy using trapezoidal pulses
US3941136 *21 Nov 19732 Mar 1976Neuronyx CorporationMethod for artificially inducing urination, defecation, or sexual excitation
US4232679 *26 Ene 197711 Nov 1980Pacesetter Systems, Inc.Programmable human tissue stimulator
US4408608 *9 Abr 198111 Oct 1983Telectronics Pty. Ltd.Implantable tissue-stimulating prosthesis
US4467809 *17 Sep 198228 Ago 1984Biolectron, Inc.Method for non-invasive electrical stimulation of epiphyseal plate growth
US4481950 *3 Abr 198113 Nov 1984Medtronic, Inc.Acoustic signalling apparatus for implantable devices
US4542753 *22 Dic 198224 Sep 1985Biosonics, Inc.Apparatus and method for stimulating penile erectile tissue
US4585005 *6 Abr 198429 Abr 1986Regents Of University Of CaliforniaMethod and pacemaker for stimulating penile erection
US4590946 *14 Jun 198427 May 1986Biomed Concepts, Inc.Surgically implantable electrode for nerve bundles
US4602624 *11 Oct 198429 Jul 1986Case Western Reserve UniversityImplantable cuff, method of manufacture, and method of installation
US4608985 *11 Oct 19842 Sep 1986Case Western Reserve UniversityAntidromic pulse generating wave form for collision blocking
US4649936 *11 Oct 198417 Mar 1987Case Western Reserve UniversityAsymmetric single electrode cuff for generation of unidirectionally propagating action potentials for collision blocking
US4702254 *30 Dic 198527 Oct 1987Jacob ZabaraNeurocybernetic prosthesis
US4867164 *26 Oct 198719 Sep 1989Jacob ZabaraNeurocybernetic prosthesis
US5095904 *4 Sep 199017 Mar 1992Cochlear Pty. Ltd.Multi-peak speech procession
US5188104 *1 Feb 199123 Feb 1993Cyberonics, Inc.Treatment of eating disorders by nerve stimulation
US5193539 *18 Dic 199116 Mar 1993Alfred E. Mann Foundation For Scientific ResearchImplantable microstimulator
US5193540 *18 Dic 199116 Mar 1993Alfred E. Mann Foundation For Scientific ResearchStructure and method of manufacture of an implantable microstimulator
US5199430 *11 Mar 19916 Abr 1993Case Western Reserve UniversityMicturitional assist device
US5211129 *25 Ene 199118 May 1993Destron/Idi, Inc.Syringe-implantable identification transponder
US5215086 *3 May 19911 Jun 1993Cyberonics, Inc.Therapeutic treatment of migraine symptoms by stimulation
US5299569 *3 May 19915 Abr 1994Cyberonics, Inc.Treatment of neuropsychiatric disorders by nerve stimulation
US5305445 *1 Dic 199219 Abr 1994Kabushiki Kaisha ToshibaSystem and method employing extended memory capacity detection
US5305745 *2 Abr 199226 Abr 1994Fred ZacoutoDevice for protection against blood-related disorders, notably thromboses, embolisms, vascular spasms, hemorrhages, hemopathies and the presence of abnormal elements in the blood
US5312439 *12 Dic 199117 May 1994Loeb Gerald EImplantable device having an electrolytic storage electrode
US5314451 *15 Ene 199324 May 1994Medtronic, Inc.Replaceable battery for implantable medical device
US5314458 *24 May 199324 May 1994University Of MichiganSingle channel microstimulator
US5324316 *3 Mar 199328 Jun 1994Alfred E. Mann Foundation For Scientific ResearchImplantable microstimulator
US5330515 *17 Jun 199219 Jul 1994Cyberonics, Inc.Treatment of pain by vagal afferent stimulation
US5358514 *17 May 199325 Oct 1994Alfred E. Mann Foundation For Scientific ResearchImplantable microdevice with self-attaching electrodes
US5400784 *15 Oct 199328 Mar 1995Case Western Reserve UniversitySlowly penetrating inter-fascicular nerve cuff electrode and method of using
US5405363 *21 Jun 199411 Abr 1995Angelon CorporationImplantable cardioverter defibrillator having a smaller displacement volume
US5405367 *3 Mar 199311 Abr 1995Alfred E. Mann Foundation For Scientific ResearchStructure and method of manufacture of an implantable microstimulator
US5439938 *7 Abr 19938 Ago 1995The Johns Hopkins UniversityTreatments for male sexual dysfunction
US5454840 *5 Abr 19943 Oct 1995Krakovsky; Alexander A.Potency package
US5501703 *24 Ene 199426 Mar 1996Medtronic, Inc.Multichannel apparatus for epidural spinal cord stimulator
US5505201 *20 Abr 19949 Abr 1996Case Western Reserve UniversityImplantable helical spiral cuff electrode
US5513636 *12 Ago 19947 May 1996Cb-Carmel Biotechnology Ltd.Implantable sensor chip
US5515848 *7 Jun 199514 May 1996Pi Medical CorporationImplantable microelectrode
US5531778 *20 Sep 19942 Jul 1996Cyberonics, Inc.Circumneural electrode assembly
US5531787 *25 Ene 19932 Jul 1996Lesinski; S. GeorgeImplantable auditory system with micromachined microsensor and microactuator
US5634462 *27 Mar 19953 Jun 1997Case Western Reserve UniversityCorrugated inter-fascicular nerve cuff method and apparatus
US5649970 *18 Ago 199522 Jul 1997Loeb; Gerald E.Edge-effect electrodes for inducing spatially controlled distributions of electrical potentials in volume conductive media
US5713922 *25 Abr 19963 Feb 1998Medtronic, Inc.Techniques for adjusting the locus of excitation of neural tissue in the spinal cord or brain
US5716318 *14 Abr 199510 Feb 1998The University Of North Carolina At Chapel HillMethod of treating cardiac arrest and apparatus for same
US5735887 *10 Dic 19967 Abr 1998Exonix CorporationClosed-loop, RF-coupled implanted medical device
US5752979 *1 Nov 199619 May 1998Medtronic, Inc.Method of controlling epilepsy by brain stimulation
US5755750 *8 Nov 199626 May 1998University Of FloridaMethod and apparatus for selectively inhibiting activity in nerve fibers
US5775331 *7 Jun 19957 Jul 1998Uromed CorporationApparatus and method for locating a nerve
US5782891 *15 Abr 199621 Jul 1998Medtronic, Inc.Implantable ceramic enclosure for pacing, neurological, and other medical applications in the human body
US5895416 *12 Mar 199720 Abr 1999Medtronic, Inc.Method and apparatus for controlling and steering an electric field
US5899933 *16 Jun 19974 May 1999Axon Engineering, Inc.Nerve cuff electrode carrier
US5938584 *14 Nov 199717 Ago 1999Cybernetic Medical Systems CorporationCavernous nerve stimulation device
US6051017 *19 Feb 199718 Abr 2000Advanced Bionics CorporationImplantable microstimulator and systems employing the same
US6058331 *27 Abr 19982 May 2000Medtronic, Inc.Apparatus and method for treating peripheral vascular disease and organ ischemia by electrical stimulation with closed loop feedback control
US6104956 *30 May 199715 Ago 2000Board Of Trustees Of Southern Illinois UniversityMethods of treating traumatic brain injury by vagus nerve stimulation
US6112116 *22 Feb 199929 Ago 2000Cathco, Inc.Implantable responsive system for sensing and treating acute myocardial infarction
US6178349 *15 Abr 199923 Ene 2001Medtronic, Inc.Drug delivery neural stimulation device for treatment of cardiovascular disorders
US6198970 *25 Ene 19996 Mar 2001Esd Limited Liability CompanyMethod and apparatus for treating oropharyngeal respiratory and oral motor neuromuscular disorders with electrical stimulation
US6205359 *26 Oct 199820 Mar 2001Birinder Bob BovejaApparatus and method for adjunct (add-on) therapy of partial complex epilepsy, generalized epilepsy and involuntary movement disorders utilizing an external stimulator
US6214032 *25 Ene 200010 Abr 2001Advanced Bionics CorporationSystem for implanting a microstimulator
US6216045 *26 Abr 199910 Abr 2001Advanced Neuromodulation Systems, Inc.Implantable lead and method of manufacture
US6226552 *16 Abr 19991 May 2001Stryker InstrumentsNeuromuscular electrical stimulation for preventing deep vein thrombosis
US6266564 *3 Nov 199924 Jul 2001Medtronic, Inc.Method and device for electronically controlling the beating of a heart
US6275737 *23 Jun 199914 Ago 2001Advanced Bionics CorporationTranscutaneous transmission pouch
US6341236 *30 Abr 199922 Ene 2002Ivan OsorioVagal nerve stimulation techniques for treatment of epileptic seizures
US6424234 *15 Sep 199923 Jul 2002Greatbatch-Sierra, Inc.Electromagnetic interference (emi) filter and process for providing electromagnetic compatibility of an electronic device while in the presence of an electromagnetic emitter operating at the same frequency
US6473652 *22 Mar 200029 Oct 2002Nac Technologies Inc.Method and apparatus for locating implanted receiver and feedback regulation between subcutaneous and external coils
US6505078 *10 Mar 20007 Ene 2003Medtronic, Inc.Technique for adjusting the locus of excitation of electrically excitable tissue
US6526318 *16 Jun 200025 Feb 2003Mehdi M. AnsariniaStimulation method for the sphenopalatine ganglia, sphenopalatine nerve, or vidian nerve for treatment of medical conditions
US6560490 *5 Mar 20016 May 2003Case Western Reserve UniversityWaveforms for selective stimulation of central nervous system neurons
US6597954 *28 Nov 200022 Jul 2003Neuropace, Inc.System and method for controlling epileptic seizures with spatially separated detection and stimulation electrodes
US6600954 *4 Abr 200129 Jul 2003Biocontrol Medical Bcm Ltd.Method and apparatus for selective control of nerve fibers
US6622048 *21 Nov 200016 Sep 2003Advanced Bionics CorporationImplantable device programmer
US6712753 *12 Nov 200130 Mar 2004Joseph ManneElectromagnetically induced anesthesia and sensory stimulation
US6782292 *15 Jun 200124 Ago 2004Advanced Bionics CorporationSystem and method for treatment of mood and/or anxiety disorders by electrical brain stimulation and/or drug infusion
US6907295 *24 Jul 200214 Jun 2005Biocontrol Medical Ltd.Electrode assembly for nerve control
US6928320 *17 May 20019 Ago 2005Medtronic, Inc.Apparatus for blocking activation of tissue or conduction of action potentials while other tissue is being therapeutically activated
US7054692 *15 May 200230 May 2006Advanced Bionics CorporationFixation device for implantable microdevices
US7072720 *14 Jun 20024 Jul 2006Emory UniversityDevices and methods for vagus nerve stimulation
US7203548 *20 Jun 200210 Abr 2007Advanced Bionics CorporationCavernous nerve stimulation via unidirectional propagation of action potentials
US20010003799 *30 Nov 200014 Jun 2001Boveja Birinder BobApparatus 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
US20020016615 *1 Oct 20017 Feb 2002Dev Nagendu B.Electrically induced vessel vasodilation
US20020022873 *10 Ago 200121 Feb 2002Erickson John H.Stimulation/sensing lead adapted for percutaneous insertion
US20020055779 *5 Mar 19979 May 2002Brian J. AndrewsNeural prosthesis
US20020099256 *12 Nov 200125 Jul 2002Joseph ManneElectromagnetically induced anesthesia and sensory stimulation
US20020099419 *4 Abr 200125 Jul 2002Biocontrol Medical Bcm Ltd.Method and apparatus for selective control of nerve fibers
US20020161415 *26 Abr 200131 Oct 2002Ehud CohenActuation and control of limbs through motor nerve stimulation
US20030004546 *8 Jul 20022 Ene 2003Casey Don E.Subcutaneously implantable power supply
US20030045909 *24 Jul 20026 Mar 2003Biocontrol Medical Ltd.Selective nerve fiber stimulation for treating heart conditions
US20030045914 *31 Ago 20016 Mar 2003Biocontrol Medical Ltd.Treatment of disorders by unidirectional nerve stimulation
US20030050677 *24 Jul 200213 Mar 2003Biocontrol Medical Ltd.Electrode assembly for nerve control
US20030100933 *24 Sep 200229 May 2003Biocontrol Medical Ltd.Nerve stimulation for treating spasticity, tremor, muscle weakness, and other motor disorders
US20030114905 *27 Ene 200319 Jun 2003Kuzma Janusz A.Implantable microdevice with extended lead and remote electrode
US20030203890 *29 May 200230 Oct 2003Steiner Joseph P.Method for treating nerve injury caused as a result of surgery
US20040034394 *15 Ago 200319 Feb 2004Woods Carla MannImplantable generator having current steering means
US20040172089 *24 Ene 20022 Sep 2004Whitehurst Todd K.Fully implantable miniature neurostimulator for stimulation as a therapy for epilepsy
US20050101878 *18 Abr 200212 May 2005Daly Christopher N.Method and apparatus for measurement of evoked neural response
Citada por
Patente citante Fecha de presentación Fecha de publicación Solicitante Título
US686248029 Nov 20011 Mar 2005Biocontrol Medical Ltd.Pelvic disorder treatment device
US710710316 Oct 200212 Sep 2006Alfred E. Mann Foundation For Scientific ResearchFull-body charger for battery-powered patient implantable device
US720050416 May 20053 Abr 2007Advanced Bionics CorporationMeasuring temperature change in an electronic biomedical implant
US720354820 Jun 200210 Abr 2007Advanced Bionics CorporationCavernous nerve stimulation via unidirectional propagation of action potentials
US72990911 Jul 200320 Nov 2007Cyberonics, Inc.Treatment of obesity by bilateral vagus nerve stimulation
US731055729 Abr 200518 Dic 2007Maschino Steven EIdentification of electrodes for nerve stimulation in the treatment of eating disorders
US732807028 Abr 20055 Feb 2008Medtronic, Inc.Multi-tube sensor for sensing urinary sphincter and urethral pressure
US734030618 Ago 20034 Mar 2008Cyberonics, Inc.Treatment of obesity by sub-diaphragmatic nerve stimulation
US736657110 Dic 200429 Abr 2008Cyberonics, Inc.Neurostimulator with activation based on changes in body temperature
US73699008 May 20046 May 2008Bojan ZdravkovicNeural bridge devices and methods for restoring and modulating neural activity
US738760330 Nov 200417 Jun 2008Ams Research CorporationIncontinence treatment device
US740610510 Jun 200429 Jul 2008Alfred E. Mann Foundation For Scientific ResearchSystem and method for sharing a common communication channel between multiple systems of implantable medical devices
US742644516 Feb 200716 Sep 2008Boston Scientific Neuromodulation CorporationMeasuring temperature change in an electronic biomedical implant
US745099416 Dic 200411 Nov 2008Advanced Bionics, LlcEstimating flap thickness for cochlear implants
US745099821 Nov 200311 Nov 2008Alfred E. Mann Foundation For Scientific ResearchMethod of placing an implantable device proximate to neural/muscular tissue
US746701627 Ene 200616 Dic 2008Cyberonics, Inc.Multipolar stimulation electrode with mating structures for gripping targeted tissue
US758205324 Sep 20031 Sep 2009Ams Research CorporationControl of urge incontinence
US75995009 Dic 20046 Oct 2009Advanced Bionics, LlcProcessing signals representative of sound based on the identity of an input element
US761009328 Abr 200527 Oct 2009Medtronic, Inc.Implantable optical pressure sensor for sensing urinary sphincter pressure
US761351628 Nov 20023 Nov 2009Ams Research CorporationPelvic disorder treatment device
US762392328 Abr 200524 Nov 2009Medtronic, Inc.Tube sensor for penile tumescence
US764388120 Ene 20065 Ene 2010Cyberonics, Inc.Neurostimulation with activation based on changes in body temperature
US764711413 Sep 200412 Ene 2010Cardiac Pacemakers, Inc.Baroreflex modulation based on monitored cardiovascular parameter
US76573123 Nov 20032 Feb 2010Cardiac Pacemakers, Inc.Multi-site ventricular pacing therapy with parasympathetic stimulation
US766063122 Abr 20059 Feb 2010Boston Scientific Neuromodulation CorporationMethods and systems for electrical and/or drug stimulation as a therapy for erectile dysfunction
US770239617 Nov 200420 Abr 2010Advanced Bionics, LlcOptimizing pitch allocation in a cochlear implant
US771141913 Jul 20054 May 2010Cyberonics, Inc.Neurostimulator with reduced size
US771591915 Oct 200311 May 2010Medtronic, Inc.Control of treatment therapy during start-up and during operation of a medical device system
US772054828 Abr 200618 May 2010MedtronicImpedance-based stimulation adjustment
US772975830 Nov 20051 Jun 2010Boston Scientific Neuromodulation CorporationMagnetically coupled microstimulators
US772977521 Mar 20061 Jun 2010Advanced Bionics, LlcSpectral contrast enhancement in a cochlear implant speech processor
US773435523 Ene 20028 Jun 2010Bio Control Medical (B.C.M.) Ltd.Treatment of disorders by unidirectional nerve stimulation
US7765013 *4 Jun 200727 Jul 2010Wisconsin Alumni Research FoundationNano- and micro-scale wireless stimulating probe
US778336021 Oct 200724 Ago 2010Bojan ZdravkovicSensory system
US778336322 Oct 200724 Ago 2010Artis Nanomedica, Inc.Neural bridge gateway and calibrator
US780160026 May 200521 Sep 2010Boston Scientific Neuromodulation CorporationControlling charge flow in the electrical stimulation of tissue
US780160224 Mar 200621 Sep 2010Boston Scientific Neuromodulation CorporationControlling stimulation parameters of implanted tissue stimulators
US78031487 Jun 200728 Sep 2010Neurosystec CorporationFlow-induced delivery from a drug mass
US781380428 Sep 200712 Oct 2010Boston Scientific Neuromodulation CorporationMethods and systems for treating a nerve compression syndrome
US781806927 Jul 200719 Oct 2010Cyberonics, Inc.Ribbon electrode
US783579629 Abr 200516 Nov 2010Cyberonics, Inc.Weight loss method and device
US78377199 May 200323 Nov 2010Daemen CollegeElectrical stimulation unit and waterbath system
US784028027 Jul 200523 Nov 2010Cyberonics, Inc.Cranial nerve stimulation to treat a vocal cord disorder
US785627328 Jul 200521 Dic 2010Cyberonics, Inc.Autonomic nerve stimulation to treat a gastrointestinal disorder
US785781930 Nov 200628 Dic 2010Boston Scientific Neuromodulation CorporationImplant tool for use with a microstimulator
US786057020 Jun 200228 Dic 2010Boston Scientific Neuromodulation CorporationImplantable microstimulators and methods for unidirectional propagation of action potentials
US786524324 Ene 20064 Ene 2011Boston Scientific Neuromodulation CorporationDevice and therapy for erectile dysfunction and other sexual dysfunction
US786986727 Oct 200611 Ene 2011Cyberonics, Inc.Implantable neurostimulator with refractory stimulation
US786988124 Dic 200311 Ene 2011Cardiac Pacemakers, Inc.Baroreflex stimulator with integrated pressure sensor
US786988426 Abr 200711 Ene 2011Cyberonics, Inc.Non-surgical device and methods for trans-esophageal vagus nerve stimulation
US786988528 Abr 200611 Ene 2011Cyberonics, IncThreshold optimization for tissue stimulation therapy
US787713628 Sep 200725 Ene 2011Boston Scientific Neuromodulation CorporationEnhancement of neural signal transmission through damaged neural tissue via hyperpolarizing electrical stimulation current
US7881803 *18 Oct 20061 Feb 2011Boston Scientific Neuromodulation CorporationMulti-electrode implantable stimulator device with a single current path decoupling capacitor
US788180414 Mar 20071 Feb 2011Kenergy, Inc.Composite waveform based method and apparatus for animal tissue stimulation
US789017617 Jun 200515 Feb 2011Boston Scientific Neuromodulation CorporationMethods and systems for treating chronic pelvic pain
US789017724 Ene 200615 Feb 2011Boston Scientific Neuromodulation CorporationDevice and therapy for erectile dysfunction and other sexual dysfunction
US789953928 Sep 20061 Mar 2011Boston Scientific Neuromodulation CorporationCavernous nerve stimulation via unidirectional propagation of action potentials
US789954029 Abr 20051 Mar 2011Cyberonics, Inc.Noninvasively adjustable gastric band
US790417526 Abr 20078 Mar 2011Cyberonics, Inc.Trans-esophageal vagus nerve stimulation
US7912537 *27 Abr 200622 Mar 2011Medtronic, Inc.Telemetry-synchronized physiological monitoring and therapy delivery systems
US79172067 Nov 200629 Mar 2011Medtronic, Inc.Signal quality monitoring and control for a medical device system
US791723030 Ene 200729 Mar 2011Cardiac Pacemakers, Inc.Neurostimulating lead having a stent-like anchor
US79209242 Oct 20085 Abr 2011Advanced Bionics, LlcEstimating flap thickness for cochlear implants
US793364613 Ago 200726 Abr 2011Medtronic, Inc.Clustering of recorded patient neurological activity to determine length of a neurological event
US79336539 Oct 200926 Abr 2011Medtronic, Inc.Implantable optical pressure sensor for sensing urinary sphincter pressure
US794532924 Jul 200917 May 2011Cranial Medical Systems, Inc.Multi-channel connector for brain stimulation system
US794940930 Ene 200724 May 2011Cardiac Pacemakers, Inc.Dual spiral lead configurations
US796221427 Jul 200714 Jun 2011Cyberonics, Inc.Non-surgical device and methods for trans-esophageal vagus nerve stimulation
US797470127 Abr 20075 Jul 2011Cyberonics, Inc.Dosing limitation for an implantable medical device
US797470513 Nov 20095 Jul 2011Proteus Biomedical, Inc.Multiplexed multi-electrode neurostimulation devices
US797470726 Ene 20075 Jul 2011Cyberonics, Inc.Electrode assembly with fibers for a medical device
US797646517 Oct 200612 Jul 2011Medtronic, IncPhase shifting of neurological signals in a medical device system
US799577125 Sep 20069 Ago 2011Advanced Bionics, LlcBeamforming microphone system
US800079323 May 200816 Ago 2011Cardiac Pacemakers, Inc.Automatic baroreflex modulation based on cardiac activity
US802405024 Dic 200320 Sep 2011Cardiac Pacemakers, Inc.Lead for stimulating the baroreceptors in the pulmonary artery
US802773328 Oct 200527 Sep 2011Advanced Bionics, LlcOptimizing pitch allocation in a cochlear stimulation system
US806891028 Abr 200529 Nov 2011Medtronic, Inc.Flexible tube sensor for sensing urinary sphincter pressure
US808366317 Jun 200927 Dic 2011Ams Research CorporationPelvic disorder treatment
US80837417 Jun 200527 Dic 2011Synthes Usa, LlcOrthopaedic implant with sensors
US810804928 Abr 200631 Ene 2012Medtronic, Inc.Impedance-based stimulation adjustment
US811875021 Oct 200521 Feb 2012Medtronic, Inc.Flow sensors for penile tumescence
US812169822 Mar 201021 Feb 2012Advanced Bionics, LlcOuter hair cell stimulation model for the use by an intra-cochlear implant
US81217024 Mar 201021 Feb 2012Medtronic, Inc.Impedance-based stimulation adjustment
US812656024 Dic 200328 Feb 2012Cardiac Pacemakers, Inc.Stimulation lead for stimulating the baroreceptors in the pulmonary artery
US813137711 Jul 20076 Mar 2012Boston Scientific Neuromodulation CorporationTelemetry listening window management for an implantable medical device
US815050829 Mar 20073 Abr 2012Catholic Healthcare WestVagus nerve stimulation method
US816071010 Jul 200717 Abr 2012Ams Research CorporationSystems and methods for implanting tissue stimulation electrodes in the pelvic region
US817066814 Jul 20061 May 2012Cardiac Pacemakers, Inc.Baroreflex sensitivity monitoring and trending for tachyarrhythmia detection and therapy
US817067922 Abr 20101 May 2012Advanced Bionics, LlcSpectral contrast enhancement in a cochlear implant speech processor
US81757176 Sep 20058 May 2012Boston Scientific Neuromodulation CorporationUltracapacitor powered implantable pulse generator with dedicated power supply
US818045520 Ene 201015 May 2012Advanced Bionics, LLVOptimizing pitch allocation in a cochlear implant
US818046218 Abr 200615 May 2012Cyberonics, Inc.Heat dissipation for a lead assembly
US818718115 Oct 200329 May 2012Medtronic, Inc.Scoring of sensed neurological signals for use with a medical device system
US81952965 May 20065 Jun 2012Ams Research CorporationApparatus for treating stress and urge incontinence
US82003314 Nov 200412 Jun 2012Cardiac Pacemakers, Inc.System and method for filtering neural stimulation
US820033218 Sep 200912 Jun 2012Cardiac Pacemakers, Inc.System and method for filtering neural stimulation
US820460325 Abr 200819 Jun 2012Cyberonics, Inc.Blocking exogenous action potentials by an implantable medical device
US821918829 Mar 200710 Jul 2012Catholic Healthcare WestSynchronization of vagus nerve stimulation with the cardiac cycle of a patient
US824437830 Ene 200714 Ago 2012Cardiac Pacemakers, Inc.Spiral configurations for intravascular lead stability
US826528625 Jun 200911 Sep 2012Advanced Bionics CorporationProcessing signals representative of sound based on the identity of an input element
US82679051 May 200618 Sep 2012Neurosystec CorporationApparatus and method for delivery of therapeutic and other types of agents
US828050510 Mar 20092 Oct 2012Catholic Healthcare WestVagus nerve stimulation method
US829593520 Mar 200723 Oct 2012University Of Florida Research Foundation, Inc.Multiple lead method for deep brain stimulation
US82959376 Sep 201123 Oct 2012Advanced Bionics, LlcOptimizing pitch allocation in a cochlear stimulation system
US829594623 May 201123 Oct 2012Cyberonics, Inc.Electrode assembly with fibers for a medical device
US829817619 Jul 201030 Oct 2012Neurosystec CorporationFlow-induced delivery from a drug mass
US83116474 Abr 201113 Nov 2012Cardiac Pacemakers, Inc.Direct delivery system for transvascular lead
US8321025 *26 Jul 200727 Nov 2012Cranial Medical Systems, Inc.Lead and methods for brain monitoring and modulation
US834078612 Jun 200825 Dic 2012Ams Research CorporationIncontinence treatment device
US836426728 Ene 200929 Ene 2013Boston Scientific Neuromodulation CorporationFixation of implantable pulse generators
US836996324 Ene 20115 Feb 2013Boston Scientific Neuromodulation CorporationMulti-electrode implantable stimulator device with a single current path decoupling capacitor
US838031230 Dic 201019 Feb 2013Ams Research CorporationMulti-zone stimulation implant system and method
US838605624 Feb 200526 Feb 2013Bio Control Medical (B.C.M.) Ltd.Parasympathetic stimulation for treating atrial arrhythmia and heart failure
US839197026 Ago 20085 Mar 2013The Feinstein Institute For Medical ResearchDevices and methods for inhibiting granulocyte activation by neural stimulation
US841233817 Nov 20092 Abr 2013Setpoint Medical CorporationDevices and methods for optimizing electrode placement for anti-inflamatory stimulation
US84123507 Mar 20112 Abr 2013Cardiac Pacemakers, Inc.Neurostimulating lead having a stent-like anchor
US84426404 Ene 201014 May 2013Cardiac Pacemakers, Inc.Neural stimulation modulation based on monitored cardiovascular parameter
US84577464 Ago 20114 Jun 2013Cardiac Pacemakers, Inc.Implantable systems and devices for providing cardiac defibrillation and apnea therapy
US845774720 Oct 20084 Jun 2013Cyberonics, Inc.Neurostimulation with signal duration determined by a cardiac cycle
US8467875 *28 Mar 200718 Jun 2013Medtronic, Inc.Stimulation of dorsal genital nerves to treat urologic dysfunctions
US84730766 Sep 201125 Jun 2013Cardiac Pacemakers, Inc.Lead for stimulating the baroreceptors in the pulmonary artery
US847841124 Oct 20112 Jul 2013Medtronic, Inc.Flexible tube sensor for sensing urinary sphincter pressure
US847842012 Jul 20062 Jul 2013Cyberonics, Inc.Implantable medical device charge balance assessment
US847842823 Abr 20102 Jul 2013Cyberonics, Inc.Helical electrode for nerve stimulation
US848383923 Feb 20129 Jul 2013Medtronic, Inc.Activity sensing for stimulator control
US84838468 Abr 20109 Jul 2013Cyberonics, Inc.Multi-electrode assembly for an implantable medical device
US850368523 Nov 20106 Ago 2013Advanced Bionics AgAuditory front end customization
US853277827 Ago 200710 Sep 2013The United States Of America As Represented By The Department Of Veterans AffairsRestoring cough using microstimulators
US8543214 *15 Oct 200324 Sep 2013Medtronic, Inc.Configuring and testing treatment therapy parameters for a medical device system
US85486046 Dic 20101 Oct 2013Boston Scientific Neuromodulation CorporationImplantable microstimulators and methods for unidirectional propagation of action potentials
US856586725 Ene 200822 Oct 2013Cyberonics, Inc.Changeable electrode polarity stimulation by an implantable medical device
US85716537 Feb 201129 Oct 2013Bio Control Medical (B.C.M.) Ltd.Nerve stimulation techniques
US857165526 Ene 201029 Oct 2013Cardiac Pacemakers, Inc.Multi-site ventricular pacing therapy with parasympathetic stimulation
US857978615 Oct 200312 Nov 2013Medtronic, Inc.Screening techniques for management of a nervous system disorder
US858323713 Sep 201012 Nov 2013Cranial Medical Systems, Inc.Devices and methods for tissue modulation and monitoring
US859479815 Oct 200326 Nov 2013Medtronic, Inc.Multi-modal operation of a medical device system
US860052127 Ene 20053 Dic 2013Cyberonics, Inc.Implantable medical device having multiple electrode/sensor capability and stimulation based on sensed intrinsic activity
US8612002 *23 Dic 201017 Dic 2013Setpoint Medical CorporationNeural stimulation devices and systems for treatment of chronic inflammation
US861530230 Mar 200924 Dic 2013Advanced Bionics AgInner hair cell stimulation model for use by a cochlear implant system
US861530929 Mar 200724 Dic 2013Catholic Healthcare WestMicroburst electrical stimulation of cranial nerves for the treatment of medical conditions
US862044511 Abr 201231 Dic 2013Advanced Bionics AgOptimizing pitch allocation in a cochlear implant
US86263013 Jun 20137 Ene 2014Cardiac Pacemakers, Inc.Automatic baroreflex modulation based on cardiac activity
US863491217 Ene 201221 Ene 2014Pacesetter, Inc.Dual-chamber leadless intra-cardiac medical device with intra-cardiac extension
US86449196 Oct 20094 Feb 2014Proteus Digital Health, Inc.Shielded stimulation and sensing system and method
US8660664 *18 Ene 201325 Feb 2014Boston Scientific Neuromodulation CorporationMethods for forming implantable medical devices
US866066610 Mar 200925 Feb 2014Catholic Healthcare WestMicroburst electrical stimulation of cranial nerves for the treatment of medical conditions
US866649328 Ene 20134 Mar 2014Boston Scientific Neuromodulation CorporationFixation of implantable pulse generators
US867084214 Dic 201211 Mar 2014Pacesetter, Inc.Intra-cardiac implantable medical device
US8700163 *29 Abr 200515 Abr 2014Cyberonics, Inc.Cranial nerve stimulation for treatment of substance addiction
US870018021 Jun 201215 Abr 2014Boston Scientific Neuromodulation CorporationMethod for improving far-field activation in peripheral field nerve stimulation
US870018117 Ene 201215 Abr 2014Pacesetter, Inc.Single-chamber leadless intra-cardiac medical device with dual-chamber functionality and shaped stabilization intra-cardiac extension
US871254728 Feb 201129 Abr 2014Boston Scientific Neuromodulation CorporationCavernous nerve stimulation via unidirectional propagation of action potentials
US87187804 Ago 20116 May 2014Boston Scientific Neuromodulation CorporationSystem for selectively performing local and radial peripheral stimulation
US872912924 Mar 200520 May 2014The Feinstein Institute For Medical ResearchNeural tourniquet
US873812610 Mar 200927 May 2014Catholic Healthcare WestSynchronization of vagus nerve stimulation with the cardiac cycle of a patient
US873813613 Ago 200727 May 2014Medtronic, Inc.Clustering of recorded patient neurological activity to determine length of a neurological event
US873815424 May 201127 May 2014Proteus Digital Health, Inc.Multiplexed multi-electrode neurostimulation devices
US875589320 Jun 201217 Jun 2014Bluewind Medical Ltd.Tibial nerve stimulation
US876846230 May 20121 Jul 2014Cardiac Pacemakers, Inc.System and method for filtering neural stimulation
US87749371 Dic 20108 Jul 2014Ecole Polytechnique Federale De LausanneMicrofabricated surface neurostimulation device and methods of making and using the same
US877494227 Mar 20128 Jul 2014Ams Research CorporationTissue anchor
US878160517 Ene 201215 Jul 2014Pacesetter, Inc.Unitary dual-chamber leadless intra-cardiac medical device and method of implanting same
US87880349 May 201222 Jul 2014Setpoint Medical CorporationSingle-pulse activation of the cholinergic anti-inflammatory pathway to treat chronic inflammation
US878804229 Jul 200922 Jul 2014Ecole Polytechnique Federale De Lausanne (Epfl)Apparatus and method for optimized stimulation of a neurological target
US8788045 *8 Jun 201022 Jul 2014Bluewind Medical Ltd.Tibial nerve stimulation
US878806412 Nov 200922 Jul 2014Ecole Polytechnique Federale De LausanneMicrofabricated neurostimulation device
US880551323 Abr 201312 Ago 2014Cardiac Pacemakers, Inc.Neural stimulation modulation based on monitored cardiovascular parameter
US880551930 Sep 201012 Ago 2014Nevro CorporationSystems and methods for detecting intrathecal penetration
US88185175 May 200626 Ago 2014Advanced Bionics AgInformation processing and storage in a cochlear stimulation system
US882517512 Ene 20122 Sep 2014Medtronic, Inc.Impedance-based stimulation adjustment
US883173731 May 20139 Sep 2014Medtronic, Inc.Activity sensing for stimulator control
US88494158 Abr 201130 Sep 2014Boston Scientific Neuromodulation CorporationMulti-channel connector for brain stimulation system
US8855767 *15 Nov 20137 Oct 2014Setpoint Medical CorporationNeural stimulation devices and systems for treatment of chronic inflammation
US886820326 Oct 200721 Oct 2014Cyberonics, Inc.Dynamic lead condition detection for an implantable medical device
US887421823 Abr 201328 Oct 2014Cyberonics, Inc.Neurostimulation with signal duration determined by a cardiac cycle
US88863399 Jun 201011 Nov 2014Setpoint Medical CorporationNerve cuff with pocket for leadless stimulator
US891411417 Nov 200416 Dic 2014The Feinstein Institute For Medical ResearchInhibition of inflammatory cytokine production by cholinergic agonists and vagus nerve stimulation
US891413121 Feb 201416 Dic 2014Pacesetter, Inc.Method of implanting a single-chamber leadless intra-cardiac medical device with dual-chamber functionality and shaped stabilization intra-cardiac extension
US894279826 Oct 200727 Ene 2015Cyberonics, Inc.Alternative operation mode for an implantable medical device based upon lead condition
US896548230 Sep 201024 Feb 2015Nevro CorporationSystems and methods for positioning implanted devices in a patient
US899610931 May 201231 Mar 2015Pacesetter, Inc.Leadless intra-cardiac medical device with dual chamber sensing through electrical and/or mechanical sensing
US8996116 *1 Nov 201031 Mar 2015Setpoint Medical CorporationModulation of the cholinergic anti-inflammatory pathway to treat pain or addiction
US901734117 Ene 201228 Abr 2015Pacesetter, Inc.Multi-piece dual-chamber leadless intra-cardiac medical device and method of implanting same
US903726125 Feb 201419 May 2015Boston Scientific Neuromodulation CorporationMethod for improving far-field activation in peripheral field nerve stimulation
US907283225 Abr 20147 Jul 2015Medtronic, Inc.Clustering of recorded patient neurological activity to determine length of a neurological event
US907290418 Ene 20137 Jul 2015Boston Scientific Neuromodulation CorporationMulti-electrode implantable stimulator device with a single current path decoupling capacitor
US907290626 Jun 20147 Jul 2015Ecole Polytechnique Federale De LausanneApparatus and method for optimized stimulation of a neurological target
US910804125 Nov 201318 Ago 2015Dignity HealthMicroburst electrical stimulation of cranial nerves for the treatment of medical conditions
US91620498 Oct 201320 Oct 2015Boston Scientific Neuromodulation CorporationDevices and methods for tissue modulation and monitoring
US91620647 Oct 201420 Oct 2015Setpoint Medical CorporationNeural stimulation devices and systems for treatment of chronic inflammation
US91740417 Nov 20143 Nov 2015Setpoint Medical CorporationNerve cuff with pocket for leadless stimulator
US91865043 Dic 201417 Nov 2015Rainbow Medical LtdSleep apnea treatment
US919276727 May 201424 Nov 2015Ecole Polytechnique Federale De LausanneMicrofabricated surface neurostimulation device and methods of making and using the same
US921140931 Mar 200915 Dic 2015The Feinstein Institute For Medical ResearchMethods and systems for reducing inflammation by neuromodulation of T-cell activity
US921141021 Jul 201415 Dic 2015Setpoint Medical CorporationExtremely low duty-cycle activation of the cholinergic anti-inflammatory pathway to treat chronic inflammation
US92208877 Jun 201229 Dic 2015Astora Women's Health LLCElectrode lead including a deployable tissue anchor
US925438421 Nov 20139 Feb 2016Advanced Bionics AgInner hair cell stimulation model for use by a cochlear implant system
US926543617 Ene 201223 Feb 2016Pacesetter, Inc.Leadless intra-cardiac medical device with built-in telemetry system
US927821824 Feb 20158 Mar 2016Pacesetter, Inc.Leadless intra-cardiac medical device with dual chamber sensing through electrical and/or mechanical sensing
US928339426 Sep 201315 Mar 2016Boston Scientific Neuromodulation CorporationImplantable microstimulators and methods for unidirectional propagation of action potentials
US92895993 Abr 201222 Mar 2016Dignity HealthVagus nerve stimulation method
US928961027 Ago 201222 Mar 2016Boston Scientific Neuromodulation CorporationFractionalized stimulation pulses in an implantable stimulator device
US931461431 Oct 201219 Abr 2016Boston Scientific Neuromodulation CorporationLead and methods for brain monitoring and modulation
US931463331 Ago 201219 Abr 2016Cyberonics, Inc.Contingent cardio-protection for epilepsy patients
US934589115 Ene 201524 May 2016Nevro CorporationSystems and methods for positioning implanted devices in a patient
US93583888 Jul 20147 Jun 2016Nevro CorporationSystems and methods for detecting intrathecal penetration
US937066026 Mar 201421 Jun 2016Rainbow Medical Ltd.Independently-controlled bidirectional nerve stimulation
US939341429 Dic 201519 Jul 2016Advanced Bionics AgInner hair cell stimulation model for use by a cochlear implant system
US939342114 Jul 201019 Jul 2016Boston Scientific Neuromodulation CorporationControlling charge flow in the electrical stimulation of tissue
US939342311 Jul 201419 Jul 2016Boston Scientific Neuromodulation CorporationFractionalized stimulation pulses in an implantable stimulator device
US939913025 Abr 200726 Jul 2016Medtronic, Inc.Cannula configured to deliver test stimulation
US940301127 Ago 20142 Ago 2016Aleva NeurotherapeuticsLeadless neurostimulator
US94030204 Oct 20122 Ago 2016Nevro CorporationModeling positions of implanted devices in a patient
US9415217 *10 Jul 201416 Ago 2016Eric Ye ChenWireless electrical stimulation system
US942757323 Jun 201130 Ago 2016Astora Women's Health, LlcDeployable electrode lead anchor
US94400781 Jul 201413 Sep 2016Cardiac Pacemakers, Inc.Neural stimulation modulation based on monitored cardiovascular parameter
US944008219 Jun 201413 Sep 2016Ecole Polytechnique Federale De LausanneMicrofabricated neurostimulation device
US945718629 Jul 20144 Oct 2016Bluewind Medical Ltd.Bilateral feedback
US94633156 Jun 201411 Oct 2016Pacesetter, Inc.Method of implanting a unitary dual-chamber leadless intra-cardiac medical device
US947489427 Ago 201425 Oct 2016Aleva NeurotherapeuticsDeep brain stimulation lead
US95266379 Sep 201227 Dic 2016Enopace Biomedical Ltd.Wireless endovascular stent-based electrodes
US953314928 Mar 20143 Ene 2017Boston Scientific Neuromodulation CorporationMethod for selectively performing local and radial peripheral stimulation
US953315110 Ene 20143 Ene 2017Dignity HealthMicroburst electrical stimulation of cranial nerves for the treatment of medical conditions
US953943318 Mar 200910 Ene 2017Astora Women's Health, LlcElectrode implantation in a pelvic floor muscular structure
US954970831 Mar 201124 Ene 2017Ecole Polytechnique Federale De LausanneDevice for interacting with neurological tissue and methods of making and using the same
US956105325 Abr 20077 Feb 2017Medtronic, Inc.Implant tool to facilitate medical device implantation
US957298326 Mar 201321 Feb 2017Setpoint Medical CorporationDevices and methods for modulation of bone erosion
US957298527 Jun 201621 Feb 2017Aleva NeurotherapeuticsMethod of manufacturing a thin film leadless neurostimulator
US958604721 Nov 20157 Mar 2017Cyberonics, Inc.Contingent cardio-protection for epilepsy patients
US959752121 Ene 201521 Mar 2017Bluewind Medical Ltd.Transmitting coils for neurostimulation
US960405519 Nov 201528 Mar 2017Ecole Polytechnique Federale De LausanneMicrofabricated surface neurostimulation device and methods of making and using the same
US966249011 Dic 201530 May 2017The Feinstein Institute For Medical ResearchMethods and systems for reducing inflammation by neuromodulation and administration of an anti-inflammatory drug
US966806830 Jun 201130 May 2017Advanced Bionics, LlcBeamforming microphone system
US9675270 *20 Abr 201613 Jun 2017Medtronic, Inc.Method and apparatus for determining a premature ventricular contraction in a medical monitoring device
US97007163 Nov 201511 Jul 2017Setpoint Medical CorporationNerve cuff with pocket for leadless stimulator
US971370712 Nov 201525 Jul 2017Bluewind Medical Ltd.Inhibition of implant migration
US973111228 Ago 201215 Ago 2017Paul J. GindeleImplantable electrode assembly
US97377132 Jun 201522 Ago 2017Boston Scientific Neuromodulation CorporationMulti-electrode implantable stimulator device with a single current path decoupling capacitor
US20030078634 *16 Oct 200224 Abr 2003Schulman Joseph H.Full-body charger for battery-powered patient implantable device
US20030236557 *20 Jun 200225 Dic 2003Whitehurst Todd K.Cavernous nerve stimulation via unidirectional propagation of action potentials
US20040015204 *20 Jun 200222 Ene 2004Whitehurst Todd K.Implantable microstimulators and methods for unidirectional propagation of action potentials
US20040024428 *1 Jul 20035 Feb 2004Burke BarrettTreatment of obesity by bilateral vagus nerve stimulation
US20040039427 *18 Ago 200326 Feb 2004Cyberonics, Inc.Treatment of obesity by sub-diaphragmatic nerve stimulation
US20040133119 *15 Oct 20038 Jul 2004Medtronic, Inc.Scoring of sensed neurological signals for use with a medical device system
US20040138516 *15 Oct 200315 Jul 2004Medtronic, Inc.Configuring and testing treatment therapy parameters for a medical device system
US20040138711 *15 Oct 200315 Jul 2004Medtronic, Inc.Control of treatment therapy during start-up and during operation of a medical device system
US20050049648 *12 Oct 20043 Mar 2005Biocontrol Medical Ltd.Pelvic disorder treatment device
US20050113881 *30 Nov 200426 May 2005Yossi GrossIncontinence treatment device
US20050125044 *17 Nov 20049 Jun 2005North Shore-Long Island Jewish Research InstituteInhibition of inflammatory cytokine production by cholinergic agonists and vagus nerve stimulation
US20050137651 *17 Nov 200423 Jun 2005Litvak Leonid M.Optimizing pitch allocation in a cochlear implant
US20050143779 *13 Sep 200430 Jun 2005Cardiac Pacemakers, Inc.Baroreflex modulation based on monitored cardiovascular parameter
US20050149143 *24 Dic 20037 Jul 2005Imad LibbusBaroreflex stimulator with integrated pressure sensor
US20050149155 *24 Dic 20037 Jul 2005Avram ScheinerStimulation lead for stimulating the baroreceptors in the pulmonary artery
US20050187586 *24 Feb 200525 Ago 2005Biocontrol Medical Ltd.Selective nerve fiber stimulation for treating heart conditions
US20050197680 *10 Jun 20048 Sep 2005Delmain Gregory J.System and method for sharing a common communication channel between multiple systems of implantable medical devices
US20050209652 *22 Abr 200522 Sep 2005Whitehurst Todd KMethods and systems for electrical and/or drug stimulation as a therapy for erectile dysfunction
US20050216069 *28 Nov 200229 Sep 2005Biocontrol Medical Ltd.Pelvic disorder treatment device
US20050222226 *22 Abr 20056 Oct 2005Sumitomo Pharmaceuticals Company, LimitedFive-membered cyclic compounds
US20050240229 *31 May 200527 Oct 2005Whitehurst Tood KMethods and systems for stimulation as a therapy for erectile dysfunction
US20050251221 *8 May 200410 Nov 2005Bojan ZdravkovicNeural bridge devices and methods for restoring and modulating neural activity
US20050282906 *24 Mar 200522 Dic 2005North Shore-Long Island Jewish Research InstituteNeural tourniquet
US20060052782 *7 Jun 20059 Mar 2006Chad MorganOrthopaedic implant with sensors
US20060095080 *4 Nov 20044 May 2006Cardiac Pacemakers, Inc.System and method for filtering neural stimulation
US20060129202 *10 Dic 200415 Jun 2006Cyberonics, Inc.Neurostimulator with activation based on changes in body temperature
US20060142802 *20 Ene 200629 Jun 2006Cyberonics, Inc.Neurostimulation with activation based on changes in body temperature
US20060173494 *28 Ene 20053 Ago 2006Cyberonics, Inc.Trained and adaptive response in a neurostimulator
US20060173495 *28 Ene 20053 Ago 2006Cyberonics, Inc.Autocapture in a neurostimulator
US20060178703 *22 Dic 200510 Ago 2006Huston Jared MTreating inflammatory disorders by electrical vagus nerve stimulation
US20060200208 *29 Abr 20057 Sep 2006Cyberonics, Inc.Cranial nerve stimulation for treatment of substance addiction
US20060229688 *24 Mar 200612 Oct 2006Mcclure Kelly HControlling stimulation parameters of implanted tissue stimulators
US20060247682 *28 Abr 20052 Nov 2006Medtronic, Inc.Tube sensor for penile tumescence
US20060247719 *29 Abr 20052 Nov 2006Cyberonics, Inc.Weight loss method and advice
US20060247721 *29 Abr 20052 Nov 2006Cyberonics, Inc.Identification of electrodes for nerve stimulation in the treatment of eating disorders
US20060247722 *29 Abr 20052 Nov 2006Cyberonics, Inc.Noninvasively adjustable gastric band
US20060247723 *28 Abr 20052 Nov 2006Medtronic, Inc.Flexible tube sensor for sensing urinary sphincter pressure
US20060247724 *28 Abr 20052 Nov 2006Medtronic, Inc.Implantable optical pressure sensor for sensing urinary sphincter pressure
US20060253174 *28 Abr 20069 Nov 2006Medtronic, Inc.Impedance-based stimulation adjustment
US20060259079 *28 Abr 200616 Nov 2006Medtronic, Inc.Impedance-based stimulation adjustment
US20060264897 *24 Ene 200623 Nov 2006Neurosystec CorporationApparatus and method for delivering therapeutic and/or other agents to the inner ear and to other tissues
US20070016263 *13 Jul 200518 Ene 2007Cyberonics, Inc.Neurostimulator with reduced size
US20070021786 *25 Jul 200525 Ene 2007Cyberonics, Inc.Selective nerve stimulation for the treatment of angina pectoris
US20070021800 *28 Sep 200625 Ene 2007Advanced Bionics Corporation, A California CorporationCavernous nerve stimulation via unidirectional propagation of action potentials
US20070027484 *28 Jul 20051 Feb 2007Cyberonics, Inc.Autonomic nerve stimulation to treat a pancreatic disorder
US20070027492 *28 Jul 20051 Feb 2007Cyberonics, Inc.Autonomic nerve stimulation to treat a gastrointestinal disorder
US20070027497 *27 Jul 20051 Feb 2007Cyberonics, Inc.Nerve stimulation for treatment of syncope
US20070027504 *27 Jul 20051 Feb 2007Cyberonics, Inc.Cranial nerve stimulation to treat a hearing disorder
US20070055308 *6 Sep 20058 Mar 2007Haller Matthew IUltracapacitor powered implantable pulse generator with dedicated power supply
US20070078493 *4 Oct 20055 Abr 2007Medtronic, Inc.Impedance-based penile tumescence sensor
US20070092862 *21 Oct 200526 Abr 2007Medtronic, Inc.Flow sensors for penile tumescence
US20070100278 *7 Nov 20063 May 2007Medtronic, Inc.Signal Quality Monitoring And Control For A Medical Device System
US20070123938 *30 Nov 200531 May 2007Haller Matthew IMagnetically coupled microstimulators
US20070179580 *27 Ene 20062 Ago 2007Cyberonics, Inc.Multipolar stimulation electrode
US20070191904 *14 Feb 200616 Ago 2007Imad LibbusExpandable stimulation electrode with integrated pressure sensor and methods related thereto
US20070219599 *14 Mar 200720 Sep 2007Cherik BulkesComposite Waveform Based Method and Apparatus for Animal Tissue Stimulation
US20070233192 *29 Mar 20074 Oct 2007Catholic Healthcare West (D/B/A St. Joseph's Hospital And Medical Center)Vagus nerve stimulation method
US20070233193 *29 Mar 20074 Oct 2007Catholic Healthcare West (D/B/A St. Joseph's Hospital And Medical Center)Microburst electrical stimulation of cranial nerves for the treatment of medical conditions
US20070233194 *29 Mar 20074 Oct 2007Catholic Healthcare West (D/B/A St. Joseph's Hospital And Medical Center)Synchronization of vagus nerve stimulation with the cardiac cycle of a patient
US20070239224 *28 Mar 200711 Oct 2007Ndi Medical, Inc.Systems and methods for bilateral stimulation of left and right branches of the dorsal genital nerves to treat urologic dysfunctions
US20070244535 *18 Abr 200618 Oct 2007Cyberonics, Inc.Heat dissipation for a lead assembly
US20070255237 *1 May 20061 Nov 2007Neurosystec CorporationApparatus and method for delivery of therapeutic and other types of agents
US20070255330 *27 Abr 20061 Nov 2007Lee Brian BTelemetry-synchronized physiological monitoring and therapy delivery systems
US20070255351 *28 Abr 20061 Nov 2007Cyberonics, Inc.Threshold optimization for tissue stimulation therapy
US20070260288 *5 May 20068 Nov 2007Yossi GrossApparatus for treating stress and urge incontinence
US20070265675 *9 May 200715 Nov 2007Ams Research CorporationTesting Efficacy of Therapeutic Mechanical or Electrical Nerve or Muscle Stimulation
US20080015641 *12 Jul 200617 Ene 2008Cyberonics, Inc.Implantable Medical Device Charge Balance Assessment
US20080027504 *26 Jul 200731 Ene 2008Cranial Medical Systems, Inc.Lead and methods for brain monitoring and modulation
US20080033508 *13 Ago 20077 Feb 2008Medtronic, Inc.Clustering of recorded patient neurological activity to determine length of a neurological event
US20080039904 *7 Ago 200714 Feb 2008Cherik BulkesIntravascular implant system
US20080051851 *27 Ago 200728 Feb 2008The U.S. Government represented by the Department of Veterans Affairs and The Regents of theRestoring cough using microstimulators
US20080064934 *13 Ago 200713 Mar 2008Medtronic, Inc.Clustering of recorded patient neurological activity to determine length of a neurological event
US20080091255 *11 Oct 200617 Abr 2008Cardiac PacemakersImplantable neurostimulator for modulating cardiovascular function
US20080097529 *18 Oct 200624 Abr 2008Advanced Bionics CorporationMulti-Electrode Implantable Stimulator Device with a Single Current Path Decoupling Capacitor
US20080103547 *20 Mar 20071 May 2008University Of Florida Research Foundation, Inc.Multiple lead method for deep brain stimulation
US20080132961 *30 Nov 20065 Jun 2008Advanced Bionics CorporationImplant tool for use with a microstimulator
US20080183186 *30 Ene 200731 Jul 2008Cardiac Pacemakers, Inc.Method and apparatus for delivering a transvascular lead
US20080183187 *30 Ene 200731 Jul 2008Cardiac Pacemakers, Inc.Direct delivery system for transvascular lead
US20080183253 *30 Ene 200731 Jul 2008Cardiac Pacemakers, Inc.Neurostimulating lead having a stent-like anchor
US20080183254 *30 Ene 200731 Jul 2008Cardiac Pacemakers, Inc.Dual spiral lead configurations
US20080183255 *30 Ene 200731 Jul 2008Cardiac Pacemakers, Inc.Side port lead delivery system
US20080183258 *26 Ene 200731 Jul 2008Inman D MichaelElectrode assembly with fibers for a medical device
US20080183259 *30 Ene 200731 Jul 2008Cardiac Pacemakers, Inc.Spiral configurations for intravascular lead stability
US20080183264 *30 Ene 200731 Jul 2008Cardiac Pacemakers, Inc.Electrode configurations for transvascular nerve stimulation
US20080183265 *30 Ene 200731 Jul 2008Cardiac Pacemakers, Inc.Transvascular lead with proximal force relief
US20080228238 *23 May 200818 Sep 2008Cardiac Pacemakers, Inc.Automatic baroreflex modulation based on cardiac activity
US20080243204 *27 Mar 20082 Oct 2008University Of Florida Research Foundation, Inc.Variational parameter neurostimulation paradigm for treatment of neurologic disease
US20080249439 *13 Mar 20089 Oct 2008The Feinstein Institute For Medical ResearchTreatment of inflammation by non-invasive stimulation
US20080269740 *25 Abr 200730 Oct 2008Medtronic, Inc.Cannula configured to deliver test stimulation
US20080269763 *25 Abr 200730 Oct 2008Medtronic, Inc.Implant tool to facilitate medical device implantation
US20080269839 *27 Abr 200730 Oct 2008Armstrong Randolph KDosing Limitation for an Implantable Medical Device
US20080275531 *2 May 20086 Nov 2008Cherik BulkesImplantable high efficiency digital stimulation device
US20080300663 *4 Jun 20074 Dic 2008Blick Robert HNano- and micro-scale wireless stimulating probe
US20090012590 *3 Jul 20078 Ene 2009Cyberonics, Inc.Neural Conductor
US20090018618 *11 Jul 200715 Ene 2009Advanced Bionics CorporationTelemetry listening window management for an implantable medical device
US20090030485 *2 Oct 200829 Ene 2009Advanced Bionics, LlcEstimating Flap Thickness For Cochlear Implants
US20090030493 *27 Jul 200729 Ene 2009Colborn John CRibbon Electrode
US20090036946 *7 Oct 20085 Feb 2009American Medical Systems, Inc.Pelvic disorder treatments
US20090043356 *22 Feb 200712 Feb 2009Ams Research CorporationElectrode Sling for Treating Stress and Urge Incontinence
US20090062874 *26 Ago 20085 Mar 2009Tracey Kevin JDevices and methods for inhibiting granulocyte activation by neural stimulation
US20090143831 *27 Oct 20084 Jun 2009Huston Jared MTreating inflammatory disorders by stimulation of the cholinergic anti-inflammatory pathway
US20090177252 *10 Mar 20099 Jul 2009Catholic Healthcare West (D/B/A St. Joseph's Hospital And Medical Center)Synchronization of vagus nerve stimulation with the cardiac cycle of a patient
US20090187237 *30 Mar 200923 Jul 2009Advanced Bionics, LlcInner Hair Cell Stimulation Model for Use by a Cochlear Implant System
US20090192555 *28 Ene 200930 Jul 2009Boston Scientific Neuromodulation CorporationFixation of implantable pulse generators
US20090222064 *8 May 20093 Sep 2009Advanced Bionics, LlcAutonomous Autoprogram Cochlear Implant
US20090247934 *31 Mar 20091 Oct 2009Tracey Kevin JMethods and systems for reducing inflammation by neuromodulation of t-cell activity
US20090270943 *25 Abr 200829 Oct 2009Maschino Steven EBlocking Exogenous Action Potentials by an Implantable Medical Device
US20090287287 *24 Jul 200919 Nov 2009Cranial Medical Systems, Inc.Multi-channel connector for brain stimulation system
US20100030297 *9 Oct 20094 Feb 2010Medtronic, Inc.Implantable optical pressure sensor for sensing urinary sphincter pressure
US20100121412 *20 Ene 201013 May 2010Advanced Bionics, LlcOptimizing Pitch Allocation in a Cochlear Implant
US20100125307 *26 Ene 201020 May 2010Pastore Joseph MMulti-site ventricular pacing therapy with parasympathetic stimulation
US20100161007 *4 Mar 201024 Jun 2010Medtronic, Inc.Impedance-based stimulation adjustment
US20100179616 *22 Mar 201015 Jul 2010Advanced Bionics, LlcOuter Hair Cell Stimulation Model for the Use by an Intra-Cochlear Implant
US20100191304 *23 Ene 200929 Jul 2010Scott Timothy LImplantable Medical Device for Providing Chronic Condition Therapy and Acute Condition Therapy Using Vagus Nerve Stimulation
US20100192374 *8 Abr 20105 Ago 2010Cyberonics, Inc.Multi-Electrode Assembly for an Implantable Medical Device
US20100211148 *29 Abr 201019 Ago 2010Caparso Anthony VImplantable neurostimulator for modulating cardiovascular function
US20100217340 *23 Feb 201026 Ago 2010Ams Research CorporationImplantable Medical Device Connector System
US20100249885 *26 Abr 201030 Sep 2010Boston Scientific Neuromodulation CorporationImplantable microstimulator with plastic housing and methods of manufacture and use
US20100280575 *14 Jul 20104 Nov 2010Boston Scientific Neuromodulation CorporationControlling charge flow in the electrical stimulation of tissue
US20100292759 *24 Mar 200518 Nov 2010Hahn Tae WMagnetic field sensor for magnetically-coupled medical implant devices
US20100312320 *9 Jun 20109 Dic 2010Faltys Michael ANerve cuff with pocket for leadless stimulator
US20100324611 *10 Dic 200923 Dic 2010Waverx, Inc.Devices, systems and methods for preventing and treating sensation loss
US20100331910 *28 Jun 201030 Dic 2010Daemen CollegeElectrical stimulation unit and waterbath system
US20100331913 *28 Oct 200530 Dic 2010Mann Alfred EHybrid multi-function electrode array
US20110022124 *13 Nov 200927 Ene 2011Mark ZdeblickMultiplexed multi-electrode neurostimulation devices
US20110069853 *23 Nov 201024 Mar 2011Advanced Bionics, LlcAuditory Front End Customization
US20110077579 *23 Mar 200631 Mar 2011Harrison William VCochlear implant with localized fluid transport
US20110106208 *1 Nov 20105 May 2011Faltys Michael AModulation of the cholinergic anti-inflammatory pathway to treat pain or addiction
US20110106216 *10 Ene 20115 May 2011Imad LibbusBaroreflex stimulator with integrated pressure sensor
US20110118797 *24 Ene 201119 May 2011Boston Scientific Neuromodulation CorporationMulti-Electrode Implantable Stimulator Device with a Single Current Path Decoupling Capacitor
US20110130809 *13 Nov 20092 Jun 2011Proteus Biomedical, Inc.Pacing and Stimulation Apparatus and Methods
US20110152877 *7 Mar 201123 Jun 2011Bly Mark JNeurostimulating lead having a stent-like anchor
US20110166464 *16 Mar 20117 Jul 2011Medtronic, Inc.Telemetry-synchronized physiological monitoring and therapy delivery systems
US20110178530 *4 Abr 201121 Jul 2011Bly Mark JDirect delivery system for transvascular lead
US20110190849 *23 Dic 20104 Ago 2011Faltys Michael ANeural stimulation devices and systems for treatment of chronic inflammation
US20110196454 *13 Nov 200911 Ago 2011Proteus Biomedical, Inc.Sensing system, device, and method for therapy modulation
US20110224749 *7 Feb 201115 Sep 2011Bio Control Medical (B.C.M.) Ltd.Nerve stimulation techniques
US20110224757 *24 May 201115 Sep 2011Mark ZdeblickMultiplexed Multi-Electrode Neurostimulation Devices
US20110224767 *23 May 201115 Sep 2011Cyberonics, Inc.Electrode assembly with fibers for a medical device
US20110301670 *8 Jun 20108 Dic 2011Rainbow Medical Ltd.Tibial nerve stimulation
US20130060103 *12 May 20117 Mar 2013Sensible Medical Innovations Ltd.Method and system for using distributed electromagnetic (em) tissue(s) monitoring
US20130125395 *18 Ene 201323 May 2013Boston Scientific Neuromodulation CorporationLead assembly for implantable microstimulator
US20130138006 *31 May 201230 May 2013Pacesetter, Inc.Single chamber leadless intra-cardiac medical device having dual chamber sensing with signal discrimination
US20150112325 *18 Oct 201323 Abr 2015Atlantic Health System, Inc., a NJ non-profit corporationNerve protecting dissection device
US20160038745 *19 Oct 201511 Feb 2016Michael A. FaltysNeural stimulation devices and systems for treatment of chronic inflammation
US20160310031 *20 Abr 201627 Oct 2016Medtronic, Inc.Method and apparatus for determining a premature ventricular contraction in a medical monitoring device
CN102573986A *9 Jun 201011 Jul 2012赛博恩特医疗器械公司Nerve cuff with pocket for leadless stimulator
CN105126248A *23 Dic 20109 Dic 2015赛博恩特医疗器械公司Neural stimulation device and system for treatment of chronic inflammation
EP2440284A2 *9 Jun 201018 Abr 2012Setpoint Medical CorporationNerve cuff with pocket for leadless stimulator
EP2440284A4 *9 Jun 201012 Dic 2012Setpoint Medical CorpNerve cuff with pocket for leadless stimulator
EP2579939A1 *5 Jun 201117 Abr 2013Rainbow Medical Ltd.Tibial nerve stimulation
EP2579939A4 *5 Jun 201128 Ene 2015Bluewind Medical LtdTibial nerve stimulation
WO2006034305A2 *20 Sep 200530 Mar 2006University Of Florida Research Foundation, Inc.Multiple lead method for deep brain stimulation
WO2006034305A3 *20 Sep 20056 Jul 2006Univ FloridaMultiple lead method for deep brain stimulation
WO2006083625A1 *20 Ene 200610 Ago 2006Cyberonics, Inc.Multi-phasic signal for stimulation by an implantable medical device
WO2007109076A1 *14 Mar 200727 Sep 2007Cherik BulkesComposite waveform based method and apparatus for animal tissue stimulation
WO2008048321A1 *18 Oct 200624 Abr 2008Boston Scientific Neuromodulation CorporationMulti-electrode implantable stimulator device with a single current path decoupling capacitor
WO2008134195A1 *4 Abr 20086 Nov 2008Medtronic, Inc.Cannula configured to deliver test stimulation
WO2013111137A2 *24 Ene 20131 Ago 2013Rainbow Medical Ltd.Wireless neurqstimulatqrs
WO2013111137A3 *24 Ene 201326 Sep 2013Rainbow Medical Ltd.Wireless neurqstimulatqrs
Clasificaciones
Clasificación de EE.UU.607/48
Clasificación internacionalA61N1/36, A61N1/372
Clasificación cooperativaA61N1/37288, A61N1/37217, A61N1/37205, A61N1/36071, A61N1/0556
Clasificación europeaA61N1/36Z, A61N1/36, A61N1/372
Eventos legales
FechaCódigoEventoDescripción
23 Oct 2002ASAssignment
Owner name: ADVANCED BIONICS CORPORATION, CALIFORNIA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:WHITEHURST, TODD K.;CARABUNARU, RAFAEL;BRADLEY, KERRY;AND OTHERS;REEL/FRAME:013194/0751
Effective date: 20020620
23 Ene 2008ASAssignment
Owner name: BOSTON SCIENTIFIC NEUROMODULATION CORPORATION, CAL
Free format text: CHANGE OF NAME;ASSIGNOR:ADVANCED BIONICS CORPORATION;REEL/FRAME:020405/0722
Effective date: 20071116
Owner name: BOSTON SCIENTIFIC NEUROMODULATION CORPORATION,CALI
Free format text: CHANGE OF NAME;ASSIGNOR:ADVANCED BIONICS CORPORATION;REEL/FRAME:020405/0722
Effective date: 20071116