US20010003799A1 - Apparatus and method for adjunct (add-on) therapy for depression, migraine, neuropsychiatric disorders, partial complex epilepsy, generalized epilepsy and involuntary movement disorders utilizing an external stimulator - Google Patents

Apparatus and method for adjunct (add-on) therapy for depression, migraine, neuropsychiatric disorders, partial complex epilepsy, generalized epilepsy and involuntary movement disorders utilizing an external stimulator Download PDF

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US20010003799A1
US20010003799A1 US09/727,570 US72757000A US2001003799A1 US 20010003799 A1 US20010003799 A1 US 20010003799A1 US 72757000 A US72757000 A US 72757000A US 2001003799 A1 US2001003799 A1 US 2001003799A1
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apparatus
electrode
lead
receiver
electrical signals
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Birinder Boveja
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/02Details
    • A61N1/04Electrodes
    • A61N1/05Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0526Head electrodes
    • A61N1/0529Electrodes for brain stimulation
    • A61N1/0536Preventing neurodegenerative response or inflammatory reaction
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/32Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36014External stimulators, e.g. with patch electrodes
    • A61N1/36017External stimulators, e.g. with patch electrodes with leads or electrodes penetrating the skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/32Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36014External stimulators, e.g. with patch electrodes
    • A61N1/36025External stimulators, e.g. with patch electrodes for treating a mental or cerebral condition
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/32Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/36064Epilepsy
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/32Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/36071Pain
    • A61N1/36075Headache or migraine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/32Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/36082Cognitive or psychiatric applications, e.g. dementia or Alzheimer's disease

Abstract

An apparatus and method for adjunct (add-on) therapy of depression, migraine, neuropsychiatric disorders, partial complex epilepsy, generalized epilepsy and involuntary movement disorders comprises an implantable lead-receiver, and an external stimulator having controlling circuitry, a power source, and a coil to inductively couple the stimulator to the lead-receiver. The external stimulator emits electrical pulses to stimulate a cranial nerve such as the left vagus nerve according to a predetermined program. In a second mode of operation, an operator may manually override the predetermined sequence of stimulation.

Description

    FIELD OF INVENTION
  • This is a Continuation-in-Part application claiming priority from pending prior application Ser. No. 09/178,060 filed Oct. 26, 1998, the prior application being incorporated herein by reference. [0001]
  • This invention relates generally to electrical stimulation therapy for neurologic and neuropsychiatric disorders, more specifically to neuromodulation therapy for depression, migraine, and neuropsychiatric disorders, as well as adjunct treatment for partial complex, generalized epilepsy and involuntary movement disorders utilizing an implanted lead-receiver and an external stimulator. [0002]
  • BACKGROUND
  • It has been observed clinically that electrical stimulation therapy for seizures produced mood improvement independent of the anti-seizure effects. This discovery led to medical research into the therapeutic effects of electrical stimulation for depression. Medical research has shown beneficial medical effects of vagus nerve stimulation (VNS) for severely depressed patients. [0003]
  • Vagus nerve stimulation, and the profound effects of electrical stimulation of the vagus nerve on central nervous system (CNS) activity, extends back to the 1930's. Medical studies in clinical neurobiology have advanced our understanding of anatomic and physiologic basis of the anti-depressive effects of vagus nerve stimulation. [0004]
  • Some of the somatic interventions for the treatment of depression include electroconvulsive therapy (ECT), transcranical magnetic stimulation, vagus nerve stimulation, and deep brain stimulation. The vagus nerve is the 10th cranial nerve, and is a direct extension of the brain. FIG. 1A, shows a diagram of the brain and spinal cord [0005] 24, with its relationship to the vagus nerve 54 and the nucleus tractus solitarius 14. FIG. 1B shows the relationship of the vagus nerve 54 with the other cranial nerves.
  • Vagus nerve stimulation is a means of directly affecting central function and is less invasive than deep brain stimulation (DBS). As shown in FIG. 1C, cranial nerves have both afferent pathway [0006] 19 (inward conducting nerve fibers which convey impulses toward the brain) and efferent pathway 21 (outward conducting nerve fibers which convey impulses to an effector). The vagus nerve is composed of 80% afferent sensory fibers carrying information to the brain from the head, neck, thorax, and abdomen. The sensory afferent cell bodies of the vagus reside in the nodose ganglion and relay information to the nucleus tractus solitarius (NTS) 14.
  • As shown schematically in FIGS. 1A and 1D, the nucleus of the solitary tract relays this incoming sensory information to the rest of the brain through three main pathways; (1) an autonomic feedback loop, (2) direct projection to the reticular formation in the medulla, and (3) ascending projections to the forebrain largely through the parabrachial nucleus (PBN) [0007] 20 and the locus ceruleus (LC) 22. The PBN 20 sits adjacent to the neucleus LC 22 (FIG. 1A). The PBN/LC 20/22 sends direct connections to every level of the forebrain, including the hypothalamus 26, and several thalamic 25 regions that control the insula and orbitofrontal 28 and prefontal cortices. Perhaps important for mood regulation, the PBN/LC 20/22 has direct connections to the amygdala 29 and the bed nucleus of the stria terminalis—structures that are implicated in emotion recognition and mood regulation.
  • In sum, incoming sensory (afferent) connections ofthe vagus nerve [0008] 54 provide direct projections to many of the brain regions implicated in nueropsychiatric disorders. These connections reveal how vagus nerve stimulation is a portal to the brainstem and connected regions. These circuits likely account for the neuropsychiatric effects of vagus nerve stimulation.
  • Increased activity of the vagus nerve is also associated with the release of more serotonin in the brain. Much of the pharmacologic therapy for treatment of migraines is aimed at increasing the levels of serotonin in the brain. Therefore, non-pharmacologic therapy of electrically stimulating the vagus nerve would have benefits for adjunct treatment of migraines and other ailments, such as obsessive compulsive disorders, that would benefit from increasing the level of serotonin in the brain. [0009]
  • The vagus nerve provides an easily accessible, peripheral route to modulate central nervous system (CNS) function. Other cranial nerves can be used for the same purpose, but the vagus nerve is preferred because of its easy accessibility. In the human body there are two vagal nerves (VN), the right VN and the left VN. Each vagus nerve is encased in the carotid sheath along with the carotid artery and jugular vein. The innervation of the right and left vagal nerves is different. The innervation of the right vagus nerve is such that stimulating it results in profound bradycardia (slowing of the heart rate). The left vagal nerve has some innervation to the heart, but mostly innervates the visceral organs such as the gastrointestinal tract. It is known that stimulation of the left vagal nerve does not cause any significant deleterious side effects. [0010]
  • Complex partial seizure is a common form of epilepsy, and some 30-40% of patients afflicted with this disorder are not well controlled by medications. Some patients have epileptogenic foci that may be identified and resected; however, many patients remain who have medically resistant seizures not amenable to resective surgery. Stimulation of the vagus nerve has been shown to reduce or abort seizures in experimental models. Early clinical trials have suggested that vagus nerve stimulation has beneficial effects for complex partial seizures and generalized epilepsy in humans. In addition, intermittent vagal stimulation has been relatively safe and well tolerated during the follow-up period available in these groups of patients. The minimal side effects of tingling sensations and brief voice abnormalities have not been distressing. [0011]
  • Most nerves in the human body are composed of thousands of fibers, of different sizes designated by groups A, B and C, which carry signals to and from the brain. The vagus nerve, for example, may have approximately 100,000 fibers ofthe three different types, each carrying signals. Each axon (fiber) of that nerve conducts only in one direction, in normal circumstances. The A and B fibers are myelinated (i.e., have a myelin sheath, constituting a substance largely composed of fat), whereas the C fibers are unmyelinated. [0012]
  • A commonly used nomenclature for peripheral nerve fibers, using Roman and Greek letters, is given in the table below, [0013] External Diameter Conduction Velocity Group (μm) (m/sec) Myelinated Fibers Aα or IA 12-20  70-120 Aβ: IB 10-15 60-80 II  5-15 30-80 3-8 15-40 Aδ or III 3-8 10-30 B 1-3  5-15 Unmyelinted fibers C or IV 0.2-1.5 0.5-2.5
  • The diameters of group A and group B fibers include the thicknesses of the myelin sheaths. Group A is further subdivided into alpha, beta, gamma, and delta fibers in decreasing order of size. There is some overlapping of the diameters of the A, B, and C groups because physiological properties, especially the form ofthe action potential, are taken into consideration when defining the groups. The smallest fibers (group C) are unmyelinated and have the slowest conduction rate, whereas the myelinted fibers of group B and group A exhibit rates of conduction that progressively increase with diameter. Group B fibers are not present in the nerves of the limbs; they occur in white rami and some cranial nerves. [0014]
  • Compared to unmyelinated fibers, myelinated fibers are typically larger, conduct faster, have very low stimulation thresholds, and exhibit a particular strength-duration curve or respond to a specific pulse width versus amplitude for stimulation. The A and B fibers can be stimulated with relatively narrow pulse widths, from 50 to 200 microseconds (μs), for example. The A fiber conducts slightly faster than the B fiber and has a slightly lower threshold. The C fibers are very small, conduct electrical signals very slowly, and have high stimulation thresholds typically requiring a wider pulse width (300-1,000 μs) and a higher amplitude for activation. Selective stimulation of only A and B fibers is readily accomplished. The requirement of a larger and wider pulse to stimulate the C fibers, however, makes selective stimulation of only C fibers, to the exclusion of the A and B fibers, virtually unachievable inasmuch as the large signal will tend to activate the A and B fibers to some extent as well. [0015]
  • The vagus nerve is composed of somatic and visceral afferents (i.e., inward conducting nerve fibers which convey impulses toward the brain) and efferents (i.e., outward conducting nerve fibers which convey impulses to an effector). Usually, nerve stimulation activates signals in both directions (bi-directionally). It is possible, however, through the use of special electrodes and waveforms, to selectively stimulate a nerve in one direction only (unidirectionally). The vast majority of vagal nerve fibers are C fibers, and a majority are visceral afferents having cell bodies lying in masses or ganglia in the skull. The central projections terminate largely in the nucleus of the solitary tract which sends fibers to various regions of the brain (e.g., the hypothalamus, thalamus, and amygdala). [0016]
  • The basic premise of vagal nerve stimulation for control of seizures is that vagal visceral afferents have a diffuse central nervous system (CNS) projection, and activation of these pathways has a widespread effect on neuronal excitability. [0017]
  • The cervical component of the vagus nerve (10th cranial nerve) transmits primarily sensory information that is important in the regulation of autonomic activity by the parasympathetic system. General visceral afferents constitute approximately 80% of the fibers of the nerve, and thus it is not surprising that vagal nerve stimulation (VNS) can profoundly affect CNS activity. With cell bodies in the nodose ganglion, these afferents originate from receptors in the heart, aorta, lungs, and gastrointestinal system and project primarily to the nucleus of the solitary tract which extends throughout the length of the medulla oblongata. A small number of fibers pass directly to the spinal trigeminal nucleus and the reticular formation. [0018]
  • As might be predicted from the electrophysiologic studies, the nucleus ofthe solitary tract has widespread projection to cerebral cortex, basal forebrain, thalamus, hypothalamus, amygdala, hippocampus, dorsal raphe, and cerebellum as shown in FIG. 1D (from [0019] Epilepsia, vol. 3, suppl.2:1990, page S2).
  • Even though observations on the profound effect of electrical stimulation of the vagus nerve on central nervous system (CNS) activity, extends back to the 1930's, in the mid-1980s it was suggested that electrical stimulation of the vagus nerve might be effective in preventing seizures. Early studies on the effects of vagal nerve stimulation (VNS) on brain function focused on acute changes in the cortical electroencephalogram (EEG) of anesthetized animals. Investigators found that VNS could temporarily synchronize or desynchronize the electroencephalogram, depending on the level of anesthesia and the frequency or intensity of the vagal stimulus. These observations had suggested that VNS exerted its anticonvulsant effect by desynchronizing cortical electrical activity. However, subsequent clinical investigations have not shown VNS-induced changes in the background EEGs of humans. A study, which used awake and freely moving animals, also showed no VNS-induced changes in background EEG activity. Taken together, the findings from animal study and recent human studies indicate that acute desynchronization of EEG activity is not a prominent feature of VNS when it is administered during physiologic wakefulness and sleep, and does not explain the anticonvulsant effect of VNS. [0020]
  • The mechanism by which vagal nerve stimulation (VNS) exerts its influence on seizures is not entirely understood. An early hypotheses had suggested that VNS utilizes the relatively specific projection from the nucleus of the solitary track to limbic structures to inhibit partial seizures, particularly those involving cortex, which regulates autonomic activity or visceral sensations such as in temporal lobe epilepsy. Afferent VNS at the onset of a partial seizure could abort the seizure in the same way somatosensory stimuli can abort a seizure from the rolandic cortex; however, chronic intermittent stimulation may also produce an alteration in limbic circuitry that outlasts the stimulus and decreases epileptogenesis or limits seizure spread. Support for this hypothesis comes from studies of fos immunoreactivity in the brain of rats in response to VNS. Fos is a nuclear protein resulting from expression of early immediate genes in highly active neurons. VNS causes a specific fos immunolabeling in amygdala and limbic neocortex, suggesting that the antiepileptic effect may be mediated in these areas. Such activation of genetic mechanisms could account for the apparent sustained antiepileptic effect of intermittent stimulation. [0021]
  • Another possible mechanism that is being explored to explain an antiseizure effect of VNS is activation of the brainstem noradrenergic nuclei, lucus ceruleus and A5, which also show fos immunolabeling. Noradrenergic mechanisms are well known to influence seizure activity in genetic epilepsy-prone rats, and the anticonvulsant effects of VNS against maximal electroshock seizures can be blocked inactivation of the loc. ceruleus. Woodbury and Woodbury (1990) suggested that VS acts through increasing release of glycine or GABA since seizures induced by both PTZ and strychnine can be blocked by VNS. Other neruotransmitter systems may also be implicated since VNS increases cerebrospinal fluid homovanilic acid and 5-hydroxyindoleacetate, suggesting modulation of dopaminergic and serotonergic systems. Finally, a nonspecific alteration of activity in the brainstem reticular system with subsequent arousal must be considered. [0022]
  • VNS appears to have similar efficacy in both partial and generalized seizures in experimental models and in human epilepsy consistent with a nonspecific effect. Furthermore, the same inhibition of interictal corticalspike activity as seen with VNS occurs in animals during electrical stimulation of the midbrain reticular formation or with thermal stimulation of somatosensory nerves in the rat tail. Reduction of experimental generalized spike wave by arousal has also been documented. Similarly, nonspecific afferent stimulation has been well demonstrated in humans to suppress focal spikes, generalized spike waves, and seizures. [0023]
  • VNS may inhibit seizures directly at the level of cerebral cortical neuronal irritability, or at the level of diffuse ascending subcortical projection systems, or both. Thus, VNS is also well suited for the treatment of medication-resistant symptomatic generalized epilepsy (SGE), in which, characteristically both focal and generalized features are found on interictal EEGs and also in clinical seizure types. [0024]
  • One type of prior non-pharmacological therapy for depression, migraines, neuropsychiatric disorders, and epilepsy is generally directed to the use of an implantable lead and an implantable pulse generator technology or “cardiac pacemaker-like” technology. In these applications, the pulse generator is programmed via a personnel computer (PC) based programmer that is modified and adapted with a programmer wand which is placed on top of the skin over the pulse generator implant site. Each parameter is programmed independent of the other parameters. Therefore, millions of different combinations of programs are possible. In the instant patent, preferably approximately nine programs are pre-selected. [0025]
  • U.S. Pat. No. 3,796,221 (Hagfors) is directed to controlling the amplitude, duration and frequency of electrical stimulation applied from an externally located transmitter to an implanted receiver by inductively coupling. Electrical circuitry is schematically illustrated for compensating for the variability in the amplitude of the electrical signal available to the receiver because of the shifting of the relative positions of the transmitter-receiver pair. By highlighting the difficulty of delivering consistent pulses, this patent points away from applications such as the current application, where consistent therapy needs to be continuously sustained over a prolonged period of time (24 hours a day for years). The methodology disclosed is focused on circuitry within the receiver, which would not be sufficient when the transmitting coil and receiving coil assume significantly different orientation, which is likely in the current application. The present invention discloses a novel approach for this problem. [0026]
  • U.S. Pat. No. 5,304,206 (Baker, Jr. et al) is directed to activation techniques for implanted medical stimulators. The system uses either a magnet to activate the reed switch in the device, or tapping which acts through the piezoelectric sensor mounted on the case of the implanted device, or a combination of magnet and tapping sequence. [0027]
  • U.S. Pat. Nos. 4,702,254, 4,867,164 and 5,025,807 (Zabara) generally disclose animal research and experimentation related to epilepsy and the like and are directed to stimulating the vagus nerve by using pacemaker technology, such as an implantable pulse generator. These patents are based on several key hypotheses, some of which have since been shown to be incorrect. The pacemaker technology concept consists of a stimulating lead connected to a pulse generator (containing the circuitry and DC power source) implanted subcutaneously or submuscularly, somewhere in the pectoral or axillary region, with an external personal computer (PC) based programmer. Once the pulse generator is programmed for the patient, the fully functional circuitry and power source are fully implanted within the patient's body. In such a system, when the battery is depleted, a surgical procedure is required to disconnect and replace the entire pulse generator (circuitry and power source). These patents neither anticipate practical problems of an inductively coupled system for adjunct therapy of epilepsy, nor suggest solutions to the same for an inductively coupled system for adjunct therapy of partial complex or generalized epilepsy. FIG. 4 in all three above Zabara patents show the stimulation electrode around the right vagus nerve. It is well known that stimulation of right vagus can lead to profound bradycardia (slowing of the heart rate), an unwanted complication. [0028]
  • U.S. Pat. No. 5,299,569 (Wernicke et al.) is directed to the use of implantable pulse generator technology for treating and controlling neuropsychiatric disorders including schizophrenia, depression, and borderline personality disorder. [0029]
  • U.S. Pat. No. 5,752,979 (Benabid) is directed to a method of controlling epilepsy with stimulation directly into the brain, utilizing an implantable generator. More specifically, Benabid discloses electrically stimulating the external segment of the globus palliaus nucleus of the brain causing increased excitation, thereby increasing inhibition of neural activity in the subthalamic nucleus and reducing excitatory input to the substantia nigra leading to a reduction in the occurrence of seizures. [0030]
  • U.S. Pat. No. 5,540,734 (Zabara) is directed to stimulation of one or both of a patient's trigeminal and glossopharyngeal nerve utilizing an implanted pulse generator. [0031]
  • U.S. Pat. No. 5,031,618 (Mullett) discloses a position sensor for chronically implanted neuro stimulator for stimulating the spinal cord. The position sensor, located in a chronically implanted programmable spinal cord stimulator, modulates the stimulation signals depending on whether the patient is erect or supine. [0032]
  • U.S. Pat. No. 4,573,481 (Bullara) is directed to an implantable helical electrode assembly configured to fit around a nerve. The individual flexible ribbon electrodes are each partially embedded in a portion of the peripheral surface of a helically formed dielectric support matrix. [0033]
  • U.S. Pat. No. 3,760,812 (Timm et al.) discloses nerve stimulation electrodes that include a pair of parallel spaced apart helically wound conductors maintained in this configuration. [0034]
  • U.S. Pat. No. 4,979,511 (Terry) discloses a flexible, helical electrode structure with an improved connector for attaching the lead wires to the nerve bundle to minimize damage. [0035]
  • An implantable pulse generator and lead with a PC based external programmer is advantageous for cardiac pacing applications for several reasons, including: [0036]
  • 1) A cardiac pacemaker must sense the intrinsic activity of the heart, because cardiac pacemakers deliver electrical output primarily during the brief periods when patients either have pauses in their intrinsic cardiac activity or during those periods of time when the heart rate drops (bradycardia) below a certain pre-programmed level. Therefore, for most of the time, in majority of patients, the cardiac pacemaker “sits” quietly monitoring the patient's intrinsic cardiac activity. [0037]
  • 2) The stimulation frequency for cardiac pacing is typically close to 1 Hz, as opposed to approximately 20 Hz or higher, typically used in nerve stimulation applications. [0038]
  • 3) Patients who require cardiac pacemaker support are typically in their 60's, 70's or 80's years of age. [0039]
  • The combined effect of these three factors is that the battery in a pacemaker can have a life of 10-15 years. Most patients in whom a pacemaker is indicated are implanted only once, with perhaps one surgical pulse generator replacement. [0040]
  • In contrast, patients with partial complex epilepsy or generalized epilepsy in whom electrical stimulation is beneficial are much younger as a group, typically ranging from 12 to 45 years in age. Also, stimulation frequency is typically 20 Hz or higher, and the total stimulation time per day is much longer than for cardiac pacemakers. As a result, battery drain is typically much higher for nerve stimulation applications than for cardiac pacemakers. [0041]
  • The net result of these factors is that the battery will not last nearly as long as in cardiac pacemakers. Because the indicated patient population is also much younger, the expense and impact of surgical generator replacement will become significant, and detract from the appeal of this therapy. In fact, it has been reported in the medical literature that the battery life can be as short as one and half years for implantable nerve stimulator. (R. S. McLachlan, p. 233). [0042]
  • There are several other advantages of the present inductively coupled system. [0043]
  • 5) The hardware components implanted in the body are much less. This is advantageous for the patient in terms of patient comfort, and it decreases the chances of the hardware getting infected in the body. Typically, when an implantable system gets infected in the body, it cannot be easily treated with antibiotics and eventually the whole implanted system has to be explanted. [0044]
  • 2) Because the power source is external, the physician can use stimulation sequences that are more effective and more demanding on the power supply, such as longer “on” time. [0045]
  • 3) With the controlling circuitry being external, the physician and the patient may easily select from a number of predetermined programs, override a program, manually operate the device or even modify the predetermined programs. [0046]
  • 4) The external inductively-coupled nerve stimulation (EINS) system is quicker and easier to implant. [0047]
  • 5) The external pulse generator does not need to be monitored for “End-of-Life” (EOL) like the implantable system, thus resulting in cost saving and convenience. [0048]
  • 6) The EINS system can be manufactured at a significantly lower cost of an implantable pulse generator and programmer system, providing the patient and medical establishment with cost effective therapies. [0049]
  • 7) The EINS system makes it more convenient for the patient or caretaker to turn the device on during an “Aura” that sometimes precedes the seizures. Also, because programming the device is much simpler, the patient or caretaker may reprogram the device at night time by simply pressing one or two buttons to improve patient comfort. [0050]
  • 8) Occasionally, an individual responds adversely to an implanted medical device and the implanted hardware must be removed. In such a case, a patient having the EINS systems has less implanted hardware to be removed and the cost ofthe pulse generator does not become a factor. [0051]
  • In the conventional manner of implanting, a cervical incision is made above the clavicle, and another infraclavicular incision is made in the deltapectoral region for the implantable stimulus generator pocket. To tunnel the lead to the cervical incision, a shunt-passing tool is passed from the cervical incision to the generator pocket, where the electrode is attached to the shunt-passing tool and the electrode is then “pulled” back to the cervical incision for attachment to the nerve. This standard technique has the disadvantage that it is time consuming and it tends to create an open space in the subcutaneous tissue. Post surgically the body will fill up this space with serous fluid, which can be undesirable. [0052]
  • To make the subcutaneous tunneling simpler and to avoid possible complication, one form of the implantable lead body is designed with a hollow lumen to aid in implanting. In this embodiment, a special tunneling tool slides into a hollow lumen. After the cervical and infraclavicular incisions are made, the tunneling tool and lead are simply “pushed” to the cervical incision and the tunneling tool is pulled out. Since the tunneling tool is inside the lead, no extra subcutaneous space is created around the lead, as the lead is pushed. This promotes better healing post-surgically. [0053]
  • The apparatus and methods disclosed herein also may be appropriate for the treatment of other conditions, as disclosed in co-pending applications filed on Oct. 26, 1998, entitled APPARATUS AND METHOD FOR ADJUNCT (ADD-ON) THERAPY OF DEMENTIA AND ALZHEIMER'S DISEASE UTILIZING AN IMPLANTABLE LEAD AND AN EXTERNAL STIMULATOR and APPARATUS AND METHOD FOR ADJUNCT (ADD-ON) THERAPY FOR PAIN SYNDROMES UTILIZING AN IMPLANTABLE LEAD AND AN EXTERNAL STIMULATOR, the disclosures of which are incorporated herein by reference. [0054]
  • SUMMARY OF THE INVENTION
  • The apparatus and methodology of this invention generally relates to the adjunct (add-on) treatment of depression, migraine, neuropsychiatric disorders, partial complex epilepsy, generalized epilepsy, and involuntary movement disorders such as in Parkinson's disease. More particularly, the apparatus and methodology in accordance with the invention provides a more adaptable and less intrusive treatment for such conditions. In one embodiment of the invention, the apparatus consists of an easy to implant lead-receiver, an external stimulator containing controlling circuitry and power supply, and an electrode containing a coil for inductively coupling the external pulse generator to the implanted lead-receiver. A separately provided tunneling tool may be used as an aid for implanting the lead-receiver. [0055]
  • In another embodiment of the invention, the external stimulator has two modes of operation: one with several pre-determined programs that may be selectively locked-out by the manufacturer or physician and another with a manual override. [0056]
  • In another embodiment of the invention, the implantable lead-receiver is inductively coupled to the external stimulator via a patch electrode containing coil. One feature of this invention is to consistently deliver energy from an external coil to an internal coil in an ambulatory patient. A design of the external patch contains means for compensating for relative movement of the axis of the external and internal coils by deflecting the energy via targets located in the external patch. [0057]
  • Another feature of this invention is to provide an apparatus to aid in implanting the lead-receiver, including a hollow lumen in the lead body to receive a tunneling tool. [0058]
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • For the purpose of illustrating the invention, there are shown in accompanying drawing forms which are presently preferred, it being understood that the invention is not intended to be limited to the precise arrangement and instrumentalities shown. [0059]
  • FIG. 1A is a diagram of the lateral view of brain and spinal cord, with its relationship to the vagus nerve. [0060]
  • FIG. 1B is a diagram of the base of brain showing the relationship of vagus nerve to the other cranial nerves. [0061]
  • FIG. 1C is a diagram of brain showing afferent and efferent pathways. [0062]
  • FIG. 1D is diagram of vagal nerve afferents through the nucleus of the solitary tract. [0063]
  • FIG. 2A is a diagram showing a patient wearing an external inductively-coupled nerve stimulator (EINS) system. [0064]
  • FIG. 2B is a diagram showing two coils along their axis, in a configuration such that the mutual inductance would be maximum. [0065]
  • FIG. 3A is a diagram showing the effects of two coils with axes at right angles. [0066]
  • FIG. 3B is a diagram showing the effects of two coils with axes at right angles, with a ferrite target included. [0067]
  • FIG. 4A is a side view of an external patch showing the transmitting coil and targets. [0068]
  • FIG. 4B is top view of an external patch showing the transmitting coil and targets. [0069]
  • FIG. 5 is a diagram showing the implanted lead-receiver and the transmitting coil. [0070]
  • FIG. 6 is a diagram showing the implanted lead-receiver underneath the skin, also showing the relative position of the external coil [0071]
  • FIG. 7 is a diagram showing the proximal end of the lead-receiver. [0072]
  • FIG. 8 is a diagram of circuitry within the proximal portion of the implanted lead-receiver. [0073]
  • FIG. 9 is a diagram of the body of the lead-receiver. [0074]
  • FIG. 10 is a diagram of a tunneling tool for aiding in the implantation of the lead-receiver. [0075]
  • FIG. 11 is diagram of another tunneling tool for aiding in the implantation of the lead-receiver. [0076]
  • FIG. 12 is a diagram of an external patch and external pulse generator. [0077]
  • FIG. 13 is a prospective view of an external pulse generator. [0078]
  • FIG. 14 is a flow diagram of the external pulse generator. [0079]
  • FIG. 15 is a diagram of a hydrogel electrode. [0080]
  • FIG. 16 is a diagram of a lead-receiver utilizing a fiber electrode at the distal end. [0081]
  • FIG. 17 is a diagram of a fiber electrode wrapped around Dacron polyester. [0082]
  • FIG. 18 is a diagram of a lead-receiver with a spiral electrode. [0083]
  • FIG. 19 is a diagram of an electrode embedded in tissue. [0084]
  • FIG. 20 is a diagram of an electrode containing steroid drug inside. [0085]
  • FIG. 21 is a diagram of an electrode containing steroid drug in a silicone collar at the base of electrode. [0086]
  • FIG. 22 is a diagram of an electrode with steroid drug coated on the surface of the electrode. [0087]
  • FIG. 23 is a diagram of cross sections of implantable lead-receiver body showing different lumens. [0088]
  • The following are reference numbers in the drawings: [0089]
  • [0090] 1. olfactory nerve
  • [0091] 2. optic nerve
  • [0092] 3. oculomotor nerve
  • [0093] 4. trochlear nerve
  • [0094] 5. trigeminal nerve
  • [0095] 6. abducens nerve
  • [0096] 7. facial nerve
  • [0097] 8. acoustic nerve
  • [0098] 9. glossopharyngeal nerve
  • [0099] 11. accessory nerve
  • [0100] 12. hypoglosal nerve
  • [0101] 14. nucleus tractus solitaris
  • [0102] 15. parabrachial nucleus (PB)
  • [0103] 17. nucleus locus coeruleus
  • [0104] 18. pons
  • [0105] 19. afferent pathway
  • [0106] 20. parabrachial nucleus (PB)
  • [0107] 21. efferent pathway
  • [0108] 22. nucleus locus coeruleus (LC)
  • [0109] 24. spinal cord
  • [0110] 25. thalamus
  • [0111] 26. hypothalamus
  • [0112] 27. cerebellum
  • [0113] 28. orbito-frontal cortex
  • [0114] 29. amygdala
  • [0115] 31. cingulate gyrus
  • [0116] 32. patient
  • [0117] 34. implantable lead-receiver
  • [0118] 35. muscle
  • [0119] 36. coil-end of the external patch
  • [0120] 37. skin receptors
  • [0121] 38. wire of external patch
  • [0122] 39. primary somatic sensory cortex
  • [0123] 40. terminal end of the external patch
  • [0124] 41. primary motor cortex
  • [0125] 42. external stimulator
  • [0126] 43. external patch electrode
  • [0127] 44. belt of external stimulator
  • [0128] 45. ferrite target
  • [0129] 46. outer (transmitting primary) coil
  • [0130] 48. inner (receiving secondary) coil
  • [0131] 49. proximal end of lead-receiver
  • [0132] 50. adhesive portion of external patch electrode
  • [0133] 51. driving voltage of transmitter coil
  • [0134] 52. distal ball electrode
  • [0135] 53. zero voltage of receiver coil
  • [0136] 54. vagus nerve
  • [0137] 55. signal voltage across receiver coil
  • [0138] 56. carotid artery
  • [0139] 57. ferrite targets in external patch
  • [0140] 58. jugular vein
  • [0141] 59. body of lead-receiver
  • [0142] 60. working lumen of lead-receiver body
  • [0143] 62. hollow lumen of lead-receiver body
  • [0144] 64. schematic of lead-receiver circuitry
  • [0145] 65. cable connecting cathode and anode
  • [0146] 68. tuning capacitor in electrical schematic and in hybrid
  • [0147] 69. selector
  • [0148] 70. zenor diode
  • [0149] 71. pre-determined programs in block diagram
  • [0150] 72. capacitor used in filtering
  • [0151] 73. patient override in block diagram
  • [0152] 74. resister used in filtering
  • [0153] 75. programmable control logic in block diagram
  • [0154] 76. capacitor to block DC component to distal electrode
  • [0155] 77. programming station in block diagram
  • [0156] 78. case of lead-receiver
  • [0157] 79. pulse frequency oscillator in block diagram
  • [0158] 80. distal electrode in schematic of lead-receiver
  • [0159] 81. battery (DC) in block diagram
  • [0160] 82. working lumen in a cross section
  • [0161] 83. amplifier in block diagram
  • [0162] 84. hollow lumen in a cross-section
  • [0163] 85. indicator in block diagram
  • [0164] 86. small handle of alternate tunneling tool
  • [0165] 87. low pass filter in block diagram
  • [0166] 88. big handle of the tunneling tool
  • [0167] 89. antenna in block diagram
  • [0168] 90. skin
  • [0169] 91. metal rod portion of the tunneling tool with big handle
  • [0170] 92. punched holes in body of the lead receiver to promote fibrosis
  • [0171] 93. metal rod portion of the alternative tunneling tool with small handle
  • [0172] 94. alternative tunneling tool
  • [0173] 95. tunneling tool with big handle
  • [0174] 96. silicone covering proximal end
  • [0175] 98. hybrid assembly
  • [0176] 100. hydrogel
  • [0177] 102. platinum electrodes around hydrogel
  • [0178] 104. fiber electrode
  • [0179] 105. spiral electrode
  • [0180] 106. Dacron polyester or Polyimide
  • [0181] 108. platinum fiber
  • [0182] 110. exposed electrode portion of spiral electrode
  • [0183] 112. polyurethane or silicone insulation in spiral electrode
  • [0184] 114. “virtual” electrode
  • [0185] 118. excitable tissue
  • [0186] 120. non-excitable tissue
  • [0187] 121. steroid plug inside an electrode
  • [0188] 122. body of electrode
  • [0189] 124. electrode tip
  • [0190] 126. silicone collar containing steroid
  • [0191] 128. steroid membrane coating
  • [0192] 130. anchoring sleeve
  • [0193] 132. A-F lumens
  • [0194] 134. A-C larger hollow lumen for lead introduction
  • DESCRIPTION OF THE INVENTION
  • FIG. 2A shows a schematic diagram of a patient [0195] 32 with an implantable lead-receiver 34 and an external stimulator 42, clipped on to a belt 44 in this case. The external stimulator 42, may alternatively be placed in a pocket or other carrying device. An external patch electrode 36 provides the coupling between the external stimulator 42 and the implantable lead-receiver 34.
  • The external stimulator [0196] 42 is inductively coupled to the lead-receiver 34. As shown in FIG. 2B, when two coils are arranged with their axes on the same line, current sent through coil 46 creates a magnetic field that cuts coil 48 which is placed subcutaneously. Consequently, a voltage will be induced in coil 48 whenever the field strength of coil 46 is changing. This induced voltage is similar to the voltage of self-induction but since it appears in the second coil because of current flowing in the first, it is a mutual effect and results from the mutual inductance between the two coils. Since these two coils are coupled, the degree of coupling depends upon the physical spacing between the coils and how they are placed with respect to each other. Maximum coupling exists when they have a common axis and are as close together as possible. The coupling is least when the coils are far apart or are placed so their axes are at right angles. As shown in FIG. 5, the coil 48 inside the lead-receiver 34 is approximately along the same axis as the coil 46 in the external skin patch 36.
  • As shown in FIG. 3A, when the axis of transmitting coil [0197] 46 is at right angles to the axis of the receiving coil 48, a given driving voltage 51 results in zero voltage 53 across the receiving coil 48. But, as shown in FIG. 3B by adding ferrite target 45, a given driving voltage 51 through the transmitting coil 46 results in a signal voltage 55 across the receiver coil 48. The efficiency is improved by having multiple ferrite targets. An alternate external patch shown in FIGS. 4A and 4B contains multiple targets 57. FIG. 4A shows a side view of the patch, and FIG. 4B shows a top view of the patch. Having multiple targets 57 in the external patch 43 compensates for non-alignment of the axis between the transmitting coil 46 and receiving coil 48. Since relative rotations between the axis of external transmitting coil 46 and internal receiving coil 48 which may occur during breathing, muscle contractions, or other artifacts are compensated for, results in continuous prolonged stimulation.
  • Referring to FIG. 6, the implantable lead-receiver [0198] 34 looks somewhat like a golf “tee” and is the only implantable portion of the system. The “head” or proximal end 49 contains the coil 48 and electronic circuitry (hybrid) 98 which is hermetically sealed, and covered with silicone. It also has four anchoring sleeves 130 for tying it to subcutaneous tissue. FIG. 7 is a close-up view of the proximal portion 49 of the lead-receiver 34 containing the circuitry (hybrid) 98. This circuitry is shown schematically in FIG. 8. A coil 48 (preferably approximately 15 turns) is directly connected to the case 78. The external stimulator 42 and external patch 36 transmit the pulsed alternating magnetic field to receiver 64 whereat the stimulus pulses are detected by coil 48 and transmitted to the stimulus site (vagus nerve 54). When exposed to the magnetic field of transmitter 36, coil 48 converts the changing magnetic field into corresponding voltages with alternating polarity between the coil ends. A capacitor 68 is used to tune coil 48 to the high-frequency of the transmitter 36. The capacitor 68 increases the sensitivity and the selectivity of the receiver 64, which is made sensitive to frequencies near the resonant frequency of the tuned circuit and less sensitive to frequencies away from the resonant frequency. A zenor diode 70 in the current path is used for regulation and to allow the current that is produced by the alternating voltage of the coil to pass in one direction only. A capacitor 72 and resistor 74 filter-out the high-frequency component of the receiver signal and thereby leave a current of the same duration as the burst ofthe high-frequency signal. Capacitor 76 blocks any net direct current to the stimulating electrode tip 80, which is made of platinum/iridium (90%-10%). Alternatively, the stimulating electrode can be made of platinum or platinum/iridium in ratio's such as 80% Platinum and 20% Iridium.
  • The circuit components are soldered in a conventional manner to an upper conductive layer on a printed circuit board. The case [0199] 78 is connected to the coil 48 and is made of titanium. The case 78 also serves as the return electrode (anode). The surface area of the anode exposed to the tissue is much greater than the surface area of the stimulating electrode 80 (cathode). Therefore, the current density at the anode is too low to unduly stimulate tissue that is in contact with the anode. Alternatively, a bipolar mode of stimulation can also be used. In the bipolar mode of stimulation the cathode and anode are in close proximity to each other.
  • The body of the lead-receiver [0200] 34 is made of medical grade silicone (available from NuSil Technology, Applied silicone or Dow Chemical). Alternatively, the lead body 59 may be made of medical grade polyurethane (PU) of 55 D or higher durometer, such as available from Dow Chemical. Polyurethane is a stiffer material than silicone. Even though silicone is a softer material, which is favorable, it is also a weaker material than PU. Therefore, silicone coated with Teflon (PTFE) is preferred for this application. PTFE coating is available from Alpa Flex, Indianapolis, Ind.
  • FIG. 9 shows a close-up of the lead body [0201] 59 showing two lumens 82, 84. Lumen 82 is the “working” lumen, containing the cable conductor 65 which connects to the stimulating electrode 52. The other lumen 84 is preferably slightly larger and is for introducing and placing the lead in the body. Alternatively, lumen 84 may have small holes 92 punched along the length of the lead. These small holes 92 will promote fibrotic tissue in-growth to stabilize the lead position and inhibit the lead from migrating.
  • Silicone in general is not a very slippery material, having a high coefficient of friction. Therefore, a lubricious coating is added to the body of the lead. Such lubricous coating is available from Coating Technologies Inc. (Scotch Plains, N.J.). Since infection still remains a problem in a small percentage of patients, the lead may be coated with antimicrobial coating such as Silver Sulfer Dizene available from STS Biopolymers, Henrietta, N.Y. The lead may also be coated with anti-inflammatory coating. [0202]
  • The distal ball electrode [0203] 52, shown in FIG. 6 is made of platinum/iridium (90% platinum and 10% iridium). Platinum/iridium electrodes have a long history in cardiac pacing applications. During the distal assembly procedure, the silicone lead body 59 is first cleaned with alcohol. The conductor cable 65 (available from Lake Region, Minn.) is passed through the “working” lumen 82. The cable is inserted into the distal electrode 52, and part of the body of electrode is crimped to the cable 65 with a crimper. Alternatively, the cable conductor 65 may be arc welded or laser welded to the distal electrode 52. The distal end of the insulation is then slided over the crimp such that only the tissue stimulating portion of the distal electrode 52 is exposed. Following this, a small needle is attached to a syringe filled with medical glue. The needle is inserted into the distal end of insulation, and small amounts of medical glue are injected between the distal end of the insulation and distal electrode 52. The assembly is then cured in an oven.
  • As shown in FIGS. 9 and 10, a tunneling tool [0204] 95 is inserted into the empty lumen 84 to push the distal end (containing the cathode electrode 52) towards the vagus nerve 54. The tunneling tool 95, is comprised of a metal rod 91 and a handle 88. As shown in FIG. 11, another tunneling tool 94 with a smaller handle 86 may also be used. Both are available from Popper and Sons, New Hyde Park, N.Y. or Needle Technology. Alternatively, the tunneling tool may be made of strong plastic or other suitable material.
  • An external patch electrode [0205] 43 for inductive coupling is shown in FIG. 12. One end of the patch electrode contains the coil 46, and the other end has an adapter 40 to fit into the external stimulator 42. The external patch electrode 43, is a modification of the patch electrode available from TruMed Technologies, Burnsville, Minn.
  • FIG. 13 shows a front view of an external stimulator [0206] 42, which preferably is slightly larger than a conventional pager. The external stimulator 42 contains the circuitry and rechargeable or replaceable power source. The external stimulator 42 has two modes of operation. In the first mode of operation there are several pre-determined programs, preferably up to nine, which differ in stimulus intensity, pulse width, frequency of stimulation, and on-off timing sequence, e.g. “on” for 10 seconds and “off” for 50 seconds in repeating cycles. For patient safety, any number of these programs may be locked-out by the manufacturer or physician. In the second mode, the patient, or caretaker may activate the stimulation on at any time. This mode is useful for epileptic patients that have the characteristic “aura”, which are sensory signs immediately preceding the convulsion that many epileptics have. When the device is turned on, a green light emitting diode (LED) indicates that the device is emitting electrical stimulation.
  • Pre-determined programs are arranged in such a way that the aggressiveness of the therapy increases from program #1 to Program #9. Thus the first three programs provide the least aggressive therapy, and the last three programs provide the most aggressive therapy. The following are examples of least aggressive therapy. [0207]
  • Program #1: [0208]
  • 1.0 mA current output, 0.2 msec pulse width, 15 Hz frequency, 15 sec ON time—1.0 min OFF time, in repeating cycles. [0209]
  • Program #2: [0210]
  • 1.5 mA current output, 0.3 msec pulse width, 20 Hz frequency, 20 sec ON time—2.0 min OFF time, in repeating cycles. [0211]
  • The following are examples of intermediate level of therapy. [0212]
  • Program #5: [0213]
  • 2.0 mA current output, 0.2 msec pulse width, 25 Hz frequency, 20 sec ON time—1.0 min OFF time, in repeating cycles. [0214]
  • Program #6: [0215]
  • 2.0 mA current output, 0.25 msec pulse width, 25 Hz frequency, 30 sec ON time—1.0 min OFF time, in repeating cycles. [0216]
  • The following are examples of most aggressive therapy. [0217]
  • Program #8: [0218]
  • [0219] 2.5 mA current output, 0.3 msec pulse width, 30 Hz frequency, 40 sec ON time— 1.5 min OFF time, in repeating cycles.
  • Program #9: [0220]
  • [0221] 3.0 mA current output, 0.4 msec pulse width, 30 Hz frequency, 30 sec ON time—1.0 min OFF time, in repeating cycles.
  • The majority of patients will fall into the category that require an intermediate level of therapy, such as program #5. The above are examples of the pre-determined programs that are delivered to the vagus nerve. The actual parameter settings for any given patient may deviate somewhat from the above. [0222]
  • FIG. 14 shows a top level block diagram of the external stimulator [0223] 42. As previously mentioned, there are two modes of stimulation with the external stimulator 42. The first mode is a series of pre-determined standard programs 71, differing in the aggressiveness of the therapy. The second mode is patient override 73, where upon pressing a button, the device immediately goes into the active mode. The selector 69 which comprises of pre-determined programs 71 and patient override 73 feeds into programmable control logic 75. The programmable control logic 75 controls the pulse frequency oscillator 79. The output of the pulse frequency oscillator 79 is amplified 83, filtered 87 and provided to the external coil (antenina) 89, which is then transmitted to the implanted receiver 34 for stimulation of the nerve. The programmable control logic 75 is connected to an indicator 85 showing on-off status, as well as the battery status. The external stimulator 42 is powered by a DC battery 81. A programming station 77 provides the capability to download and change programs if the need arises.
  • Conventional integrated circuits are used for the logic, control and timing circuits. Conventional bipolar transistors are used in radio-frequency oscillator, pulse amplitude ramp control and power amplifier. A standard voltage regulator is used in low-voltage detector. The hardware and software to deliver these predetermined programs is well known to those skilled in the art. [0224]
  • The fabrication of the lead-receiver [0225] 34 is designed to be modular. Thus, several different components can be mixed and matched without altering the functionality of the device significantly. As shown in FIG. 6, the lead-receiver 34 components are the proximal end 49 (containing coil 48, electrical circuitry 98, and case 78), the lead body 59 containing the conductor 65, and the distal electrode (cathode) 52. In the modular design concept, several design variables are possible, as shown in the table below. Table of lead-receiver design variables Proximal Distal End End Circuitry Conductor and Lead Lead body- (connecting Return body- Insulation proximal and Electrode - Electrode - electrode Lumens materials Lead-Coating distal ends) Material Type Bipolar Single Polyurethane Lubricious Alloy of Pure Standard ball (PVP) Nickal-Cobalt Platinum electrode Unipolar Double Silicone Antimicrobial Platinum- Hydrogel Iridium electrode (Pt/Ir) alloy Triple Silicone with Anti- Pt/Ir Spiral Polytetrafluor inflammatory coated with electrode oethylene Titanium (PTFE) Nitride Coaxial Carbon Steroid eluting Fiber electrode
  • Either silicone or polyurethane is suitable material for this implantable lead body [0226] 59. Both materials have proven to have desirable qualities which are not available in the other. Permanently implantable pacemaker leads made of polyurethane are susceptible to some forms of degradation over time. The identified mechanisms are Environmental Stress Cracking (ESC) and Metal Ion Oxidation (MIO). For this reason silicone material is slightly preferred over polyurethane.
  • Nerve-electrode interaction is an integral part of the stimulation system. As a practical benefit of modular design, any type of electrode described below can be used as the distal (cathode) stimulating electrode, without changing fabrication methodology or procedure significantly. When a standard ball electrode made of platinum or platinum/iridium is placed next to the nerve, and secured in place, it promotes an inflammatory response that leads to a thin fibrotic sheath around the electrode over a period of 1 to 6 weeks. This in turn leads to a stable position of electrode relative to the nerve, and a stable electrode-tissue interface, resulting in reliable stimulation of the nerve chronically without damaging the nerve. [0227]
  • Alternatively, other electrode forms that are non-traumatic to the nerve such as hydrogel, platinum fiber, or steroid elution electrodes may be used with this system. The concept of hydrogel electrode for nerve stimulation is shown schematically in FIG. 15. The hydrogel material [0228] 100 is wrapped around the nerve 54, with tiny platinum electrodes 102 being pulled back from nerve. Over a period of time in the body, the hydrogel material 100 will undergo degradation and there will be fibrotic tissue buildup. Because of the softness of the hydrogel material 100, these electrodes are non-traumatic to the nerve.
  • The concept of platinum fiber electrodes is shown schematically in FIG. 16. The distal fiber electrode [0229] 104 attached to the lead-receiver 34 may be platinum fiber or cable, or the electrode may be thin platinum fiber wrapped around Dacron polyester or Polyimide 106. As shown in FIG. 17, the platinum fibers 108 may be woven around Dacron polyester fiber 106 or platinum fibers 108 may be braided. At implant, the fiber electrode 104 is loosely wrapped around the surgically isolated nerve, then tied loosely so as not to constrict the nerve or put pressure on the nerve. As a further extension, the fiber electrode may be incorporated into a spiral electrode 105 as is shown schematically in FIG. 18. The fiber electrode 110 is on the inner side of polyurethane or silicone insulation 112 which is heat treated to retain its spiral shape.
  • Alternatively, steroid elution electrodes may be used. After implantation of a lead in the body, during the first few weeks there is buildup of fibrotic tissue in-growth over the electrode and to some extent around the lead body. This fibrosis is the end result of body's inflammatory response process which begins soon after the device is implanted. The fibrotic tissue sheath has the net effect of increasing the distance between the stimulation electrode (cathode) and the excitable tissue, which is the vagal nerve in this case. This is shown schematically in FIG. 19, where electrode [0230] 52 when covered with fibrotic tissue becomes the “virtual” electrode 114. Non-excitable tissue is depicted as 120 and excitable tissue as 118. A small amount of corticosteroid, dexamethasone sodium phosphate commonly referred to as “steroid” or “dexamethasone” placed inside or around the electrode, has significant beneficial effect on the current or energy threshold, i.e. the amount of energy required to stimulate the excitable tissue. This is well known to those familiar in the art, as there is a long history of steroid elution leads in cardiac pacing application. It takes only about 1 mg of dexamethasone to produce the desirable effects. Three separate ways of delivering the steroid drug to the electrode nerve-tissue interface are being disclosed here. Dexamethasone can be placed inside an electrode with microholes, it can be placed adjacent to the electrode in a silicone collar, or it can be coated on the electrode itself.
  • Dexamethasone inside the stimulating electrode is shown schematically in FIG. 20. A silicone core that is impregnated with a small quantity of dexamethasone [0231] 121, is incorporated inside the electrode. The electrode tip is depicted as 124 and electrode body as 122. Once the lead is implanted in the body, the steroid 121 elutes out through the small holes in the electrode. The steroid drug then has anti-inflammatory action at the electrode tissue interface, which leads to a much thinner fibrotic tissue capsule.
  • Another way of having a steroid eluting nerve stimulating electrode, is to have the steroid agent placed outside the distal electrode [0232] 52 in a silicone collar 126. This is shown schematically in FIG. 21. Approximately 1 mg of dexamethasone is contained in a silicone collar 126, at the base of the distal electrode 52. With such a method, the steroid drug elutes around the electrode 52 in a similar fashion and with similar pharmacokinetic properties, as with the steroid drug being inside the electrode.
  • Another method of steroid elution for nerve stimulation electrodes is by coating of steroid on the outside (exposed) surface area of the electrode. This is shown schematically in FIG. 22. Nafion is used as the coating matrix. Steroid membrane coating on the outside of the electrode is depicted as [0233] 128. The advantages of this method are that it can easily be applied to any electrode, fast and easy manufacturing, and it is cost effective. With this method, the rate of steroid delivery can be controlled by the level of sulfonation.
  • A schematic representation of the cross section of different possible lumens is shown in FIG. 23. The lead body [0234] 59 can have one, two, or three lumens for conducting cable, with or without a hollow lumen. In the cross sections, 132A-F represents lumens(s) for conducting cable, and 134A-C represents hollow lumen for aid in implanting the lead.
  • Additionally, different classes of coating may be applied to the implantable lead-receiver [0235] 34 after fabrication. These coatings fall into three categories, lubricious coating, antimicrobial coating, and anti-inflammatory coating.
  • The advantage of modular fabrication is that with one technology platform, several derivative products or models can be manufactured. As a specific practical example, using a silicone lead body platform, three separate derivative or lead models can be manufactured by using three different electrodes such as standard electrode, steroid electrode or spiral electrode. This is made possible by designing the fabrication steps such that the distal electrodes are assembled at the end, and as long as the electrodes are mated to the insulation and conducting cable, the shape or type of electrode does not matter. Similarly, different models can be produced by taking a finished lead and then coating it with lubricious coating or antimicrobial coating. In fact, considering the design variables disclosed in table 1, a large number of combinations are possible. Of these large number of possible combinations, about 6 or 7 models are planned for manufacturing. These include lead body composed of silicone and PTFE with standard ball electrodes made of platinum/iridium alloy, and silicone lead body with spiral electrode. [0236]
  • In addition to the neuromodulation of a cranial nerve such as the vagus nerve described above, neuromodulation of other nerves in the body can be performed. For example, neuromodulation of sacral nerve, which has beneficial effects for urinary incontinance, can be performed using an implantable lead-receiver and an external stimulator containing predetermined program, where the two are inductively coupled. In such a case, the secondary coil wold be implanted in the lower abdominal region. [0237]
  • While various embodiments of the present invention have been described in detail, it is apparent that modifications and adaptations of those embodiments will occur to those skilled in the art. However, it is to be expressly understood that such modifications and adaptations are within the spirit and scope of the present invention. [0238]

Claims (24)

What is claimed is:
1. An apparatus for electrical stimulation therapy for treatment of at least one of depression, migraine and neuropsychiatric disorders comprising:
a) an implantable lead-receiver comprising a secondary coil and at least one electrode capable of stimulating a cranial nerve;
b) an external stimulator comprising a power source, circuitry to emit electrical signals, at least two predetermined programs to control said electrical signals, and a primary coil;
c) said primary coil of said external stimulator and said secondary coil of said implantable lead-receiver being capable of forming an electrical connection by inductive coupling,
whereby said external stimulator is capable of controlling the stimulation of said cranial nerve.
2. The apparatus of
claim 1
wherein said neuropsychiatric disorder comprises obsessive compulsive disorders.
3. The apparatus of
claim 1
, wherein said cranial nerve is the left vagus nerve.
4. The apparatus of
claim 1
, wherein said external stimulator comprises a patient override mechanism to manually activate said external stimulator.
5. The apparatus of
claim 1
, wherein said predetermined programs are capable of being modified to modify said electrical signals.
6. The apparatus of
claim 1
, further comprising a program selection mechanism wherein said at least two predetermined programs may be selectively operated.
7. The apparatus of
claim 1
, wherein said primary coil of said external stimulator is adapted to be in contact with the skin of the patient.
8. The apparatus of
claim 1
, wherein said lead-receiver comprises a lead body with at least one lumen, a lead body insulation, a conductor, at least one electrode and a coil.
9. The apparatus of
claim 8
, wherein said at least one lumen is selected from the group consisting of single, double, triple and coaxial lumens.
10. The apparatus of
claim 8
wherein said lead body insulation is selected from the group consisting of polyurethane, silicone and silicone with polytetrafluoroethylene.
11. The apparatus of
claim 8
wherein said lead body further comprises a coating selected from the group consisting of lubricious PVP, antimicrobial and anti-inflammatory coatings.
12. The apparatus of
claim 8
wherein said electrode comprises amaterial selected from the group consisting of platinum, platinum/iridium alloy, platinum/iridium alloy coated with titanium nitride and carbon.
13. The apparatus of
claim 8
wherein said electrode is selected from the group consisting of standard ball electrodes, hydrogel electrodes, spiral electrodes, steroid eluting electrodes, and fiber electrodes.
14. The apparatus of
claim 1
, wherein said electrical signals comprise at least one variable component selected from the group consisting of the current amplitude, pulse width, frequency and on-off timing sequence, and said at least two predetermined programs controls said variable component of said electrical signals.
15. A method to provide therapy for at least one of depression, migraine and neuropsychiatric disorders, comprising;
a) providing an implantable lead-receiver comprising a secondary coil and at least one electrode to stimulate a cranial nerve;
b) providing an external stimulator comprising circuitry to emit electrical signals, at least two programs to control said electrical signals, an external coil and a power supply;
c) activating one of said at least two programs of said external stimulator to emit said electrical signals to said external coil;
d) inductively transferring said electrical signals from said external coil of said external stimulator to said secondary coil of said lead-receiver;
whereby said electrical signals stimulate said cranial nerve according to at least one of said at least two predetermined programs.
16. The method of
claim 15
, wherein said cranial nerve is the left vagus nerve.
17. The method of
claim 15
, wherein said cranial nerve is stimulated by bipolar stimulation.
18. The method of
claim 15
, wherein said cranial nerve is stimulated by unipolar stimulation.
19. The method of
claim 15
, wherein the step of activating one of said at least two predetermined programs is manually performed.
20. The method of
claim 15
, further comprising manually controlling said electrical signals to stimulate said cranial nerve.
21. The method of
claim 15
, wherein
a) said electrical signals comprise at least one variable component selected from the group consisting of the current amplitude, pulse width, frequency, and on-off timing sequence; and
b) said at least two predetermined programs controls said variable component of said electrical signals.
22. The method of
claim 15
, further comprising manually disengaging said at least two predetermined programs.
23. A method for treating symptoms of depression, migraine or neuropsychiatric disorders comprising:
a) selecting a predetermined program to control the output of an external stimulator;
b) activating said external stimulator to emit electrical signals in accordance with said predetermined program; and
c) inductively coupling said external stimulator with an implantable lead-receiver to stimulate a cranial nerve.
24. The method of
claim 21
, further comprising implanting beneath the skin of a patient said lead-receiver in direct electrical contact with said cranial nerve.
US09/727,570 1998-10-26 2000-11-30 Apparatus and method for adjunct (add-on) therapy for depression, migraine, neuropsychiatric disorders, partial complex epilepsy, generalized epilepsy and involuntary movement disorders utilizing an external stimulator Expired - Fee Related US6356788B2 (en)

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US09/837,512 US6668191B1 (en) 1998-10-26 2001-04-19 Apparatus and method for electrical stimulation adjunct (add-on) therapy of atrial fibrillation, inappropriate sinus tachycardia, and refractory hypertension with an external stimulator
US09/837,661 US6611715B1 (en) 1998-10-26 2001-04-19 Apparatus and method for neuromodulation therapy for obesity and compulsive eating disorders using an implantable lead-receiver and an external stimulator
US09/837,660 US6615081B1 (en) 1998-10-26 2001-04-19 Apparatus and method for adjunct (add-on) treatment of diabetes by neuromodulation with an external stimulator
US09/837,662 US6564102B1 (en) 1998-10-26 2001-04-19 Apparatus and method for adjunct (add-on) treatment of coma and traumatic brain injury with neuromodulation using an external stimulator

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US09/837,662 Continuation-In-Part US6564102B1 (en) 1998-10-26 2001-04-19 Apparatus and method for adjunct (add-on) treatment of coma and traumatic brain injury with neuromodulation using an external stimulator
US09/837,660 Continuation-In-Part US6615081B1 (en) 1998-10-26 2001-04-19 Apparatus and method for adjunct (add-on) treatment of diabetes by neuromodulation with an external stimulator
US09/837,512 Continuation-In-Part US6668191B1 (en) 1998-10-26 2001-04-19 Apparatus and method for electrical stimulation adjunct (add-on) therapy of atrial fibrillation, inappropriate sinus tachycardia, and refractory hypertension with an external stimulator

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Cited By (87)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020062060A1 (en) * 1998-10-06 2002-05-23 Yossi Gross Incontinence treatment device
US20030082884A1 (en) * 2001-10-26 2003-05-01 International Business Machine Corporation And Kabushiki Kaisha Toshiba Method of forming low-leakage dielectric layer
US20030083698A1 (en) * 2001-11-01 2003-05-01 Whitehurst Todd K. Thrombolysis and chronic anticoagulation therapy
US20030171789A1 (en) * 2001-11-01 2003-09-11 Medtronic, Inc. Method and apparatus for programming an implantable medical device
US20030236557A1 (en) * 2002-06-20 2003-12-25 Whitehurst Todd K. Cavernous nerve stimulation via unidirectional propagation of action potentials
US20030236558A1 (en) * 2002-06-20 2003-12-25 Whitehurst Todd K. Vagus nerve stimulation via unidirectional propagation of action potentials
US20040015205A1 (en) * 2002-06-20 2004-01-22 Whitehurst Todd K. Implantable microstimulators with programmable multielectrode configuration and uses thereof
US20040015204A1 (en) * 2002-06-20 2004-01-22 Whitehurst Todd K. Implantable microstimulators and methods for unidirectional propagation of action potentials
US20040243205A1 (en) * 2003-05-30 2004-12-02 Medtronic, Inc. Implantable cortical neural lead and method
US20050027158A1 (en) * 2002-10-21 2005-02-03 Becker Paul F. Method and apparatus for the treatment of physical and mental disorders with low frequency, low flux density magnetic fields
US20050049651A1 (en) * 2000-06-20 2005-03-03 Whitehurst Todd K. Treatment of mood and/or anxiety disorders by electrical brain stimulation and/or drug infusion
US20050049650A1 (en) * 2000-10-30 2005-03-03 Medtronic, Inc. Method for treating obsessive-compulsive disorder with electrical stimulation of the brain internal capsule
WO2005039693A1 (en) * 2003-10-27 2005-05-06 Jorge Alberto Morales Sanchez Device for emitting electric impulses directed to the brain
US20050182287A1 (en) * 2002-10-21 2005-08-18 Becker Paul F. Method and apparatus for the treatment of physical and mental disorders with low frequency, low flux density magnetic fields
US20050182467A1 (en) * 2003-11-20 2005-08-18 Angiotech International Ag Electrical devices and anti-scarring agents
US20050209652A1 (en) * 2001-04-26 2005-09-22 Whitehurst Todd K Methods and systems for electrical and/or drug stimulation as a therapy for erectile dysfunction
US20050240229A1 (en) * 2001-04-26 2005-10-27 Whitehurst Tood K Methods and systems for stimulation as a therapy for erectile dysfunction
US20050251212A1 (en) * 2000-09-27 2005-11-10 Cvrx, Inc. Stimulus regimens for cardiovascular reflex control
US20060025829A1 (en) * 2004-07-28 2006-02-02 Armstrong Randolph K Power supply monitoring for an implantable device
US20060052856A1 (en) * 2004-09-08 2006-03-09 Kim Daniel H Stimulation components
US20060111626A1 (en) * 2003-03-27 2006-05-25 Cvrx, Inc. Electrode structures having anti-inflammatory properties and methods of use
US20060161219A1 (en) * 2003-11-20 2006-07-20 Advanced Neuromodulation Systems, Inc. Electrical stimulation system and method for stimulating multiple locations of target nerve tissue in the brain to treat multiple conditions in the body
US20060206162A1 (en) * 2005-03-11 2006-09-14 Wahlstrand Carl D Implantable neurostimulator device
US20060206163A1 (en) * 2005-03-11 2006-09-14 Wahlstrand Carl D Neurostimulation site screening
US20060229688A1 (en) * 2005-04-08 2006-10-12 Mcclure Kelly H Controlling stimulation parameters of implanted tissue stimulators
US20060258950A1 (en) * 2002-02-04 2006-11-16 Synergistic Neurotherapy Adjustment Process, Inc. (Trade At Synaps) Method and apparatus for utilizing amplitude-modulated pulse-width modulation signals for neurostimulation and treatment of neurological disorders using electrical stimulation
US20060280655A1 (en) * 2005-06-08 2006-12-14 California Institute Of Technology Intravascular diagnostic and therapeutic sampling device
US7151961B1 (en) * 2002-05-24 2006-12-19 Advanced Bionics Corporation Treatment of movement disorders by brain stimulation
US20070021790A1 (en) * 2000-09-27 2007-01-25 Cvrx, Inc. Automatic baroreflex modulation responsive to adverse event
US20070027504A1 (en) * 2005-07-27 2007-02-01 Cyberonics, Inc. Cranial nerve stimulation to treat a hearing disorder
US20070118183A1 (en) * 2005-11-18 2007-05-24 Mark Gelfand System and method to modulate phrenic nerve to prevent sleep apnea
US20070123938A1 (en) * 2005-11-30 2007-05-31 Haller Matthew I Magnetically coupled microstimulators
US20070260288A1 (en) * 2006-03-03 2007-11-08 Yossi Gross Apparatus for treating stress and urge incontinence
US20080015642A1 (en) * 2006-07-17 2008-01-17 Sherwood Services Ag Method for stimulation of the vagus nerve
US20080097142A1 (en) * 2006-10-20 2008-04-24 Paul Savage Magnetic field generator, method of generating a pulsed sinusoidal magnetic wave and magnetic field generator system
US20080177350A1 (en) * 2000-09-27 2008-07-24 Cvrx, Inc. Expandable Stimulation Electrode with Integrated Pressure Sensor and Methods Related Thereto
US20080208282A1 (en) * 2007-01-22 2008-08-28 Mark Gelfand Device and method for the treatment of breathing disorders and cardiac disorders
US20090112282A1 (en) * 2007-10-26 2009-04-30 Medtronic, Inc. Occipital nerve stimulation
US20090112962A1 (en) * 2007-10-31 2009-04-30 Research In Motion Limited Modular squaring in binary field arithmetic
US7570999B2 (en) 2005-12-20 2009-08-04 Cardiac Pacemakers, Inc. Implantable device for treating epilepsy and cardiac rhythm disorders
US7627383B2 (en) 2005-03-15 2009-12-01 Boston Scientific Neuromodulation Corporation Implantable stimulator
US20100030227A1 (en) * 2008-07-31 2010-02-04 Medtronic, Inc. Medical lead implantation
US7734355B2 (en) 2001-08-31 2010-06-08 Bio Control Medical (B.C.M.) Ltd. Treatment of disorders by unidirectional nerve stimulation
US20100217340A1 (en) * 2009-02-23 2010-08-26 Ams Research Corporation Implantable Medical Device Connector System
US7801600B1 (en) 2005-05-26 2010-09-21 Boston Scientific Neuromodulation Corporation Controlling charge flow in the electrical stimulation of tissue
US7803148B2 (en) 2006-06-09 2010-09-28 Neurosystec Corporation Flow-induced delivery from a drug mass
US7865243B1 (en) 2000-04-07 2011-01-04 Boston Scientific Neuromodulation Corporation Device and therapy for erectile dysfunction and other sexual dysfunction
US7877136B1 (en) 2007-09-28 2011-01-25 Boston Scientific Neuromodulation Corporation Enhancement of neural signal transmission through damaged neural tissue via hyperpolarizing electrical stimulation current
US20110060380A1 (en) * 2009-09-10 2011-03-10 Mark Gelfand Respiratory rectification
US20110077579A1 (en) * 2005-03-24 2011-03-31 Harrison William V Cochlear implant with localized fluid transport
US7949400B2 (en) 2000-09-27 2011-05-24 Cvrx, Inc. Devices and methods for cardiovascular reflex control via coupled electrodes
US20110295332A1 (en) * 2010-05-26 2011-12-01 Flint Hills Scientific, L.L.C. Quantitative multivariate analysis of seizures
US8160710B2 (en) 2006-07-10 2012-04-17 Ams Research Corporation Systems and methods for implanting tissue stimulation electrodes in the pelvic region
US20120184801A1 (en) * 2009-03-20 2012-07-19 ElectroCore, LLC Nerve stimulation methods for averting imminent onset or episode of a disease
US20120185020A1 (en) * 2009-03-20 2012-07-19 ElectroCore, LLC. Nerve stimulation methods for averting imminent onset or episode of a disease
US8380318B2 (en) 2009-03-24 2013-02-19 Spinal Modulation, Inc. Pain management with stimulation subthreshold to paresthesia
US8380312B2 (en) 2009-12-31 2013-02-19 Ams Research Corporation Multi-zone stimulation implant system and method
US20130066395A1 (en) * 2009-03-20 2013-03-14 ElectroCore, LLC. Nerve stimulation methods for averting imminent onset or episode of a disease
US8433412B1 (en) 2008-02-07 2013-04-30 Respicardia, Inc. Muscle and nerve stimulation
US8518092B2 (en) 2006-12-06 2013-08-27 Spinal Modulation, Inc. Hard tissue anchors and delivery devices
US20130245486A1 (en) * 2009-03-20 2013-09-19 ElectroCore, LLC. Devices and methods for monitoring non-invasive vagus nerve stimulation
US8571651B2 (en) 2006-09-07 2013-10-29 Bio Control Medical (B.C.M.) Ltd. Techniques for reducing pain associated with nerve stimulation
US8571653B2 (en) 2001-08-31 2013-10-29 Bio Control Medical (B.C.M.) Ltd. Nerve stimulation techniques
US8606359B2 (en) 2000-09-27 2013-12-10 Cvrx, Inc. System and method for sustained baroreflex stimulation
GB2504196A (en) * 2012-06-01 2014-01-22 Bioinduction Ltd Precision delivery of electrical therapy
US8774942B2 (en) 2007-07-10 2014-07-08 Ams Research Corporation Tissue anchor
US8805494B2 (en) 2005-05-10 2014-08-12 Cardiac Pacemakers, Inc. System and method to deliver therapy in presence of another therapy
US8983624B2 (en) 2006-12-06 2015-03-17 Spinal Modulation, Inc. Delivery devices, systems and methods for stimulating nerve tissue on multiple spinal levels
US9044592B2 (en) 2007-01-29 2015-06-02 Spinal Modulation, Inc. Sutureless lead retention features
US9056197B2 (en) 2008-10-27 2015-06-16 Spinal Modulation, Inc. Selective stimulation systems and signal parameters for medical conditions
US9205261B2 (en) 2004-09-08 2015-12-08 The Board Of Trustees Of The Leland Stanford Junior University Neurostimulation methods and systems
US9220887B2 (en) 2011-06-09 2015-12-29 Astora Women's Health LLC Electrode lead including a deployable tissue anchor
US9259569B2 (en) 2009-05-15 2016-02-16 Daniel M. Brounstein Methods, systems and devices for neuromodulating spinal anatomy
US9314618B2 (en) 2006-12-06 2016-04-19 Spinal Modulation, Inc. Implantable flexible circuit leads and methods of use
US9327110B2 (en) 2009-10-27 2016-05-03 St. Jude Medical Luxembourg Holdings SMI S.A.R.L. (“SJM LUX SMI”) Devices, systems and methods for the targeted treatment of movement disorders
US9370660B2 (en) 2013-03-29 2016-06-21 Rainbow Medical Ltd. Independently-controlled bidirectional nerve stimulation
US9427570B2 (en) 2006-12-06 2016-08-30 St. Jude Medical Luxembourg Holdings SMI S.A.R.L. (“SJM LUX SMI”) Expandable stimulation leads and methods of use
US9427573B2 (en) 2007-07-10 2016-08-30 Astora Women's Health, Llc Deployable electrode lead anchor
US9486633B2 (en) 2004-09-08 2016-11-08 The Board Of Trustees Of The Leland Stanford Junior University Selective stimulation to modulate the sympathetic nervous system
US9539433B1 (en) 2009-03-18 2017-01-10 Astora Women's Health, Llc Electrode implantation in a pelvic floor muscular structure
US9616234B2 (en) 2002-05-03 2017-04-11 Trustees Of Boston University System and method for neuro-stimulation
US9731112B2 (en) 2011-09-08 2017-08-15 Paul J. Gindele Implantable electrode assembly
US9782584B2 (en) 2014-06-13 2017-10-10 Nervana, LLC Transcutaneous electrostimulator and methods for electric stimulation
US9987488B1 (en) 2007-06-27 2018-06-05 Respicardia, Inc. Detecting and treating disordered breathing
US10105540B2 (en) 2015-11-09 2018-10-23 Bluewind Medical Ltd. Optimization of application of current
US10130809B2 (en) 2014-06-13 2018-11-20 Nervana, LLC Transcutaneous electrostimulator and methods for electric stimulation
US10406366B2 (en) 2006-11-17 2019-09-10 Respicardia, Inc. Transvenous phrenic nerve stimulation system

Families Citing this family (157)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7799337B2 (en) 1997-07-21 2010-09-21 Levin Bruce H Method for directed intranasal administration of a composition
US7403820B2 (en) * 1998-08-05 2008-07-22 Neurovista Corporation Closed-loop feedback-driven neuromodulation
US7853329B2 (en) * 1998-08-05 2010-12-14 Neurovista Corporation Monitoring efficacy of neural modulation therapy
US9375573B2 (en) 1998-08-05 2016-06-28 Cyberonics, Inc. Systems and methods for monitoring a patient's neurological disease state
US9415222B2 (en) 1998-08-05 2016-08-16 Cyberonics, Inc. Monitoring an epilepsy disease state with a supervisory module
US7277758B2 (en) * 1998-08-05 2007-10-02 Neurovista Corporation Methods and systems for predicting future symptomatology in a patient suffering from a neurological or psychiatric disorder
US9042988B2 (en) 1998-08-05 2015-05-26 Cyberonics, Inc. Closed-loop vagus nerve stimulation
US8762065B2 (en) * 1998-08-05 2014-06-24 Cyberonics, Inc. Closed-loop feedback-driven neuromodulation
US7747325B2 (en) * 1998-08-05 2010-06-29 Neurovista Corporation Systems and methods for monitoring a patient's neurological disease state
US7209787B2 (en) * 1998-08-05 2007-04-24 Bioneuronics Corporation Apparatus and method for closed-loop intracranial stimulation for optimal control of neurological disease
US20070067004A1 (en) * 2002-05-09 2007-03-22 Boveja Birinder R Methods and systems for modulating the vagus nerve (10th cranial nerve) to provide therapy for neurological, and neuropsychiatric disorders
US6269270B1 (en) * 1998-10-26 2001-07-31 Birinder Bob Boveja Apparatus and method for adjunct (add-on) therapy of Dementia and Alzheimer's disease utilizing an implantable lead and external stimulator
US8914114B2 (en) 2000-05-23 2014-12-16 The Feinstein Institute For Medical Research Inhibition of inflammatory cytokine production by cholinergic agonists and vagus nerve stimulation
US7493172B2 (en) * 2001-01-30 2009-02-17 Boston Scientific Neuromodulation Corp. Methods and systems for stimulating a nerve originating in an upper cervical spine area to treat a medical condition
US7167751B1 (en) 2001-03-01 2007-01-23 Advanced Bionics Corporation Method of using a fully implantable miniature neurostimulator for vagus nerve stimulation
US6892098B2 (en) * 2001-04-26 2005-05-10 Biocontrol Medical Ltd. Nerve stimulation for treating spasticity, tremor, muscle weakness, and other motor disorders
US6622047B2 (en) * 2001-07-28 2003-09-16 Cyberonics, Inc. Treatment of neuropsychiatric disorders by near-diaphragmatic nerve stimulation
US6626680B2 (en) * 2001-08-24 2003-09-30 Wilson Greatbatch Ltd. Wire bonding surface
EP1487494A2 (en) * 2002-02-26 2004-12-22 North Shore-Long Island Jewish Research Institute Inhibition of inflammatory cytokine production by stimulation of brain muscarinic receptors
US20050209654A1 (en) * 2002-05-09 2005-09-22 Boveja Birinder R Method and system for providing adjunct (add-on) therapy for depression, anxiety and obsessive-compulsive disorders by providing electrical pulses to vagus nerve(s)
US20060009815A1 (en) * 2002-05-09 2006-01-12 Boveja Birinder R Method and system to provide therapy or alleviate symptoms of involuntary movement disorders by providing complex and/or rectangular electrical pulses to vagus nerve(s)
US20050216070A1 (en) * 2002-05-09 2005-09-29 Boveja Birinder R Method and system for providing therapy for migraine/chronic headache by providing electrical pulses to vagus nerve(s)
US7076307B2 (en) * 2002-05-09 2006-07-11 Boveja Birinder R Method and system for modulating the vagus nerve (10th cranial nerve) with electrical pulses using implanted and external components, to provide therapy neurological and neuropsychiatric disorders
US20050154426A1 (en) * 2002-05-09 2005-07-14 Boveja Birinder R. Method and system for providing therapy for neuropsychiatric and neurological disorders utilizing transcranical magnetic stimulation and pulsed electrical vagus nerve(s) stimulation
US20050165458A1 (en) * 2002-05-09 2005-07-28 Boveja Birinder R. Method and system to provide therapy for depression using electroconvulsive therapy(ECT) and pulsed electrical stimulation to vagus nerve(s)
US20050182453A1 (en) * 2002-05-24 2005-08-18 Whitehurst Todd K. Treatment of epilepsy by high frequency electrical stimulation and/or drug stimulation
EP1562674A4 (en) * 2002-10-15 2008-10-08 Medtronic Inc Control of treatment therapy during start-up and during operation of a medical device system
AU2003287162A1 (en) * 2002-10-15 2004-05-04 Medtronic Inc. Configuring and testing treatment therapy parameters for a medical device system
US7149572B2 (en) * 2002-10-15 2006-12-12 Medtronic, Inc. Phase shifting of neurological signals in a medical device system
WO2004034885A2 (en) * 2002-10-15 2004-04-29 Medtronic Inc. Signal quality monitoring and control for a medical device system
US8738136B2 (en) * 2002-10-15 2014-05-27 Medtronic, Inc. Clustering of recorded patient neurological activity to determine length of a neurological event
AU2003301368A1 (en) * 2002-10-15 2004-05-04 Medtronic Inc. Scoring of sensed neurological signals for use with a medical device system
AU2003301370A1 (en) 2002-10-15 2004-05-04 Medtronic Inc. Multi-modal operation of a medical device system
WO2004034879A2 (en) 2002-10-15 2004-04-29 Medtronic Inc. Screening techniques for management of a nervous system disorder
US7189204B2 (en) * 2002-12-04 2007-03-13 Cardiac Pacemakers, Inc. Sleep detection using an adjustable threshold
US8064994B2 (en) * 2003-01-14 2011-11-22 The United States Of America As Represented By The Department Of Veterans Affairs Cervical vagal stimulation induced weight loss
CN1964630A (en) * 2003-02-13 2007-05-16 耶希瓦大学艾伯塔·爱恩斯坦医学院 Regulation of food intake and glucose production by modulation of long-chain fatty acyl-coa levels in the hypothalamus
US7155279B2 (en) 2003-03-28 2006-12-26 Advanced Bionics Corporation Treatment of movement disorders with drug therapy
US20040225335A1 (en) * 2003-05-08 2004-11-11 Whitehurst Todd K. Treatment of Huntington's disease by brain stimulation
US20050197678A1 (en) * 2003-05-11 2005-09-08 Boveja Birinder R. Method and system for providing therapy for Alzheimer's disease and dementia by providing electrical pulses to vagus nerve(s)
US20060079936A1 (en) * 2003-05-11 2006-04-13 Boveja Birinder R Method and system for altering regional cerebral blood flow (rCBF) by providing complex and/or rectangular electrical pulses to vagus nerve(s), to provide therapy for depression and other medical disorders
US20060074450A1 (en) * 2003-05-11 2006-04-06 Boveja Birinder R System for providing electrical pulses to nerve and/or muscle using an implanted stimulator
US7444184B2 (en) * 2003-05-11 2008-10-28 Neuro And Cardial Technologies, Llc Method and system for providing therapy for bulimia/eating disorders by providing electrical pulses to vagus nerve(s)
US20050187590A1 (en) * 2003-05-11 2005-08-25 Boveja Birinder R. Method and system for providing therapy for autism by providing electrical pulses to the vagus nerve(s)
US8606356B2 (en) 2003-09-18 2013-12-10 Cardiac Pacemakers, Inc. Autonomic arousal detection system and method
US9050469B1 (en) 2003-11-26 2015-06-09 Flint Hills Scientific, Llc Method and system for logging quantitative seizure information and assessing efficacy of therapy using cardiac signals
WO2005062829A2 (en) * 2003-12-19 2005-07-14 Advanced Bionics Corporation Skull-mounted electrical stimulation system and method for treating patients
US7422555B2 (en) * 2003-12-30 2008-09-09 Jacob Zabara Systems and methods for therapeutically treating neuro-psychiatric disorders and other illnesses
AU2005225458B2 (en) * 2004-03-25 2008-12-04 The Feinstein Institutes For Medical Research Neural tourniquet
US7747323B2 (en) 2004-06-08 2010-06-29 Cardiac Pacemakers, Inc. Adaptive baroreflex stimulation therapy for disordered breathing
US7596413B2 (en) * 2004-06-08 2009-09-29 Cardiac Pacemakers, Inc. Coordinated therapy for disordered breathing including baroreflex modulation
WO2006041922A2 (en) * 2004-10-08 2006-04-20 Dara Biosciences, Inc. Agents and methods for administration to the central nervous system
US8565867B2 (en) * 2005-01-28 2013-10-22 Cyberonics, Inc. Changeable electrode polarity stimulation by an implantable medical device
US9314633B2 (en) 2008-01-25 2016-04-19 Cyberonics, Inc. Contingent cardio-protection for epilepsy patients
WO2006088798A2 (en) * 2005-02-14 2006-08-24 Albert Einstein College Of Medicine Of Yeshiva University Modulation of hypothalamic atp-sensitive potassium channels
US7711419B2 (en) * 2005-07-13 2010-05-04 Cyberonics, Inc. Neurostimulator with reduced size
US7499752B2 (en) * 2005-07-29 2009-03-03 Cyberonics, Inc. Selective nerve stimulation for the treatment of eating disorders
US20070027499A1 (en) * 2005-07-29 2007-02-01 Cyberonics, Inc. Neurostimulation device for treating mood disorders
US8428731B2 (en) 2005-10-27 2013-04-23 Cyberonics, Inc. Sequenced therapy protocols for an implantable medical device
US7555344B2 (en) * 2005-10-28 2009-06-30 Cyberonics, Inc. Selective neurostimulation for treating epilepsy
US8694118B2 (en) 2005-10-28 2014-04-08 Cyberonics, Inc. Variable output ramping for an implantable medical device
US8868172B2 (en) * 2005-12-28 2014-10-21 Cyberonics, Inc. Methods and systems for recommending an appropriate action to a patient for managing epilepsy and other neurological disorders
US20070149952A1 (en) * 2005-12-28 2007-06-28 Mike Bland Systems and methods for characterizing a patient's propensity for a neurological event and for communicating with a pharmacological agent dispenser
US8725243B2 (en) 2005-12-28 2014-05-13 Cyberonics, Inc. Methods and systems for recommending an appropriate pharmacological treatment to a patient for managing epilepsy and other neurological disorders
US8109879B2 (en) 2006-01-10 2012-02-07 Cardiac Pacemakers, Inc. Assessing autonomic activity using baroreflex analysis
US7996079B2 (en) 2006-01-24 2011-08-09 Cyberonics, Inc. Input response override for an implantable medical device
US7974697B2 (en) * 2006-01-26 2011-07-05 Cyberonics, Inc. Medical imaging feedback for an implantable medical device
US7657310B2 (en) 2006-01-26 2010-02-02 Cyberonics, Inc. Treatment of reproductive endocrine disorders by vagus nerve stimulation
US7801601B2 (en) * 2006-01-27 2010-09-21 Cyberonics, Inc. Controlling neuromodulation using stimulus modalities
US20070287931A1 (en) * 2006-02-14 2007-12-13 Dilorenzo Daniel J Methods and systems for administering an appropriate pharmacological treatment to a patient for managing epilepsy and other neurological disorders
WO2007115118A1 (en) * 2006-03-29 2007-10-11 Catholic Healthcare West Vagus nerve stimulation method
US7869885B2 (en) * 2006-04-28 2011-01-11 Cyberonics, Inc Threshold optimization for tissue stimulation therapy
US7962220B2 (en) 2006-04-28 2011-06-14 Cyberonics, Inc. Compensation reduction in tissue stimulation therapy
US20080021341A1 (en) * 2006-06-23 2008-01-24 Neurovista Corporation A Delware Corporation Methods and Systems for Facilitating Clinical Trials
US7869867B2 (en) 2006-10-27 2011-01-11 Cyberonics, Inc. Implantable neurostimulator with refractory stimulation
US8295934B2 (en) 2006-11-14 2012-10-23 Neurovista Corporation Systems and methods of reducing artifact in neurological stimulation systems
US7706875B2 (en) 2007-01-25 2010-04-27 Cyberonics, Inc. Modulation of drug effects by vagus nerve stimulation
EP2126785A2 (en) 2007-01-25 2009-12-02 NeuroVista Corporation Systems and methods for identifying a contra-ictal condition in a subject
US20080183097A1 (en) 2007-01-25 2008-07-31 Leyde Kent W Methods and Systems for Measuring a Subject's Susceptibility to a Seizure
US20080208074A1 (en) * 2007-02-21 2008-08-28 David Snyder Methods and Systems for Characterizing and Generating a Patient-Specific Seizure Advisory System
AU2008224943A1 (en) * 2007-03-13 2008-09-18 The Feinstein Institute For Medical Research Treatment of inflammation by non-invasive stimulation
US8036736B2 (en) 2007-03-21 2011-10-11 Neuro Vista Corporation Implantable systems and methods for identifying a contra-ictal condition in a subject
US7869884B2 (en) * 2007-04-26 2011-01-11 Cyberonics, Inc. Non-surgical device and methods for trans-esophageal vagus nerve stimulation
US7904175B2 (en) 2007-04-26 2011-03-08 Cyberonics, Inc. Trans-esophageal vagus nerve stimulation
US7962214B2 (en) 2007-04-26 2011-06-14 Cyberonics, Inc. Non-surgical device and methods for trans-esophageal vagus nerve stimulation
US7974701B2 (en) * 2007-04-27 2011-07-05 Cyberonics, Inc. Dosing limitation for an implantable medical device
US9788744B2 (en) 2007-07-27 2017-10-17 Cyberonics, Inc. Systems for monitoring brain activity and patient advisory device
WO2009029614A1 (en) 2007-08-27 2009-03-05 The Feinstein Institute For Medical Research Devices and methods for inhibiting granulocyte activation by neural stimulation
WO2009065101A1 (en) * 2007-11-16 2009-05-22 Mclean Hospital Corporation Intracranial electrical seizure therapy (icest)
US20090171168A1 (en) * 2007-12-28 2009-07-02 Leyde Kent W Systems and Method for Recording Clinical Manifestations of a Seizure
US9259591B2 (en) * 2007-12-28 2016-02-16 Cyberonics, Inc. Housing for an implantable medical device
US8260426B2 (en) 2008-01-25 2012-09-04 Cyberonics, Inc. Method, apparatus and system for bipolar charge utilization during stimulation by an implantable medical device
US9211409B2 (en) * 2008-03-31 2015-12-15 The Feinstein Institute For Medical Research Methods and systems for reducing inflammation by neuromodulation of T-cell activity
US9662490B2 (en) 2008-03-31 2017-05-30 The Feinstein Institute For Medical Research Methods and systems for reducing inflammation by neuromodulation and administration of an anti-inflammatory drug
US8204603B2 (en) 2008-04-25 2012-06-19 Cyberonics, Inc. Blocking exogenous action potentials by an implantable medical device
US8473062B2 (en) * 2008-05-01 2013-06-25 Autonomic Technologies, Inc. Method and device for the treatment of headache
US20090275997A1 (en) * 2008-05-01 2009-11-05 Michael Allen Faltys Vagus nerve stimulation electrodes and methods of use
US9211410B2 (en) 2009-05-01 2015-12-15 Setpoint Medical Corporation Extremely low duty-cycle activation of the cholinergic anti-inflammatory pathway to treat chronic inflammation
US8457747B2 (en) 2008-10-20 2013-06-04 Cyberonics, Inc. Neurostimulation with signal duration determined by a cardiac cycle
US8417344B2 (en) 2008-10-24 2013-04-09 Cyberonics, Inc. Dynamic cranial nerve stimulation based on brain state determination from cardiac data
US8412338B2 (en) * 2008-11-18 2013-04-02 Setpoint Medical Corporation Devices and methods for optimizing electrode placement for anti-inflamatory stimulation
EP2369986A4 (en) * 2008-12-23 2013-08-28 Neurovista Corp Brain state analysis based on select seizure onset characteristics and clinical manifestations
US8412336B2 (en) 2008-12-29 2013-04-02 Autonomic Technologies, Inc. Integrated delivery and visualization tool for a neuromodulation system
US8849390B2 (en) 2008-12-29 2014-09-30 Cyberonics, Inc. Processing for multi-channel signals
US8588933B2 (en) * 2009-01-09 2013-11-19 Cyberonics, Inc. Medical lead termination sleeve for implantable medical devices
US9320908B2 (en) * 2009-01-15 2016-04-26 Autonomic Technologies, Inc. Approval per use implanted neurostimulator
US20100185249A1 (en) * 2009-01-22 2010-07-22 Wingeier Brett M Method and Devices for Adrenal Stimulation
US20100191304A1 (en) * 2009-01-23 2010-07-29 Scott Timothy L Implantable Medical Device for Providing Chronic Condition Therapy and Acute Condition Therapy Using Vagus Nerve Stimulation
US8494641B2 (en) 2009-04-22 2013-07-23 Autonomic Technologies, Inc. Implantable neurostimulator with integral hermetic electronic enclosure, circuit substrate, monolithic feed-through, lead assembly and anchoring mechanism
US8827912B2 (en) 2009-04-24 2014-09-09 Cyberonics, Inc. Methods and systems for detecting epileptic events using NNXX, optionally with nonlinear analysis parameters
US8239028B2 (en) * 2009-04-24 2012-08-07 Cyberonics, Inc. Use of cardiac parameters in methods and systems for treating a chronic medical condition
US8786624B2 (en) 2009-06-02 2014-07-22 Cyberonics, Inc. Processing for multi-channel signals
US8886339B2 (en) 2009-06-09 2014-11-11 Setpoint Medical Corporation Nerve cuff with pocket for leadless stimulator
US8996116B2 (en) 2009-10-30 2015-03-31 Setpoint Medical Corporation Modulation of the cholinergic anti-inflammatory pathway to treat pain or addiction
EP2515996B1 (en) 2009-12-23 2019-09-18 Setpoint Medical Corporation Neural stimulation devices and systems for treatment of chronic inflammation
US9643019B2 (en) 2010-02-12 2017-05-09 Cyberonics, Inc. Neurological monitoring and alerts
US20110219325A1 (en) * 2010-03-02 2011-09-08 Himes David M Displaying and Manipulating Brain Function Data Including Enhanced Data Scrolling Functionality
US20110218820A1 (en) * 2010-03-02 2011-09-08 Himes David M Displaying and Manipulating Brain Function Data Including Filtering of Annotations
US8562536B2 (en) 2010-04-29 2013-10-22 Flint Hills Scientific, Llc Algorithm for detecting a seizure from cardiac data
US8649871B2 (en) 2010-04-29 2014-02-11 Cyberonics, Inc. Validity test adaptive constraint modification for cardiac data used for detection of state changes
US8831732B2 (en) 2010-04-29 2014-09-09 Cyberonics, Inc. Method, apparatus and system for validating and quantifying cardiac beat data quality
US8594806B2 (en) 2010-04-30 2013-11-26 Cyberonics, Inc. Recharging and communication lead for an implantable device
US8788045B2 (en) 2010-06-08 2014-07-22 Bluewind Medical Ltd. Tibial nerve stimulation
US8679009B2 (en) 2010-06-15 2014-03-25 Flint Hills Scientific, Llc Systems approach to comorbidity assessment
US8641646B2 (en) 2010-07-30 2014-02-04 Cyberonics, Inc. Seizure detection using coordinate data
US8571643B2 (en) 2010-09-16 2013-10-29 Flint Hills Scientific, Llc Detecting or validating a detection of a state change from a template of heart rate derivative shape or heart beat wave complex
US8382667B2 (en) 2010-10-01 2013-02-26 Flint Hills Scientific, Llc Detecting, quantifying, and/or classifying seizures using multimodal data
US8684921B2 (en) 2010-10-01 2014-04-01 Flint Hills Scientific Llc Detecting, assessing and managing epilepsy using a multi-variate, metric-based classification analysis
US8337404B2 (en) 2010-10-01 2012-12-25 Flint Hills Scientific, Llc Detecting, quantifying, and/or classifying seizures using multimodal data
US9457186B2 (en) 2010-11-15 2016-10-04 Bluewind Medical Ltd. Bilateral feedback
US9186504B2 (en) 2010-11-15 2015-11-17 Rainbow Medical Ltd Sleep apnea treatment
US9504390B2 (en) 2011-03-04 2016-11-29 Globalfoundries Inc. Detecting, assessing and managing a risk of death in epilepsy
US8725239B2 (en) 2011-04-25 2014-05-13 Cyberonics, Inc. Identifying seizures using heart rate decrease
US9402550B2 (en) 2011-04-29 2016-08-02 Cybertronics, Inc. Dynamic heart rate threshold for neurological event detection
CN103619405B (en) 2011-05-09 2015-11-25 赛博恩特医疗器械公司 The individual pulse being used for the treatment of the cholinergic anti-inflammatory pathway of chronic inflammatory disease activates
US9833621B2 (en) 2011-09-23 2017-12-05 Setpoint Medical Corporation Modulation of sirtuins by vagus nerve stimulation
US9549677B2 (en) 2011-10-14 2017-01-24 Flint Hills Scientific, L.L.C. Seizure detection methods, apparatus, and systems using a wavelet transform maximum modulus algorithm
WO2013112920A1 (en) 2012-01-25 2013-08-01 Nevro Corporation Lead anchors and associated systems and methods
US9572983B2 (en) 2012-03-26 2017-02-21 Setpoint Medical Corporation Devices and methods for modulation of bone erosion
US10448839B2 (en) 2012-04-23 2019-10-22 Livanova Usa, Inc. Methods, systems and apparatuses for detecting increased risk of sudden death
US9343923B2 (en) 2012-08-23 2016-05-17 Cyberonics, Inc. Implantable medical device with backscatter signal based communication
US9935498B2 (en) 2012-09-25 2018-04-03 Cyberonics, Inc. Communication efficiency with an implantable medical device using a circulator and a backscatter signal
WO2014087337A1 (en) 2012-12-06 2014-06-12 Bluewind Medical Ltd. Delivery of implantable neurostimulators
US9435830B2 (en) 2013-01-18 2016-09-06 Cyberonics, Inc. Implantable medical device depth estimation
US10220211B2 (en) 2013-01-22 2019-03-05 Livanova Usa, Inc. Methods and systems to diagnose depression
US9056195B2 (en) 2013-03-15 2015-06-16 Cyberonics, Inc. Optimization of cranial nerve stimulation to treat seizure disorderse during sleep
US9265935B2 (en) 2013-06-28 2016-02-23 Nevro Corporation Neurological stimulation lead anchors and associated systems and methods
US9585611B2 (en) 2014-04-25 2017-03-07 Cyberonics, Inc. Detecting seizures based on heartbeat data
US9302109B2 (en) 2014-04-25 2016-04-05 Cyberonics, Inc. Cranial nerve stimulation to treat depression during sleep
US10004896B2 (en) 2015-01-21 2018-06-26 Bluewind Medical Ltd. Anchors and implant devices
US9764146B2 (en) 2015-01-21 2017-09-19 Bluewind Medical Ltd. Extracorporeal implant controllers
US9597521B2 (en) 2015-01-21 2017-03-21 Bluewind Medical Ltd. Transmitting coils for neurostimulation
US9782589B2 (en) 2015-06-10 2017-10-10 Bluewind Medical Ltd. Implantable electrostimulator for improving blood flow
US9713707B2 (en) 2015-11-12 2017-07-25 Bluewind Medical Ltd. Inhibition of implant migration
EP3405255A4 (en) 2016-01-20 2019-10-16 Setpoint Medical Corp Implantable microstimulators and inductive charging systems
US10039923B2 (en) 2016-02-03 2018-08-07 The Charles Stark Draper Laboratory, Inc. Neural implant for microstimulation
US10124178B2 (en) 2016-11-23 2018-11-13 Bluewind Medical Ltd. Implant and delivery tool therefor

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2533360A1 (en) * 1975-07-25 1977-02-17 Cooper Irving S Brain stimulating electrical impulse apparatus - has two sets of electrodes applied to cerebellum with alternating pulse bursts
US5441528A (en) * 1992-09-25 1995-08-15 Symtonic, S.A. Method and system for applying low energy emission therapy

Cited By (204)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6896651B2 (en) 1998-10-06 2005-05-24 Biocontrol Medical Ltd. Mechanical and electrical sensing for incontinence treatment
US20020062060A1 (en) * 1998-10-06 2002-05-23 Yossi Gross Incontinence treatment device
US7387603B2 (en) 1998-10-06 2008-06-17 Ams Research Corporation Incontinence treatment device
US20050113881A1 (en) * 1998-10-06 2005-05-26 Yossi Gross Incontinence treatment device
US7865243B1 (en) 2000-04-07 2011-01-04 Boston Scientific Neuromodulation Corporation Device and therapy for erectile dysfunction and other sexual dysfunction
US7890177B1 (en) 2000-04-07 2011-02-15 Boston Scientific Neuromodulation Corporation Device and therapy for erectile dysfunction and other sexual dysfunction
US8412334B2 (en) 2000-06-20 2013-04-02 Boston Scientific Neuromodulation Corporation Treatment of mood and/or anxiety disorders by electrical brain stimulation and/or drug infusion
US20050049651A1 (en) * 2000-06-20 2005-03-03 Whitehurst Todd K. Treatment of mood and/or anxiety disorders by electrical brain stimulation and/or drug infusion
US8718779B2 (en) 2000-06-20 2014-05-06 Boston Scientific Neuromodulation Corporation Treatment of mood and/or anxiety disorders by electrical brain stimulation and/or drug infusion
US8046076B2 (en) * 2000-06-20 2011-10-25 Boston Scientific Neuromodulation Corporation Treatment of mood and/or anxiety disorders by electrical brain stimulation and/or drug infusion
US7949400B2 (en) 2000-09-27 2011-05-24 Cvrx, Inc. Devices and methods for cardiovascular reflex control via coupled electrodes
US8606359B2 (en) 2000-09-27 2013-12-10 Cvrx, Inc. System and method for sustained baroreflex stimulation
US7813812B2 (en) 2000-09-27 2010-10-12 Cvrx, Inc. Baroreflex stimulator with integrated pressure sensor
US7840271B2 (en) 2000-09-27 2010-11-23 Cvrx, Inc. Stimulus regimens for cardiovascular reflex control
US8290595B2 (en) 2000-09-27 2012-10-16 Cvrx, Inc. Method and apparatus for stimulation of baroreceptors in pulmonary artery
US9427583B2 (en) 2000-09-27 2016-08-30 Cvrx, Inc. Electrode structures and methods for their use in cardiovascular reflex control
US8060206B2 (en) 2000-09-27 2011-11-15 Cvrx, Inc. Baroreflex modulation to gradually decrease blood pressure
US20080177350A1 (en) * 2000-09-27 2008-07-24 Cvrx, Inc. Expandable Stimulation Electrode with Integrated Pressure Sensor and Methods Related Thereto
US20070021790A1 (en) * 2000-09-27 2007-01-25 Cvrx, Inc. Automatic baroreflex modulation responsive to adverse event
US9044609B2 (en) 2000-09-27 2015-06-02 Cvrx, Inc. Electrode structures and methods for their use in cardiovascular reflex control
US20070038255A1 (en) * 2000-09-27 2007-02-15 Cvrx, Inc. Baroreflex stimulator with integrated pressure sensor
US8712531B2 (en) 2000-09-27 2014-04-29 Cvrx, Inc. Automatic baroreflex modulation responsive to adverse event
US20050251212A1 (en) * 2000-09-27 2005-11-10 Cvrx, Inc. Stimulus regimens for cardiovascular reflex control
US8880190B2 (en) 2000-09-27 2014-11-04 Cvrx, Inc. Electrode structures and methods for their use in cardiovascular reflex control
US8838246B2 (en) 2000-09-27 2014-09-16 Cvrx, Inc. Devices and methods for cardiovascular reflex treatments
US8086314B1 (en) 2000-09-27 2011-12-27 Cvrx, Inc. Devices and methods for cardiovascular reflex control
US8718789B2 (en) 2000-09-27 2014-05-06 Cvrx, Inc. Electrode structures and methods for their use in cardiovascular reflex control
US8583236B2 (en) 2000-09-27 2013-11-12 Cvrx, Inc. Devices and methods for cardiovascular reflex control
US6871098B2 (en) 2000-10-30 2005-03-22 Medtronic, Inc. Method for treating obsessive-compulsive disorder with electrical stimulation of the brain internal capsule
US7616998B2 (en) 2000-10-30 2009-11-10 Medtronic, Inc. Electrical stimulation of structures within the brain
US20050049650A1 (en) * 2000-10-30 2005-03-03 Medtronic, Inc. Method for treating obsessive-compulsive disorder with electrical stimulation of the brain internal capsule
US20050240229A1 (en) * 2001-04-26 2005-10-27 Whitehurst Tood K Methods and systems for stimulation as a therapy for erectile dysfunction
US7660631B2 (en) 2001-04-26 2010-02-09 Boston Scientific Neuromodulation Corporation Methods and systems for electrical and/or drug stimulation as a therapy for erectile dysfunction
US20050209652A1 (en) * 2001-04-26 2005-09-22 Whitehurst Todd K Methods and systems for electrical and/or drug stimulation as a therapy for erectile dysfunction
US8571653B2 (en) 2001-08-31 2013-10-29 Bio Control Medical (B.C.M.) Ltd. Nerve stimulation techniques
US7734355B2 (en) 2001-08-31 2010-06-08 Bio Control Medical (B.C.M.) Ltd. Treatment of disorders by unidirectional nerve stimulation
US20090228065A1 (en) * 2001-09-26 2009-09-10 Cvrx, Inc. Implantable vascular structures and methods for their use
US20030082884A1 (en) * 2001-10-26 2003-05-01 International Business Machine Corporation And Kabushiki Kaisha Toshiba Method of forming low-leakage dielectric layer
US20080286327A1 (en) * 2001-11-01 2008-11-20 Whitehurst Todd K Thombolysis and chronic anticoagulation therapy
US7877137B2 (en) 2001-11-01 2011-01-25 Boston Scientific Neuromodulation Corporation Thrombolysis and chronic anticoagulation therapy
US7308303B2 (en) 2001-11-01 2007-12-11 Advanced Bionics Corporation Thrombolysis and chronic anticoagulation therapy
WO2003037430A3 (en) * 2001-11-01 2003-12-18 Medtronic Inc Method and apparatus for programming an implantable medical device
US20030171789A1 (en) * 2001-11-01 2003-09-11 Medtronic, Inc. Method and apparatus for programming an implantable medical device
US20030083698A1 (en) * 2001-11-01 2003-05-01 Whitehurst Todd K. Thrombolysis and chronic anticoagulation therapy
US7187978B2 (en) 2001-11-01 2007-03-06 Medtronic, Inc. Method and apparatus for programming an implantable medical device
US20060258950A1 (en) * 2002-02-04 2006-11-16 Synergistic Neurotherapy Adjustment Process, Inc. (Trade At Synaps) Method and apparatus for utilizing amplitude-modulated pulse-width modulation signals for neurostimulation and treatment of neurological disorders using electrical stimulation
US8280502B2 (en) 2002-02-04 2012-10-02 Cerephex Corporation Method and apparatus for utilizing amplitude-modulated pulse-width modulation signals for neurostimulation and treatment of neurological disorders using electrical stimulation
US20100204750A1 (en) * 2002-02-04 2010-08-12 Cerephex Corporation Method and apparatus for utilizing amplitude-modulated pulse-width modulation signals for neurostimulation and treatment of neurological disorders using electrical stimulation
US7715910B2 (en) 2002-02-04 2010-05-11 Cerephex Corporation Method and apparatus for utilizing amplitude-modulated pulse-width modulation signals for neurostimulation and treatment of neurological disorders using electrical stimulation
US9616234B2 (en) 2002-05-03 2017-04-11 Trustees Of Boston University System and method for neuro-stimulation
US20070100393A1 (en) * 2002-05-24 2007-05-03 Whitehurst Todd K Treatment of movement disorders by brain stimulation
US7151961B1 (en) * 2002-05-24 2006-12-19 Advanced Bionics Corporation Treatment of movement disorders by brain stimulation
US8401634B2 (en) 2002-05-24 2013-03-19 Boston Scientific Neuromodulation Corporation Treatment of movement disorders by brain stimulation
US20100331807A1 (en) * 2002-05-24 2010-12-30 Boston Scientific Neuromodulation Corporation Treatment of movement disorders by brain stimulation
US7292890B2 (en) * 2002-06-20 2007-11-06 Advanced Bionics Corporation Vagus nerve stimulation via unidirectional propagation of action potentials
US7203548B2 (en) 2002-06-20 2007-04-10 Advanced Bionics Corporation Cavernous nerve stimulation via unidirectional propagation of action potentials
US20030236557A1 (en) * 2002-06-20 2003-12-25 Whitehurst Todd K. Cavernous nerve stimulation via unidirectional propagation of action potentials
US20070021800A1 (en) * 2002-06-20 2007-01-25 Advanced Bionics Corporation, A California Corporation Cavernous nerve stimulation via unidirectional propagation of action potentials
US8548604B2 (en) 2002-06-20 2013-10-01 Boston Scientific Neuromodulation Corporation Implantable microstimulators and methods for unidirectional propagation of action potentials
US20030236558A1 (en) * 2002-06-20 2003-12-25 Whitehurst Todd K. Vagus nerve stimulation via unidirectional propagation of action potentials
US20040015205A1 (en) * 2002-06-20 2004-01-22 Whitehurst Todd K. Implantable microstimulators with programmable multielectrode configuration and uses thereof
US7783362B2 (en) 2002-06-20 2010-08-24 Boston Scientific Neuromodulation Corporation Vagus nerve stimulation via unidirectional propagation of action potentials
US20040015204A1 (en) * 2002-06-20 2004-01-22 Whitehurst Todd K. Implantable microstimulators and methods for unidirectional propagation of action potentials
US7899539B2 (en) 2002-06-20 2011-03-01 Boston Scientific Neuromodulation Corporation Cavernous nerve stimulation via unidirectional propagation of action potentials
US7860570B2 (en) 2002-06-20 2010-12-28 Boston Scientific Neuromodulation Corporation Implantable microstimulators and methods for unidirectional propagation of action potentials
US8712547B2 (en) 2002-06-20 2014-04-29 Boston Scientific Neuromodulation Corporation Cavernous nerve stimulation via unidirectional propagation of action potentials
US9409028B2 (en) 2002-06-20 2016-08-09 Boston Scientific Neuromodulation Corporation Implantable microstimulators with programmable multielectrode configuration and uses thereof
US9283394B2 (en) 2002-06-20 2016-03-15 Boston Scientific Neuromodulation Corporation Implantable microstimulators and methods for unidirectional propagation of action potentials
US20050027158A1 (en) * 2002-10-21 2005-02-03 Becker Paul F. Method and apparatus for the treatment of physical and mental disorders with low frequency, low flux density magnetic fields
US7276020B2 (en) 2002-10-21 2007-10-02 Becker Paul F Method and apparatus for the treatment of physical and mental disorders with low frequency, low flux density magnetic fields
US6899667B2 (en) * 2002-10-21 2005-05-31 Paul F. Becker Method and apparatus for the treatment of physical and mental disorders with low frequency, low flux density magnetic fields
US7819794B2 (en) 2002-10-21 2010-10-26 Becker Paul F Method and apparatus for the treatment of physical and mental disorders with low frequency, low flux density magnetic fields
US20100298624A1 (en) * 2002-10-21 2010-11-25 Becker Paul F Method and apparatus for the treatment of physical and mental disorders with low frequency, low flux density magnetic fields
US7988613B2 (en) 2002-10-21 2011-08-02 Becker Paul F Method and apparatus for the treatment of physical and mental disorders with low frequency, low flux density magnetic fields
US20050182287A1 (en) * 2002-10-21 2005-08-18 Becker Paul F. Method and apparatus for the treatment of physical and mental disorders with low frequency, low flux density magnetic fields
US20060111626A1 (en) * 2003-03-27 2006-05-25 Cvrx, Inc. Electrode structures having anti-inflammatory properties and methods of use
US7107104B2 (en) 2003-05-30 2006-09-12 Medtronic, Inc. Implantable cortical neural lead and method
US20040243205A1 (en) * 2003-05-30 2004-12-02 Medtronic, Inc. Implantable cortical neural lead and method
WO2005039693A1 (en) * 2003-10-27 2005-05-06 Jorge Alberto Morales Sanchez Device for emitting electric impulses directed to the brain
US20060161219A1 (en) * 2003-11-20 2006-07-20 Advanced Neuromodulation Systems, Inc. Electrical stimulation system and method for stimulating multiple locations of target nerve tissue in the brain to treat multiple conditions in the body
US20100268288A1 (en) * 2003-11-20 2010-10-21 Angiotech International Ag Electrical devices and anti-scarring agents
US20050182467A1 (en) * 2003-11-20 2005-08-18 Angiotech International Ag Electrical devices and anti-scarring agents
US7751891B2 (en) * 2004-07-28 2010-07-06 Cyberonics, Inc. Power supply monitoring for an implantable device
US20060025829A1 (en) * 2004-07-28 2006-02-02 Armstrong Randolph K Power supply monitoring for an implantable device
US20060052838A1 (en) * 2004-09-08 2006-03-09 Kim Daniel H Methods of neurostimulating targeted neural tissue
US8229565B2 (en) 2004-09-08 2012-07-24 Spinal Modulation, Inc. Methods for stimulating a dorsal root ganglion
US8082039B2 (en) 2004-09-08 2011-12-20 Spinal Modulation, Inc. Stimulation systems
US9205259B2 (en) 2004-09-08 2015-12-08 The Board Of Trustees Of The Leland Stanford Junior University Neurostimulation system
US9205261B2 (en) 2004-09-08 2015-12-08 The Board Of Trustees Of The Leland Stanford Junior University Neurostimulation methods and systems
US20060052856A1 (en) * 2004-09-08 2006-03-09 Kim Daniel H Stimulation components
US9205260B2 (en) 2004-09-08 2015-12-08 The Board Of Trustees Of The Leland Stanford Junior University Methods for stimulating a dorsal root ganglion
US10232180B2 (en) 2004-09-08 2019-03-19 The Board Of Trustees Of The Leland Stanford Junior University Selective stimulation to modulate the sympathetic nervous system
US20080167698A1 (en) * 2004-09-08 2008-07-10 Spinal Modulation, Inc. Neurostimulation system
US7580753B2 (en) 2004-09-08 2009-08-25 Spinal Modulation, Inc. Method and system for stimulating a dorsal root ganglion
US20090210041A1 (en) * 2004-09-08 2009-08-20 Kim Daniel H Methods for stimulating a dorsal root ganglion
US7447546B2 (en) 2004-09-08 2008-11-04 Spinal Modulation, Inc. Methods of neurostimulating targeted neural tissue
US20060052836A1 (en) * 2004-09-08 2006-03-09 Kim Daniel H Neurostimulation system
US20060052839A1 (en) * 2004-09-08 2006-03-09 Kim Daniel H Methods for stimulating a dorsal root ganglion
US20060052826A1 (en) * 2004-09-08 2006-03-09 Kim Daniel H Pulse generator for high impedance electrodes
US10159838B2 (en) 2004-09-08 2018-12-25 The Board Of Trustees Of The Leland Stanford Junior University Methods for stimulating a dorsal root ganglion
US8712546B2 (en) 2004-09-08 2014-04-29 Spinal Modulation, Inc. Neurostimulation system
US7502651B2 (en) 2004-09-08 2009-03-10 Spinal Modulation, Inc. Methods for stimulating a dorsal root ganglion
US20060052827A1 (en) * 2004-09-08 2006-03-09 Kim Daniel H Stimulation systems
US20060052835A1 (en) * 2004-09-08 2006-03-09 Kim Daniel H Methods for stimulating the spinal cord and nervous system
US7450993B2 (en) 2004-09-08 2008-11-11 Spinal Modulation, Inc. Methods for selective stimulation of a ganglion
US9486633B2 (en) 2004-09-08 2016-11-08 The Board Of Trustees Of The Leland Stanford Junior University Selective stimulation to modulate the sympathetic nervous system
US7555345B2 (en) 2005-03-11 2009-06-30 Medtronic, Inc. Implantable neurostimulator device
US8620437B2 (en) 2005-03-11 2013-12-31 Medtronic, Inc. Method for delivery of electrical stimulation with bendable housing
US8744582B2 (en) 2005-03-11 2014-06-03 Medtronic, Inc. Implantable neurostimulator device with bellows-like element coupling first and second housing portions
US7231256B2 (en) 2005-03-11 2007-06-12 Medtronic, Inc. Neurostimulation site screening
US20060206162A1 (en) * 2005-03-11 2006-09-14 Wahlstrand Carl D Implantable neurostimulator device
US20090234420A1 (en) * 2005-03-11 2009-09-17 Medtronic, Inc. Implantable neurostimulator device
US20060206163A1 (en) * 2005-03-11 2006-09-14 Wahlstrand Carl D Neurostimulation site screening
US8295936B2 (en) 2005-03-11 2012-10-23 Medtronic, Inc. Implantable neurostimulator device
US7664552B2 (en) 2005-03-11 2010-02-16 Medtronic, Inc. Neurostimulation site screening
US20070162087A1 (en) * 2005-03-11 2007-07-12 Medtronic, Inc. Neurostimulation site screening
US20070208391A1 (en) * 2005-03-11 2007-09-06 Medtronic, Inc. Neurostimulation site screening
US20100049277A1 (en) * 2005-03-11 2010-02-25 Medtronic, Inc. Implantable neurostimulator device
US7676271B2 (en) 2005-03-11 2010-03-09 Medtronic, Inc. Neurostimulation site screening
US9149628B2 (en) 2005-03-11 2015-10-06 Medtronic, Inc. Neurostimulator for treating occipital neuralgia with housing sized and curved to conform to a subcutaneous neck region
US7627383B2 (en) 2005-03-15 2009-12-01 Boston Scientific Neuromodulation Corporation Implantable stimulator
US20110077579A1 (en) * 2005-03-24 2011-03-31 Harrison William V Cochlear implant with localized fluid transport
US20060229688A1 (en) * 2005-04-08 2006-10-12 Mcclure Kelly H Controlling stimulation parameters of implanted tissue stimulators
US7801602B2 (en) 2005-04-08 2010-09-21 Boston Scientific Neuromodulation Corporation Controlling stimulation parameters of implanted tissue stimulators
US8805494B2 (en) 2005-05-10 2014-08-12 Cardiac Pacemakers, Inc. System and method to deliver therapy in presence of another therapy
US9504836B2 (en) 2005-05-10 2016-11-29 Cardiac Pacemakers, Inc. System and method to deliver therapy in presence of another therapy
US9393421B2 (en) 2005-05-26 2016-07-19 Boston Scientific Neuromodulation Corporation Controlling charge flow in the electrical stimulation of tissue
US7801600B1 (en) 2005-05-26 2010-09-21 Boston Scientific Neuromodulation Corporation Controlling charge flow in the electrical stimulation of tissue
US10065039B2 (en) 2005-05-26 2018-09-04 Boston Scientific Neuromodulation Corporation Controlling charge flow in the electrical stimulation of tissue
US20100280575A1 (en) * 2005-05-26 2010-11-04 Boston Scientific Neuromodulation Corporation Controlling charge flow in the electrical stimulation of tissue
US20060280655A1 (en) * 2005-06-08 2006-12-14 California Institute Of Technology Intravascular diagnostic and therapeutic sampling device
US20110125136A1 (en) * 2005-06-08 2011-05-26 Morteza Gharib Intravascular diagnostic and therapeutic sampling device
US20070027504A1 (en) * 2005-07-27 2007-02-01 Cyberonics, Inc. Cranial nerve stimulation to treat a hearing disorder
US10518090B2 (en) 2005-11-18 2019-12-31 Respicardia, Inc. System and method to modulate phrenic nerve to prevent sleep apnea
US20070118183A1 (en) * 2005-11-18 2007-05-24 Mark Gelfand System and method to modulate phrenic nerve to prevent sleep apnea
US8244359B2 (en) * 2005-11-18 2012-08-14 Respicardia, Inc. System and method to modulate phrenic nerve to prevent sleep apnea
US20070123938A1 (en) * 2005-11-30 2007-05-31 Haller Matthew I Magnetically coupled microstimulators
US7729758B2 (en) 2005-11-30 2010-06-01 Boston Scientific Neuromodulation Corporation Magnetically coupled microstimulators
US7570999B2 (en) 2005-12-20 2009-08-04 Cardiac Pacemakers, Inc. Implantable device for treating epilepsy and cardiac rhythm disorders
US9889298B2 (en) 2006-03-03 2018-02-13 Astora Women's Health, Llc Electrode sling for treating stress and urge incontinence
US20070260288A1 (en) * 2006-03-03 2007-11-08 Yossi Gross Apparatus for treating stress and urge incontinence
US20090043356A1 (en) * 2006-03-03 2009-02-12 Ams Research Corporation Electrode Sling for Treating Stress and Urge Incontinence
US8195296B2 (en) 2006-03-03 2012-06-05 Ams Research Corporation Apparatus for treating stress and urge incontinence
US7803148B2 (en) 2006-06-09 2010-09-28 Neurosystec Corporation Flow-induced delivery from a drug mass
US20110071493A1 (en) * 2006-06-09 2011-03-24 Neurosystec Corporation Flow-Induced Delivery from a Drug Mass
US8298176B2 (en) 2006-06-09 2012-10-30 Neurosystec Corporation Flow-induced delivery from a drug mass
US8160710B2 (en) 2006-07-10 2012-04-17 Ams Research Corporation Systems and methods for implanting tissue stimulation electrodes in the pelvic region
US20080015642A1 (en) * 2006-07-17 2008-01-17 Sherwood Services Ag Method for stimulation of the vagus nerve
US8571651B2 (en) 2006-09-07 2013-10-29 Bio Control Medical (B.C.M.) Ltd. Techniques for reducing pain associated with nerve stimulation
US20080097142A1 (en) * 2006-10-20 2008-04-24 Paul Savage Magnetic field generator, method of generating a pulsed sinusoidal magnetic wave and magnetic field generator system
US10406366B2 (en) 2006-11-17 2019-09-10 Respicardia, Inc. Transvenous phrenic nerve stimulation system
US9623233B2 (en) 2006-12-06 2017-04-18 St. Jude Medical Luxembourg Holdings SMI S.A.R.L. (“SJM LUX SMI”) Delivery devices, systems and methods for stimulating nerve tissue on multiple spinal levels
US9314618B2 (en) 2006-12-06 2016-04-19 Spinal Modulation, Inc. Implantable flexible circuit leads and methods of use
US8518092B2 (en) 2006-12-06 2013-08-27 Spinal Modulation, Inc. Hard tissue anchors and delivery devices
US9427570B2 (en) 2006-12-06 2016-08-30 St. Jude Medical Luxembourg Holdings SMI S.A.R.L. (“SJM LUX SMI”) Expandable stimulation leads and methods of use
US8983624B2 (en) 2006-12-06 2015-03-17 Spinal Modulation, Inc. Delivery devices, systems and methods for stimulating nerve tissue on multiple spinal levels
US10300270B2 (en) 2007-01-22 2019-05-28 Respicardia, Inc. Device and method for the treatment of breathing disorders and cardiac disorders
US20080208282A1 (en) * 2007-01-22 2008-08-28 Mark Gelfand Device and method for the treatment of breathing disorders and cardiac disorders
US8909341B2 (en) 2007-01-22 2014-12-09 Respicardia, Inc. Device and method for the treatment of breathing disorders and cardiac disorders
US9744351B1 (en) 2007-01-22 2017-08-29 Respicardia, Inc. Device and method for the treatment of breathing disorders and cardiac disorders
US9044592B2 (en) 2007-01-29 2015-06-02 Spinal Modulation, Inc. Sutureless lead retention features
US9987488B1 (en) 2007-06-27 2018-06-05 Respicardia, Inc. Detecting and treating disordered breathing
US8774942B2 (en) 2007-07-10 2014-07-08 Ams Research Corporation Tissue anchor
US9427573B2 (en) 2007-07-10 2016-08-30 Astora Women's Health, Llc Deployable electrode lead anchor
US7877136B1 (en) 2007-09-28 2011-01-25 Boston Scientific Neuromodulation Corporation Enhancement of neural signal transmission through damaged neural tissue via hyperpolarizing electrical stimulation current
US9008782B2 (en) 2007-10-26 2015-04-14 Medtronic, Inc. Occipital nerve stimulation
US20090112282A1 (en) * 2007-10-26 2009-04-30 Medtronic, Inc. Occipital nerve stimulation
US9427572B2 (en) 2007-10-26 2016-08-30 Medtronic, Inc. Implantable medical device with connector blocks
US20090112962A1 (en) * 2007-10-31 2009-04-30 Research In Motion Limited Modular squaring in binary field arithmetic
US9295846B2 (en) 2008-02-07 2016-03-29 Respicardia, Inc. Muscle and nerve stimulation
US8433412B1 (en) 2008-02-07 2013-04-30 Respicardia, Inc. Muscle and nerve stimulation
US20100030227A1 (en) * 2008-07-31 2010-02-04 Medtronic, Inc. Medical lead implantation
US9056197B2 (en) 2008-10-27 2015-06-16 Spinal Modulation, Inc. Selective stimulation systems and signal parameters for medical conditions
US9409021B2 (en) 2008-10-27 2016-08-09 St. Jude Medical Luxembourg Holdings SMI S.A.R.L. Selective stimulation systems and signal parameters for medical conditions
US20100217340A1 (en) * 2009-02-23 2010-08-26 Ams Research Corporation Implantable Medical Device Connector System
US9539433B1 (en) 2009-03-18 2017-01-10 Astora Women's Health, Llc Electrode implantation in a pelvic floor muscular structure
US10286212B2 (en) * 2009-03-20 2019-05-14 Electrocore, Inc. Nerve stimulation methods for averting imminent onset or episode of a disease
US9254383B2 (en) * 2009-03-20 2016-02-09 ElectroCore, LLC Devices and methods for monitoring non-invasive vagus nerve stimulation
US10252074B2 (en) * 2009-03-20 2019-04-09 ElectroCore, LLC Nerve stimulation methods for averting imminent onset or episode of a disease
US20120185020A1 (en) * 2009-03-20 2012-07-19 ElectroCore, LLC. Nerve stimulation methods for averting imminent onset or episode of a disease
US20120184801A1 (en) * 2009-03-20 2012-07-19 ElectroCore, LLC Nerve stimulation methods for averting imminent onset or episode of a disease
US20160367808A9 (en) * 2009-03-20 2016-12-22 ElectroCore, LLC Nerve stimulation methods for averting imminent onset or episode of a disease
US20130066395A1 (en) * 2009-03-20 2013-03-14 ElectroCore, LLC. Nerve stimulation methods for averting imminent onset or episode of a disease
US10220207B2 (en) * 2009-03-20 2019-03-05 Electrocore, Inc. Nerve stimulation methods for averting imminent onset or episode of a disease
US20130245486A1 (en) * 2009-03-20 2013-09-19 ElectroCore, LLC. Devices and methods for monitoring non-invasive vagus nerve stimulation
US8380318B2 (en) 2009-03-24 2013-02-19 Spinal Modulation, Inc. Pain management with stimulation subthreshold to paresthesia
US9468762B2 (en) 2009-03-24 2016-10-18 St. Jude Medical Luxembourg Holdings SMI S.A.R.L. (“SJM LUX SMI”) Pain management with stimulation subthreshold to paresthesia
US9259569B2 (en) 2009-05-15 2016-02-16 Daniel M. Brounstein Methods, systems and devices for neuromodulating spinal anatomy
US20110060380A1 (en) * 2009-09-10 2011-03-10 Mark Gelfand Respiratory rectification
US8233987B2 (en) 2009-09-10 2012-07-31 Respicardia, Inc. Respiratory rectification
US9999768B2 (en) 2009-09-10 2018-06-19 Respicardia, Inc. Respiratory rectification
US9327110B2 (en) 2009-10-27 2016-05-03 St. Jude Medical Luxembourg Holdings SMI S.A.R.L. (“SJM LUX SMI”) Devices, systems and methods for the targeted treatment of movement disorders
US8380312B2 (en) 2009-12-31 2013-02-19 Ams Research Corporation Multi-zone stimulation implant system and method
US20110295332A1 (en) * 2010-05-26 2011-12-01 Flint Hills Scientific, L.L.C. Quantitative multivariate analysis of seizures
US10321841B2 (en) * 2010-05-26 2019-06-18 Flint Hills Scientific, Llc Quantitative multivariate analysis of seizures
US9220887B2 (en) 2011-06-09 2015-12-29 Astora Women's Health LLC Electrode lead including a deployable tissue anchor
US9731112B2 (en) 2011-09-08 2017-08-15 Paul J. Gindele Implantable electrode assembly
GB2504196B (en) * 2012-06-01 2015-04-29 Bioinduction Ltd Precision delivery of electrical therapy
GB2504196A (en) * 2012-06-01 2014-01-22 Bioinduction Ltd Precision delivery of electrical therapy
US9597520B2 (en) 2012-06-01 2017-03-21 Bioinduction Limited Electrical stimulation of the carotid artery
US9370660B2 (en) 2013-03-29 2016-06-21 Rainbow Medical Ltd. Independently-controlled bidirectional nerve stimulation
US9782584B2 (en) 2014-06-13 2017-10-10 Nervana, LLC Transcutaneous electrostimulator and methods for electric stimulation
US10130809B2 (en) 2014-06-13 2018-11-20 Nervana, LLC Transcutaneous electrostimulator and methods for electric stimulation
US10105540B2 (en) 2015-11-09 2018-10-23 Bluewind Medical Ltd. Optimization of application of current

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