US20140142669A1 - Extracranial implantable devices, systems and methods for the treatment of medical disorders - Google Patents

Extracranial implantable devices, systems and methods for the treatment of medical disorders Download PDF

Info

Publication number
US20140142669A1
US20140142669A1 US13/994,512 US201113994512A US2014142669A1 US 20140142669 A1 US20140142669 A1 US 20140142669A1 US 201113994512 A US201113994512 A US 201113994512A US 2014142669 A1 US2014142669 A1 US 2014142669A1
Authority
US
United States
Prior art keywords
nerve
disorders
stimulation
trigeminal
disorder
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US13/994,512
Other languages
English (en)
Inventor
Ian A. Cook
Christopher M. Degiorgio
Leon Ekchian
Patrick Miller
Antonio Desalles
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
US Department of Veterans Affairs
Neurosigma Inc
University of California San Diego UCSD
Original Assignee
University of California San Diego UCSD
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by University of California San Diego UCSD filed Critical University of California San Diego UCSD
Priority to US13/994,512 priority Critical patent/US20140142669A1/en
Assigned to THE REGENTS OF THE UNIVERSITY OF CALIFORNIA reassignment THE REGENTS OF THE UNIVERSITY OF CALIFORNIA ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: DEGIORGIO, CHRISTOPHER M., MILLER, PATRICK, COOK, IAN A.
Publication of US20140142669A1 publication Critical patent/US20140142669A1/en
Assigned to NEUROSIGMA, INC. reassignment NEUROSIGMA, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: EKCHIAN, LEON
Assigned to UNITED STATES GOVERNMENT DEPARTMENT OF VETERANS AFFAIRS, THE REGENTS OF THE UNIVERSITY OF CALIFORNIA reassignment UNITED STATES GOVERNMENT DEPARTMENT OF VETERANS AFFAIRS ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: DE SALLES, ANTONIO
Abandoned legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36128—Control systems
    • A61N1/36146—Control systems specified by the stimulation parameters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0551—Spinal or peripheral nerve electrodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0504—Subcutaneous electrodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0526—Head electrodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36053—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for vagal stimulation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/36064—Epilepsy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/36082—Cognitive or psychiatric applications, e.g. dementia or Alzheimer's disease
    • A61N1/36085—Eating disorders or obesity
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/36082—Cognitive or psychiatric applications, e.g. dementia or Alzheimer's disease
    • A61N1/36089—Addiction or withdrawal from substance abuse such as alcohol or drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/36082—Cognitive or psychiatric applications, e.g. dementia or Alzheimer's disease
    • A61N1/36096—Mood disorders, e.g. depression, anxiety or panic disorder
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/361—Phantom sensations, e.g. tinnitus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/3611—Respiration control
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/36114—Cardiac control, e.g. by vagal stimulation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36128—Control systems
    • A61N1/36146—Control systems specified by the stimulation parameters
    • A61N1/3615—Intensity
    • A61N1/3616—Voltage density or current density
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36128—Control systems
    • A61N1/36146—Control systems specified by the stimulation parameters
    • A61N1/36167—Timing, e.g. stimulation onset
    • A61N1/36171—Frequency
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36128—Control systems
    • A61N1/36146—Control systems specified by the stimulation parameters
    • A61N1/36167—Timing, e.g. stimulation onset
    • A61N1/36178—Burst or pulse train parameters

Definitions

  • the present disclosure generally relates to implantable neurostimulator systems, devices and methods of using the same and more particularly relates to implantable neurostimulator systems, devices and methods including at least one implantable electrode for the treatment of medical disorders, such as neuropsychiatric disorders including mood, cognitive and behavioral disorders, heart disease and other cardiac related disorders, and fatigue, by stimulating superficial, cutaneous elements of cranial nerve(s).
  • medical disorders such as neuropsychiatric disorders including mood, cognitive and behavioral disorders, heart disease and other cardiac related disorders, and fatigue, by stimulating superficial, cutaneous elements of cranial nerve(s).
  • DBS deep brain stimulation
  • VNS vagus nerve stimulation
  • an implantable electrode assembly configured for trigeminal nerve stimulation.
  • a method of treating medical disorders using the disclosed implantable electrode assembly is provided.
  • first electrode and the second electrode are configured to contact a portion of the patient's face overlying the cutaneous distribution of a same branch of the trigeminal nerve. In another embodiment, the first electrode and the second electrode are configured to contact a portion of the patient's face overlying the cutaneous distribution of a different branch of the trigeminal nerve.
  • the stimulation may be provided uni- or bilaterally.
  • the system is configured for minimal current penetration into a brain of a patient.
  • the system may further include a closed loop device configured to provide self-tuning adaptive feedback control to the system.
  • stimulation of the at least one branch of the trigeminal nerve is determined based on measurement of activity in a brain region to detect an acute biological change.
  • the at least one branch of the trigeminal nerve is stimulated at a first set of stimulation parameters for a first time period, at a second set of stimulation parameters for a second time period, and at a third set of stimulation parameters for a third time period.
  • the at least one branch of the trigeminal nerve is stimulated at the first, second and third set of parameters in a cycle at least twice.
  • the body system is a vagus nerve circuit, and wherein stimulation of the at least one branch of the trigeminal nerve modulates the vagus nerve circuit to treat a cardiac related disorder.
  • the medical disorder is fatigue, wherein the body system is a locus coeruleus or a reticular activating system, and wherein stimulation of the at least one branch of the trigeminal nerve modulates the locus coeruleus or modulates the reticular activating system to treat fatigue.
  • the medical disorder is selected from the group consisting of obesity and other disorders related to weight and feeding, inflammation, disorders of regulation of breathing, disorders of gastrointestinal function, autonomic regulation in menopausal hot flashes, regulation of hemostasis and sleep/insomnia, wherein the body system is a vagus nerve circuit, and wherein stimulation of the at least one branch of the trigeminal nerve modulates the vagus nerve circuit to treat said medical disorder.
  • the medical disorder is a dementing disorder wherein the body system is a vagus nerve circuit or a trigeminal nerve cardiac reflex, and wherein stimulation of the at least one branch of the trigeminal nerve modulates the vagus nerve circuit or the trigeminal nerve cardiac reflex to treat said medical disorder.
  • the assembly produces minimal current penetration into a brain of a patient.
  • step of applying electrical signals comprises applying electrical signals at a frequency between approximately 20 and 300 Hertz, at a current of 0.05 to 5 milliamperes (mA) and at a pulse duration of less than or equal to 500 microseconds.
  • the step of applying electrical signals comprises applying electrical signals at a frequency between approximately 20 and 300 Hertz, at a pulse duration between approximately 50 and 500 microseconds, at an output current density of not greater than approximately 10 mA/cm 2 and a charge density of not greater than approximately 10 microCoulomb/cm 2 at the cerebral cortex.
  • the step of applying electrical signals comprises applying electrical signals at an output current density of not greater than approximately 10 mA/cm 2 .
  • the medical disorder is fatigue, wherein the body system is a locus coeruleus or a reticular activating system, and wherein stimulation of the at least one branch of the trigeminal nerve modulates the locus coeruleus or modulates the reticular activating system to treat fatigue.
  • the medical disorder is selected from the group consisting of obesity and other disorders related to weight and feeding, inflammation, disorders of regulation of breathing, disorders of gastrointestinal function, autonomic regulation in menopausal hot flashes, regulation of hemostasis and sleep/insomnia, wherein the body system is a vagus nerve circuit, and wherein stimulation of the at least one branch of the trigeminal nerve modulates the vagus nerve circuit to treat said medical disorder.
  • kits for trigeminal nerve stimulation for treatment of a medical disorder includes an implantable electrode assembly as disclosed elsewhere herein and instructions for applying the electrode assembly to a patient for treatment of a medical disorder, wherein the medical disorder is selected from the group consisting of: cardiac related disorders, fatigue, tinnitus, obesity, diabetes, dyslipidemia, metabolic syndrome, obstructive sleep apnea, arthritis, cachexia/anorexia, inflammation, asthma, inflammatory bowel disease, atopic dermatitis, sepsis, hepatitis, disorders of regulation of breathing, disorders of gastrointestinal function, gastroesophageal reflux, diarrhea and constipation, dysphagia and other disturbances of swallowing, gastroparesis, functional bowel syndromes, post-operative ileus, dyspepsia, motion sickness, chemotherapy-related nausea and emesis, autonomic regulation in menopausal hot flashes, regulation of hemostasis, sleep/insomnia and
  • a method for initiation, activation or stimulation of a vagus nerve circuit by trigeminal nerve stimulation for treatment of a medical disorder may include implanting an implantable electrode assembly in a patient, the electrode assembly comprising: a first electrode comprising at least one contact configured for subcutaneous or percutaneous placement at a first region of the patient's face and configured to be implanted in proximity to, adjacent to or in contact with at least one branch of the trigeminal nerve, which is an ophthalmic nerve, supraorbital nerve, or an infraorbital nerve; and applying electrical signals to the electrode assembly to stimulate the at least one branch of the trigeminal nerve to modulate the vagus nerve circuit for treatment of a medical disorder which may benefit from vagus nerve stimulation via the trigeminal nerve.
  • the medical disorder is selected from the group consisting of obesity and other disorders related to weight and feeding, inflammation, disorders of regulation of breathing, disorders of gastrointestinal function, autonomic regulation in menopausal hot flashes, regulation of hemostasis and sleep/insomnia, and wherein stimulation of the at least one branch of the trigeminal nerve modulates the vagus nerve circuit to treat said medical disorder.
  • the medical disorder is a dementing disorder and wherein stimulation of the at least one branch of the trigeminal nerve modulates the vagus nerve circuit to treat said medical disorder.
  • an implantable device for polycranial nerve stimulation for treatment of a medical disorder includes a pulse generator; and an implantable electrode assembly in electrical communication with the pulse generator.
  • the assembly includes at least one electrode for subcutaneous or percutaneous placement at a first region of the patient's ear and configured to be implanted in proximity to, adjacent to or in contact with at least one branch of the trigeminal nerve, and wherein stimulation of the at least one branch of the trigeminal nerve modulates a system in the body to treat a medical disorder.
  • the at least one branch of the trigeminal nerve is selected from the group consisting of: ophthalmic nerve, infraorbital nerve, supraorbital nerve, mentalis nerve, supratrochlear nerve, infratrochlear nerve, zygomaticotemporal nerve, zygomaticofacial nerve, zygomaticoorbital nerve, nasal nerve, and auriculotemporal nerve.
  • the device further includes a second electrode comprising at least one contact configured for subcutaneous or percutaneous placement at a second region of the patient's face, wherein the second electrode is configured to be implanted in proximity to, adjacent to or in contact with at least one branch of the trigeminal nerve, wherein the at least one branch of the trigeminal nerve is selected from the group consisting of: ophthalmic nerve, infraorbital nerve, supraorbital nerve, mentalis nerve, supratrochlear nerve, infratrochlear nerve, zygomaticotemporal nerve, zygomaticofacial nerve, zygomaticoorbital nerve, nasal nerve, and auriculotemporal nerve.
  • ophthalmic nerve infraorbital nerve, supraorbital nerve, mentalis nerve, supratrochlear nerve, infratrochlear nerve, zygomaticotemporal nerve, zygomaticofacial nerve, zygomaticoorbital nerve, nasal nerve, and auriculotemporal nerve.
  • the first electrode and the second electrode are configured for implantation in proximity to, adjacent to or in contact with a same branch of the trigeminal nerve. In one embodiment, the first electrode and the second electrode are configured for implantation in proximity to, adjacent to or in contact with a different branch of the trigeminal nerve.
  • the device produces minimal current penetration into a brain of a patient.
  • the device may further include a closed loop device configured to provide self-tuning adaptive feedback control to the system. Stimulation of the at least one branch of the trigeminal nerve is determined based on measurement of activity in a brain region to detect an acute biological change.
  • the at least one branch of the trigeminal nerve is stimulated at a first set of stimulation parameters for a first time period, at a second set of stimulation parameters for a second time period, and at a third set of stimulation parameters for a third time period.
  • the at least one branch of the trigeminal nerve is stimulated at the first, second and third set of parameters in a cycle at least twice.
  • the pulse generator is configured to apply electrical signals at a frequency between approximately 1 and 300 Hertz, at a pulse duration between approximately 50 and 500 microseconds, at an output current density of not greater than approximately 10 mA/cm 2 and an output charge density of not greater than approximately 10 microCoulomb/cm 2 at the cerebral cortex.
  • the pulse generator is configured to apply electrical signals at an output current density of not greater than approximately 10 mA/cm 2 . In one embodiment, the pulse generator is configured to apply electrical signals at an output current density of between approximately 2.5 and 5 mA/cm 2 . In one embodiment, the pulse generator is configured to apply electrical signals at an output current density of not greater than approximately 7 mA/cm 2 . In one embodiment, the pulse generator is configured to apply electrical signals at an output current density of not greater than approximately 5 mA/cm 2 .
  • the medical disorder is selected from the group consisting of: neurological disorders, cardiac related disorders, fatigue, tinnitus, obesity, diabetes, dyslipidemia, metabolic syndrome, obstructive sleep apnea, arthritis, cachexia/anorexia, inflammation, asthma, inflammatory bowel disease, atopic dermatitis, sepsis, hepatitis, disorders of regulation of breathing, disorders of gastrointestinal function, gastroesophageal reflux, diarrhea and constipation, dysphagia and other disturbances of swallowing, gastroparesis, functional bowel syndromes, post-operative ileus, dyspepsia, motion sickness, chemotherapy-related nausea and emesis, autonomic regulation in menopausal hot flashes, regulation of hemostasis, sleep/insomnia and a neuropsychiatric disorder selected from the group consisting of depression, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), autism and autism spectrum disorders (ASD), substance use disorders and related behavioral addictions, eating disorders and obs
  • the medical disorder is a cardiac related disorder selected from the group consisting of heart disease, cardiac arrhythmias, myocardial infarction, sudden cardiac death after myocardial infarction, heart failure, cerebral ischemia, sudden infant death syndrome (SIDS), impaired blood flow conditions, atrial fibrillation or sudden death in epilepsy.
  • the at least one branch of the trigeminal nerve is an ophthalmic nerve or an infraorbital nerve, wherein the body system is a trigeminal nerve cardiac reflex and wherein stimulation of the ophthalmic nerve or the infraorbital nerve modulates or activates the trigeminal nerve cardiac reflex to treat or prevent a cardiac related disorder.
  • the medical disorder is a cardiac related disorder selected from the group consisting of heart disease, cardiac arrhythmias, myocardial infarction, sudden cardiac death after myocardial infarction, heart failure, cerebral ischemia, sudden infant death syndrome (SIDS), impaired blood flow conditions, atrial fibrillation or sudden death in epilepsy.
  • the at least one branch of the trigeminal nerve is an ophthalmic nerve or an infraorbital nerve, wherein the body system is a trigeminal nerve cardiac reflex and wherein stimulation of the ophthalmic nerve or the infraorbital nerve modulates or activates the trigeminal nerve cardiac reflex to treat or prevent a cardiac related disorder.
  • FIG. 3 shows average PET scanning data from a pair of adults being treated using aspects of the present disclosure and demonstrating brain regions with decreased regional blood flow;
  • FIG. 10C is a graph illustrating the change over time of the data shown in FIG. 10A ;
  • FIG. 11 summarizes one embodiment of current, charge, current density and charge density parameters for a subject exposed to cutaneous stimulation of the supraorbital nerve
  • FIG. 12 illustrates patient response to cutaneous stimulation of the supraorbital and infraorbital nerve according to one aspect of the present disclosure
  • the present disclosure relates to methods, devices and systems used for the treatment of various medical disorders via stimulation of the superficial elements of the trigeminal nerve.
  • the medical disorders may include, but are not limited to, neuropsychiatric disorders, neurological disorders, cardiac related disorders, fatigue, tinnitus, obesity, diabetes, dyslipidemia, metabolic syndrome, obstructive sleep apnea, arthritis, cachexia/anorexia, inflammation, asthma, inflammatory bowel disease, atopic dermatitis, sepsis, hepatitis, disorders of regulation of breathing, disorders of gastrointestinal function, gastroesophageal reflux, diarrhea and constipation, dysphagia and other disturbances of swallowing, gastroparesis, functional bowel syndromes, post-operative ileus, dyspepsia, motion sickness, chemotherapy-related nausea and emesis, autonomic regulation in menopausal hot flashes, regulation of hemostasis and sleep/insomnia.
  • the mentalis branch of the mandibular nerve is referred to as the V 3 division.
  • the supraorbital nerve supplies sensory information about pain, temperature, and light touch to the skin of the forehead, the upper eyelid, the anterior part of the nose, and the eye.
  • the infraorbital branch supplies sensory information about pain, temperature, and light touch sensation to the lower eyelid, cheek, and upper lip.
  • the mentalis branch supplies similar sensory modalities to the skin of the lower face (e.g. jaw and tongue) and lips.
  • the supraorbital nerve or ophthalmic nerve exits at foramen 1 , approximately 2.1-2.6 cm from the nasal midline (in adults), and is located immediately above the orbital ridge that is located below the eyebrow.
  • the infraorbital branch or maxillary nerve exits at foramen 2 , approximately 2.4-3.0 cm from the nasal midline (in adults) and the mentalis nerve exits at foramen 3 , approximately 2.0-2.3 cm from the nasal midline (in adults).
  • Other sensory branches including the zygomaticofacial, zygomaticoorbital, zygomaticotemporal, and auriculotemporal, arise from other foramina.
  • the trigeminal nucleus has reciprocal projections to the nucleus tractus solitarius or nucleus of the solitary tract (NTS), the locus coeruleus, the cerebral cortex and the vagus nerve.
  • the NTS receives afferents from the vagus nerve and trigeminal nerve.
  • the NTS integrates input from multiple sources, and projects to structures in the brainstem and forebrain, including the locus coeruleus.
  • FIG. 1C which is a modified reproduction from Ruffoli, R. et al, is a diagram of the principal afferent and efferent projections of the nucleus of the solitary tract. (see Ruffoli, R.
  • the trigeminal nerve is connected to the vagus nerve.
  • Afferent sensory fibers from the three trigeminal divisions V 1 , V 2 , V 3 ) project to the Gasserian ganglion, synapse there, and then project to the main sensory nucleus of the trigeminal nerve.
  • Axons from the sensory nucleus then project via the Internucial fibers of the Reticular Formation to the Dorsal Motor Nucleus of the vagus nerve (the tenth cranial nerve, also designated as Cranial Nerve X or CN X) in the dorsal medulla.
  • the disclosure describes the application of trigeminal nerve stimulation to treat medical disorders including: neuropsychiatric and neurological disorders, cardiac related disorders, fatigue, tinnitus and other medical disorders.
  • Stimulation of peripheral and cutaneous branches of the trigeminal nerve in the face, ear or scalp can be applied and stimulated at safe frequencies, pulse durations and amplitudes.
  • Such treatment and prevention is advantageous over the currently used pharmacological approaches which often have undesirable side effects or lack specificity in their actions.
  • the unique anatomy of the trigeminal nerve, and its direct and indirect connections with key areas of the brainstem, thalamus, amygdala, insula, anterior cingulate and other cortical and subcortical areas involved with sensory processing, attention, emotion, cognition, and autonomic function, may allow the use of external stimulation for a variety of neuropsychiatric conditions in which stimulation may be desirable.
  • the present disclosure relates to methods, devices and systems used for the treatment of mood, anxiety, post traumatic stress disorder, neuropsychiatric disorders, including mood (such as depression), anxiety (such as post-traumatic stress disorder) and psychotic disorders (e.g. schizophrenia), and cognitive and behavioral disorders as well as well as attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), autism and autism spectrum disorders (ASD), substance use disorders and related behavioral addictions, eating disorders, psychotic disorders and obsessive compulsive disorder (OCD) (collectively, neuropsychiatric disorders) via stimulation of the superficial elements of the trigeminal nerve (“TNS”).
  • mood such as depression
  • anxiety such as post-traumatic stress disorder
  • psychotic disorders e.g. schizophrenia
  • ADD attention deficit disorder
  • ADHD attention deficit hyperactivity disorder
  • ASD autism and autism spectrum disorders
  • OCD obsessive compulsive disorder
  • neuropsychiatric disorders via stimulation of the superficial elements of the trigeminal nerve (“TNS”).
  • subcutaneous and percutaneous methods of stimulation of the superficial branches of the trigeminal nerve located extracranially in the face namely the supraorbital, supratrochlear, infraorbital, auriculotemporal, zygomaticotemporal, zygomaticoorbital, zygomaticofacial, infratrochlear, nasal and mentalis nerves (also referred to collectively as the superficial trigeminal nerve) are disclosed herein.
  • the PET scan data of FIGS. 2 and 3 support the use of TNS in humans for treatment of neuropsychiatric disorders, namely depression and anxiety disorders, such as PTSD.
  • the PET scans show sections of the brain with increased activity ( FIG. 3 ) and decreased activity ( FIG. 3 ).
  • increased activity is seen in the medial prefrontal cortex, including the ACC, (see FIG. 2 , which is indicated by the color (darker) pixels in panels (a) and (b)).
  • Increased activity of the dorsolateral prefrontal cortex is also shown in FIG. 2 , panel c as the large colored (darker) area in the lower right of the image.
  • Increased activity is also seen in the orbitofrontal cortex, as shown in FIG.
  • FIG. 2 shows an increased activity in the medial prefrontal cortex, including the ACC, which is indicated by the color (darker) pixels in panels (a) and (b). Increased activity in the superior frontal gyms is seen in panels (c) and (d), on the upper (superior) surface of the brain, while the increased activity in the lateral frontal cortex is seen most clearly in panel (c), in the lower-right part of that image.
  • FIG. 2 shows an increased activity in the medial prefrontal cortex, including the ACC, which is indicated by the color (darker) pixels in panels (a) and (b). Increased activity in the superior frontal gyms is seen in panels (c) and (d), on the upper (superior) surface of the brain, while the increased activity in the lateral frontal cortex is seen most clearly in panel (c), in the lower-right part of that image.
  • FIG. 3 shows a decreased activity in the superior parietal cortex which is seen in panel (a) as the colored (darker) region in the upper left of that image, panel (b) as the colored (darker) pixels in the upper right, panel (c) as the upper two regions of color (darker) pixels, and in panel (d) as the colored (darker) region near the top of the brain.
  • the decreased activity in the cortex is consistent with the antiepileptic effects of TNS.
  • the temporal-occipital cortex is seen in panel (c) as the largest colored (darker) region, and in panel (d) as the middle of the three colored areas.
  • ADD attention deficit disorder
  • ADHD attention deficit hyperactivity disorder
  • ASD autism and autism spectrum disorders
  • substance use disorders and related behavioral addictions eating disorders
  • psychotic disorders and obsessive compulsive disorder (OCD).
  • AD Attention Deficit Disorder
  • ADHD Attention Deficit Hyperactivity Disorder
  • ASD Autism Spectrum Disorders
  • ADHD attention deficit/hyperactivity disorder
  • ACC anterior cingulate cortex
  • parietal cortex e.g., Makris et al., 2010 , J Atten Disord 13(4):407-13; Dickstein S G, et al. 2006 J Child Psychol Psychiatry. 47(10):1051-62).
  • autism also termed autistic disorder
  • Disorders of substance abuse and dependence are defined as disorders of maladaptive patterns of behavior, as defined by the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 4th edition, 2000), and include criteria such as tolerance to a substance, withdrawal upon discontinuing use, an inability to cut down or control use of the substance, and giving up important social, occupational, or recreational activities because of using the substance.
  • Behavioral addictions e.g., internet addiction, sexual addiction, pathological gambling
  • PET scan data showed acute alterations in regional brain activity with exposure to TNS; these areas include those regions implicated in substance use disorders and in behavioral addictions. Modulation of activity in these and other brain structures, which are shown to be affected by trigeminal nerve stimulation, could assist in improving the cognitive and behavioral symptoms of substance use and behavioral addiction disorders.
  • Eating disorders include illnesses such as anorexia nervosa, bulimia nervosa, and other disorders related to eating (e.g., binge eating), as defined by the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 4th edition, 2000); in all, problems center disorders of eating behaviors, predominantly related to perceived body image, consumption of food, and/or expenditure of energy (e.g. excessive exercise); these behaviors can lead to abnormal weight and potentially life-threatening states of malnutrition or metabolic abnormalities.
  • Obsessive Compulsive Disorder as defined by the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 4th edition, 2000), is marked by the presence of obsessive, ruminative thoughts (e.g. fears of contamination with dirt or germs), and compulsive behaviors (e.g., ritualized handwashing).
  • OCD Obsessive Compulsive Disorder
  • ruminative thoughts e.g. fears of contamination with dirt or germs
  • compulsive behaviors e.g., ritualized handwashing.
  • neuroimaging studies have implicated several brain regions in these disorders, including ACC, caudate nucleus, striatum, prefrontal cortex, and parietal cortex (e.g., Huyser C, et al., 2010 . J Am Acad Child Adolesc Psychiatry.
  • the clinical response to TNS can arise directly from trigeminal effects independent of the vagus nerve or mediated through, and in combination with, the vagus nerve and its circuits.
  • trigeminal nerve stimulation can be used as a safe and non-invasive method to deliver stimulation to vagus nerve circuits, without implanting a vagus nerve stimulator, and without direct stimulation of the cervical vagus nerve or its branches. Stimulation of the vagus nerve circuits via trigeminal nerve reduces seizure activity. As described elsewhere herein, our data demonstrates a 4% reduction in heart rate via acute stimulation of the trigeminal nerve (e.g.
  • the cause(s) of psychotic illnesses such as schizophrenia
  • findings from neuroimaging studies implicate specific brain regions in the development of symptoms, such as hallucinations, delusions, impaired reality testing, and disorganized thought processes.
  • Areas such as the temporo-parietal cortex, bilateral prefrontal cortical regions, and the anterior cingulate cortex have been linked to psychosis (e.g., Fusar-Poli P, et al. Neuroanatomy of vulnerability to psychosis: a voxel-based meta-analysis. Neurosci Biobehav Rev. 2011. 35(5):1175-85).
  • Reflex bradycardia, hypotension and occasionally asystole as a result of the TCR have been reported for many years as a complication encountered during ophthalmologic and neurosurgical procedures. These adverse events arise from stimulation of the TCR in an uncontrolled and nonspecific fashion.
  • the TCR can be activated (or utilized) in a controlled fashion to provide therapeutic ends including protection of the brain and the heart, as well as modulation of the activity of these organs.
  • Stimulation of peripheral and cutaneous branches of the trigeminal nerve in the face, ear or scalp and the vagus nerves can be applied and stimulated at safe frequencies, pulse durations and amplitudes.
  • An external device can be applied in, for example, the ambulance, emergency room, intensive care unit or other setting, to activate the TCR (or the allied oculo-cardiac reflex in the setting of ophthalmic nerve stimulation).
  • Heart Failure is characterized by an increase in heart rate in response to diminished ventricular function.
  • the increased heart rate results in increased energy demands upon an injured and dysfunctional myocardium.
  • there is abnormal parasympathetic control of the heart as measured by a depressed baro-receptor reflex, which can lead to arrhythmias, and is associated with increased mortality.
  • Vagus nerve stimulation using implantable electrodes attached to the cervical portion of the vagus nerve, reduces heart rate and improves left ventricular function in animals and humans.
  • Schwartz et al. 2009 Annegers et al., Epilepsia 2000; 41:549-53.
  • Vagus nerve activity is significantly reduced and impaired after myocardial infarction.
  • Myocardial infarction As a result, there is reduced protection against severe life threatening arrhythmias and an increased risk of sudden death.
  • Immediately after myocardial infarction there is a surge in sympathetic activity, resulting in an increased heart rate, and increased stress on the myocardium.
  • Unopposed sympathetic activity can result in worsening of the infarction, and the propensity for lethal arrhythmias.
  • implanted vagus nerve stimulation significantly reduced the risk of lethal arrhythmias (e.g.
  • Sudden unexpected death in epilepsy is a major cause of death in people with epilepsy, accounting for 20-30% of the mortality associated with epilepsy.
  • Sudden Unexpected Death in Epilepsy is generally defined as: “sudden, unexpected, witnessed, or unwitnessed, non-traumatic, and non-drowning death in an individual with epilepsy, with or without evidence of a seizure . . .
  • trigeminal nerve stimulation represents a novel and less invasive method to improve parasympathetic autonomic function, reduce heart rate variability and protect the brain and heart. Therefore, trigeminal nerve stimulation can be utilized to improve the degree of vagus nerve-mediated autonomic control of the heart, and help to prevent sudden death in epilepsy.
  • the TCR is a cerebral protective reflex, which protects the brain during hypoxia, utilizing it in patients at risk for sudden death in epilepsy may protect brain and heart function during and after seizures, when hypoxia may commonly occur.
  • the use of trigeminal nerve stimulation may also include conditions in which impairment of blood flow to the brain may cause and/or worsen the progression of these conditions (collectively, “impaired blood flow conditions”).
  • impaired blood flow conditions many forms of dementia (e.g., Alzheimer's Disease, Vascular Dementia, Frontotemporal Dementia) are associated with impairments in blood flow to the brain, and interventions which may enhance delivery of blood to the brain may be clinically useful.
  • other conditions of the brain such as multiple sclerosis, Pick's disease, the transient hypoxia produced by sleep apnea, or infectious disease of the brain (e.g. Lyme Disease, HIV/AIDS) may also have a course which may be worsened by impairments in blood flow and may be improved through the neuroprotective actions of the TCR, and therefore could benefit from TNS.
  • the unique anatomy of the trigeminal nerve, and its direct and indirect connections with key areas of the brainstem (including pons and medulla) and other structures of the nervous system involved with the vagus nerve may allow the use of cutaneous stimulation of the TNS as a method to modulate the vagus nerve or vagus nerve circuits to, surprisingly, treat various medical disorders, including, but not limited to, neurological disorders such as epilepsy, seizure related disorders, acute brain injury, chronic brain injury, chronic daily headache, migraine, disorders related to migraine and headache and movement disorders, and neuropsychiatric disorders, such as depression, mood disorders, cognitive disorders, behavioral disorders and anxiety disorders and others as disclosed elsewhere herein, obesity and other disorders related to weight and feeding, inflammation, disorders of regulation of breathing, disorders of gastrointestinal function, autonomic regulation in menopausal hot flashes, regulation of hemostasis and sleep/insomnia.
  • neurological disorders such as epilepsy, seizure related disorders, acute brain injury, chronic brain injury, chronic daily headache, migraine, disorders related to migraine
  • mechanisms of action by which TNS may counter fatigue include, but are not limited to: (a) influence on the activity of the locus coeruleus, a brain center involved in the production and regulation of the neurotransmitter norepinephrine, and (b) influence on the activity of the reticular activating system (RAS), a brain system involved in regulating levels of consciousness, arousal, wakefulness and attention, and (c) influence on activity of the vagus nerve, which allows for signaling between the brain and multiple internal organs and body systems (e.g. immune), as detailed below.
  • RAS reticular activating system
  • Tinnitus sometimes called “ringing in the ears,” is a condition in which a person has the experience of hearing a sound in the absence of corresponding external sound Tinnitus is common, affecting 20% of the population above the age of 55. It is commonly associated with injury to the auditory system and it can arise in many contexts, including exposure to abnormally loud sounds, ear infections, foreign objects in the ear, nose allergies that prevent (or induce) fluid drain, as a side effect of some medications, as a part of aging, or as a part of a congenital hearing loss. Without wishing to be bound by any particular theory, stimulation of the trigeminal nerve may be able to treat the symptoms of tinnitus.
  • the cochlear nuclei are the principal brainstem structures responsible for hearing.
  • the paired cochlear nuclei are located in the dorsal and lateral portions of the right and left medulla.
  • the cochlear nuclei are divided into two predominant regions, the dorsal cochlear nucleus (DCN) and the ventral cochlear nucleus (VCN).
  • DCN dorsal cochlear nucleus
  • VCN ventral cochlear nucleus
  • the cochlear nuclei receive auditory (hearing) input from the cochlear nerves, which receives its input from the ear, specifically the cochlea. Fibers from the cochlear nuclei project to the central auditory pathways, including the lateral lemniscus, inferior colliculus, medical geniculate body, and finally to the primary auditory cortex.
  • the cochlear nuclei When the cochlear nerve is injured, the cochlear nuclei (especially the DCN) exhibit enhanced sensitivity to trigeminal input, and increased inhibition of the cochlear nuclei. (Shore et al. 2008) This enhanced sensitivity may play a role in the pathogenesis of tinnitus. (Shore et al. 2008)
  • TNS may be used to calm the dorsal cochlear nucleus (or other relevant structure) with a feedback control loop that may allow the patient in real-time to provide an audiologist with information on which stimulation parameters (such as frequency, pulse width, duty cycle) best mitigate the ringing in the patient's ears.
  • stimulation parameters such as frequency, pulse width, duty cycle
  • self-tuning control algorithms can adjust the stimulation parameters to mitigate accommodation effects and changes in the ringing frequency spectrum.
  • TNS can be used to modulate vagus nerve activity to treat inflammatory processes in the body.
  • Conditions related to these inflammatory processes that may also be treated by modulating vagus nerve activity include: asthma, inflammatory bowel disease, atopic dermatitis, sepsis and hepatitis.
  • journal articles may include studies that show an effect on inflammatory processes and other conditions in which inflammation plays a role, by modulating vagus nerve activity: inflammatory processes: Minutoli L, et al., Melanocortin 4 receptor stimulation decreases pancreatitis severity in rats by activation of the cholinergic anti-inflammatory pathway, Crit Care Med, 2011 May; 39(5):1089-96.; Lehrer P, et al., Voluntarily produced increases in heart rate variability modulate autonomic effects of endotoxin induced systemic inflammation: an exploratory study, Appl Psychophysiol Biofeedback, 2010 December; 35(4):303-15; Ottani A, et al., Melanocortins counteract inflammatory and apoptotic responses to prolonged myocardial ischemia/reperfusion through a vagus nerve-mediated mechanism, Eur J Pharmacol, 2010 Jul.
  • asthma Li H F and Yu J., Airway chemosensitive receptors in vagus nerve perform neuro-immune interaction for lung-brain communication, Adv Exp Med Biol, 2009; 648:421-6.
  • inflammatory bowel disease Meregnani J, et al., Anti-inflammatory effect of vagus nerve stimulation in a rat model of inflammatory bowel disease, Auton Neurosci, 2011 Feb. 24; 160(1-2):82-9, Epub 2010 Nov.
  • Sleep disturbances can arise in a range of conditions, including sleep apnea, hyperthyroidism, depression, and primary insomnia. Stimulation of the trigeminal nerve may be able to treat sleep disturbances by means of its influences on brain systems related to wake/sleep cycles and arousal.
  • projections from the trigeminal nerve to the nucleus of the tractus solitarius (NTS) convey signals to the NTS and then to other brain regions involved in the regulation of sleep and wakefulness, for example, via the parabrachial nucleus, to the hypothalamus, amygdala, insula, lateral prefrontal cortex, and other regions of relevance (A. Jean.
  • insomnia items of the Quick Inventory of Depressive Symptomatology (www.ids-qids.org), for ten adults with major depression who participated in a clinical trial of TNS.
  • sleep onset insomnia i.e., delay in falling asleep
  • nocturnal insomnia awakening during the night
  • insomnia early morning insomnia (awakening earlier than intended and being unable to return to sleep).
  • Summing the responses to these three items gives an index of severity of insomnia in these subjects, ranging from zero (no symptoms) to six (maximal disturbance across all three types of insomnia symptom). Over the course of this 8 week trial, this measure of insomnia severity fell from an average of 2.5 (1.8 s.d.) to 1.2 (1.0 s.d.), a decrease of over 50% which achieved statistical significance (2-tail paired t-test p ⁇ 0.05).
  • the implanted electrodes are positioned adjacent to the foramina of the supraorbital or ophthalmic nerves ( FIG. 1A , Foramen 1 ) since unilateral stimulation or bilateral stimulation of the trigeminal nerve is achievable by placing single or separate electrodes on the right and/or left sides.
  • the electrode assembly is configured for unilateral stimulation.
  • the electrode assembly is configured for bilateral stimulation.
  • bilateral stimulation may offer similar or better efficacy than unilateral stimulation because the function of different brain structures may not be the same on right and left. There may also be synergistic effects that arise with bilateral stimulation.
  • FIG. 1A the implanted electrodes are positioned adjacent to the foramina of the supraorbital or ophthalmic nerves ( FIG. 1A , Foramen 1 ) since unilateral stimulation or bilateral stimulation of the trigeminal nerve is achievable by placing single or separate electrodes on the right and/or left sides.
  • the electrode assembly is configured for unilateral stimulation.
  • bilateral stimulation may offer similar or better efficacy than unilateral stimulation because the function of different brain structures
  • the method of treating fatigue and other medical disorders includes implanting electrodes over a plurality of superficial foramina in the face and simultaneously or asynchronously stimulating different trigeminal nerves.
  • the stimulation may take place in the cutaneous territories of branches of the trigeminal nerves, without attachment to the nerves.
  • electrodes may penetrate percutaneously, i.e., through the surface of the skin, in order to be placed in proximity to the intended branch(es) of the trigeminal nerve, while the pulse generator remains external to the body.
  • percutaneous TNS or pTNS percutaneous TNS or pTNS
  • some elements of the system are implanted in the tissues of the skin, while other elements are not implanted.
  • a system 200 for treatment of medical disorders via TNS includes an electrode assembly 20 , electrical cable or wire 40 and a neurostimulator or pulse generator 30 .
  • the pulse generator may be any type of appropriate stimulating, signal generating device.
  • the pulse generator 30 may include electronic circuitry for receiving data and/or power from outside the body by inductive, radio-frequency (RF), or other electromagnetic coupling.
  • electronic circuitry includes an inductive coil for receiving and transmitting RF data and/or power, an integrated circuit (IC) chip for decoding and storing stimulation parameters and generating stimulation pulses, and additional discrete electronic components required to complete the electronic circuit functions, e.g. capacitor(s), resistor(s), transistor(s), coil(s), and the like.
  • neurostimulator 30 may include a programmable memory for storing a set(s) of data, stimulation, and control parameters.
  • memory may allow stimulation and control parameters to be adjusted to settings that are safe and efficacious with minimal discomfort for each individual.
  • Specific parameters may provide therapeutic advantages for various medical disorders. For instance, some patients may respond favorably to intermittent stimulation, while others may require continuous stimulation to treat their symptoms.
  • the neurostimulator 30 may include a power source and/or power storage device.
  • a power source and/or power storage device Possible options for providing power to the system include but are not limited to: an external power source coupled to neurostimulator 30 , e.g., via an RF link, a self-contained power source utilizing any suitable means of generation or storage of energy (e.g., a primary battery, a replenishable or rechargeable battery such as a lithium ion battery, an electrolytic capacitor, a super-capacitor, a kinetic generator, or the like), and if the self-contained power source is replenishable or rechargeable, means of replenishing or recharging the power source (e.g., an RF link, an optical link, a thermal link, an inductive link, or other energy-coupling link).
  • a self-contained power source utilizing any suitable means of generation or storage of energy (e.g., a primary battery, a replenishable or rechargeable battery such as a lithium ion battery
  • neurostimulator 30 operates independently. In other embodiments, neurostimulator 30 operates in coordination with other implanted device(s) or other device(s) external to the patient's body.
  • a neurostimulator may communicate with other implanted neurostimulators, other implanted devices, and/or devices external to a patient's body via, e.g., an RF link, an ultrasonic link, a thermal link, an optical link, or the like.
  • a neurostimulator may communicate with an external remote control (e.g., patient and/or physician programmer) that is capable of sending commands and/or data to a neurostimulator and that may also be capable of receiving commands and/or data from a neurostimulator.
  • an external remote control e.g., patient and/or physician programmer
  • the electrical cable or wire 40 is configured to provide a physical and electrical link between the pulse generator 30 and the electrode assembly 20 .
  • the pulse generator 30 and the electrode assembly 20 communicate wirelessly (i.e. the wire 40 is not used).
  • the system 200 and/or the electrode assembly 20 may be part of a kit.
  • the kit may also include instructions for treatment of various medical disorder according to a method disclosed herein.
  • the kit may also include instructions for monitoring the clinical effects of the stimulation to achieve proper adjustment of stimulation parameters and system configuration. The instructions may be provided in any readable format or as a link to a website.
  • the system may include a regulation device.
  • the regulation device is configured to be attached to the neurostimulator 30 and, in some embodiments, is configured to govern the maximum charge balanced output current below approximately 1-25 mA to minimize current penetration to the brain and increase patient tolerance.
  • the regulation device may be internally programmed to range from 0.25-5.0 mA, 0-10 mA, 0-15 mA, depending on the surface area, placement, and orientation of the electrode, and whether the electrode is stimulating near or adjacent to the skull, or away from the skull, where current ranges may be higher or lower.
  • the system may utilize a closed loop design and may include a closed loop device or sensing device.
  • the closed loop device may include the stimulating electrode or additional set of electrodes, indwelling catheters, or cutaneous or implantable physiologic monitors.
  • the device may be configured to detect heart rate, pulse oximetry, cerebral blood flow, systolic, diastolic blood pressure, or mean arterial pressure, transcranial Doppler, cardiac parameters (ejection fraction, pulmonary, atrial, or ventricular pressures), heart rate variability (using time, frequency, or non-linear or other measures of heart rate variability), the presence of molecules that could signify a potentially-dangerous condition (e.g., tropinin in the bloodstream, a biomaker that may indicate injury to the heart muscle tissue, as might be treated in an ambulance, an emergency room, and/or an intensive care unit) or the achievement of a desired clinical effect (e.g., levels of proinflammatory cytokines), or other physiologic parameters to provide self-tuning adaptive feedback control for the neurostimulator including, but not limited to, fuzzy controllers, LQG controllers and artificial neural networks (ANN).
  • ANN artificial neural networks
  • an electrode assembly 20 may include electrodes 20 a , 20 b configured for the bilateral simultaneous and asynchronous stimulation of the ophthalmic nerves and other nerves as described herein.
  • the electrodes 20 a , 20 b of the electrode assembly 20 comprise a first pair of contacts 112 a , 112 b configured for implantation in a first region of the patient's face, such as the patient's right forehead, and a second pair of contacts 112 c , 112 d configured for implantation in a second region of the patient's face, such as in the patient's left forehead.
  • the first and second regions of the patient's face may be on the same side of the face, e.g.
  • the geometry or layout of the electrode assembly may be a linear electrode with a single contact or a series or plurality of conductive contacts and insulating spaces, or a flatter, “ribbon” or “strip” electrode, also with the possibility of one or more conductive area(s) and insulated area(s) on the surface(s).
  • a flatter, “ribbon” or “strip” electrode also with the possibility of one or more conductive area(s) and insulated area(s) on the surface(s).
  • the electrode assembly may be implanted unilaterally.
  • the electrode assembly may also be configured to stimulate more than one nerve.
  • the electrode assembly is configured to be placed at, near or over a plurality of superficial foramina in the face and simultaneously or asynchronously stimulate different trigeminal nerves (e.g. the supraorbital nerve and the infraorbital nerve).
  • the electrode assembly 20 is configured to stimulate both the right and left ophthalmic nerves either simultaneously or asynchronously.
  • the placement of the first implanted electrode with contact pair 112 a , 112 b and the second electrode with contact pair 112 c , 112 d on opposite sides of the nasal midline assures that stimulation current moves orthodromically or in the direction of the afferent ophthalmic or supraorbital nerve.
  • this configuration of the electrode assembly 20 allows the electrode contact points 112 a / 112 b and 112 c / 112 d to be stimulated independently and/or unilaterally, as the response to stimulus may be localized and thus varied from one side of the midline to the other side.
  • Electrode assembly 20 may be made of a noble or refractory metal or compound, such as titanium, titanium nitride, platinum, iridium, tantalum, niobium, rhenium, palladium, gold, nichrome, stainless steel, or alloys of any of these, in order to avoid corrosion or electrolysis which could damage the surrounding tissues and the device.
  • a noble or refractory metal or compound such as titanium, titanium nitride, platinum, iridium, tantalum, niobium, rhenium, palladium, gold, nichrome, stainless steel, or alloys of any of these, in order to avoid corrosion or electrolysis which could damage the surrounding tissues and the device.
  • Other compounds for implantable electrodes will be apparent to one skilled in the art.
  • both external, transcutaneous electrodes and implanted electrodes are used to simultaneously or asynchronously stimulate one or more branches of the trigeminal nerves.
  • sensing electrodes are included in the electrode array to monitor physiological parameters, such as electrocardiographic data, or other relevant physiologic data such as oxygen saturation, carbon dioxide, blood pressure, basal metabolic rate, or other measures, and permit a feedback system that can adaptively adjust the stimulation parameters to optimize therapeutic benefit and safety.
  • physiological parameters such as electrocardiographic data, or other relevant physiologic data such as oxygen saturation, carbon dioxide, blood pressure, basal metabolic rate, or other measures
  • the sensing electrode is one of the stimulating electrodes and is used for sensing during the ‘off’ part of the duty cycle.
  • the sensing electrode is an additional electrode and is dedicated to sensing only.
  • the electrode assembly 20 is implanted in the soft tissues of the forehead of the patient 20 .
  • the electrode 20 is then connected to an implanted neurostimulator 30 via the implanted electrical cables 40 , which are placed under the patient's skin.
  • the stimulation via the neurostimulator 30 is via electrical cables 40 .
  • the electrical stimulation can be performed wirelessly, with an external, non-implanted neurostimulator, which uses inductive coupling to deliver energy to the implanted electrode assembly 20 .
  • the stimulation is carried out at the above-described values of the operational parameters.
  • the values of the operational parameters are advantageously selected such that a patient will experience a stimulation sensation, such as mild tingling over the forehead and scalp, without causing the patient significant discomfort or pain and with minimal current penetration to the brain. These values may vary according to the treatment of interest.
  • the electrode assembly 20 is placed in the patient's skin, while the non-implanted neurostimulator is placed externally, and the two are connected via electrical cables 40 .
  • stimulation can be applied to aspects of the trigeminal nerve which innervate portions of the ear, particularly the auricle (external ear) 317 and the ear canal 315 , 316 .
  • auricle extra ear
  • auricle extra ear
  • a single anatomical structure in this area of the body, more than one nerve may supply adjacent and/or overlapping areas of a single anatomical structure.
  • Sensory signals from these skin areas may be conveyed to centers in the brain by nerves including the auriculotemporal nerve, a branch of the trigeminal nerve, and also by other nerves (e.g., posterior auricular nerve, from the facial nerve, or the auricular branch of the vagus nerve).
  • nerves including the auriculotemporal nerve, a branch of the trigeminal nerve, and also by other nerves (e.g., posterior auricular nerve, from the facial nerve, or the auricular branch of the vagus nerve).
  • electrodes may be placed under the skin of the auricle and/or of the ear canal. Such embodiments are less noticeable when worn by a patient and may increase patient use and/or compliance.
  • Accepted standards of safe stimulation may be incorporated for chronic stimulation. Parameters may be selected or calculated to deliver no stimulation or negligible stimulation to the surface of the brain.
  • the currently accepted safe parameters for chronic stimulation are less than a charge per phase of ⁇ 20 ⁇ C/cm 2 /phase at the surface of the brain (Exp Neurol 1983; 79:397-41). In general, for any region of the surface of the brain, the cumulative charge per phase resulting from all the electrode contacts should not exceed this threshold. It is recognized that these guidelines are subject to change, and that parameters should be selected which deliver no current or negligible current to the surface of the brain, while still being sufficient to stimulate the nerves disclosed herein.
  • the output current density is less than 7 mA, or less than 6 mA, depending on the size, impedance, resistance, or configuration of the electrode(s). In some embodiments, the output current density is between about 2.5 mA and about 5 mA. In still another embodiment, the output current may be limited to an exact current, e.g. 5 mA, up to a maximum of a fixed current of 7 mA, depending on the size, resistance, or impedance of the electrode. In another embodiment, the output current is limited to a range not to exceed 10 mA, or 7 mA, or 5 mA. In general, the stimulation would yield no or negligible charge densities at the cerebral cortex. In some cases, stimulation can be provided for less than one-half hour per day.
  • the method of selecting operational parameters includes evaluating variables such as the pulse duration, the electrode current, the duty cycle and the stimulation frequency; the parameters are selected to ensure that the total charge, the charge density, and charge per phase are well within accepted safety limits for the scalp or facial tissue, nerve and brain. Additionally, in some embodiments, selection of the electrical stimulation parameters, electrode design, and inter-electrode distance is made such that the electrical stimulation zone includes the superficial elements of the trigeminal nerves (approximately 3-4 mm deep), while preventing or minimizing current penetration beneath the bone tissue of the skull.
  • the stimulation parameters delivered by the implanted pulse generator may be determined (programmed) at the time the device is surgically implanted. In other embodiments, these parameters may be modified, controlled, or otherwise programmed by an external device. This external programming element communicates with the implanted components wirelessly. This may take place, for example, by radiofrequency signals, by inductive coupling, or other means apparent to one skilled in the art.
  • the stimulation is delivered at a specific pulse width or range of pulse widths.
  • the stimulation can be set to deliver pulse widths in the range greater than and/or less than one or more of 10 ⁇ s, 20 ⁇ s, 30 ⁇ s, 40 ⁇ s, 50 ⁇ s, 60 ⁇ s, 70 ⁇ s, 80 ⁇ s, 90 ⁇ s, 100 ⁇ s, 120 ⁇ s, 125 ⁇ s, 150 ⁇ s, 175 ⁇ s, 200 ⁇ s, 225 ⁇ s, 250 ⁇ s, 300 ⁇ s, up to 500 ⁇ s.
  • Those of skill in the art will recognized that one or more of the above times can be used as a border of a range of pulse widths.
  • the stimulation amplitude is delivered as a voltage or current controlled stimulation. In other embodiments it can be delivered as a capacitive discharge.
  • the current amplitude can be in any range within a lower limit of about 300 ⁇ A and an upper limit of about 25 mA, depending on the surface area of the electrodes, inter-electrode distance, the branch(es) stimulated, and the modeling data as described above. In some embodiments, the current used will range from 1 mA to 25 mA. In other embodiments, the current used will range from 5-25 mA.
  • the amplitude can be in a range greater than and/or less than one or more of 50 ⁇ A, 75 ⁇ A, 100 ⁇ A, 125 ⁇ A, 150 ⁇ A, 175 ⁇ A, 200 ⁇ A, 225 ⁇ A, 250 ⁇ A, 275 ⁇ A, 300 ⁇ A, 325 ⁇ A, 350 ⁇ A, 375 ⁇ A, 400 ⁇ A, 425 ⁇ A, 450 ⁇ A, 475 ⁇ A, 500 ⁇ A, 525 ⁇ A, 550 ⁇ A, 575 ⁇ A, 600 ⁇ A, 625 ⁇ A, 650 ⁇ A, 675 ⁇ A, 700 ⁇ A, 725 ⁇ A, 850 ⁇ A, 875 ⁇ A, 900 ⁇ A, 925 ⁇ A, 950 ⁇ A, 975 ⁇ A, 1 mA, 2 mA, 3 mA, 4 mA, 5 mA, 6 mA, 7 mA, 875 ⁇ A,
  • the current amplitudes are less than 7 mA, or less than 6 mA, depending on the size, impedance, resistance, or configuration of the electrode(s). In some embodiments, the current amplitude is between about 2.5 mA and about 5 mA. In still another embodiment, the output current may be limited to an exact current, e.g. 5 mA, up to a maximum of a fixed current of 7 mA, depending on the size, resistance, or impedance of the electrode. In another embodiment, the output current is limited to a range not to exceed 10 mA, 7 mA, or 5 mA.
  • amplitudes can be used as a border of a range of amplitudes, and that devices which use a voltage-based output can deliver a voltage output which at a range of electrode impedances would yield similar currents.
  • the current may be delivered constantly or intermittently.
  • treatment at a given current amplitude is delivered so as to minimize or eliminate any spread of current to the cerebral cortex, while ensuring that accepted limits of charge density and charge per phase at the brain surface (e.g., generally ⁇ 20 ⁇ C/cm 2 /phase, Exp Neurol 1983; 79:397-411) are adhered to, for the safety of the patient.
  • accepted limits of charge density and charge per phase at the brain surface e.g., generally ⁇ 20 ⁇ C/cm 2 /phase, Exp Neurol 1983; 79:397-411
  • charge densities may be employed because more fibers within the nerves may be engaged in the neurostimulation process.
  • the stimulation can be delivered at one or more frequencies, or within a range of frequencies. In some embodiments, the frequency used will range from 1 Hz to 150 Hz.
  • the stimulation can be set to be delivered at frequencies less than, and/or greater than one or more of 50 Hz, 45 Hz, 40 Hz, 35 Hz, 30 Hz, 25 Hz, 20 Hz, 15 Hz, 10 Hz, 5 Hz or 1 Hz. In various embodiments, the stimulation can be set to be delivered at frequencies greater than, and/or less than, one or more of 20 Hz, 30 Hz, 40 Hz, 50 Hz, 60 Hz, 70 Hz, 80 Hz, 90 Hz, 100 Hz, 120 Hz, 125 Hz, 150 Hz, up to 300 Hz.
  • the upper bound of the frequency may be 10,000 Hz (10 kHz).
  • the stimulation is delivered at a specific duty cycle or range of duty cycles.
  • the stimulation can be set to be delivered at a duty cycle in the range greater than and/or less than one or more of 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%.
  • a duty cycle of 10% to 50% may be preferable.
  • duty cycles up to 100% may be useful in particular circumstances. Those of skill in the art will recognized that one or more of the above percentages can be used as a border of a range of duty cycles.
  • interferential stimulation two (or more) signals are applied to the tissue of the body, and these signals are designed to differ from each other in such a way that when they combine (“heterodyne” or “interfere”) within the tissue, they produce the desired signal (interference signal).
  • This approach to creating a desired signal within nerve tissue may be advantageous in some clinical circumstances because the impedance of skin and adjacent tissue depends upon frequency, and this approach may allow for application of lower amounts of energy of the tissue to accomplish a clinically-effective level of nerve stimulation.
  • the varying may take on a variety of patterns, such as a triangular or trapezoidal ramp or a sinusoidal or similar modulation pattern. Also, varying the duty cycle or on-off times, for example ranging the duty cycle from 10% to 50% over 1-24 hours, 50% to 10% over 1-24 hours, than 50% to 100%, or other intervals and time periods so as to prevent or respond to accommodation of the nerve or its related target brainstem, brain structures, and associated brain regions.
  • a method of evaluating the use of deep brain stimulation for treatment of fatigue or other medical disorder in a patient is disclosed herein.
  • the method may include applying a transcutaneous system for stimulation of the trigeminal nerve to the patient and monitoring the patient for at least one of evidence of a useful therapeutic response or evidence of tolerability of TNS treatment thereby generating external measurement criteria, providing a subcutaneous or implantable electrode assembly or system as disclosed herein, implanting the subcutaneous electrode assembly or system as disclosed herein in the patient for treatment of fatigue or other medical disorder, monitoring the patient for at least one of a useful therapeutic response or tolerability of the implanted device, thereby generating extracranial measurement criteria, and analyzing the external measurement criteria and extracranial measurement criteria to determine whether the patient will benefit from deep brain stimulation.
  • electrodes are placed in proximity to the trigeminal nerve branches (e.g., in the forehead), either implanted subcutaneously or placed percutaneously, and gentle electrical signals are used to stimulate the nerve, typically for 8 hours (while sleeping), using stimulation parameters such as a pulse width of 250 microsec, repetition rate of 120 Hz, duty cycle of 30 s on then 30 s off, and current of up to 25 mA.
  • stimulation parameters such as a pulse width of 250 microsec, repetition rate of 120 Hz, duty cycle of 30 s on then 30 s off, and current of up to 25 mA.
  • the electrical signals have been shown to lead to selective activation or inhibition of a set of brain structures, such as the locus coeruleus and the anterior cingulate.
  • FIG. 8 illustrates the sequential employment of N sets of parameters, with Parameter Set 1 500, Parameter Set 2 501, on through the final, Nth set 502 Parameter Set N.
  • the first parameter set 500 (Parameter Set 1) is employed by the stimulation generator for the duration specified in the parameter set.
  • a second parameter set 501 (Parameter Set 2) is employed, and this sequential utilization of different parameter sets continues until the final (Nth) parameter set 502 (Parameter Set N) is employed, after which the sequence may begin again. This cycling through the N different parameter sets may occur repeatedly during the treatment administration.
  • a plurality of stimulation parameters may be used to improve the clinical treatment effects.
  • several sets of parameters are utilized and the system may automatically vary the stimulation among the sets of parameters.
  • This plurality of sets is intended to avoid any adaptation of the patient's nervous system to repeated exposure to the same unvarying stimulation pattern.
  • the stimulation pattern is selected to prevent or minimize current penetration into the brain.
  • parameters may be selected for use in a clinical research study in order to have a set of parameters which is unlikely to produce the desired clinical effect (i.e., for use as a sham (placebo) control condition). Additionally, this approach may be used to determine if there is penetration of current into the brain tissue directly from the stimulating electrodes.
  • FIG. 9 depicts a system 610 for determining patient specific stimulation parameters.
  • the system 610 includes a biological sensing device 601 , a measurement or measuring device 602 and a stimulation generator 604 .
  • the biological sensing device may be a neuroimaging device, such as a magnetic resonance imaging (MRI) scanner, a positron emission tomography (PET) scanner, or similar device; or a physiologic device, such as an electroencephalograph (EEG), an electrocardiograph (ECG or EKG), a blood pressure sensory, pulse oximeter, or other similar device.
  • MRI magnetic resonance imaging
  • PET positron emission tomography
  • EEG electroencephalograph
  • EKG electrocardiograph
  • blood pressure sensory pulse oximeter
  • a patient 600 is placed in proximity to a biological sensing device 601 , which is coupled, either directly or indirectly to a measurement or measuring device 602 .
  • Output from the measuring device 602 is observed by the prescribing physician or other clinician 603 and adjustments may be made to the stimulation parameters as disclosed elsewhere herein that are supplied by the stimulation generator 604 to the trigeminal nerve of patient 600 .
  • Inclusion Criteria were: Age 18-65 years old who met DSM-IV criteria for an acute, recurrent episode of Major Depressive Disorder (MDD) and were in a major depressive episode (MDE) of moderate severity. Other inclusion criteria were: the current MDE must be ⁇ 4 months in duration, no response to at least one antidepressant over at least six weeks during the current MDE, and concomitant use of at least one antidepressant. All had prominent residual symptoms, with mean Hamilton Depression Rating Scale (HDRS-28) scores at study entry of 25.4 (3.9 s.d.), range 19 to 29. Subjects placed stimulating electrodes over the supraorbital branches of the trigeminal nerve for at least 8 hours per day (primarily while asleep), with current adjusted to maintain comfortable levels. Five subjects completed the trial. Primary outcome was change in HDRS at 8 weeks.
  • HDRS-28 Hamilton Depression Rating Scale
  • Subjects underwent stimulation using an electrical stimulator such as for example the EMS Model 7500 commercially available from TENS Products, Inc. (www.tensproducts.com) operated at a frequency of 120 Hertz, a current less than 20 mA, a pulse duration of 250 ⁇ sec, and a duty cycle at 30 seconds on and 30 seconds off, for a minimum of 8 hours per day.
  • an electrical stimulator such as for example the EMS Model 7500 commercially available from TENS Products, Inc. (www.tensproducts.com) operated at a frequency of 120 Hertz, a current less than 20 mA, a pulse duration of 250 ⁇ sec, and a duty cycle at 30 seconds on and 30 seconds off, for a minimum of 8 hours per day.
  • the symptom severity of each subject was quantified using the Hamilton Depression Rating Scale (HDRS, scored using both 17- and 28-item versions), the Beck Depression Inventory (BDI), and the Quick Inventory of Depressive Symptomatology (QIDS), with the group average values on each of these scales being tabulated in the table shown in FIG. 6A . All three are assessment instruments designed to measure the severity of depression.
  • HDRS Hamilton Depression Rating Scale
  • BDI Beck Depression Inventory
  • QIDS Quick Inventory of Depressive Symptomatology
  • BDI emphasizes cognitive symptoms of depression, while the HDRS weights neurovegetative symptoms prominently), and all are commonly used in clinical trials in major depression; the use of multiple scales allowed a more comprehensive assessment of the effects of trigeminal nerve stimulation than any single scale in this initial study of this treatment for major depression.
  • Cutaneous electrical stimulation of the supraorbital branch of the trigeminal nerve with round 1.25-inch TENS patch electrodes results in current densities and charge density/phase that are well within the limits of safety.
  • the maximum current comfortably tolerated by TNS patients studied previously is approximately 25 mA, and patients typically are stimulated at an amplitude setting well below 25 mA (6-10 mA).
  • the 1.25-inch TENS electrodes are circular electrodes with a radius of 1.59 cm.
  • typical stimulation current ranges from 6-10 mA at pulse durations of 150-250 usec.
  • the charge density is generally 12 to 120 fold less at the stimulating electrode than the maximum allowed at the cerebral cortex. Since the cortex is a minimum of 10-13 mm from the stimulating electrodes, and given the interposed layers of skin, fat, bone, dura, and CSF, the actual charge densities will be significantly lower. This is of importance in avoiding the undesired passage of current directly through brain tissue as a bulk conductor.
  • FIG. 12 illustrates the response to TNS at 120 Hz, 10-30 seconds on/30 seconds off, infraorbital or supraorbital stimulation in patients with epilepsy. Note the measured and mild reductions in heart rate, consistent with activation of the Trigeminal Cardiac Reflex. This reflects the effects of vagus nerve stimulation from Trigeminal Nerve Stimulation. Mild reductions in heart rate occur without significant changes in systolic or diastolic blood pressure. The reduction in heart rate is protective in the setting of myocardial infarction, heart failure, tachyarrhythmia's, and conditions associated with the risk of sudden death.
  • FIGS. 14A-14B illustrate a sample protocol for mitigating the potential effects of accommodation.

Landscapes

  • Health & Medical Sciences (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Electrotherapy Devices (AREA)
  • Electroluminescent Light Sources (AREA)
US13/994,512 2010-12-14 2011-12-14 Extracranial implantable devices, systems and methods for the treatment of medical disorders Abandoned US20140142669A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US13/994,512 US20140142669A1 (en) 2010-12-14 2011-12-14 Extracranial implantable devices, systems and methods for the treatment of medical disorders

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US42300810P 2010-12-14 2010-12-14
US201161440802P 2011-02-08 2011-02-08
US201161445454P 2011-02-22 2011-02-22
US201161479779P 2011-04-27 2011-04-27
PCT/US2011/065003 WO2012082961A2 (en) 2010-12-14 2011-12-14 Extracranial implantable devices, systems and methods for the treatment of medical disorders
US13/994,512 US20140142669A1 (en) 2010-12-14 2011-12-14 Extracranial implantable devices, systems and methods for the treatment of medical disorders

Related Parent Applications (3)

Application Number Title Priority Date Filing Date
US12/898,685 Continuation-In-Part US8958880B2 (en) 2009-10-05 2010-10-05 Extracranial implantable devices, systems and methods for the treatment of neuropsychiatric disorders
US12/898,696 Continuation-In-Part US20110106220A1 (en) 2009-10-05 2010-10-05 Extracranial implantable devices, systems and methods for the treatment of neurological disorders
PCT/US2011/065003 A-371-Of-International WO2012082961A2 (en) 2009-10-05 2011-12-14 Extracranial implantable devices, systems and methods for the treatment of medical disorders

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US15/624,640 Continuation US20170348521A1 (en) 2009-10-05 2017-06-15 Extracranial implantable devices, systems and methods for the treatment of medical disorders

Publications (1)

Publication Number Publication Date
US20140142669A1 true US20140142669A1 (en) 2014-05-22

Family

ID=46245360

Family Applications (3)

Application Number Title Priority Date Filing Date
US13/994,512 Abandoned US20140142669A1 (en) 2010-12-14 2011-12-14 Extracranial implantable devices, systems and methods for the treatment of medical disorders
US15/624,640 Abandoned US20170348521A1 (en) 2009-10-05 2017-06-15 Extracranial implantable devices, systems and methods for the treatment of medical disorders
US15/949,987 Active US10238862B2 (en) 2009-10-05 2018-04-10 Extracranial implantable devices, systems and methods for the treatment of medical disorders

Family Applications After (2)

Application Number Title Priority Date Filing Date
US15/624,640 Abandoned US20170348521A1 (en) 2009-10-05 2017-06-15 Extracranial implantable devices, systems and methods for the treatment of medical disorders
US15/949,987 Active US10238862B2 (en) 2009-10-05 2018-04-10 Extracranial implantable devices, systems and methods for the treatment of medical disorders

Country Status (5)

Country Link
US (3) US20140142669A1 (enExample)
EP (1) EP2651497B1 (enExample)
JP (1) JP6559395B2 (enExample)
CA (1) CA2821721A1 (enExample)
WO (1) WO2012082961A2 (enExample)

Cited By (43)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140135886A1 (en) * 2010-12-14 2014-05-15 United States Government Department Of Veterans Affairs Devices, systems and methods for the treatment of medical disorders
US20150119898A1 (en) * 2012-04-05 2015-04-30 Teh Regents Of The University Of California Subcutaneous electrodes for cranial nerve stimulation
US9042991B2 (en) 2013-08-14 2015-05-26 Syntilla Medical LLC Implantable head mounted neurostimulation system for head pain
US9238139B2 (en) 2009-10-05 2016-01-19 The Regents Of The University Of California Devices, systems and methods for treatment of neuropsychiatric disorders
US20160045739A1 (en) * 2013-03-11 2016-02-18 Ohio State Innovation Foundation Systems for treating anxiety and anxiety-associated disorders
US20160184585A1 (en) * 2013-04-24 2016-06-30 Neurosigma, Inc. Modulation of Autonomic Nervous System Activity and Integrated Electrode Assemblies for Trigeminal Neurostimulation
US9427566B2 (en) 2013-08-14 2016-08-30 Syntilla Medical LLC Implantable neurostimulation lead for head pain
US9498635B2 (en) 2013-10-16 2016-11-22 Syntilla Medical LLC Implantable head located radiofrequency coupled neurostimulation system for head pain
US20170143972A1 (en) * 2015-11-19 2017-05-25 Boston Scientific Neuromodulation Corporation Neuromodulation for neuroinflammation treatments with parameters controlled using biomarkers
US9707406B1 (en) 2016-01-06 2017-07-18 Syntilla Medical LLC Charging system incorporating receive coil de-tuning within an implanted device
US9839777B2 (en) 2013-08-14 2017-12-12 Syntilla Medical LLC Implantable neurostimulation lead for head pain
US10016601B2 (en) 2010-11-30 2018-07-10 The Regents Of The University Of California Pulse generator for cranial nerve stimulation
US10238862B2 (en) 2009-10-05 2019-03-26 The Regents Of The University Of California Extracranial implantable devices, systems and methods for the treatment of medical disorders
US10258805B2 (en) 2013-10-23 2019-04-16 Syntilla Medical, Llc Surgical method for implantable head mounted neurostimulation system for head pain
WO2019111261A1 (en) * 2017-12-06 2019-06-13 Technion Research & Development Foundation Limited Methods of neural inhibition for treating bowel diseases and disorders
US10406360B2 (en) * 2016-09-13 2019-09-10 Richard Charles Niemtzow Electrical acupuncture eye treatment
WO2021011165A1 (en) * 2019-07-14 2021-01-21 Spark Biomedical, Inc. Systems and methods for delivering therapy using an auricular stimulation device
US20210023372A1 (en) * 2019-07-22 2021-01-28 Ismail Mohammed Yousif Musallam Neuromodulation for treatment of brain and eye strokes and/or acute dysregulated reduced cerebral or ocular blood flow
US10960215B2 (en) 2013-10-23 2021-03-30 Nuxcel, Inc. Low profile head-located neurostimulator and method of fabrication
US10967182B2 (en) 2018-12-10 2021-04-06 Spark Biomedical, Inc. Devices and methods for reducing inflammation using electrical stimulation
US11235156B2 (en) 2019-09-11 2022-02-01 Bose Corporation Wearable audio device with vagus nerve stimulation
US11241574B2 (en) 2019-09-11 2022-02-08 Bose Corporation Systems and methods for providing and coordinating vagus nerve stimulation with audio therapy
US11273283B2 (en) 2017-12-31 2022-03-15 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement to enhance emotional response
US11351370B2 (en) 2018-12-10 2022-06-07 Spark Biomedical, Inc. Devices and methods for treating cognitive dysfunction and depression using electrical stimulation
US20220184405A1 (en) * 2020-12-11 2022-06-16 Advanced Neuromodulation Systems, Inc. Systems and methods for labeling data in active implantable medical device systems
US11364361B2 (en) 2018-04-20 2022-06-21 Neuroenhancement Lab, LLC System and method for inducing sleep by transplanting mental states
WO2022187592A1 (en) * 2021-03-04 2022-09-09 Washington University Transcutaneous auricular vagal nerve stimulation for subarachnoid hemorrhages
US11452839B2 (en) 2018-09-14 2022-09-27 Neuroenhancement Lab, LLC System and method of improving sleep
US11467665B2 (en) 2018-06-14 2022-10-11 Meron Gribetz Virtual user interface system and methods for use thereof
US11623088B2 (en) 2018-12-10 2023-04-11 Spark Biomedical, Inc. Devices and methods for the treatment of substance use disorders
US20230166110A1 (en) * 2017-09-29 2023-06-01 Cochlear Limited Hearing prosthesis
US11717686B2 (en) 2017-12-04 2023-08-08 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement to facilitate learning and performance
US11723579B2 (en) 2017-09-19 2023-08-15 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement
US11724120B2 (en) * 2016-10-17 2023-08-15 Wave Neuroscience, Inc. High frequency magnetic foot stimulation
US12017068B2 (en) 2022-05-27 2024-06-25 Spark Biomedical, Inc. Devices and methods for treating motion sickness using electrical stimulation
US12029893B1 (en) 2023-06-14 2024-07-09 Spark Biomedical, Inc. Wearable auricular neurostimulator and methods of use
US12280219B2 (en) 2017-12-31 2025-04-22 NeuroLight, Inc. Method and apparatus for neuroenhancement to enhance emotional response
US12290371B2 (en) 2019-02-07 2025-05-06 Inner Cosmos Inc. Intracalvarial BCI systems and methods for their making, implantation and use
US12311170B2 (en) 2020-05-04 2025-05-27 Btl Healthcare Technologies A.S. Device and method for unattended treatment of a patient
US12311114B2 (en) 2013-08-30 2025-05-27 Neuromod Devices Limited Method and apparatus for treating a neurological disorder
US12427307B2 (en) 2020-05-04 2025-09-30 Btl Healthcare Technologies A.S. Device and method for unattended treatment of a patient
US12485277B2 (en) 2020-01-14 2025-12-02 Inner Cosmos Inc. Devices, systems and methods for cortical stimulation
US12502527B2 (en) 2023-01-06 2025-12-23 Spark Biomedical, Inc. Devices and methods for treating stress and improving alertness using electrical stimulation

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016119654A1 (zh) * 2015-01-26 2016-08-04 周常安 生理反馈系统及发光装置
US10596378B2 (en) * 2016-10-18 2020-03-24 Joseph Rustick Method for treatment of depression using synaptic pathway training
US12403306B2 (en) 2017-10-23 2025-09-02 Cardiac Pacemakers, Inc. Electric field shaping leads for treatment of cancer
US11894148B2 (en) * 2017-12-22 2024-02-06 Electrocore, Inc. Systems and methods for treating patients with diseases associated with viruses
TWI667860B (zh) * 2018-02-09 2019-08-01 鉅旺生技股份有限公司 植入式醫材遠距離無線充電強化結構
CN109045468B (zh) * 2018-08-09 2022-05-24 西安科悦医疗技术有限公司 一种耳部迷走神经刺激系统及其装置
WO2020123704A1 (en) * 2018-12-13 2020-06-18 Livanova Usa, Inc. Neuromodulation therapy for auto-immune and inflammatory disorders
US12109412B2 (en) 2019-04-22 2024-10-08 Boston Scientific Scimed, Inc. Combination electrical and chemotherapeutic treatment of cancer
EP3958954B1 (en) * 2019-04-22 2024-04-24 Boston Scientific Scimed Inc. Electrical stimulation devices for cancer treatment
WO2020219517A2 (en) 2019-04-23 2020-10-29 Boston Scientific Scimed, Inc. Electrical stimulation for cancer treatment with internal and external electrodes
CN113747936B (zh) 2019-04-23 2024-06-18 波士顿科学国际有限公司 用于电刺激来治疗癌症的电极
JP7476231B2 (ja) 2019-04-23 2024-04-30 ボストン サイエンティフィック サイムド，インコーポレイテッド 温熱療法又は熱モニタと共に行われる電気刺激
US11065461B2 (en) 2019-07-08 2021-07-20 Bioness Inc. Implantable power adapter
WO2021173509A1 (en) 2020-02-24 2021-09-02 Boston Scientific Scimed, Inc. Systems and methods for treatment of pancreatic cancer
TWI894280B (zh) * 2020-05-26 2025-08-21 南韓商愛思阿爾法數字醫療科技有限公司 用以治療癌症惡病質之系統、用以治療癌症惡病質之運算系統及其操作方法、以及非暫態電腦可讀取媒體
WO2023091469A1 (en) * 2021-11-17 2023-05-25 The Board Of Trustees Of The Leland Stanford Junior University Targeting periosteal tissue for delivery of therapeutics

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6405079B1 (en) * 2000-09-22 2002-06-11 Mehdi M. Ansarinia Stimulation method for the dural venous sinuses and adjacent dura for treatment of medical conditions
US7003352B1 (en) * 2002-05-24 2006-02-21 Advanced Bionics Corporation Treatment of epilepsy by brain stimulation
US20070173908A1 (en) * 2006-01-20 2007-07-26 Cyberonics, Inc. Transcutaneous trigeminal nerve stimulation to treat motion sickness
US20110093033A1 (en) * 2009-10-16 2011-04-21 Stanford University Eliciting analgesia by transcranial electrical stimulation
US20110112603A1 (en) * 2009-10-05 2011-05-12 The Regents Of The University Of California Extracranial implantable devices, systems and methods for the treatment of neuropsychiatric disorders
US20140135886A1 (en) * 2010-12-14 2014-05-15 United States Government Department Of Veterans Affairs Devices, systems and methods for the treatment of medical disorders

Family Cites Families (107)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3279468A (en) 1963-05-14 1966-10-18 Vine Sidney Le Electrotherapeutic facial mask apparatus
US3709228A (en) 1971-01-07 1973-01-09 D Barker Apparatus for facial stimulation
US4233986A (en) 1978-07-18 1980-11-18 Agar Ginosar Electronics And Metal Products Apparatus and method for controlling pain by transcutaneous electrical stimulation (TES)
US4305402A (en) 1979-06-29 1981-12-15 Katims Jefferson J Method for transcutaneous electrical stimulation
US4635641A (en) 1985-10-16 1987-01-13 Murray Electronics Associates Limited Multi-element electrode
SU1718976A1 (ru) 1989-10-31 1992-03-15 1-Й Московский Медицинский Институт Им.И.М.Сеченова Способ купировани болей при невралгии тройничного нерва
RU2086227C1 (ru) 1994-04-05 1997-08-10 Российский научно-исследовательский нейрохирургический институт им.проф.А.Л.Поленова Способ лечения поражений нервно-сосудистых структур орбиты
JPH07289649A (ja) 1994-04-22 1995-11-07 Hayashibara Takeshi 眼神経の刺激信号発生装置
US5540734A (en) 1994-09-28 1996-07-30 Zabara; Jacob Cranial nerve stimulation treatments using neurocybernetic prosthesis
US5514175A (en) 1994-11-09 1996-05-07 Cerebral Stimulation, Inc. Auricular electrical stimulator
US5549734A (en) 1995-03-08 1996-08-27 Astec Industries, Inc. Baghouse cleaning method
JPH08299141A (ja) 1995-05-08 1996-11-19 Mori Mihoko 枕カバー
US5814095A (en) 1996-09-18 1998-09-29 Implex Gmbh Spezialhorgerate Implantable microphone and implantable hearing aids utilizing same
US6016449A (en) 1997-10-27 2000-01-18 Neuropace, Inc. System for treatment of neurological disorders
US20070060975A1 (en) 1999-07-08 2007-03-15 Mannheimer Jeffrey S Combination electrode-battery and programming assembly for a miniature wireless transcutaneous electrical neuro or muscular-stimulation unit
US7200446B2 (en) 1999-07-21 2007-04-03 Borkan William N Catheter leads for the intrathecal space and method of use
US6567702B1 (en) 1999-10-15 2003-05-20 The Board Of Trustees Of The Leland Stanford Junior University Eliciting analgesia by transcranial electrical stimulation
US6466822B1 (en) 2000-04-05 2002-10-15 Neuropace, Inc. Multimodal neurostimulator and process of using it
US7158832B2 (en) 2000-09-27 2007-01-02 Cvrx, Inc. Electrode designs and methods of use for cardiovascular reflex control devices
US6549808B1 (en) 2000-10-19 2003-04-15 Heinz R. Gisel Devices and methods for the transcutaneous delivery of ions and the electrical stimulation of tissue and cells at targeted areas in the eye
US6950707B2 (en) 2000-11-21 2005-09-27 Advanced Bionics Corporation Systems and methods for treatment of obesity and eating disorders by electrical brain stimulation and/or drug infusion
RU2185092C1 (ru) 2000-12-21 2002-07-20 Ремнев Андрей Геннадьевич Способ диагностики поражения первой и второй ветвей тройничного нерва
US20060064140A1 (en) 2001-01-30 2006-03-23 Whitehurst Todd K Methods and systems for stimulating a trigeminal nerve to treat a psychiatric disorder
US6735475B1 (en) 2001-01-30 2004-05-11 Advanced Bionics Corporation Fully implantable miniature neurostimulator for stimulation as a therapy for headache and/or facial pain
US6788975B1 (en) 2001-01-30 2004-09-07 Advanced Bionics Corporation Fully implantable miniature neurostimulator for stimulation as a therapy for epilepsy
US7171276B2 (en) 2001-06-29 2007-01-30 Abbott Laboratories Hydrogel and scrim assembly for use with electro-acupuncture device with stimulation electrodes
US20030045922A1 (en) 2001-08-29 2003-03-06 Nancy Northrop Skin treatment method and apparatus
US20140046407A1 (en) 2001-08-31 2014-02-13 Bio Control Medical (B.C.M.) Ltd. Nerve stimulation techniques
US8565896B2 (en) 2010-11-22 2013-10-22 Bio Control Medical (B.C.M.) Ltd. Electrode cuff with recesses
US6954668B1 (en) 2001-10-11 2005-10-11 Cuozzo John W Apparatus and method for intra-oral stimulation of the trigeminal nerve
US7689277B2 (en) 2002-03-22 2010-03-30 Leptos Biomedical, Inc. Neural stimulation for treatment of metabolic syndrome and type 2 diabetes
US20030195588A1 (en) 2002-04-16 2003-10-16 Neuropace, Inc. External ear canal interface for the treatment of neurological disorders
JP2003339884A (ja) * 2002-05-31 2003-12-02 Fes:Kk 顔面電気刺激装置
US7158834B2 (en) 2002-06-13 2007-01-02 Atlantic Medical, Inc. Method and apparatus for performing microcurrent stimulation (MSC) therapy
AU2003265509A1 (en) 2002-08-19 2004-03-03 Arizona Board Regents Neurostimulator
US20040138097A1 (en) 2002-11-01 2004-07-15 Bahman Guyuron Method and treatment for treating and preventing pain associated with compression of a nerve
WO2005000090A2 (en) 2003-05-30 2005-01-06 Medi-Screw, Inc. Medical implant systems
US8190248B2 (en) 2003-10-16 2012-05-29 Louisiana Tech University Foundation, Inc. Medical devices for the detection, prevention and/or treatment of neurological disorders, and methods related thereto
WO2005062829A2 (en) 2003-12-19 2005-07-14 Advanced Bionics Corporation Skull-mounted electrical stimulation system and method for treating patients
EP1706178B1 (en) 2004-01-22 2013-04-24 Rehabtronics Inc. System for routing electrical current to bodily tissues via implanted passive conductors
US7844344B2 (en) 2004-03-30 2010-11-30 Medtronic, Inc. MRI-safe implantable lead
US7565197B2 (en) 2004-06-18 2009-07-21 Medtronic, Inc. Conditional requirements for remote medical device programming
WO2006019764A2 (en) 2004-07-15 2006-02-23 Northstar Neuroscience, Inc. Systems and methods for enhancing or affecting neural stimulation efficiency and/or efficacy
US20060050912A1 (en) 2004-09-09 2006-03-09 Earcraft, Inc. Shell and tip for hearing aid
WO2006034305A2 (en) 2004-09-21 2006-03-30 University Of Florida Research Foundation, Inc. Multiple lead method for deep brain stimulation
JP2008516696A (ja) 2004-10-18 2008-05-22 ルイジアナ テック ユニバーシティ ファウンデーション 神経障害の検出、予防および／または治療のための医療装置ならびにその医療装置に関連する方法
US7685817B2 (en) 2004-10-18 2010-03-30 Ceti, Inc. Method and system for providing a rotational output using a non-combustion heat source
US7613520B2 (en) 2004-10-21 2009-11-03 Advanced Neuromodulation Systems, Inc. Spinal cord stimulation to treat auditory dysfunction
FR2877583B1 (fr) 2004-11-10 2007-05-11 Patrick Cosson Dispositif d'electrotherapie
EP1671670A1 (fr) 2004-12-14 2006-06-21 STX Sprl Appareil pour l'electro-inhibition des muscles de la face
US8825166B2 (en) 2005-01-21 2014-09-02 John Sasha John Multiple-symptom medical treatment with roving-based neurostimulation
DE102005003735B4 (de) 2005-01-26 2008-04-03 Cerbomed Gmbh Vorrichtung zur transkutanen Stimulation eines Nervs des menschlichen Körpers
US8700163B2 (en) 2005-03-04 2014-04-15 Cyberonics, Inc. Cranial nerve stimulation for treatment of substance addiction
JP5086235B2 (ja) 2005-03-09 2012-11-28 クティセンセ アクティーゼルスカブ マイクロ電子システムを内部に埋め込んだ三次元接着デバイス
US7853321B2 (en) 2005-03-14 2010-12-14 Boston Scientific Neuromodulation Corporation Stimulation of a stimulation site within the neck or head
US7920915B2 (en) 2005-11-16 2011-04-05 Boston Scientific Neuromodulation Corporation Implantable stimulator
US20060206165A1 (en) * 2005-03-14 2006-09-14 Jaax Kristen N Occipital nerve stimulation to treat headaches and other conditions
EP1861160B1 (en) 2005-03-24 2011-11-16 Metacure Limited Wireless leads for gastrointestinal tract applications
US7499752B2 (en) 2005-07-29 2009-03-03 Cyberonics, Inc. Selective nerve stimulation for the treatment of eating disorders
US20070025608A1 (en) 2005-07-29 2007-02-01 Cyberonics, Inc. Enhancing intrinsic neural activity using a medical device to treat a patient
JP2007054299A (ja) 2005-08-24 2007-03-08 Sharp Corp 電気治療装置、およびそれを構成するためのシステム
JP2007061267A (ja) 2005-08-30 2007-03-15 Nova Medico:Kk 鼻炎又は結膜炎治療器具
US20070150027A1 (en) * 2005-12-22 2007-06-28 Rogers Lesco L Non-invasive device and method for electrical stimulation of neural tissue
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
ATE441452T1 (de) 2006-01-23 2009-09-15 Koninkl Philips Electronics Nv Verbesserte biomedizinische elektrode zur längeren anwendung bei patienten mit einem deckel oder schnapper, der von der haltedichtung isoliert ist
US7801601B2 (en) 2006-01-27 2010-09-21 Cyberonics, Inc. Controlling neuromodulation using stimulus modalities
GB0603464D0 (en) 2006-02-21 2006-04-05 Goreszeniuk Teodor Improvements in & relating to external neurostimulation
EP3069752B1 (en) 2006-03-29 2018-03-28 Dignity Health Microburst electrical stimulation of cranial nerves for the treatment of medical conditions
JP2009537226A (ja) 2006-05-18 2009-10-29 エヌディーアイ メディカル， エルエルシー 機能的または治療的神経刺激を提供する携帯アッセンブリ、システム、および方法
US20080128215A1 (en) 2006-05-24 2008-06-05 Gershon Nowitz Portable Scissor Lift
US8909342B2 (en) * 2006-08-15 2014-12-09 Andres M. Lozano Method for treating eating disorders
US7940933B2 (en) 2006-08-18 2011-05-10 Medtronic, Inc. Secure telemetric link
US7774072B2 (en) 2006-11-30 2010-08-10 Medtronic, Inc. Attached implantable medical elongated members
US20080140151A1 (en) 2006-12-11 2008-06-12 Brodkey Jason A Nerve stimulation apparatus and method for the treatment of head pain
US7890178B2 (en) 2006-12-15 2011-02-15 Medtronic Xomed, Inc. Method and apparatus for assisting deglutition
US9913593B2 (en) 2006-12-27 2018-03-13 Cyberonics, Inc. Low power device with variable scheduling
US8696724B2 (en) 2007-01-11 2014-04-15 Scion Neurostim, Llc. Devices for vestibular or cranial nerve stimulation
US20080171929A1 (en) 2007-01-11 2008-07-17 Katims Jefferson J Method for standardizing spacing between electrodes, and medical tape electrodes
JP4961558B2 (ja) 2007-03-30 2012-06-27 国立大学法人信州大学 三叉神経固有知覚枝刺激装置
WO2008128215A1 (en) 2007-04-13 2008-10-23 Alejandro Covalin Apparatus and method for the treatment of headache
US20080262566A1 (en) 2007-04-23 2008-10-23 Boston Scientific Neuromodulation Corporation Methods and systems of treating medication overuse headache
US8954162B2 (en) * 2007-04-25 2015-02-10 Medtronic, Inc. Medical device implantation
CN101686808B (zh) 2007-07-06 2012-11-28 皇家飞利浦电子股份有限公司 屏蔽的生物医学电极贴片
EP2195084A4 (en) 2007-09-26 2010-10-20 Univ Duke METHOD FOR TREATING PARKINSON DISEASE AND OTHER MOTION FLUCTUATIONS
US9180303B2 (en) 2007-10-24 2015-11-10 Medtronic, Inc. Transmission of power source usage information over a network
US8849407B1 (en) 2008-01-04 2014-09-30 Yuri P. Danilov Non-invasive neuromodulation (NINM) for rehabilitation of brain function
EP2092951A1 (fr) * 2008-02-20 2009-08-26 Stx-Med Sprl Appareil pour le traîtement électrothérapeutique des céphalées de tension
CA2724234A1 (en) * 2008-05-13 2009-11-19 Cerbomed Gmbh Method to enhance neural tissue operation
US20090326602A1 (en) * 2008-06-27 2009-12-31 Arkady Glukhovsky Treatment of indications using electrical stimulation
WO2010009141A1 (en) 2008-07-14 2010-01-21 Arizona Board Of Regents For And On Behalf Of Arizona State University Methods and devices for modulating cellular activity using ultrasound
US20100030227A1 (en) 2008-07-31 2010-02-04 Medtronic, Inc. Medical lead implantation
US8512715B2 (en) 2008-08-14 2013-08-20 The Cleveland Clinic Foundation Apparatus and method for treating a neuromuscular defect
CN102202725B (zh) 2008-10-21 2016-06-01 Med-El电气医疗器械有限公司 用于面神经刺激的系统和方法
US8666498B2 (en) 2008-10-27 2014-03-04 Serene Medical, Inc. Treatment of headache
DE102008043973B4 (de) 2008-11-21 2011-12-01 Burkhard Brocke Vorrichtung zur transkraniellen Neurostimulation
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
US9339645B2 (en) 2010-05-02 2016-05-17 Nervive, Inc. Modulating function of the facial nerve system or related neural structures via the ear
US8702584B2 (en) 2010-05-12 2014-04-22 Cefaly Technology Sprl Neurostimulation method to induce relaxation or sleep
WO2012075192A2 (en) 2010-11-30 2012-06-07 The Regents Of The University Of California Pulse generator for cranial nerve stimulation
EP2651497B1 (en) 2010-12-14 2019-02-20 The Regents of The University of California Extracranial implantable systems for the treatment of medical disorders
US20120203301A1 (en) 2011-02-07 2012-08-09 Advanced Neuromodulation Systems, Inc. Methods using trigeminal nerve stimulation to treat neurological diseases
GB2505808A (en) 2011-05-11 2014-03-12 Alejandro Covalin Headache-treatment device with gel dispensing kit and method
BE1020458A3 (fr) 2012-01-13 2013-10-01 Stx Med Sprl Appareil electronique autonome et dipositif de fixation de celui-ci sur une electrode localisee au niveau de la tete pour une utilisation en position couchee du patient.
JP2015513980A (ja) 2012-04-05 2015-05-18 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア 脳神経刺激のための皮下電極
US20140039572A1 (en) 2012-08-03 2014-02-06 Boston Scientific Neuromodulation Corporation System and method for treating depression and epilepsy
CN103830841B (zh) 2012-11-26 2018-04-06 赛威医疗公司 可穿戴的经皮肤的电刺激设备及其使用方法
US10220211B2 (en) 2013-01-22 2019-03-05 Livanova Usa, Inc. Methods and systems to diagnose depression

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6405079B1 (en) * 2000-09-22 2002-06-11 Mehdi M. Ansarinia Stimulation method for the dural venous sinuses and adjacent dura for treatment of medical conditions
US7003352B1 (en) * 2002-05-24 2006-02-21 Advanced Bionics Corporation Treatment of epilepsy by brain stimulation
US20070173908A1 (en) * 2006-01-20 2007-07-26 Cyberonics, Inc. Transcutaneous trigeminal nerve stimulation to treat motion sickness
US20110112603A1 (en) * 2009-10-05 2011-05-12 The Regents Of The University Of California Extracranial implantable devices, systems and methods for the treatment of neuropsychiatric disorders
US20110218590A1 (en) * 2009-10-05 2011-09-08 The Regents Of The University Of California Devices, systems and methods for treatment of neuropsychiatric disorders
US8380315B2 (en) * 2009-10-05 2013-02-19 The Regents Of The University Of California Devices, systems and methods for treatment of neuropsychiatric disorders
US8700164B2 (en) * 2009-10-05 2014-04-15 The Regents Of The University Of California Devices, systems and methods for treatment of neuropsychiatric disorders
US8958880B2 (en) * 2009-10-05 2015-02-17 The Regents Of The University Of California Extracranial implantable devices, systems and methods for the treatment of neuropsychiatric disorders
US20110093033A1 (en) * 2009-10-16 2011-04-21 Stanford University Eliciting analgesia by transcranial electrical stimulation
US20140135886A1 (en) * 2010-12-14 2014-05-15 United States Government Department Of Veterans Affairs Devices, systems and methods for the treatment of medical disorders

Cited By (83)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9682236B2 (en) 2009-10-05 2017-06-20 The Regents Of The University Of California Devices, systems and methods for treatment of neuropsychiatric disorders
US10639468B2 (en) 2009-10-05 2020-05-05 The Regents Of The University Of California Devices, systems and methods for the treatment of medical disorders
US10322283B2 (en) 2009-10-05 2019-06-18 The Regents Of The University Of California Devices, systems and methods for treatment of neuropsychiatric disorders
US9238139B2 (en) 2009-10-05 2016-01-19 The Regents Of The University Of California Devices, systems and methods for treatment of neuropsychiatric disorders
US10238862B2 (en) 2009-10-05 2019-03-26 The Regents Of The University Of California Extracranial implantable devices, systems and methods for the treatment of medical disorders
US10195435B2 (en) 2009-10-05 2019-02-05 The Regents Of The University Of California Extracranial implantable devices, systems and methods for the treatment of neuropsychiatric disorders
US10058704B2 (en) 2009-10-05 2018-08-28 The Regents Of The University Of California Systems, devices and methods for the treatment of neurological disorders and conditions
US9504827B2 (en) 2009-10-05 2016-11-29 The Regents Of The University Of California Systems, devices and methods for the treatment of neurological disorders and conditions
US9511223B2 (en) 2009-10-05 2016-12-06 The Regents Of The University Of California Extracranial implantable devices, systems and methods for the treatment of neuropsychiatric disorders
US10016601B2 (en) 2010-11-30 2018-07-10 The Regents Of The University Of California Pulse generator for cranial nerve stimulation
US20140135886A1 (en) * 2010-12-14 2014-05-15 United States Government Department Of Veterans Affairs Devices, systems and methods for the treatment of medical disorders
US10035013B2 (en) * 2012-04-05 2018-07-31 The Regents Of The University Of California Subcutaneous electrodes for cranial nerve stimulation
US20150119898A1 (en) * 2012-04-05 2015-04-30 Teh Regents Of The University Of California Subcutaneous electrodes for cranial nerve stimulation
US20160045739A1 (en) * 2013-03-11 2016-02-18 Ohio State Innovation Foundation Systems for treating anxiety and anxiety-associated disorders
US9731127B2 (en) * 2013-04-24 2017-08-15 Neurosigma, Inc. Modulation of autonomic nervous system activity and integrated electrode assemblies for trigeminal neurostimulation
US20160184585A1 (en) * 2013-04-24 2016-06-30 Neurosigma, Inc. Modulation of Autonomic Nervous System Activity and Integrated Electrode Assemblies for Trigeminal Neurostimulation
US9974968B2 (en) 2013-08-14 2018-05-22 Syntilla Medical LLC Implantable head mounted neurostimulation system for head pain
US9042991B2 (en) 2013-08-14 2015-05-26 Syntilla Medical LLC Implantable head mounted neurostimulation system for head pain
US9839777B2 (en) 2013-08-14 2017-12-12 Syntilla Medical LLC Implantable neurostimulation lead for head pain
US9427566B2 (en) 2013-08-14 2016-08-30 Syntilla Medical LLC Implantable neurostimulation lead for head pain
US9884190B2 (en) 2013-08-14 2018-02-06 Syntilla Medical LLC Surgical method for implantable head mounted neurostimulation system for head pain
US12311114B2 (en) 2013-08-30 2025-05-27 Neuromod Devices Limited Method and apparatus for treating a neurological disorder
US9498635B2 (en) 2013-10-16 2016-11-22 Syntilla Medical LLC Implantable head located radiofrequency coupled neurostimulation system for head pain
US10946205B2 (en) 2013-10-23 2021-03-16 Nuxcel, Inc. Implantable head mounted neurostimulation system for head pain
US11623100B2 (en) 2013-10-23 2023-04-11 Shiratronics, Inc. Low profile head-located neurostimulator
US9889308B2 (en) 2013-10-23 2018-02-13 Syntilla Medical LLC Implantable head located radiofrequency coupled neurostimulation system for head pain
US11400302B2 (en) 2013-10-23 2022-08-02 Shiratronics, Inc. Surgical method for implantable neurostimulation system for pain
US10960215B2 (en) 2013-10-23 2021-03-30 Nuxcel, Inc. Low profile head-located neurostimulator and method of fabrication
US11612756B2 (en) 2013-10-23 2023-03-28 Shiratronics, Inc. Implantable head mounted neurostimulation system for head pain
US12070610B2 (en) 2013-10-23 2024-08-27 Shiratronics, Inc. Low profile head-located neurostimulator
US9498636B2 (en) 2013-10-23 2016-11-22 Syntilla Medical LLC Implantable head located radiofrequency coupled neurostimulation system for head pain
US10258805B2 (en) 2013-10-23 2019-04-16 Syntilla Medical, Llc Surgical method for implantable head mounted neurostimulation system for head pain
US11357995B2 (en) 2013-10-23 2022-06-14 Shiratronics, Inc. Implantable head located radiofrequency coupled neurostimulation system for head pain
US10850112B2 (en) 2013-10-23 2020-12-01 Nuxcel, Inc. Surgical method for implantable neurostimulation system for pain
US10695571B2 (en) 2013-10-23 2020-06-30 Nuxcel, Inc. Implantable head located radiofrequency coupled neurostimulation system for head pain
US9539432B2 (en) 2013-10-23 2017-01-10 Syntilla Medical LLC Implantable head located radiofrequency coupled neurostimulation system for head pain
US11040204B2 (en) 2015-11-19 2021-06-22 Boston Scientific Neuromodulation Corporation Neuromodulation for neuroinflammation treatments with parameters controlled using biomarkers
US20170143972A1 (en) * 2015-11-19 2017-05-25 Boston Scientific Neuromodulation Corporation Neuromodulation for neuroinflammation treatments with parameters controlled using biomarkers
US11957911B2 (en) 2015-11-19 2024-04-16 Boston Scientific Neuromodulation Corporation Neuromodulation for neuroinflammation treatments with parameters controlled using biomarkers
US9833629B2 (en) 2016-01-06 2017-12-05 Syntilla Medical LLC Charging system providing adjustable transmitted power to improve power efficiency within an implanted device
US10022549B2 (en) 2016-01-06 2018-07-17 Syntilla Medical LLC Charging system incorporating data communication and power transmission using opposite polarity half-wave rectified signals received by implanted device
US9707406B1 (en) 2016-01-06 2017-07-18 Syntilla Medical LLC Charging system incorporating receive coil de-tuning within an implanted device
US9713726B1 (en) 2016-01-06 2017-07-25 Syntilla Medical LLC Charging system incorporating feedback excitation control of resonant coil driver amplifier
US9717917B2 (en) 2016-01-06 2017-08-01 Syntilla Medical LLC Charging system incorporating independent charging and communication with multiple implanted devices
US9757575B2 (en) 2016-01-06 2017-09-12 Syntilla Medical LLC Charging system including transmit coil current sensing circuitry
US9839788B2 (en) 2016-01-06 2017-12-12 Syntilla Medical LLC Charging system incorporating bi-directional communication with implanted device
US10406360B2 (en) * 2016-09-13 2019-09-10 Richard Charles Niemtzow Electrical acupuncture eye treatment
US11724120B2 (en) * 2016-10-17 2023-08-15 Wave Neuroscience, Inc. High frequency magnetic foot stimulation
US11723579B2 (en) 2017-09-19 2023-08-15 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement
US12076563B2 (en) * 2017-09-29 2024-09-03 Cochlear Limited Hearing prosthesis
US20230166110A1 (en) * 2017-09-29 2023-06-01 Cochlear Limited Hearing prosthesis
US11717686B2 (en) 2017-12-04 2023-08-08 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement to facilitate learning and performance
WO2019111261A1 (en) * 2017-12-06 2019-06-13 Technion Research & Development Foundation Limited Methods of neural inhibition for treating bowel diseases and disorders
US11724119B2 (en) 2017-12-06 2023-08-15 Technion Research & Development Foundation Limited Methods of neural inhibition for treating bowel diseases and disorders
US11273283B2 (en) 2017-12-31 2022-03-15 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement to enhance emotional response
US12397128B2 (en) 2017-12-31 2025-08-26 NeuroLight, Inc. Method and apparatus for neuroenhancement to enhance emotional response
US12280219B2 (en) 2017-12-31 2025-04-22 NeuroLight, Inc. Method and apparatus for neuroenhancement to enhance emotional response
US11478603B2 (en) 2017-12-31 2022-10-25 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement to enhance emotional response
US12383696B2 (en) 2017-12-31 2025-08-12 NeuroLight, Inc. Method and apparatus for neuroenhancement to enhance emotional response
US11318277B2 (en) 2017-12-31 2022-05-03 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement to enhance emotional response
US11364361B2 (en) 2018-04-20 2022-06-21 Neuroenhancement Lab, LLC System and method for inducing sleep by transplanting mental states
US11467665B2 (en) 2018-06-14 2022-10-11 Meron Gribetz Virtual user interface system and methods for use thereof
US11452839B2 (en) 2018-09-14 2022-09-27 Neuroenhancement Lab, LLC System and method of improving sleep
US11623088B2 (en) 2018-12-10 2023-04-11 Spark Biomedical, Inc. Devices and methods for the treatment of substance use disorders
US11351370B2 (en) 2018-12-10 2022-06-07 Spark Biomedical, Inc. Devices and methods for treating cognitive dysfunction and depression using electrical stimulation
US10967182B2 (en) 2018-12-10 2021-04-06 Spark Biomedical, Inc. Devices and methods for reducing inflammation using electrical stimulation
US12290371B2 (en) 2019-02-07 2025-05-06 Inner Cosmos Inc. Intracalvarial BCI systems and methods for their making, implantation and use
WO2021011165A1 (en) * 2019-07-14 2021-01-21 Spark Biomedical, Inc. Systems and methods for delivering therapy using an auricular stimulation device
US20210023372A1 (en) * 2019-07-22 2021-01-28 Ismail Mohammed Yousif Musallam Neuromodulation for treatment of brain and eye strokes and/or acute dysregulated reduced cerebral or ocular blood flow
US12179021B2 (en) 2019-07-22 2024-12-31 Ismail Mohammed Yousif Musallam Neuromodulation for treatment of brain and eye strokes and/or acute dysregulated reduced cerebral or ocular blood flow
US11911620B2 (en) * 2019-07-22 2024-02-27 Ismail Mohammed Yousif Musallam Neuromodulation for treatment of brain and eye strokes and/or acute dysregulated reduced cerebral or ocular blood flow
US11235156B2 (en) 2019-09-11 2022-02-01 Bose Corporation Wearable audio device with vagus nerve stimulation
US11241574B2 (en) 2019-09-11 2022-02-08 Bose Corporation Systems and methods for providing and coordinating vagus nerve stimulation with audio therapy
US12485277B2 (en) 2020-01-14 2025-12-02 Inner Cosmos Inc. Devices, systems and methods for cortical stimulation
US12311170B2 (en) 2020-05-04 2025-05-27 Btl Healthcare Technologies A.S. Device and method for unattended treatment of a patient
US12427307B2 (en) 2020-05-04 2025-09-30 Btl Healthcare Technologies A.S. Device and method for unattended treatment of a patient
US20220184405A1 (en) * 2020-12-11 2022-06-16 Advanced Neuromodulation Systems, Inc. Systems and methods for labeling data in active implantable medical device systems
WO2022187592A1 (en) * 2021-03-04 2022-09-09 Washington University Transcutaneous auricular vagal nerve stimulation for subarachnoid hemorrhages
US12017068B2 (en) 2022-05-27 2024-06-25 Spark Biomedical, Inc. Devices and methods for treating motion sickness using electrical stimulation
US12214193B2 (en) 2022-05-27 2025-02-04 Spark Biomedical, Inc. Devices and methods for treating motion sickness using electrical stimulation
US12502527B2 (en) 2023-01-06 2025-12-23 Spark Biomedical, Inc. Devices and methods for treating stress and improving alertness using electrical stimulation
US12337167B2 (en) 2023-06-14 2025-06-24 Spark Biomedical, Inc. Wearable auricular neurostimulator and methods of use
US12029893B1 (en) 2023-06-14 2024-07-09 Spark Biomedical, Inc. Wearable auricular neurostimulator and methods of use

Also Published As

Publication number Publication date
EP2651497A4 (en) 2014-06-04
CA2821721A1 (en) 2012-06-21
JP2014501139A (ja) 2014-01-20
EP2651497B1 (en) 2019-02-20
US20180229029A1 (en) 2018-08-16
WO2012082961A3 (en) 2012-08-09
US10238862B2 (en) 2019-03-26
US20170348521A1 (en) 2017-12-07
EP2651497A2 (en) 2013-10-23
WO2012082961A2 (en) 2012-06-21
JP6559395B2 (ja) 2019-08-14

Similar Documents

Publication Publication Date Title
US10238862B2 (en) Extracranial implantable devices, systems and methods for the treatment of medical disorders
US10639468B2 (en) Devices, systems and methods for the treatment of medical disorders
US20230093826A1 (en) Devices, systems and methods for the treatment of neurological disorders and neuropsychiatric disorders
JP2014501139A5 (enExample)
JP2014501138A5 (enExample)
AU2015264876A1 (en) Devices, Systems and Methods for Treatment of Neuropsychiatric Disorders

Legal Events

Date Code Title Description
AS Assignment

Owner name: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, CALIF

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:COOK, IAN A.;DEGIORGIO, CHRISTOPHER M.;MILLER, PATRICK;SIGNING DATES FROM 20120104 TO 20120302;REEL/FRAME:030806/0904

AS Assignment

Owner name: NEUROSIGMA, INC., CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:EKCHIAN, LEON;REEL/FRAME:039124/0023

Effective date: 20160708

AS Assignment

Owner name: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, CALIF

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:DE SALLES, ANTONIO;REEL/FRAME:043096/0190

Effective date: 20110429

Owner name: UNITED STATES GOVERNMENT DEPARTMENT OF VETERANS AF

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:DE SALLES, ANTONIO;REEL/FRAME:043096/0190

Effective date: 20110429

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO PAY ISSUE FEE