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WO2013165697A1 - Neuromodulation du trijumeau indirecte et non invasive pour le traitement d'une maladie - Google Patents

Neuromodulation du trijumeau indirecte et non invasive pour le traitement d'une maladie Download PDF

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Publication number
WO2013165697A1
WO2013165697A1 PCT/US2013/037147 US2013037147W WO2013165697A1 WO 2013165697 A1 WO2013165697 A1 WO 2013165697A1 US 2013037147 W US2013037147 W US 2013037147W WO 2013165697 A1 WO2013165697 A1 WO 2013165697A1
Authority
WO
WIPO (PCT)
Prior art keywords
neuromodulating
done
stimulating
nerve
electrode
Prior art date
Application number
PCT/US2013/037147
Other languages
English (en)
Inventor
Denise Barbut
Allan Rozenberg
Axel Heinemann
Original Assignee
Vigilant Medical Solutions, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Vigilant Medical Solutions, Inc. filed Critical Vigilant Medical Solutions, Inc.
Publication of WO2013165697A1 publication Critical patent/WO2013165697A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0526—Head electrodes
    • A61N1/0546—Nasal electrodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36014—External stimulators, e.g. with patch electrodes
    • A61N1/3603—Control systems
    • A61N1/36031—Control systems using physiological parameters for adjustment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
    • A61F7/12—Devices for heating or cooling internal body cavities
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy

Definitions

  • the present invention relates to a system and method for non-invasive trigeminal neuro-modulation.
  • the invention involves non-invasively stimulating the trigeminal nerve and the accompanying autonomic fibers within the nasal or oral cavity.
  • DBS Deep brain stimulation
  • VNS Vagal nerve stimulation
  • epilepsy also requires a surgical procedure to position the stimulating wire around the vagus nerve in the neck.
  • stimulating sympathetic and parasympathetic ganglia requires invasive procedures for access. For example, stimulating the cervical chain requires a cut down in the neck and stimulating the sphenopalatine ganglion requires needle insertion through the mucosa of the palate.
  • the trigeminal branches to be accessed for neuromodulation can involve the surface branches of any of the 3 divisions of the trigeminal nerve, ophthalmic, maxillary and mandibular nerves. Further, the trigeminal and autonomic ganglia cannot be accessed non-invasively but the postganglionic fibers can be stimulated non-invasively by direct contact at the nerve endings.
  • the method in accordance with the invention stimulates the trigeminal nerve and the accompanying autonomic fibers within the nasal or oral cavity, without having precise knowledge of the position of the catheter.
  • a method of neuromodulation of postganglionic nerve fibers that does not require direct contact with the nerve or the ganglion is provided.
  • a method of non-invasive stimulation of the trigeminal nerve for the purpose of increasing cerebral blood flow in cerebral ischemia is provided.
  • the modulation may be performed non- invasively without requiring implantation or a surgical procedure.
  • a method of non-invasively stimulating the trigeminal nerve for the purpose of increasing cerebral blood flow in Alzheimer's disease is provided.
  • a method of non-invasively stimulating the trigeminal nerve for the purpose of decreasing neurogenic inflammation is provided.
  • the trigeminal nerve and the accompanying autonomic fibers within the nasal or oral cavity are modulated using ultrasound, cryotherapy, radiofrequency, heat therapy, electrically, electromagnetic wave mediated treatment and combinations of the foregoing.
  • the stimulation may be done in the nose, the mouth, any of the cutaneous or mucosal divisions of the three branches of the trigeminal nerve, and combinations of the foregoing.
  • the non-invasive stimulation of the trigeminal nerve may be done for the purpose of decreasing neurogenic inflammation in the lung, such as acute respiratory distress syndrome and for increasing or decreasing blood pressure.
  • an apparatus and method for non- invasively stimulating the trigeminal nerve to treat migraine or other forms of headache is provided.
  • a method of neuromodulating post-ganglionic nerve fibers in a patient comprising: non-directly contacting of the nerve or the ganglion.
  • a method of neuromodulating a nerve comprising: non-invasively stimulating a trigeminal nerve of a patient; and increasing cerebral blood flow. 19. The method of clause 18 wherein the stimulating is done in any of the three divisions of the trigeminal nerve.
  • a method of neuromodulating a nerve comprising: non-invasively stimulating a trigeminal nerve in a patient; and increasing cerebral blood flow in cerebral ischemia.
  • a method of neuromodulating a nerve comprising: non-invasively stimulating the trigeminal nerve; and increasing cerebral blood flow in patients having Alzheimer's disease.
  • a method of neuromodulating a nerve comprising: non-invasively stimulating a trigeminal nerve of a patient; and decreasing neurogenic inflammation.
  • a method of neuromodulating a nerve comprising: non-invasively stimulating a trigeminal nerve of a patient; and decreasing neurogenic inflammation in a brain of the patient suffering from stroke, head injury or cardiac arrest.
  • a method of neuromodulating a nerve comprising: non-invasively stimulating a trigeminal nerve of a patient; and decreasing neurogenic inflammation in the lung wherein said neurogenic inflammation is caused by acute respiratory stress syndrome.
  • a method of neuromodulating a nerve comprising: non-invasively stimulating a trigeminal nerve; and decreasing inflammation in a medical condition of a patient.
  • a method of neuromodulating a nerve comprising: non-invasively stimulating a trigeminal nerve of a patient; and increasing or decreasing blood pressure of the patient.
  • a method of modulating a trigeminal nerve of a patient comprising: non- invasively stimulating the trigeminal nerve; and increasing cerebral blood flow wherein the absorption of medication following oro-nasal or facial delivery is enhanced.
  • a device comprising a stimulating electrode configured to contact the mucous membranes of the nose or mouth to neuromodulate the trigeminal nerve; and a conductive gel in contact with the electrode for enhancing electrical contact of said electrode.
  • conductive gel is a hydrogel which is formed around the electrode wire.
  • a device comprising: a plurality of stimulating electrodes configured to contact a portion of a skin of a patient over any of three divisions of a trigeminal nerve wherein the electrode contact is enhanced by means of a conductive gel.
  • conductive gel is a hydrogel which is formed around the electrode wire.
  • conductive gel contains a medication.
  • a method of neuromodulating a nerve comprising non-invasively stimulating a trigeminal nerve; and dissipating the effects of a migraine headache.
  • FIG. 1 is a graph illustrating the effect of non-specific intranasal electrical stimulation on cerebral blood flow.
  • FIG. 2 is a perspective view of an intranasal delivery catheter for noninvasive neuromodulation of the trigeminal nerve and associated autonomic fibers in accordance with the invention.
  • FIG. 3 is a perspective view of another aspect of an intranasal device for non-invasive neuromodulation of the trigeminal nerve and associated autonomic fibers in accordance with the invention.
  • FIG. 4 is an illustration of the device of FIG. 4 inserted in intranasal cavity including a stimulator with electrodes in accordance with the invention. DETAILED DESCRIPTION OF THE INVENTION
  • the method in accordance with the invention does not involve an invasive procedure or surgical procedure. There is no breach of the skin or of the mucous membrane, no direct contact with a ganglion or a post-ganglionic nerve and no requirement for implantation of the stimulating electrode.
  • a stimulation wire is positioned within the nasal cavity, preferably several centimeters beyond the entrance to the nares and stimulation performed.
  • the wires can be held in place by a variety of devices for the duration of the stimulation and then removed.
  • the method has several advantages. Firstly, it would allow access to anatomically difficult locations and enable the procedure to be performed even by those not entirely familiar with the anatomy; secondly it would constitute a totally non-invasive method of neuromodulation, without any breach of skin or mucous membrane. Thirdly, it would enable treatment of a variety of conditions outside of catheterization laboratories and in places such as emergency rooms or ambulances.
  • the inventors of the present invention have tested this method of neuromodulation intranasally and determined that stimulation "at a distance," as hereinafter disclosed, increases cerebral blood flow.
  • Stimulating catheters were placed about 1cm into the nares in the rat and stimulation performed at varying stimulation parameters. Cerebral blood flow was measured in the brain using cortical Laser Doppler technique.
  • stimulation at a distance from any of the known trigeminal branches increases cerebral blood flow in a dose-dependent fashion.
  • the increase was observed at 5-7V, increased at 10V and increased further at 20V.
  • Response occurred within seconds of initiating the stimulation and returned to baseline values immediately after discontinuing the stimulation.
  • non-invasive trigeminal stimulation at a distance from the post-ganglionic nerve fibers increases cerebral blood flow in the rat
  • the method in accordance with the invention may also be used to treat other conditions non-invasively.
  • Such conditions may include hypertension, neurovascular conditions such as migraine or neurogenic inflammation as might occur after head injury, cardiac arrest or stroke, or even seizure disorders.
  • the method in accordance with the invention is disclosed herein as being performed intranasally, it may also be performed intra- orally or over the anterior cranium and face or in any of the cutaneous dermatomes of the trigeminal nerve including the back of the pinna, the forehead or temple, the gums or palate and the skin over the face.
  • the stimulating electrode may also be positioned in proximity of the target neural structure by being fastened alongside nasal prongs for gas delivery. Patients requiring oxygen or other gases, such as volatile anesthetic agents, may simultaneously be positioned for neuromodulation if the need arises.
  • the electrode may be attached to a securing device such as a spring loaded nasal septal clip as best seen in FIGS. 3 and 4 to keep the electrode in position during the modulation.
  • Stimulating branches of cranial nerves containing autonomic nerve fibers can generate a neurovascular response such as subcutaneous vascular dilatation. This may potentially, increase the absorption of drugs transcutaneously or transmucosally.
  • a conductive (and/or medicated) gel may be placed in the location being stimulated separately from the stimulating wire or may be delivered through a second lumen on the catheter containing the stimulating wire.
  • the branches of the trigeminal nerve may be accessed in this manner and stimulated without penetration through the nasal or oral mucosa or facial skin and without directly contacting the target nerve.
  • the stimulator electrode would be positioned in close proximity of the nerve branch in the nose or mouth or on the surface of the skin following placement of a conductive gel containing medication. Following the discontinuation of the stimulation, the stimulator electrode would be easily removed since it was never in direct contact with the tissue in question.
  • the pulse duration may be between 0.1-20 millisecond, preferably 0.2-2 millisecond, and more preferably 0.5 millisecond.
  • the duration of the stimulation may be 3 seconds to 24 hours.
  • the degree of stimulation may be coupled to feedback from cerebral or systemic physiologic parameters. For example, when stimulating the forehead or the retro-auricular space, feedback from cerebral oximetry or EEG may be used to modify the stimulation parameters. Furthermore, the stimulating wire may be physically coupled to the EEG or oximetry patch.
  • the neuromodulation technique in accordance with the invention is limited to electrical stimulation but may also include ultrasound, radiofrequency, cryotherapy, heat treatment, infrared, ultraviolet or other electromagnetic spectrum frequencies as well as other methods of activating nerves.
  • cerebral blood flow using the inventive method of stimulation may also be of value in chronic conditions involving diminished blood flow, such as Alzheimer's or other dementias or in neurogenic inflammation, such as brain swelling, acute respiratory stress syndrome or systemic inflammatory conditions.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Radiology & Medical Imaging (AREA)
  • Animal Behavior & Ethology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biophysics (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Physiology (AREA)
  • Otolaryngology (AREA)
  • Cardiology (AREA)
  • Electrotherapy Devices (AREA)

Abstract

L'invention concerne un appareil et un procédé pour une neuromodulation d'un nerf trijumeau pour traiter divers états médicaux. L'appareil comprend une pluralité d'électrodes de stimulation configurées pour entrer en contact avec une partie de la peau d'un patient sur l'une quelconque de trois divisions d'un nerf trijumeau, le contact d'électrode étant amélioré au moyen d'un gel conducteur. Le procédé comprend la neuromodulation d'un nerf trijumeau, comprenant la stimulation non invasive d'un nerf trijumeau d'un patient ; et l'augmentation du débit sanguin cérébral.
PCT/US2013/037147 2012-04-30 2013-04-18 Neuromodulation du trijumeau indirecte et non invasive pour le traitement d'une maladie WO2013165697A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201261640623P 2012-04-30 2012-04-30
US61/640,623 2012-04-30

Publications (1)

Publication Number Publication Date
WO2013165697A1 true WO2013165697A1 (fr) 2013-11-07

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Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016014436A1 (fr) * 2014-07-21 2016-01-28 ElectroCore, LLC Téléphone mobile pour stimuler le nerf trijumeau pour traiter des troubles
US9440065B2 (en) 2013-04-19 2016-09-13 Oculeve, Inc. Nasal stimulation devices and methods
US9687652B2 (en) 2014-07-25 2017-06-27 Oculeve, Inc. Stimulation patterns for treating dry eye
US9737712B2 (en) 2014-10-22 2017-08-22 Oculeve, Inc. Stimulation devices and methods for treating dry eye
US9770583B2 (en) 2014-02-25 2017-09-26 Oculeve, Inc. Polymer formulations for nasolacrimal stimulation
USD826420S1 (en) 2014-04-18 2018-08-21 Oculeve, Inc. Nasal stimulator device
US10207108B2 (en) 2014-10-22 2019-02-19 Oculeve, Inc. Implantable nasal stimulator systems and methods
US10252048B2 (en) 2016-02-19 2019-04-09 Oculeve, Inc. Nasal stimulation for rhinitis, nasal congestion, and ocular allergies
US10328262B2 (en) 2010-11-16 2019-06-25 The Board Of Trustees Of The Leland Stanford Junior University Stimulation devices and methods
US10426958B2 (en) 2015-12-04 2019-10-01 Oculeve, Inc. Intranasal stimulation for enhanced release of ocular mucins and other tear proteins
US10537469B2 (en) 2013-03-12 2020-01-21 Oculeve, Inc. Implant delivery devices, systems, and methods
US10610695B2 (en) 2014-10-22 2020-04-07 Oculeve, Inc. Implantable device for increasing tear production
US10610095B2 (en) 2016-12-02 2020-04-07 Oculeve, Inc. Apparatus and method for dry eye forecast and treatment recommendation
WO2020257001A1 (fr) * 2019-06-17 2020-12-24 Oculeve, Inc. Stimulateur nasal portatif doté d'un mécanisme de sécurité
US10918864B2 (en) 2016-05-02 2021-02-16 Oculeve, Inc. Intranasal stimulation for treatment of meibomian gland disease and blepharitis
CN112717261A (zh) * 2021-01-19 2021-04-30 西安交通大学第二附属医院 一种基于生物电信号和压力双反馈的压迫用球囊装置
RU207766U1 (ru) * 2021-03-10 2021-11-15 Кирилл Владимирович Винокуров Низкочастотный модулятор нейроактивности
US12357817B2 (en) 2021-04-06 2025-07-15 Aerin Medical Inc. Nasal neuromodulation devices and methods

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US20050153885A1 (en) * 2003-10-08 2005-07-14 Yun Anthony J. Treatment of conditions through modulation of the autonomic nervous system
US20110093033A1 (en) * 2009-10-16 2011-04-21 Stanford University Eliciting analgesia by transcranial electrical stimulation
US20110106220A1 (en) * 2009-10-05 2011-05-05 The Regents Of The University Of California Extracranial implantable devices, systems and methods for the treatment of neurological disorders
US20110282129A1 (en) * 2010-05-12 2011-11-17 Stx-Med Sprl Neurostimulation Method to Induce Relaxation or Sleep

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050153885A1 (en) * 2003-10-08 2005-07-14 Yun Anthony J. Treatment of conditions through modulation of the autonomic nervous system
US20110106220A1 (en) * 2009-10-05 2011-05-05 The Regents Of The University Of California Extracranial implantable devices, systems and methods for the treatment of neurological disorders
US20110093033A1 (en) * 2009-10-16 2011-04-21 Stanford University Eliciting analgesia by transcranial electrical stimulation
US20110282129A1 (en) * 2010-05-12 2011-11-17 Stx-Med Sprl Neurostimulation Method to Induce Relaxation or Sleep

Cited By (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10328262B2 (en) 2010-11-16 2019-06-25 The Board Of Trustees Of The Leland Stanford Junior University Stimulation devices and methods
US10835748B2 (en) 2010-11-16 2020-11-17 Oculeve, Inc. Stimulation devices and methods
US10537469B2 (en) 2013-03-12 2020-01-21 Oculeve, Inc. Implant delivery devices, systems, and methods
US10835738B2 (en) 2013-04-19 2020-11-17 Oculeve, Inc. Nasal stimulation devices and methods
US9737702B2 (en) 2013-04-19 2017-08-22 Oculeve, Inc. Nasal stimulation devices and methods
US10967173B2 (en) 2013-04-19 2021-04-06 Oculeve, Inc. Nasal stimulation devices and methods for treating dry eye
US10155108B2 (en) 2013-04-19 2018-12-18 Oculeve, Inc. Nasal stimulation devices and methods
US9440065B2 (en) 2013-04-19 2016-09-13 Oculeve, Inc. Nasal stimulation devices and methods
US10799695B2 (en) 2013-04-19 2020-10-13 Oculeve, Inc. Nasal stimulation devices and methods
US10238861B2 (en) 2013-04-19 2019-03-26 Oculeve, Inc. Nasal stimulation devices and methods for treating dry eye
US9770583B2 (en) 2014-02-25 2017-09-26 Oculeve, Inc. Polymer formulations for nasolacrimal stimulation
US9956397B2 (en) 2014-02-25 2018-05-01 Oculeve, Inc. Polymer Formulations for nasolacrimal stimulation
US10799696B2 (en) 2014-02-25 2020-10-13 Oculeve, Inc. Polymer formulations for nasolacrimal stimulation
USD837396S1 (en) 2014-04-18 2019-01-01 Oculeve, Inc. Nasal stimulator probe
USD907791S1 (en) 2014-04-18 2021-01-12 Oculeve, Inc. Nasal stimulator body
USD826420S1 (en) 2014-04-18 2018-08-21 Oculeve, Inc. Nasal stimulator device
WO2016014436A1 (fr) * 2014-07-21 2016-01-28 ElectroCore, LLC Téléphone mobile pour stimuler le nerf trijumeau pour traiter des troubles
US10722713B2 (en) 2014-07-25 2020-07-28 Oculeve, Inc. Stimulation patterns for treating dry eye
US9687652B2 (en) 2014-07-25 2017-06-27 Oculeve, Inc. Stimulation patterns for treating dry eye
US10610695B2 (en) 2014-10-22 2020-04-07 Oculeve, Inc. Implantable device for increasing tear production
US10112048B2 (en) 2014-10-22 2018-10-30 Oculeve, Inc. Stimulation devices and methods for treating dry eye
US10780273B2 (en) 2014-10-22 2020-09-22 Oculeve, Inc. Stimulation devices and methods for treating dry eye
US10207108B2 (en) 2014-10-22 2019-02-19 Oculeve, Inc. Implantable nasal stimulator systems and methods
US9737712B2 (en) 2014-10-22 2017-08-22 Oculeve, Inc. Stimulation devices and methods for treating dry eye
US10426958B2 (en) 2015-12-04 2019-10-01 Oculeve, Inc. Intranasal stimulation for enhanced release of ocular mucins and other tear proteins
US10252048B2 (en) 2016-02-19 2019-04-09 Oculeve, Inc. Nasal stimulation for rhinitis, nasal congestion, and ocular allergies
US10940310B2 (en) 2016-02-19 2021-03-09 Oculeve, Inc. Nasal stimulation for rhinitis, nasal congestion, and ocular allergies
US10918864B2 (en) 2016-05-02 2021-02-16 Oculeve, Inc. Intranasal stimulation for treatment of meibomian gland disease and blepharitis
US10610095B2 (en) 2016-12-02 2020-04-07 Oculeve, Inc. Apparatus and method for dry eye forecast and treatment recommendation
WO2020257001A1 (fr) * 2019-06-17 2020-12-24 Oculeve, Inc. Stimulateur nasal portatif doté d'un mécanisme de sécurité
CN112717261A (zh) * 2021-01-19 2021-04-30 西安交通大学第二附属医院 一种基于生物电信号和压力双反馈的压迫用球囊装置
RU207766U1 (ru) * 2021-03-10 2021-11-15 Кирилл Владимирович Винокуров Низкочастотный модулятор нейроактивности
US12357817B2 (en) 2021-04-06 2025-07-15 Aerin Medical Inc. Nasal neuromodulation devices and methods

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