# US 2019/0167987 A1 · Engaging the cervical spinal cord circuitry to re-enable volitional control of hand function in tetraplegic subjects > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2019/0167987 A1 - Document ID: US20190167987A1 - Status: Published application - Kind: A1 - Application number: 16/200,467 - Filed: 2018-11-26 - Published: 2019-06-06 - Earliest claimed: 2013-09-27 - Assignees: The Regents of the University of California - Applicants: The Regents of the University of California - Inventors: Daniel C. Lu; V. Reggie Edgerton; Roland R. Roy; Yury P. Gerasimenko - Web page: https://patentgrep.com/patent/US20190167987A1 ## CPC - A61K 31/137: Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone} - A61K 31/4168: having a nitrogen attached in position 2, e.g. clonidine - A61K 31/4178: not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin - A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin - A61K 31/4985: Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems - A61K 31/506: not condensed and containing further heterocyclic rings - A61K 31/517: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine - A61K 31/527: spiro-condensed - A61N 1/0456: {Specially adapted for transcutaneous electrical nerve stimulation [TENS]} - A61N 1/0551: {Spinal or peripheral nerve electrodes} - A61N 1/36003: {of motor muscles, e.g. for walking assistance} - A61N 1/36034: {specified by the stimulation parameters} - A61N 1/36067: {Movement disorders, e.g. tremor or Parkinson disease (stimulating motor muscle A61N1/36003)} - A61N 1/36171: {Frequency} - A61P 25/02: for peripheral neuropathies - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract In various embodiments, methods are provided for applying transcutaneous and/or epidural spinal cord stimulation with and without selective pharmaceuticals to restore voluntary control of hand function in tetraplegic subjects. ## Claims ### Claim 1 A method of improving motor control and/or strength in a hand of a subject with a neuromotor disorder affecting motor control of the hand, said method comprising: neuromodulating the cervical spinal cord of said subject by administering transcutaneous stimulation to the cervical spinal cord or a region thereof; and/or neuromodulating the cervical spinal cord of said subject by administering epidural stimulation to the cervical spinal cord or a region thereof; and/or by administering to said subject at least one monoaminergic agonist. ### Claim 2 (depends on 1) The method of claim 1, wherein said method comprises administering transcutaneous stimulation or epidural stimulation to the cervical spinal cord or a region thereof. ### Claim 3 (canceled) ### Claim 4 (depends on 1) The method of claim 1, wherein said method comprises administering a monoaminergic agonist to said subject. ### Claim 5 (depends on 1) The method of claim 1, wherein said method comprises administering transcutaneous or epidural stimulation to the cervical spinal cord or a region thereof in conjunction with administration of a monoaminergic agonist. ### Claim 6 (canceled) ### Claim 7 (depends on 1) The method of claim 1, wherein said method comprises administering transcutaneous stimulation to the cervical spinal cord or a region thereof in conjunction with epidural stimulation of the cervical spinal cord or a region thereof. ### Claim 8 (depends on 1) The method of claim 1, wherein said method comprises administering transcutaneous stimulation to the cervical spinal cord or a region thereof in conjunction with epidural stimulation of the cervical spinal cord or a region thereof in conjunction with administration of a monoaminergic agonist to said subject. ### Claim 9 (depends on 1) The method of claim 1, wherein: said transcutaneous stimulation is at a frequency ranging from about 3 Hz, or from about 5 Hz, or from about 10 Hz to about 100 Hz, or to about 80 Hz, or to about 40 Hz, or from about 3 Hz or from about 5 Hz to about 80 Hz, or from about 5 Hz to about 30 Hz, or to about 40 Hz, or to about 50 Hz; and/or said epidural stimulation is at a frequency ranging from about 3 Hz, or from about 5 Hz, or from about 10 Hz to about 100 Hz, or to about 80 Hz, or to about 40 Hz, or from about 3 Hz or from about 5 Hz to about 80 Hz, or from about 5 Hz to about 30 Hz, or to about 40 Hz, or to about 50 Hz. ### Claim 10 (depends on 1) The method of claim 1, wherein: said transcutaneous stimulation is applied at an intensity ranging from about 10 mA to about 150 mA, or from about 20 mA to about 50 mA or to about 100 mA, or from about 20 mA or from about 30 mA, or from about 40 mA to about 50 mA, or to about 60 mA, or to about 70 mA or to about 80 mA; and/or said epidural stimulation is at an amplitude ranging from 0.05 mA to about 30 mA, or from about 0.1 mA to about 20 mA, or from about 0.1 mA to about 15 mA or to about 10 mA. ### Claim 11 (depends on 1) The method of claim 1, wherein said transcutaneous stimulation and/or epidural stimulation is at a frequency and amplitude sufficient to improve hand strength and/or fine hand control. ### Claim 12 (depends on 1) The method of claim 1, wherein transcutaneous stimulation is applied to the dorsal aspect of the neck in the area of C5. ### Claim at position 13 13-14. (canceled) ### Claim 15 (depends on 1) The method of claim 1, wherein said stimulation comprises a signal having a pulse width that ranges from about 150 μs to about 600 μs, or from about 200 μs to about 500 μs, or from about 200 μs to about 450 μs. ### Claim 16 (canceled) ### Claim 17 (depends on 1) The method of claim 1, wherein said transcutaneous stimulation and/or said epidural stimulation is applied paraspinally over vertebrae spanning C2 to T1. ### Claim 18 (canceled) ### Claim 19 (depends on 1) The method of claim 1, wherein epidural stimulation is applied via a permanently implanted electrode array. ### Claim 20 (canceled) ### Claim 21 (depends on 1) The method of claim 1, wherein said method comprises administering to said subject at least one monoaminergic agonist that comprises an agent selected from the group consisting of a serotonergic drug, a dopaminergic drug, a noradrenergic drug, a GABAergic drug, and a glycinergic drug. ### Claim 22 (depends on 21) The method of claim 21, wherein said agent is selected from the group consisting of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 4-(benzodioxan-5-yl)1-(indan-2-yl)piperazine (S15535), N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridinyl)cyclo-hexanecarboxamide (WAY 100.635), Quipazine, Ketanserin, 4-amino-(6-chloro-2-pyridyl)-1 piperidine hydrochloride (SR 57227A), Ondanesetron, Buspirone, Methoxamine, Prazosin, Clonidine, Yohimbine, 6-chloro-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol (SKF-81297), 7-chloro-3-methyl-1-phenyl-1,2,4,5-tetrahydro-3-benzazepin-8-ol (SCH-23390), Quinpirole, and Eticlopride. ### Claim 23 (canceled) ### Claim 24 (depends on 1) The method of claim 1, wherein a combination of transcutaneous and/or epidural stimulation and monoaminergic agonist provides a synergistic improvement in hand strength and/or fine hand control. ### Claim 25 (depends on 1) The method of claim 1, wherein said subject is a human. ### Claim 26 (depends on 1) The method of claim 1, wherein said subject has a spinal cord injury, or an ischemic brain injury, or a neurodegenerative pathology. ### Claim 27 (depends on 26) The method of claim 26, wherein said subject has a spinal cord injury that is clinically classified as motor complete or that is clinically classified as motor incomplete. ### Claim at position 27 28-29. (canceled) ### Claim 30 (depends on 26) The method of claim 26, wherein said subject has an ischemic brain injury that is brain injury from stroke or acute trauma. ### Claim 31 (canceled) ### Claim 32 (depends on 26) The method of claim 26, wherein said subject has a neurodegenerative pathology that is associated with a condition selected from the group consisting of Parkinson's disease, Huntington's disease, Alzhiemer's disease, amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), dystonia, and cerebral palsy. ### Claim 33 (depends on 1) The method of claim 1, wherein the stimulation is under control of the subject. ### Claim 34 (depends on 1) The method of claim 1, wherein said method further comprises physical training of said subject. ### Claim 35 (depends on 34) The method of claim 34, wherein said physical training comprises: hand contraction against a resistance; and/or tracing a displayed pattern by hand manipulation of a hand controller. ### Claim 36 (canceled) ### Claim 37 (depends on 1) An electrical stimulator configured to induce epidural and/or transcutaneous electrical stimulation in the cervical region of a subject according to claim 1.