Engaging the cervical spinal cord circuitry to re-enable volitional control of hand function in tetraplegic subjects

• US 10,137,299 B2
• Filed: 09/26/2014
• Issued: 11/27/2018
• Est. Priority Date: 09/27/2013
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Lu, Daniel C., Edgerton, V. Reggie, Roy, Roland R., Gerasimenko, Yury P.
• Primary Examiner(s): Layno, Carl H
• Assistant Examiner(s): Morales, Jon Eric C
• Application Number:
  US15/025,201
• Publication Number:
  US 20160235977A1
• Time in Patent Office: 1,523 Days
• Field of Search: 607 48
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/4168 having a nitrogen attached in position 2, e.g. clonidine
• CPC Class Codes: A61K 31/4178 not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/4985 Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/517 ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• CPC Class Codes: A61K 31/527 spiro-condensed
• CPC Class Codes: A61N 1/0456 Specially adapted for transcutaneous electrical nerve stimulation [TENS]
• CPC Class Codes: A61N 1/0551 Spinal or peripheral nerve electrodes
• CPC Class Codes: A61N 1/36003 of motor muscles, e.g. for walking assistance
• CPC Class Codes: A61N 1/36034 specified by the stimulation parameters
• CPC Class Codes: A61N 1/36067 Movement disorders, e.g. tremor or Parkinson disease stimulating motor muscle A61N1/36003
• CPC Class Codes: A61N 1/36171 Frequency
• CPC Class Codes: A61P 25/02 for peripheral neuropathies

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

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 a 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; and

wherein said method additionally comprises physical training of said subject where said physical training comprises;

hand contraction against a resistance; and

/or

tracing a displayed pattern by hand manipulation of a hand controller.

2. The method of claim 1, wherein said method comprises administering transcutaneous stimulation or epidural stimulation to the cervical spinal cord or a region thereof.

3. The method of claim 1, wherein said method comprises administering a monoaminergic agonist to said subject.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. The method of claim 1, wherein transcutaneous stimulation is applied to a dorsal aspect of a neck in an area of C5.

11. The method according of claim 1, wherein said stimulation comprise a signal having a pulse width that ranges from about 150 μ

s to about 600 μ

s, or from about 200 μ

s to about 500 μ

s, or from about 200 μ

s to about 450 μ

s.

12. The method of claim 1, wherein said transcutaneous stimulation and/or said epidural stimulation is applied paraspinally over vertebrae spanning C2 to T1.

13. The method of claim 1, wherein epidural stimulation is applied via a permanently implanted electrode array.

14. The method of claim 1, wherein said method comprises administering to said subject at least one monoaminergic agonist that comprises an agent selected from a group consisting of a serotonergic drug, a dopaminergic drug, a noradrenergic drug, a GABAergic drug, and a glycinergic drug.

15. The method of claim 14, wherein said agent is selected from a group consisting of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 4-(benzodioxan-5-yl)l-(indan-2-yl)piperazine (S15535), N-{2-[4-(2-methoxyphenyl)-l-piperazinyl]ethyl}-N- (2-pyridinyl)cyclo-hexanecarboxamide (WAY 100.635), Quipazine, Ketanserin, 4-amino-(6-chloro-2-pyridyl)-l piperidine hydrochloride (SR 57227A), Ondanesetron, Buspirone, Methoxamine, Prazosin, Clonidine, Yohimbine, 6-chloro-l-phenyl-2,3,4,5-tetrahydro-IH-3-benzazepine-7,8-diol (SKF-81297), 7-chloro-3-methyl-l-phenyl-1,2,4,5-tetrahydro-3-benzazepin-8-ol (SCH-23390), Quinpirole, and Eticlopride.

16. 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.

17. The method of claim 1, wherein said subject is a human.

18. The method of claim 1, wherein said subject has a spinal cord injury, or an ischemic brain injury, or a neurodegenerative pathology.

19. The method of claim 18, wherein said subject has a spinal cord injury that is clinically classified as motor complete or that is clinically classified as motor incomplete.

20. The method of claim 18, wherein said subject has an ischemic brain injury that is brain injury from stroke or acute trauma.

21. The method of claim 18, wherein said subject has a neurodegenerative pathology that is associated with a condition selected from a group consisting of Parkinson'"'"'s disease, Huntington'"'"'s disease, Alzheimer'"'"'s disease, amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), dystonia, and cerebral palsy.

22. The method of claim 1, wherein the stimulation is under control of the subject.