# US 11,298,533 B2 · Concerted use of noninvasive neuromodulation device with exoskeleton to enable voluntary movement and greater muscle activation when stepping in a chronically paralyzed subject > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,298,533 B2 - Document ID: US11298533B2 - Status: Granted - Kind: B2 - Application number: 15/753,963 - Filed: 2016-08-26 - Published: 2018-10-04 - Granted: 2022-04-12 - Earliest claimed: 2015-08-26 - Assignees: The Regents of the University of California - Applicants: The Regents of the University of California - Inventors: Victor Reggie Edgerton; Yury P. Gerasimenko; Parag Gad - Web page: https://patentgrep.com/patent/US11298533B2 ## CPC - A61N 1/36003: {of motor muscles, e.g. for walking assistance} - A61F 5/01: Orthopaedic devices, e.g. long-term immobilising or pressure directing devices for treating broken or deformed bones such as splints, casts or braces - A61G 5/14: Standing-up or sitting-down aids - A61H 1/024: {Knee (A61H1/0255 takes precedence)} - A61H 1/0244: {Hip (A61H1/0255 takes precedence)} - A61H 1/0262: {Walking movement; Appliances for aiding disabled persons to walk (A61H3/00 takes precedence)} - A61H 3/00: Appliances for aiding patients or disabled persons to walk about (apparatus for helping babies to walk A47D13/04 {; applying electrical currents by contact electrodes for stimulating motor muscles, e.g. walking assistance A61N1/36003}) - A61N 1/0408: {Use-related aspects} - A61N 1/0456: {Specially adapted for transcutaneous electrical nerve stimulation [TENS]} - A61N 1/0476: {Array electrodes (including any electrode arrangement with more than one electrode for at least one of the polarities)} - A61N 1/0484: {Garment electrodes worn by the patient} - A61N 1/36034: {specified by the stimulation parameters} - B25J 9/0006: {Exoskeletons, i.e. resembling a human figure} - A61H 1/0277: {Elbow} - A61H 1/0281: {Shoulder} - A61H 3/02: Crutches - A61H 2201/10: with further special therapeutic means, e.g. electrotherapy, magneto therapy or radiation therapy, chromo therapy, infrared or ultraviolet therapy - A61H 2201/1207: with electric or magnetic drive - A61H 2201/1614: Shoulder, e.g. for neck stretching - A61H 2201/1623: Back - A61H 2201/1628: Pelvis - A61H 2201/1635: Hand or arm, e.g. handle - A61H 2201/164: Feet or leg, e.g. pedal - A61H 2201/165: Wearable interfaces - A61H 2201/50: Control means thereof - A61H 2201/5025: Activation means - A61H 2201/5061: Force sensors - A61H 2201/5064: Position sensors - A61N 1/36031: {using physiological parameters for adjustment} - A61N 1/36057: {adapted for stimulating afferent nerves} - 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) - 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 (dental prosthetics A61C) - A61G: TRANSPORT, PERSONAL CONVEYANCES OR ACCOMMODATION SPECIALLY ADAPTED FOR PATIENTS OR DISABLED PERSONS (appliances for aiding patients or disabled persons to walk A61H3/00); OPERATING TABLES OR CHAIRS; CHAIRS FOR DENTISTRY; FUNERAL DEVICES (embalming corpses A01N1/00) - A61H: PHYSICAL THERAPY APPARATUS, e.g. DEVICES FOR LOCATING OR STIMULATING REFLEX POINTS IN THE BODY; ARTIFICIAL RESPIRATION; MASSAGE; BATHING DEVICES FOR SPECIAL THERAPEUTIC OR HYGIENIC PURPOSES OR SPECIFIC PARTS OF THE BODY (electrotherapy, magnetotherapy, radiation therapy or ultrasound therapy A61N) - B25J: MANIPULATORS; CHAMBERS PROVIDED WITH MANIPULATION DEVICES ({manipulators specially adapted for use in surgery A61B34/70; manipulators used in cleaning hollow articles B08B9/04}; manipulators associated with rolling mills B21B39/20; manipulators associated with forging machines B21J13/10; {manipulators associated with picking-up and placing mechanisms B23P19/007}; means for holding wheels or parts thereof B60B30/00; {vehicles with ground-engaging propulsion means, e.g. walking members B62D57/02, B62D57/032; devices for picking-up and depositing articles or materials between conveyors B65G47/90, B65G47/91; manipulators with gripping or holding means for transferring packages B65H67/065}; cranes B66C; {manipulators used in the protection or supervision of pipe-line installations F17D5/00; walking equipment adapted for nuclear steam-generators F22B37/006}; manipulators specially adapted for, or associated with, nuclear reactors G21C; {apparatus used for handling wafers during manufacture or treatment of semiconductor H10P72/50}) ## Abstract In various embodiments a method of synergistically using a neuromodulation stimulator and a robotic exoskeleton for the restoration of voluntary movement and greater muscle activation in chronically paralyzed subjects is provided. The noninvasive neuromodulation system delivers signals to facilitate the restoration and/or enhancement of neurological function where at least one effect is strengthened stepping capacity that can be further substantiated when coupled with robotic exoskeleton assistance. ## Claims ### Claim 1 A method for assisting a human subject with one or more functions, the human subject having at least one of: a spinal cord injury, a brain injury, and a neurodegenerative pathology, and the one or more functions comprising at least one of: postural stabilization, postural strength, locomotor activity, locomotor strength, reaching activity, and reaching strength, said method comprising: applying transcutaneous stimulation to at least one of: a spinal cord, a brainstem, a brain, and sacral nerves of said subject, thereby activating neural networks of the spinal cord; utilizing an exoskeletal system to expose said subject to proprioceptive signals associated with at least one of: postural changes, weight bearing, locomotor activity, and reaching; and whereby utilizing a combination of the transcutaneous stimulation and the exoskeletal system assists said subject in said one or more functions. ### Claim 2 (depends on 1) The method of claim 1, wherein the combination of said transcutaneous stimulation and said exoskeletal system modulates in real time spinal circuits in said subject so said spinal circuits are activated by proprioceptive signals produced in said subject by utilization of said exoskeletal system. ### Claim 3 (depends on 1) The method of claim 1, wherein the assistance provided by the combination of said transcutaneous stimulation and said exoskeletal system is synergistic. ### Claim 4 (depends on 1) The method of claim 1, wherein said exoskeletal system is configured for at least one of: partially or fully controlling movement of a leg, an arm, and/or a hand of said subject; and/or partially or fully controlling a load bearing positional change in a region of the subject where locomotor activity is to be facilitated; providing variable assistance where corrective assistance is provided based on an extent of deviation by the subject from a healthy or predetermined motion, or by a variation in resistance to a load provided by the subject; providing assistance to said subject in a standing position; providing assistance to said subject in rising to a standing position from a seated or reclining position; providing assistance to said subject in stepping; providing assistance to said subject in sitting down or laying down; providing assistance to said subject in stabilizing a sitting or a standing posture; providing assistance to said subject in reaching; and providing assistance to said subject in grasping. ### Claim 5 (depends on 1) The method of claim 1, wherein said transcutaneous stimulation comprises one or more of: a frequency comprising a range from about 0.5 Hz up to about 1,000 Hz, an amplitude comprising a range from 10 mA up to about 500 mA, and a pulse width comprising a range from about 100 μs up to about 200 ms. ### Claim 6 (depends on 1) The method of claim 1, wherein said transcutaneous stimulation is superimposed on a high frequency carrier signal. ### Claim 7 (depends on 6) The method of claim 6, wherein said high frequency carrier signal comprises one or more of: a frequency comprising a range from about 3 kHz up to about 100 kHz, and or an amplitude comprising a range from about 30 mA up to about 500 mA. ### Claim 8 (depends on 1) The method of claim 1, wherein said transcutaneous stimulation comprises one or more of: a monopolar configuration, a bipolar configuration, a monophasic configuration, a biphasic configuration, a tonic stimulation, stimulation of a single region of the spinal cord, and simultaneous or sequential stimulation of different spinal cord regions. ### Claim 9 (depends on 1) The method of claim 1, wherein said transcutaneous stimulation is applied on one or more skin surfaces associated with one or more of: a cervical spine a region, a thoracic spine region, a lumbosacral spine region, a region associated with the spinal cord that controls the lower limbs to stimulate locomotor activity or strength or to improve postural control, a thoracic spinal cord region, a lumbar spinal cord region, a region comprising T11, a region comprising the coccygeal nerve Co1, a region of the spinal cord that controls the upper limbs to improve reaching activity and/or reaching strength, and a region comprising the cervical spinal cord. ### Claim 10 (depends on 1) The method of claim 1, wherein the transcutaneous stimulation is under control of the subject, and/or said exoskeletal system is under control of the subject. ### Claim 11 (depends on 1) The method of claim 1, wherein said exoskeletal system comprises a wearable powered orthotic system. ### Claim 12 (depends on 11) The method of claim 11, wherein said wearable powered orthotic system comprises: a torso portion configured to be coupled to an upper body of said subject; a lower limb powered orthotic component configured to provide assistance in locomotion of a lower limb; an upper limb powered orthotic component configured to provide assistance in locomotion of an upper limb; a plurality of sensors for monitoring positions of said lower limb powered orthotic component and/or said upper limb powered orthotic component; and a controller configured to control assistance provided by said lower limb powered orthotic component and/or configured to control assistance provided by said upper limb powered orthotic component. ### Claim 13 (depends on 11) The method of claim 11, wherein said exoskeletal system comprises: a torso portion configurable to be coupled to an upper body of said subject; a lower limb orthotic component comprising at least one leg support configurable to be coupled to a first lower limb of said subject, with the at least one leg support including at least a thigh link rotatably connected to said torso portion at a hip joint, and a shank link rotatably connected to the thigh link at a knee joint; a first lower limb actuator for controlling motion of said hip joint; and a second lower limb actuator for controlling motion of said knee joint. ### Claim 14 (depends on 11) The method of claim 11, wherein said exoskeletal system comprises: a torso portion configurable to be coupled to an upper body of said subject; an upper limb orthotic component comprising at least one arm support configured to be coupled to a first upper limb of said subject, with the at least one arm support including at least an upper arm link rotatably connected to said torso portion at a shoulder joint, and a forearm link rotatably connected to the upper arm link at an elbow joint; a first upper limb actuator for controlling motion of said shoulder joint; and a second upper limb actuator for controlling motion of said elbow joint. ### Claim 15 (depends on 11) The method of claim 11, wherein said wearable powered orthotic system comprises: a torso portion configured to be coupled to an upper body of said subject; and a lower limb powered orthotic component configured to provide assistance in locomotion of a lower limb. ### Claim 16 (depends on 15) The method of claim 15, wherein said wearable powered orthotic system comprises: a plurality of sensors for monitoring positions of said lower limb powered orthotic component; and a controller configured to control assistance provided by said lower limb powered orthotic component. ### Claim 17 (depends on 11) The method of claim 11, wherein said wearable powered orthotic system comprises: a torso portion configured to be coupled to an upper body of said subject; and an upper limb powered orthotic component configured to provide assistance in locomotion of an upper limb. ### Claim 18 (depends on 17) The method of claim 17, wherein said wearable powered orthotic system comprises: a plurality of sensors for monitoring positions of said upper limb powered orthotic component; and a controller configured to control assistance provided by said upper limb powered orthotic component. ### Claim 19 (depends on 1) The method of claim 1, wherein said exoskeletal system is configured to perform one or more of: gait functions for the subject based on a predetermined level of assistance, gait functions where the level of assistance is adaptively varied based on performance of the subject, arm movements for the subject based on a predetermined level of assistance, and; arm movements where the level of assistance is adaptively varied based on performance of the subject. ### Claim 20 (depends on 1) The method of claim 1, further comprising administering to said subject at least one of: a neuromodulatory drug, a monoaminergic agonist, a monoaminergic agonist comprising a first agent selected from the group consisting of: a serotonergic drug, a dopaminergic drug, a noradrenergic drug, a GABAergic drug, and a glycinergic drug, a second agent 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, a neuromodulatory drug that activates an α2c adrenergic receptor subtype and/or that blocks an α2a adrenergic receptor subtype, a neuromodulatory drug that activates an α2c adrenergic receptor subtype is 2-[(4,5-Dihydro-1H-imidazol-2-yl)methyl]-2,3-dihydro-1-methyl-1H-isoindole (BRL-44408), a neuromodulatory drug that is (R)-3-nitrobiphenyline and/or a compound according to the formula: a neuromodulatory drug that is Clonidine, and a neuromodulatory drug that is a 5-HT1 and/or a 5-HT7 serotonergic agonist. ### Claim 21 (depends on 1) The method of claim 1, wherein said subject has at least one of: a motor complete spinal cord injury, a motor incomplete spinal cord injury, an ischemic brain injury, and a neurodegenerative pathology associated with one or more of: stroke, Parkinson's disease, Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), dystonia, and cerebral palsy. ### Claim 22 (depends on 1) The method of claim 1, wherein said locomotor activity comprises standing and/or stepping. ### Claim 23 (depends on 1) The method of claim 1, wherein said locomotor activity comprises reaching.