US-12623070-B2 - Transcutaneous electrical spinal cord neuromodulator and uses thereof

US12623070B2US 12623070 B2US12623070 B2US 12623070B2US-12623070-B2

Abstract

In various embodiments electrical stimulators are provided for transcutaneous and/or epidural stimulation. In certain embodiments the stimulator provides one or more channels configured to provide one or more of the following stimulation patterns: i) monophasic electrical stimulation with a DC offset; ii) monophasic electrical stimulation with charge balance; iii) delayed biphasic electrical stimulation with a DC offset; iv) delayed biphasic electrical stimulation with charge balance; v) amplitude modulated dynamic stimulation; and/or vi) frequency modulated dynamic stimulation.

Inventors

Parag Gad
Victor Reggie Edgerton
Giuliano Taccola
Evgeniy I. Kreydin

Assignees

THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Scuola Internazionale Superiore di Studi Avanzati (SISSA)
UNIVERSITY OF SOUTHERN CALIFORNIA

Dates

Publication Date: 20260512
Application Date: 20200520

Claims (14)

1 . A transcutaneous electrical spinal cord stimulator, said stimulator comprising: a plurality of array electrodes configured to be placed in contact with an outer skin surface of a patient directly over a spinal cord on a back positioned between vertebral processes; a pulse modulator unit connected to the microprocessor; one or more channels configured to provide one or more transcutaneous electrical spinal cord stimulation patterns, via the plurality of array electrodes, to a plurality of nerves in the spinal cord to provide therapy for a disorder of a connection between a brain and a spinal cord of a patient, at least one of which includes a plurality of delayed biphasic electrical stimulation pulses; a microprocessor unit in communication with the plurality of array electrodes, the pulse modulator unit, and the one or more channels; and a memory in communication with the microprocessor unit and having instructions stored thereon that, when executed, cause the microprocessor unit to: receive a plurality of treatment parameters corresponding to the one or more electrical spinal cord stimulation patterns, wherein the plurality of treatment parameters comprises a motor threshold; execute the plurality of treatment parameters using the plurality of array electrodes and the pulse modulator unit; detect an EMG response; and store the plurality of treatment parameters, wherein the motor threshold comprises an intensity that excites or inhibits certain neurons or interneurons within the spinal cord to treat connectivity impaired by the disorder of the connection between the brain and the spinal cord of the patient, wherein said neurons or interneurons are remote from a site of said stimulation; and wherein the plurality of delayed biphasic electrical stimulation pulses includes an anodic phase and a cathodic phase configured to independently provide therapy to the spinal cord.
2 . The electrical stimulator of claim 1 , wherein said stimulator comprises two or more or four or more independently configurable channels each capable of independently providing one or more of said stimulation patterns.
3 . The electrical stimulator of claim 2 , wherein: said two or more or said four or more channels provide said stimulation patterns with respect to a common neutral line; or each of said two or more or each of said four or more channels provide said stimulation patterns with respect to neutral line for that channel.
4 . The electrical stimulator of claim 1 , wherein the one or more transcutaneous electrical spinal cord stimulation patterns comprises bursts of low frequency therapeutic pulses configured to activate or inhibit certain neurons or interneurons within the spinal cord and impaired by the disorder, wherein said low frequency therapeutic pulses comprise a frequency and an amplitude of high frequency pulses configured to reduce or block pain caused by said bursts of low frequency therapeutic pulses, wherein said high frequency pulses range in frequency from about 5 kHz up to about 100 kHz, or from about 10 kHz up to about 50 kHz, or from about 10 kHz up to about 30 kHz, or from about 10 kHz up to about 20 kHz; and wherein the low frequency therapeutic pulses range in frequency from about 1 Hz up to about 100 Hz, or from about 10 Hz up to about 50 Hz, or from about 30 Hz up to about 50 Hz, or from a bout 20 kHz up to about 30 kHz.
5 . The electrical stimulator of claim 1 , wherein: one or more channels of said electrical stimulator is configured to provide monophasic electrical stimulation with a DC offset; and/or one or more of channels of said electrical stimulator is configured to provide monophasic electrical stimulation with charge balance; and/or one or more channels of said electrical stimulator is configured to provide delayed biphasic electrical stimulation with a DC offset; and/or one or more channels of said electrical stimulator is configured to provide delayed biphasic electrical stimulation with charge balance; and/or one or more channels of said electrical stimulator is configured to provide delayed biphasic electrical stimulation with charge balance where the delay in said biphasic electrical stimulation ranges from about 0.1 μsec up to about 2 μsec, or from about 0.1 μsec up to about 1 μsec; and/or one or more channels of said electrical stimulator is configured to provide dynamic stimulation with amplitude modulation; and/or one or more channels of said electrical stimulator is configured to provide dynamic stimulation with frequency modulation; and/or one or more channels of said electrical stimulator is configured to provide frequency modulated dynamic stimulation where the one or more channels of said frequency modulated dynamic stimulation ranges in frequency from about 1 Hz to about 1000 Hz.
6 . The electrical stimulator of claim 5 , wherein: said dynamic stimulation is sourced from a biosignal; and/or said dynamic stimulation is sourced from a biosignal that comprises a signal derived from an EMG, and EEG, or an EKG; and/or said dynamic stimulation is sourced from a biosignal wherein said biosignal is recorded from a mammal; and/or said dynamic stimulation is sourced from a biosignal where said biosignal is recorded from a human or from a non-human primate; and/or said dynamic stimulation is sourced from a biosignal where said biosignal comprises a biosignal recorded from a mammal when the mammal is standing, stepping, moving the arms, storing/emptying the bladder, storing/emptying the bowel, breathing.
7 . The electrical stimulator of claim 1 , wherein: said electrical stimulator is configured to provide a stimulation amplitude ranging from about 1 mA, or from about 3 mA, or from about 5 mA up to about 500 mA, or up to about 400 mA, or up to about 300 mA, or up to about 250 mA, or up to about 200 mA for each of said one or more channels; and/or said electrical stimulator is configured to provide a stimulation amplitude ranging from about 5 mA up to about 200 mA for each of said one or more channels; and/or said stimulator is configured to provide pulses that pass a current of 300 mA peak through an impedance of about 300 to about 2000 ohms, or from about 300 to about 900 ohms for each of said one or more channels; and/or said electrical stimulator is configured to provide a stimulation having a DC offset ranging from about 1 mA to about 30 mA, or from about 1 mA to about 20 mA; and/or said stimulator is configured to provide a stimulation frequency (burst frequency) for one or more of said channels ranging in frequency from 0.2 Hz up to 10 kHz; and/or said stimulator provides stimulation frequency control in steps of 1 Hz at a frequency ranging from 0.2 Hz to 100 Hz; and/or said stimulator provides stimulation frequency control, in steps of 100 Hz at a frequency ranging from 100 Hz to 1 kHz; and/or said stimulator provides stimulation frequency control in steps of 1 kHz at a frequency ranging from 1 kHz to 10 kHz; and/or said stimulator is configured to provide a stimulation pulse (burst) width ranging from about 0.1 ms up to about 20 ms, or up to about 10 ms, or up to about 5 ms, or up to about 4 ms, or from about 0.2 ms up to about 3 ms; and/or said stimulator is configured to provide a stimulation pulse (burst) width controllable in steps of 0.1 ms; and/or aid stimulator is configured to provide a pulse width fixed at 1 ms at stimulation frequencies over 10 kHz; and/or said stimulator is configured to control the timing between stimulation signals delivered by different channels.
8 . The electrical stimulator of claim 1 , wherein said electrical stimulator comprises: a microprocessor unit for receiving and/or programming and/or storing a stimulation pattern for one or more channels comprising said stimulator; a pulse generating unit under control of said microprocessor; a pulse modulator (gating) unit under control of said microprocessor; and an input/output unit providing user control over said electrical stimulator.
9 . The electrical stimulator of claim 8 , wherein: said electrical stimulator further comprises a DC shift (offset) generating unit under control of said microprocessor; and/or said electrical stimulator further comprises a DC shift (offset) generating unit under control of said microprocessor where said DC shift generating unit comprises a component of said pulse generating unit; and/or said electrical stimulator further comprises a charge balancing unit; and/or said electrical stimulator further comprises a current control unit; and/or said electrical stimulator further comprises a monitoring unit; and/or said electrical stimulator further comprises a monitoring unit where said monitoring unit monitors lead impedance; and/or said electrical stimulator further comprises a monitoring unit where said monitoring unit monitors output current; and/or said input output unit is directly electrically connected to said stimulator; and/or said input output unit is operably coupled to said stimulator through a wireless connection, a network connection, a wifi connection, or a Bluetooth connection; and/or said electrical stimulator comprises a smart card reader and/or a biometric reader; and/or said electrical stimulator comprises a smart card reader configured to input a patient identifier, and optionally, a treatment protocol associated with said patient identifier; and/or said electrical stimulator comprises a biometric reader; and/or said electrical stimulator comprises a biometric reader that recognizes a fingerprint, a face, and/or an iris; and/or said electrical stimulator comprises a biometric reader that identifies a subject to be treated.
10 . The electrical stimulator of claim 1 , wherein said electrical stimulator is operably coupled to a database.
11 . The electrical stimulator of claim 10 , wherein: said database provides treatment protocols; and/or said database provides treatment protocols for a subject identified to said stimulator by said smart card reader and/or by said biometric reader.
12 . The electrical stimulator of claim 1 , wherein said stimulator is configured to provide two modes of operation: i) an administrator mode for clinicians and researchers; and ii) a patient mode.
13 . The electrical stimulator of claim 12 , wherein: said administrator mode provides the ability to input and store one or more programs comprising stimulation parameters for one or more of said one or more channels; and/or said administration mode provides the ability to store up to 5 stimulation programs, or up to 10 stimulation programs; and/or said administrator mode provides the ability to input and store electrode placement locations for presentation in patient mode; and/or said administrator mode provides the ability to measure impedance across each channel and display it to the administrator; and/or said patient mode permits program selection using a patient identifier; and/or said patient mode permits program selection using a patient identifier selected from the group consisting of a smart card, a patient biometric (eye, facial recognition, thumb or fingerprint recognition) reader, an alphanumeric patient ID, a medical bracelet, smartphone app/tap, smartwatch app/tap, smart ring tap; and/or said patient mode identifies for the patient sites for transcutaneous stimulation electrodes to be placed; and/or said patient mode turns on the therapy; and/or said patient mode turns on therapy after detecting placement of the necessary electrodes; and/or said patient mode permits the user to set ramp rate options; and/or said patient mode permits the user to set up ramp rate options ranging from about 1 mA/sec to about 10 mA/sec.
14 . The electrical stimulator of claim 1 , wherein: each active channel of said stimulator is electrically coupled to one or more electrodes for transcutaneous electrical stimulation; and/or each active channel of said stimulator is electrically coupled to one or more electrodes for transcutaneous electrical stimulation wherein said electrodes comprise paddle electrodes; and/or each active channel of said stimulator is electrically coupled to one or more electrodes for transcutaneous electrical stimulation; and/or each active channel of said stimulator is electrically coupled to one or more paddle electrodes for transcutaneous electrical stimulation wherein: said paddle electrodes are disposed in clothing; or said paddle electrodes are disposed on a toilet seat; or said paddle electrodes are disposed on a chair or couch; or each active channel of said stimulator is electrically coupled to one or more needle electrodes.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application is a U.S. 371 National Phase of PCT/US2020/033830, filed on May 20, 2020, which claims benefit of and priority to U.S. Ser. No. 62/876,583, filed on Jul. 19, 2019, and to U.S. Ser. No. 62/851,572, filed on May 22, 2019, all of which are incorporated herein by reference in their entirety for all purposes. STATEMENT OF GOVERNMENTAL SUPPORT This invention was made with government support under Grant Number EB007165, awarded by the National Institutes of Health. The government has certain rights in the invention. BACKGROUND Serious spinal cord injuries (SCI) affect approximately 1.3 million people in the United States, and roughly 12-15,000 new injuries occur each year. Of these injuries, approximately 50% are complete spinal cord injuries in which there is essentially total loss of sensory and/or motor function and autonomic function below the level of the spinal lesion. Additionally, numerous neurodegenerative conditions (e.g., stroke, Parkinson's disease, Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), dystonia, cerebral palsy, and the like) and other traumas (e.g., hemispherictomy, dorsal and/or ventral root rhizotomy or avulsion, and the like) can result in partial or total loss of sensory and/or motor function and autonomic function. Further, Overactive Bladder (OAB) leading to urgency, increased frequency and urinary incontinence and is one of the most prevalent conditions in the US and affects approximately 37M Americans. This condition, although not life-threatening, is a huge burden and takes a significant toll on the quality of life for anyone living with this condition. and negatively affects people both physically, psychologically, economically and may lead people to alter their lives. Neuronal networks formed by the interneurons of the spinal cord that are located in the brainstem, cervical, thoracic, and lumbar enlargements, such as the spinal networks (SNs), can play an important role in the control of posture, locomotion, movements of the upper limbs, trunk, breathing, speech, coughing, eating, vision and cardiovascular, bladder and/or bowel and sexual function. Most researchers believe that essentially all mammals, including humans, have spinal networks in the various regions of the spinal cord. Normally, the activity of spinal cord networks is regulated supraspinally and by peripheral sensory input. In the case of disorders of the connections between the brain and spinal cord, e.g., as a result of traumatic spinal cord lesions or various neurodegenerative conditions, motor tasks can be enabled by electrical stimulation of the lumbosacral and cervical segments as well as the brainstem. Such stimulation has been provided using epidural stimulation or transcutaneous electrical stimulation (see, e.g., PCT/US2014/057886, PCT/US2014/029340, PCT/US2016/045898, PCT/US2015/047268, PCT/US2015/046378, PCT/US2016/049129, and the like). However, the use of systems to provide transcutaneous electrical stimulation has been hampered by the necessity to deliver relatively high voltage stimulation at the skin surface often resulting in discomfort and/or irritation and reduced subject compliance. SUMMARY In various embodiments electrical stimulators are provided for transcutaneous and/or epidural stimulation. In certain embodiments the stimulator provides one or more channels configured to provide one or more of the following stimulation patterns: i) monophasic electrical stimulation with a DC offset; ii) monophasic electrical stimulation with charge balance; iii) delayed biphasic electrical stimulation with a DC offset; iv) delayed biphasic electrical stimulation with charge balance; v) amplitude modulated dynamic stimulation; and/or vi) frequency modulated dynamic stimulation. Various embodiments contemplated herein may include, but need not be limited to, one or more of the following: Embodiment 1: A transcutaneous or epidural electrical spinal cord stimulator, said stimulator comprising one or more channels configured to provide one or more of the following stimulation patterns: i) monophasic electrical stimulation with a DC offset;ii) monophasic electrical stimulation with charge balance;iii) delayed biphasic electrical stimulation with a DC offset;iv) delayed biphasic electrical stimulation with charge balance;v) amplitude modulated dynamic stimulation; and/orvi) frequency modulated dynamic stimulation. Embodiment 2: The electrical stimulator of embodiment 1, wherein said stimulator comprises two or more independently configurable channels each capable of independently providing one or more of said stimulation patterns. Embodiment 3: The electrical stimulator of embodiment 1, wherein said stimulator comprises four or more independently configurable channels each capable of independently providing one or more of said stimulation patterns. Embodiment 4: The electrical stimulator of embod