Methods and systems for regulating and restoring independent stepping in patients with motor pathology

Abstract

This invention relates to the recovery of motor activity for gait dysfunction. The invention provides a method for using electrical stimulation of the spinal cord, comprising simultaneous and continuous stimulation of the spinal cord at the level of at least the T11-T12 vertebrae, and spatiotemporally and spatially selective stimulation of the root of the spinal cord at the level of the T11 and L1 vertebrae. The invention also provides a neuroprosthetic system comprising a multichannel stimulator for percutaneous electrical stimulation of the spinal cord, the multichannel stimulator including at least one storage device and one or more programs loaded into the at least one storage device, wherein the one or more programs include instructions; electrodes or an electrode array connected to the stimulator; at least one recording device for detecting contact and / or disengagement of a walking aid resting on the lower limb and / or upper limb during movement; and means for triggering or terminating stimulation.

Description

Technical Field

[0001] This disclosure relates to medicine and medical devices, and more specifically to neurophysiology and rehabilitation. Background Technology

[0002] Invasive methods for stimulating the spinal cord of monkeys with hindlimb paralysis (Marco Capogrosso et al., “Brain-spinal interface to alleviate gait deficits following spinal cord injury in primates,” *Nature*, Vol. 539, pp. 284–288 (2016)) and invasive methods for stimulating the spinal cord of mice with hindlimb paralysis (Parag Gad et al., “Forelimb EMG-based trigger for controlling an electronic spinal bridge to enable hindlimb stepping in mice after complete spinal cord injury,” *Journal of Neuroengineering & Rehabilitation* (2012)) are known. Rhythmic electrical stimulation of the motor cisterns of the hindlimb flexors and extensors, triggered by signals from the cerebral cortex, detects the phases of the motor cycle in monkeys with unilateral spinal cord transects (hemisci).

[0003] Motor movement in paralyzed hind limbs was initiated by electrical stimulation of the lumbar region of the spinal cord, triggered by signals from the forelimb muscles of the rats. These rats, whose spinal cords were completely severed in the thoracic region, moved along a treadmill. It was found that stimulation of the spinal cord resulted in incoordination of the rats' forelimbs and hind limbs. The transmission of commands from the brain to the motor cisterns of the hind limbs required circumventing the damaged portion of the spinal cord separating these areas; both studies addressed this issue. Motor function was modulated by stimulating the spinal cord at a level below the level of injury.

[0004] The two methods described above are invasive stimulation techniques associated with brain and spinal cord surgery in animals (Marco Capogrosso et al.) or spinal cord and forelimb muscle surgery (Parag Gad et al.). When using invasive stimulation methods, the necessity of postoperative care, the risk of inflammatory reactions, and the possibility of implant rejection must be considered. Furthermore, in both cases, movement was only achieved during spinal cord stimulation, indicating that this method compensates for motor function rather than representing functional recovery.

[0005] It is known that non-invasive magnetic stimulation of the spinal cord can be initiated through rhythmic arm movements, which trigger rhythmic electromagnetic stimulation of the spinal cord (Syusaku Sasada et al., “Voluntary walking achieved through stimulation of the human lumbar motor center by upper limb muscle control”, Journal of Neuroscience, August 13, 2014, Vol. 34, No. 33).

[0006] Magnetic stimulation has lower precision (targeting) than electrical stimulation. The magnetic coils that generate the magnetic field to impact the spinal cord have considerable mass and complex shapes. Therefore, additional fixation devices or auxiliary devices to hold the coil in place near the spinal cord are required. Consequently, magnetic stimulation cannot provide patients with independent stepping on flat surfaces. Magnetic stimulation of the spinal cord, even for short periods of motor activity (the duration of which coincides with the duration of magnetic stimulation), requires high signal intensity, necessitating a significantly larger battery capacity compared to electrical stimulation.

[0007] Recently, even with intensive rehabilitation, epidural electrical stimulation of the spinal cord has been able to control gait performance in humans who have suffered spinal cord injuries more than four years prior and have permanent motor deficits or complete paralysis. (“Targeted neurotechniques restore independent gait in patients with spinal cord injuries,” Nature, Vol. 563, pp. 65–71 (2018)). Spinal cord stimulation was performed using an implanted pulse generator capable of triggering real-time stimulation and an electrode array placed on the posterior surface of the spinal cord in the lumbosacral region. Information on the patient’s gait kinematics was processed in real time, including measurements of the electrical activity of the leg muscles (electromyography, EMG).

[0008] Spatiotemporally selective stimulation of the posterior root of the spinal cord was performed in sync with a phase of the stepping cycle (standing or limb transfer) to activate the motor pools of flexors and extensors at intervals required for stepping performance. Stepping characteristics improved during the rehabilitation process. Several months later, patients with incomplete spinal cord injuries regained voluntary control of previously paralyzed muscles without stimulation; patients were able to walk or cycle outside the laboratory during spinal cord stimulation.

[0009] The use of such stimulation is limited by the number of patients without contraindications for neurosurgery involving epidural electrode implantation. Any surgical procedure must consider the risks of the surgery itself, the risk of postoperative complications, the risk of rejection of the implantable device, and the necessity and duration of postoperative care, all of which depend on numerous factors. Furthermore, the transmission of commands to initiate and control stepping from the brain to the motor cisterns of the hindlimbs requires circumventing the spinal cord injury separating these areas, a problem that the aforementioned stimulation does not address. This movement is "mechanical," and because brain-controlled movement is impossible during such stimulation, it is unsuitable for these environmental conditions. Summary of the Invention

[0010] The purpose of this invention is to improve the neurological recovery of motor activity and quality of life in patients with brain and / or spinal cord diseases and injuries that lead to gait dysfunction, as well as to increase the efficiency and shorten the rehabilitation period, providing patients with the possibility of independent walking outside of hospital conditions.

[0011] The technical result achieved by this invention is the development of a non-invasive (surgery-free) spatiotemporal electrical stimulation method for the spinal cord:

[0012] - This method can utilize the natural coordination of upper and lower limb movements to enable patients with stepping dysfunction to achieve stepping function;

[0013] - This method enables the instruction to initiate spinal cord stimulation (which triggers stepping) from the movement of the upper body (arms, head, torso) and the control of stepping performance;

[0014] - This method enables the simultaneous stimulation of the spinal cord at different levels based on different selected algorithms, and can simultaneously use: stimulation of the cervical enlargement to ensure increased arm movement; stimulation of the lumbar enlargement region to increase its excitability.

[0015] - This method can promote independent stepping and also restore and provide independent stepping for patients with impairments caused by brain and / or spinal cord diseases and / or injuries, and can restore motor function of the upper and lower limbs.

[0016] Another technical result of this invention is the development of an apparatus for implementing the above-described method.

[0017] The technical results of the present invention are achieved by a method for promoting autonomous independent stepping using transcutaneous electrical stimulation of the spinal cord, the method comprising simultaneous and continuous stimulation of the spinal cord at the level of at least T11-T12 vertebrae in a patient with spinal cord and / or brain injury and / or disease, and spatiotemporally and spatially selective stimulation of the spinal cord root at the level of T11 and L1 vertebrae.

[0018] This involves triggering and stopping transcutaneous electrical stimulation of the spinal cord through external control.

[0019] In some implementations, one of the movements performed to control the device used to trigger or stop the stimulus may be externally controlled: movement of at least one intact upper or lower limb, head movement, shoulder elevation, trunk movement.

[0020] Furthermore, the trigger for spatiotemporal and spatial selective stimulation of the spinal cord root at the level of the T11 and L1 vertebrae is movement of the intact upper or lower limb.

[0021] The current intensity in transcutaneous electrical stimulation is individually selected based on the patient's motor response excitability and threshold, as well as pain sensitivity. In some embodiments, monopolar or bipolar rectangular pulses with modulation frequencies in the range of 5 kHz to 10 kHz are used for transcutaneous electrical stimulation of the spinal cord, wherein the frequency for continuous stimulation of the spinal cord at the level of at least T11-T12 vertebrae is selected in the range of 30 Hz to 45 Hz, the frequency for stimulation of the spinal cord root at the level of L1 vertebrae is selected in the range of 10 Hz to 30 Hz, and the frequency for stimulation of the spinal cord root at the level of T11 vertebrae is selected in the range of 30 Hz to 50 Hz. Irrelevant electrodes (anodes) are located on the skin above the iliac crest or on the abdomen. These anodes are symmetrically located in the left and right clavicular regions or on the iliac crest during stimulation of the spinal cord at the cervical level.

[0022] In another implementation, these stimuli are performed on patients with mild hemiplegia, where the patients walk on the ground or on a mobile treadmill by leaning their upper limbs against a fixed support (handrail) or by partially compensating for their weight with the aid of a suspension system during continuous stimulation of the spinal cord and spatiotemporally and spatially selective stimulation of the spinal cord roots.

[0023] In another implementation, the method includes the following steps:

[0024] 1) The stimulation was initiated by triggering and activating continuous stimulation at the level of at least T11-T12 vertebrae with the aid of external control, and by triggering spatiotemporal and spatial selective stimulation of the spinal cord root at the level of T11 and L1 vertebrae.

[0025] 2) When the intact lower limb begins to swing, activate stimulation of the spinal cord root on the injured side at the level of the L1 vertebra.

[0026] 3) When the intact lower limb begins to stand, stop the stimulation of the spinal cord root on the injured side at the level of the L1 vertebra, and at the same time activate the stimulation of the spinal cord root on the injured side at the level of the T11 vertebra.

[0027] 4) When the paralyzed lower limb begins to swing, stimulate the spinal cord root on the injured side at the level of the T11 vertebra.

[0028] 5) When the paralyzed lower limb begins to stand, stop stimulating the spinal cord root on the injured side at the level of the T11 vertebra.

[0029] 6) Repeat steps 2)-5) any number of times.

[0030] 7) Continuous stimulation of the spinal cord at least at the level of the T11-T12 vertebrae was stopped due to external control, and spatiotemporal and spatial selective stimulation of the spinal cord roots at the levels of the T11 and L1 vertebrae was stopped, which stopped the stimulation.

[0031] Furthermore, in implementing the steps of the above method, continuous stimulation of the spinal cord can be performed at the level of the C5-C6 vertebrae.

[0032] In another implementation, a patient with mild hemiplegia uses a support device to step on the ground or on a mobile treadmill during continuous stimulation of the spinal cord and spatiotemporally and spatially selective stimulation of the spinal cord roots, the support device being located in the intact upper limb.

[0033] In some implementations, the walking aid is selected from: walking sticks, canes, and crutches.

[0034] In some implementations, patients use a suspension system to perform stepping exercises.

[0035] In another implementation, the method includes the following steps:

[0036] 1) Continuous stimulation at the level of at least T11-T12 vertebrae is triggered and activated by external control, and spatiotemporal selective stimulation of the spinal cord root at the level of T11 and L1 vertebrae is initiated, which initiates the stimulation.

[0037] 2) When the intact lower limb begins to swing, activate stimulation of the spinal cord root on the injured side at the level of the L1 vertebra.

[0038] 3) When the intact lower limb begins to stand, stop stimulating the spinal cord root on the injured side at the level of the L1 vertebra.

[0039] 4) At the moment the walker is lifted off the surface, stimulation of the spinal cord root on the injured side at the level of the T11 vertebra is activated.

[0040] 5) When the paralyzed lower limb begins to swing, stimulate the spinal cord root on the injured side at the level of the T11 vertebra.

[0041] 6) When the paralyzed lower limb begins to stand, stop stimulating the spinal cord root on the injured side at the level of the T11 vertebra.

[0042] 7) Repeat steps 2)-6) any number of times.

[0043] 8) Due to external control, continuous stimulation of the spinal cord at the level of T11-T12 vertebrae and at the level of C5-C6 vertebrae was stopped, and spatiotemporal and spatial selective stimulation of the spinal cord roots at the level of T11 and L1 vertebrae was also stopped, thus ceasing stimulation.

[0044] In addition, continuous stimulation of the spinal cord can be performed at the level of the C5-C6 vertebrae. Triggering and activation of continuous stimulation are first performed at the level of the T11-T12 vertebrae, and then at the level of the C5-C6 vertebrae. Transcutaneous electrical stimulation is performed using a multichannel stimulator.

[0045] In some implementations, at least one recording device is used for detection:

[0046] - The contact between the walking aid on which the lower limb or intact upper limb rests and the surface;

[0047] - A walking aid with the lower limb or intact upper limb resting on it is off the surface;

[0048] And when the aforementioned event is detected, the at least one recording device sends a control signal to the stimulator.

[0049] In some embodiments, the stimulator includes at least one storage device and one or more programs loaded into the at least one storage device, wherein the one or more programs include instructions for: triggering and stopping stimulation according to a control signal received from a device for triggering or stopping stimulation during external control; activating and stopping continuous stimulation by adjusting the current supply to the corresponding electrode according to a control signal received from a device for triggering or stopping stimulation during external control; and activating and stopping spatiotemporally and spatially selective stimulation of the spinal cord root by adjusting the current supply to the corresponding electrode according to a control signal received from at least one device for recording the detection of contact and / or departure of a walker resting on an intact lower limb and / or a slightly paralyzed lower limb and / or an intact upper limb.

[0050] The technical results are also achieved by the following: a spinal nerve prosthesis that promotes voluntary stepping performance in patients with spinal cord or brain injury and / or disease includes a multichannel stimulator for transcutaneous electrical stimulation of the spinal cord, the multichannel stimulator including at least one storage device and one or more programs loaded into the at least one storage device, wherein the one or more programs include instructions for implementing the above-described method; and electrodes connected to the specific stimulator; at least one recording device for detecting contact and / or disengagement of a walking aid resting on the intact lower limb and / or slightly paralyzed lower limb and / or intact upper limb during stepping; and a device for triggering or terminating stimulation.

[0051] In addition, the at least one recording device may be selected from: a surface contact sensor, or a surface contact sensor of a walking aid.

[0052] In addition, the device for triggering or stopping the stimulus can be made in the form of an electromechanical switch or a radio frequency switch.

[0053] In addition, spinal nerve prostheses may include accelerometers and / or angular velocity sensors and / or joint angle sensors. Attached Figure Description

[0054] The features of the present invention will become more apparent from the following detailed description, with reference to the accompanying drawings, as follows:

[0055] Figure 1 The posture of the subjects in a biomechanical training machine used for neurorehabilitation of motor and visceral functions is shown.

[0056] Figure 2 A protocol for studying how voluntary arm movements affect the characteristics of involuntary leg movements induced by transcutaneous electrical stimulation of the spinal cord (TESSC) is presented.

[0057] Figure 3 This document records how arm movements affect the characteristics of involuntary leg movements induced by TESSC.

[0058] Figure 4 The results of recording and analysis of the effects of arm movements on the characteristics of movements induced by TESSC are shown.

[0059] Figure 5 This study demonstrates how periodic TESSCs at different roots of the spinal cord (spatiotemporal TESSCs) applied at different stages of stepping modulate the characteristics of human stepping movements during the study of subjects’ postures.

[0060] Figure 6 The cathode locations in the projection sites of the spinal cord and spinal cord root are shown during the study of the effects of spatiotemporal TESSC on the characteristics of human stepping motion.

[0061] Figure 7 The study shows EMG activity of the leg muscles and angles in the knee joint during the subjects' pedaling on the treadmill.

[0062] Figure 8 The movement trajectory of the legs during stepping on a treadmill is shown in the absence of stimulation and in the presence of continuous and periodic TESSC at different levels. Detailed Implementation

[0063] Definitions of some terms used in this specification are listed below. Unless otherwise stated, the technical and scientific terms used in this application have the standard meanings generally accepted in scientific and technical literature.

[0064] The terms “include,” “contain,” “have,” “supply,” “include,” and their other grammatical forms are not intended to be interpreted in an exclusive sense, but rather are used in a non-exclusive sense (i.e., in the sense of “having in its combination”).

[0065] The terms “motion regulation” and “motion control” generally refer to the control of stepping characteristics (speed, stepping amplitude, duration) and their components, such as the phases of the stepping cycle (swinging, standing).

[0066] "Movement facilitation" refers to specific situations of motor regulation in which managing motor characteristics guides improvements in coordination, gait stability, and movement speed.

[0067] The term “stimulus” refers to an alternating current electric shock, where “continuous stimulation” refers to stimulation whose start and end are independent of the rhythmic movements of the intact (unaffected by the pathological process causing hemiplegia) arm and leg; “intermittent (rhythmic) stimulation” refers to stimulation whose start and end are synchronized with the rhythmic movements of the intact arm and leg; “spatially selective stimulation” is understood as intermittent (rhythmic) stimulation in which the level of stimulation and the lateralization (right or left) of the stimulation depend on the movement phase of the intact arm and leg; and “spatiotemporal stimulation” refers to spatially selective stimulation in which the start and end of the stimulation depend on the movement phase of the intact arm and leg.

[0068] The terms “synergy,” “motor synergy,” and “motor coordination” refer to the associated and coordinated contraction and relaxation of arm and leg muscles during stepping movements. It has been shown that the control of human and animal movement is achieved not as the control of individual muscles, but as the control of motor synergy (Aleksandrov et al., “Sustainable control of posture and movement of standing human figures based on the principle of natural human synergy,” Russian Journal of Biomechanics, 2013, Vol. 17, No. 59, pp. 94-109).

[0069] The term "synergistic activation of movement" refers to the associated and coordinated contraction and relaxation of leg muscle groups during movements of the arms and other parts of the body. The benefits of synergistic activation include promoting movement induced by transcutaneous stimulation of the spinal cord (TESSC) and facilitating the activation of intrinsic mechanisms for controlling movement.

[0070] Examples of brain and / or spinal cord disorders include stroke leading to impaired motor function, degenerative and inflammatory diseases of the brain or spinal cord, and iatrogenic diseases. Examples of brain and / or spinal cord injuries include concussion, brain compression, brain injury, cerebral hemorrhage due to head impact, spinal cord concussion, spinal cord injury, spinal cord compression, anatomical rupture of the spinal cord, spinal cord hemorrhage, spinal cord thrombosis, injury to the main blood vessels of the spinal cord, and injury to the spinal nerve roots.

[0071] Furthermore, the terms “first,” “second,” “third,” etc., are simply used as conditional markers without imposing any numerical, order, or other restrictions on the listed objects.

[0072] The term "connection" refers to functional interconnection and any number or combination of intermediate elements between interconnected components (including the absence of intermediate elements).

[0073] Human movement involves the coordinated movement of all four limbs, in which the neural networks controlling upper limb movement interact closely with the neural networks controlling lower limb movement coordination (Zehr EP, Duysens J., "Regulation of arm and leg movements during human movement", Neuroscientist, 2004, Vol. 10, No. 4, p. 347; Selionov VA et al., "Interlimb interactions in periodic in-phase and out-of-phase movements of the hands and feet and their dependence on afferent influences", Human Physiology, 2014, Vol. 40, No. 4, pp. 410-421).

[0074] Unlike most other mammals, although humans are characterized by bipedal locomotion, arm movements modulate leg movements during walking. Significant changes were recorded in leg muscle reflex parameters recorded when subjects walking on a treadmill were instructed to move at a rhythmic pace. The measured characteristics of these reflexes were influenced by the phase and speed of arm movements, as well as other features of arm movement. (Zehr EP, Chua R, 2000, “Modulation of human skin reflexes during rhythmic and periodic arm movements,” Exp Brain Res, Vol. 135, pp. 241-250; Zehr EP, Kido A, 2001, “Neural control of rhythmic and periodic human arm movements: task-dependent, neural specificity and phase modulation of skin reflexes,” J Physiol (Lond), Vol. 537, pp. 1033-1045; Zehr EP, Collins DF, Frigon A, Hoogenboom N, 2003, “Neural control of rhythmic human arm movements: phase dependence and task modulation of Hoffmann reflexes in forearm muscles,” J Neurophysiol, Vol. 89, pp. 12-21).

[0075] Studies on healthy volunteers have shown that if the right and left arms move vigorously in the opposite phase to the ipsilateral leg, arm movements at speeds of 1–7 km / h increase stability during pedaling on a treadmill. However, if they do not move during walking or move in the same phase as the ipsilateral leg, stability is not affected (Punt M. et al., “The Influence of Arm Swing Strategies on Local Dynamic Stability of Human Gait”, Gait & Posture, 2015, Vol. 41, No. 2, pp. 504–509).

[0076] The study also showed that the spatial organization of human limb movement is a fundamental factor determining muscle activity. (Selionov V.A. et al., “Interlimb interactions and their dependence on afferent influences in periodic in-phase and out-of-phase movements of the hands and feet”, Human Physiology, 2014, Vol. 40, No. 4, pp. 410-421).

[0077] Muscle activity in the upper and lower limbs was recorded during individual and combined periodic movements of the arms and legs in 10 healthy subjects in a prone position, with different phase relationships between limb movements. Antiphase active arm movements were characterized by greater muscle activity than in-phase movements. Significantly increased activity was observed in the biceps brachii, tibialis anterior, and biceps femoris muscles of the arm during a motor task involving combined in-phase movements of the upper and lower limbs, compared to a motor task involving combined in-phase movements of the upper and lower limbs.

[0078] It has been shown that arm training during motor rehabilitation in stroke patients affects stepping performance due to activation of interneuronal connections (Kaupp C, Pearcey GE, Klarner T, Sun Y, Cullen H, Barss TS, Zehr EP, “Rhythmic arm cycle training improves stepping performance and neurophysiological integrity in chronic stroke: the arm can assist the leg in rehabilitation,” J Neurophysiol, Vol. 119, pp. 1095–1112, 2018). In these patients, cycled arm movements modulated the magnitude of reflexive motor responses in leg muscles, increased leg muscle strength, coordination of muscle activity during stepping, and coordination between the arm and leg during movement.

[0079] The purpose of this invention is to provide a system and method for regulating and restoring independent stepping in patients with various etiologies of motor pathology by using multi-segment transcutaneous electrical electrical stimulation (TESSC) and activating intrinsic interlimb motor coordination.

[0080] Transcutaneous electrical stimulation (TES) induces simultaneous activation of several spinal cord segments. Therefore, it is possible to simultaneously activate spinal structures that regulate movement, both directly and indirectly. Direct rhythmic stimulation is associated with targeted activation of the motor pool of muscle groups involved in different phases of stepping. Continuous stimulation targets the neuromotor network that generates movement patterns, i.e., sets rhythmic motor structures and defines motor structures. Thus, during stimulation-induced movement of the unaffected upper and / or lower limbs (arms or legs), the affected lower and / or upper limb muscle groups exhibit combined and coordinated contraction and relaxation, incorporating intrinsic motor control mechanisms.

[0081] The stimulus consists of continuous stimuli and intermittent (rhythmic) stimuli.

[0082] Provide continuous stimulation to promote movement of intact limbs. Use continuous stimulation of the lumbar enlargement of the spinal cord at the level of the T11-T12 vertebrae to promote leg movement. If increased arm movement is desired, additionally perform continuous stimulation of the cervical region of the spinal cord (cervical enlargement) at the level of the C5-C6 vertebrae. Additional continuous stimulation may also be applied to the thoracic and / or sacral regions of the spinal cord.

[0083] In the presence of continuous stimulation of at least one of the aforementioned spinal cord regions, intermittent (rhythmic) stimulation of the spinal cord roots at the level of the T11 and L1 vertebrae occurs to achieve a specific type or phase of movement synchronized with the rhythmic movement of the intact upper and / or lower limbs (arms and legs).

[0084] The rhythm or continuous stimulation pattern is prescribed by an expert / physician and determined by the pathology and characteristics of movement in intact parts of the body.

[0085] The pattern of stimulation and stepping typically consists of several phases characterizing the process of stepping. Stepping comprises a propulsion phase, a swinging phase, and a standing phase (based on the kinematics of leg movement). Information about the specific phases of stepping is detected, where spatially selective rhythmic stimulation of spinal cord sites is synchronized with the type of movement performed within a given time period. The movement phases of the intact arms and legs (spatial-temporal rhythmic stimulation) determine the start and end of the stimulus.

[0086] Information about the stepping phase is needed to activate spinal cord stimulation at the correct time and location: extensors need activation during the standing phase, and flexors need activation during the swinging phase. Therefore, rhythmic stimulation of the upper segment of the lumbar enlargement of the spinal cord is performed during the detectable stepping and swinging phases to activate flexors. Stimulation of the lower segment of the lumbar enlargement of the spinal cord is performed during the detectable standing phase to activate leg extensors. Stimulation of the right spinal cord root modulates movement of the right leg, and stimulation of the left spinal cord root modulates movement of the left leg. The accuracy of percutaneous “to-root” stimulation makes it possible to target muscle activity as follows: right or left side muscle activity, flexor and extensor activity.

[0087] The duration of a single phase of rhythmic stimulation is determined by the characteristics of the patient’s gait and movement of the intact upper and / or lower limbs, and in particular, depends on the phase and speed of the movement of the patient’s upper and / or lower limbs.

[0088] Transcutaneous electrical stimulation of the spinal cord is achieved using monopolar or bipolar rectangular pulses with a current amplitude of 1 to 200 mA and a modulation frequency in the range of 5 kHz to 10 kHz.

[0089] In a preferred embodiment, the current amplitude does not exceed 100mA, as it is intended for use on patients with intact sensation to stimulate the spinal cord.

[0090] The current intensity during stimulation is prescribed by a specialist / physician, but can be adjusted by the patient within a limited range. The current intensity is selected individually based on the patient's excitability of motor response, individual threshold values, and pain sensitivity.

[0091] The frequency of transcutaneous electrical stimulation (TES) ranges from 1 to 99 Hz. In some cases, the frequency of continuous stimulation of the spinal cord at least at the level of T11-T12 vertebrae is selected in the range of 30 to 45 Hz. In some cases, if simultaneous continuous stimulation of the spinal cord at the levels of C5-C6 and T11-T12 vertebrae is required, the stimulation frequency is selected in the range of 30 to 45 Hz. In specific cases, the frequency of rhythmic stimulation of the spinal cord root at the level of L1 vertebrae is selected in the range of 10 to 30 Hz. In specific cases, the frequency of rhythmic stimulation of the spinal cord root at the level of T11 vertebrae is selected in the range of 30 to 50 Hz.

[0092] Multi-segmental stimulation exposure of the spinal cord structures is performed via individual electrodes or electrode arrays fixed in the patient's spinal region. Electrode arrays for percutaneous stimulation of the spinal cord can be placed on the skin above the spine in the thoracic, cervical, and / or lumbar regions of the spinal cord, at the projection sites of corresponding neurons and neural networks in the spinal cord.

[0093] The triggering and termination of the stimulus can be performed from a device for triggering or terminating the stimulus, which receives a signal characterizing any external control. Movement of at least one of the intact upper / lower limbs, head movement, shoulder elevation, trunk movement, and any other movement can be selected as external control.

[0094] For example, movements in the shoulder joint detected when leaning against a walking aid (which includes a walking stick, cane, crutch, etc.) held by the patient's appropriate arm can act as external control. Movements in the patient's shoulder joint trigger stimuli, causing the contralateral leg to lift off the surface.

[0095] For example, in cases where at least one arm can move while stepping, the movement of the intact upper limb (arm) can act as external control. In this case, the movement of at least one arm triggers a stimulus and causes the contralateral leg to leave the surface.

[0096] In some cases, when the pathology of the injury allows the patient to stand and walk slightly, but the arm is unable to move or has been amputated, spatiotemporal stimulation of the spinal cord may be triggered in any way that the patient can use, such as by turning the head or raising the shoulder, even though it is impossible to use interlimb coordination.

[0097] The present invention also relates to a spinal nerve prosthesis by means of which transcutaneous electrical stimulation of the spinal cord is performed, and which modulates and restores independent stepping in patients with motor deficits of various causes. The spinal nerve prosthesis serves as a device for transport and rehabilitation, and its use not only guides the restoration of normal stepping but also guides the restoration of mobility in the slightly paralyzed arm of a stroke patient.

[0098] A spinal nerve prosthesis is a composite of a multichannel stimulator for percutaneous electrical stimulation of the spinal cord and electrodes connected to the stimulator or an electrode array attached to the skin above the patient's spine. The electrodes or electrode array are designed for reusability and have high conductivity. Furthermore, the spinal prosthesis includes at least one recording device for detecting specific phases characterizing stepping performance, and a device for triggering or terminating stimulation.

[0099] The recording device is designed to detect contact between a walking aid resting on a lower limb or intact upper limb and a surface, and for the walking aid resting on a lower limb or intact upper limb to leave the surface, wherein the recording device is designed to send a control signal to a stimulator when the aforementioned events are detected.

[0100] The data transmission facility is selected from devices designed to enable communication between different devices via wired and / or wireless communication. In particular, such devices may be: GPS modems, BLE modules, or Bluetooth, Wi-Fi transceivers, etc.

[0101] The stimulator provides a specific form of current supply to the corresponding electrodes based on control signals received from the recording device, according to a specific algorithm. A program containing the necessary instructions for adjusting and restoring independent stepping based on the pathology of the patient's motor activity is included in at least one storage medium of the stimulator.

[0102] Storage devices can be hard disk drives (HDDs), solid-state drives (SSDs), flash memory (NAND-flash, EEPROM, DataFlash, etc.), mini drives, or combinations thereof.

[0103] The microcontroller performs the main computational work to implement the algorithm for supplying current to the electrodes based on the received data. The components of the stimulator are interconnected via a data bus.

[0104] The stimulator's microcontroller provides triggering and termination of stimulation based on control signals received from means for triggering or terminating stimulation during external control. Specifically, the microcontroller provides a current supply of a given shape and frequency to one or another channel of the stimulator, and thus provides a current supply of that given shape and frequency to the corresponding electrode connected to the microcontroller.

[0105] The stimulator's microcontroller provides activation and cessation of continuous stimulation by adjusting the current supply to the corresponding electrodes, based on control signals received from a device for triggering or terminating stimulation during external control.

[0106] Devices for triggering or stopping stimulation can be implemented using buttons pressed with the chin or shoulder, walkers, myostats of the patient's moving parts, or any other means. Devices for triggering or stopping stimulation can be made in the form of electromechanical switches or radio frequency switches.

[0107] The microcontroller of the stimulator provides on and off intermittent (rhythmic) stimulation of the spinal cord root by adjusting the current supply to the corresponding electrodes, based on control signals received from a device for detecting contact and / or departure of a walker on which the intact and / or slightly paralyzed lower limb and / or intact upper limb rest.

[0108] The recording device can be made into the form of a sensor that contacts a surface or a sensor that contacts a surface on a walking aid.

[0109] Accelerometers and / or angular velocity sensors and / or angle change sensors connected to a microcontroller via data transmission devices in the joint may also be included in the spinal nerve prosthesis kit.

[0110] Further details on the steps for adjusting and restoring a patient's independent gait are provided by the example of mild hemiplegia. Mild hemiplegia can occur as a standalone phenomenon, or it can be a stage in the development of hemiplegia, or it can be detected only when limb function recovers after hemiplegia.

[0111] During training, patients can walk on a fixed or moving treadmill by resting their unaffected upper limb on a fixed support (handrail). For example, a patient may stand on the treadmill or between parallel bars while simultaneously gripping a bar on a training machine with their unaffected arm, or a patient may stand on the floor while resting their unaffected arm on a handrail.

[0112] In an alternative implementation, when a patient has poor coordination, a suspension system can be used to train independent stepping with partial weight compensation. Additionally, this type of training can be used for patients with hemiplegia of the upper limbs who have bilateral arm paralysis. For example, the patient can be secured to the pelvic region with straps and suspended in an upright position, allowing the lower limbs to be free while the patient leans against a support. The patient's body is in a pendulum position.

[0113] In another alternative implementation, the patient can walk on a fixed or movable surface using a walking aid with their relatively intact arm resting on it. Walking canes, forearm crutches, orthopedic canes, etc., used for cross-country walking can be used as walking aids.

[0114] The preparation phase is performed before training begins. An electrode array is placed on the skin, above the spine at the level of certain parts of the spinal cord. Electrodes within the array can be used independently, or individual electrodes can be placed for percutaneous spinal cord stimulation (TSSC).

[0115] More specifically, the cathodes are placed and fixed in the midline between the T11 and T12 vertebrae and 1-3 cm posterior to the midline, above the spinal cord root on the affected side at the level of the T11 and L1 vertebrae. The common anode for all these cathodes is located only above the iliac crest on the cathode side or both sides.

[0116] Additionally, the cathode is placed and fixed in the midline between the C5 and C6 vertebrae, and the anode is placed above the iliac crest to stimulate the enlarged neck region. In specific cases (for more selective stimulation of the enlarged neck region), the anode is located above the clavicle.

[0117] After the electrodes or electrode arrays are installed, they are connected to a multichannel stimulator for transcutaneous electrical stimulation.

[0118] The choice of stimulation intensity is performed by a specialist / physician and the patient. For continuous and rhythmic stimulation (30-40Hz), the current intensity should be at a level that causes paresthesia (tingling, burning, mild pain, heaviness in the cathode area) or 5-10% lower. Stimulation using a central cathode placed in the midline between the C5-C6 and T11-T12 vertebrae should not cause discomfort or pain.

[0119] A single stimulation at a frequency of 10-50 Hz, lasting 1 second (1 ms), to induce leg muscle contraction is used for stimulation with lateral cathodes (T11 and L1). This intensity of current is then used for walking, but it should not cause discomfort. Otherwise, the intensity should be reduced.

[0120] The current selection occurs only once, not before each use of the spinal nerve prosthesis. The current selection is repeated if the electrodes (cathode / anode) are changed or if the nerve prosthesis has not been used for an extended period (a week or more). The value of the selected current intensity is stored in a data storage device for the TESSC multichannel stimulator, which is included in the spinal nerve prosthesis. Stimulation is initiated in a standing or sitting position. Triggering is arbitrary, as external controls use the aforementioned triggering and stopping devices to initiate stimulation. The stimulator channels for the TESSC are sequentially switched, supplying current to cathodes located at the level of the T11-T12 and C5-C6 vertebrae. Stimulation of these cathodes begins and ends only after arbitrary switching on and off. Additionally, the stimulator channels supplying current to lateral cathodes located above the spinal cord root on the affected side at the level of the T11 and L1 vertebrae are sequentially triggered.

[0121] At the moment of activation, the current intensity on the lateral cathodes is zero. During movement of the intact upper and / or lower body (conditionally healthy arms and legs), the stimulator channels connected to the lateral electrodes are switched on, and modulated monopolar or bipolar pulses of rectangular current are applied to electrodes located above the spinal cord roots on the affected side at the level of the T11 and L1 vertebrae. Therefore, arbitrary triggering of stimulation of the lateral cathodes is essentially permission for stimulation of these cathodes.

[0122] Simultaneously, continuous stimulation is performed at the levels of the T11-T12 and C5-C6 vertebrae throughout the training period. In one implementation, the triggering and activation of continuous stimulation occurs only at the level of the T11-T12 vertebrae to activate the neuromotor network of the spinal cord at the level of the lumbar enlargement. In another implementation, the triggering and activation of continuous stimulation occurs at the levels of both the T11-T12 and C5-C6 vertebrae to simultaneously activate the neuromotor networks that regulate leg and arm movements, respectively.

[0123] In one implementation, when a patient is, for example, leaning on an intact upper limb and standing on a fixed surface, the method for regulating and restoring the patient's independent movement is as follows:

[0124] Following the preparation phase and arbitrary triggering stimulation, continuous stimulation is applied at least at the level of the T11-T12 vertebrae, and spatiotemporally and spatially selective stimulation of the spinal cord roots at the levels of the T11 and L1 vertebrae is triggered. The patient uses their intact upper limb to lean against and stand on a fixed surface. Walking is initiated from the standing position.

[0125] The patient moves the intact lower limb as if moving without removing the fixed walking aid, shifting the body weight forward onto the intact side. As the intact lower limb begins its swinging phase, stimulation is activated on the spinal cord root at the level of the L1 vertebra on the injured side. The duration of this stimulation is determined by the time from the moment the intact lower limb is lifted off the surface until it is placed back on it. Therefore, the intact lower limb (the conditionally healthy leg) is positioned in front of the paralyzed lower limb.

[0126] With the intact lower limb placed on the surface, stimulation of the lateral cathode T11, located above the spinal cord root on the injured side at the level of the T11 vertebra, is activated and maintained, while stimulation of the spinal cord root on the injured side at the level of the L1 vertebra is terminated. This stimulation induces movement of the contralateral hemiparesis lower limb, which lifts off the surface and transfers forward to the position of the intact lower limb to bear weight. Stimulation of the spinal cord root on the injured side at the level of the T11 vertebra is terminated when the hemiparesis lower limb contacts the surface.

[0127] This cycle can be repeated any number of times. Stimulation termination is arbitrarily executed via external control by a device used to trigger and terminate stimulation. The patient sits down and the connection to the spinal nerve prosthesis is disconnected upon cessation of walking.

[0128] In one implementation, when a patient stands on a fixed surface, for example using a walking aid with their intact upper limb resting on it, the method for adjusting and restoring the patient's independent stepping is performed as follows:

[0129] Following the preparation phase and arbitrary initial stimulation, sequential stimulation is activated at the level of the T11-T12 vertebrae, followed by sequential stimulation at the level of the C5-C6 vertebrae if necessary, and spatiotemporally and spatially selective stimulation of the spinal cord roots at the levels of the T11 and L1 vertebrae is triggered. The patient stands on a fixed surface, leaning on a walker with their unaffected upper limb. The unaffected upper limb on the conditionally healthy side of the patient's body is leaned on the walker (walking stick, cane, crutch). The walker is positioned on the fixed surface and slightly forward relative to the patient's lower limb for stability. Stepping is initiated from the standing position.

[0130] The patient moves the intact lower limb as if walking without removing the walker, shifting the body weight forward onto the unaffected side. As the intact lower limb leaves the surface, stimulation of the spinal cord root at the level of the L1 vertebra is activated. The duration of this stimulation is determined by the time from the moment the intact lower limb is lifted off the surface until it is placed back on it. Stimulation of the spinal cord root at the level of the L1 vertebra is discontinued after the intact lower limb has been placed on the surface. Therefore, the intact lower limb (the conditionally healthy leg) is placed in front of the paralyzed lower limb and the walker.

[0131] Furthermore, the intact upper limb, resting on the walker, removes the walker from the surface and moves it slightly forward relative to the intact lower limb. At the instant the walker's device leaves the surface, stimulation of the lateral cathode T11, located above the spinal cord root on the injured side at the level of the T11 vertebra, is activated. This stimulation induces movement in the contralateral hemiplegic lower limb, which leaves the surface and shifts forward to the position of the intact lower limb, thereby bearing weight. When the hemiplegic lower limb contacts the surface, stimulation of the spinal cord root on the injured side at the level of the T11 vertebra is interrupted.

[0132] This cycle can be repeated any number of times. Stimulation termination is arbitrarily executed via external control by a device used to trigger and terminate stimulation. The connection to the spinal nerve prosthesis is disconnected upon cessation of walking.

[0133] The above methods, while including the function of using a walking aid to maintain body weight support, can also be extended to mild paralysis of the lower limbs (spinal cord injuries with similar motor impairments at ASIA level D or E severity, cerebral palsy, brain injury, demyelinating diseases, etc. at GMFCS level 1-3 severity).

[0134] In this case, the stimulation will also be spatiotemporal. The triggering of the stimulation can occur from the intact upper limb (arm). For example, the right arm triggers stimulation of the muscles that provide support for the standing and transfer phases of the left leg, and symmetrically, the left arm triggers stimulation of the muscles that provide support for the standing and transfer phases of the right leg. This method may also be used to treat quadriplegia when the patient has the opportunity to stand with or without a walking aid. Arm movement can be increased by stimulating the neck region.

[0135] It is important to note that multi-segmental non-invasive stimulation of the cervical and lumbar regions of the spinal cord is intended to modulate interlimb coordination. Therefore, stimulation of the cervical region will also restore motor function in the mildly paralyzed arm while ensuring interlimb coordination. It has been shown that TESSC in the cervical region guides the recovery of upper limb function in paralyzed patients (Inanici F. et al., “Percutaneous spinal electrical stimulation promotes long-term recovery of upper limb function in patients with chronic quadriplegia,” IEEE Transactions on Neurological and Rehabilitation Engineering, 2018; Gad P. et al., “Non-invasive activation of the cervical network after severe paralysis,” Journal of Neurotrauma, January 2018).

[0136] The results of using the technology of the present invention are demonstrated in the embodiments provided below. It should be understood that these and all embodiments given in the application materials are not limiting and are only used to illustrate the present invention.

[0137] Example 1. Voluntary arm movements increased involuntary leg movements induced by transcutaneous electrical stimulation of the spinal cord. Amplitude.

[0138] This study was conducted to demonstrate that rhythmic arm movements enhance the exercise effects induced by TESSC.

[0139] method

[0140] This study was conducted at the Velikie Luki State Academy of Physical Education and Sports (VLSAPEC). Healthy volunteers—young men, VLSAPEC employees, and students (N=11, 20–35 years old)—participated in the study. Informed written consent was obtained from participants in accordance with the principles of the Declaration of Helsinki.

[0141] refer to Figure 1 Subjects were in a biomechanical training machine used for neurorehabilitation of motor and visceral functions. In a semi-reclining position Figure 1The training machine provides arbitrary or forced movements of the legs and / or arms. Leg movements are performed at the hip, knee, and ankle joints, simulating walking in the field. Arm movements are performed at the shoulder, elbow, and wrist joints, directed to the shoulder, and pushed off levers in the sagittal plane. Percutaneous stimulation of the spinal cord in subjects is performed at three levels: between the T12-L1, L1-L2, and C4-C5 vertebrae. The TESSC method has been described in detail previously [Gerasimenko Y. et al., “Initiation and Modulation of Motor Circuit Output of Spinal Cord Using Multi-Site Percutaneous Electrical Stimulation in Uninjured Subjects,” *Journal of Neurophysiology*, 2014, Vol. 113, No. 3, pp. 834-842]. The five-channel programmable neurostimulator Biostim-5 (Grishin et al., 2017), which can be used in diagnostic and therapeutic procedures using non-invasive electrical stimulation of the spinal cord, was used for TESSC. Rectangular monopole pulses modulated with a carrier frequency of 5 kHz and a duration of 1 ms were used. The pulse repetition frequency was 30 Hz. Stimulation intensity was selected individually, with pulse amplitude gradually increased from 5 mA to achieve motor responses in all recorded leg muscles during stimulation at the lumbar level, and subject perception during stimulation at the neck level. The maximum current intensity was 70 mA during stimulation at the lumbar level and 30 mA during stimulation at the neck level. Electromuscular activity (EMG) of the hip, biceps femoris, rectus femoris, gastrocnemius, and tibialis anterior muscles of both legs was recorded using conductive plastic skin electrodes with adhesive surfaces (Kendal). An elbow goniometer was used to record arm movements. The hardware-software complex Mega (Finland) was used to record EMG and limb movements. Video recording was also performed using the Qualisys medical video capture system, attaching reflective markers to the subject's body from both sides of the flexion points of the shoulder, hip, knee, and ankle joints, as well as on the big toe.

[0142] refer to Figure 2 Zero on the timeline corresponds to the start of motion recording; T12-L1, L1-L2, and C4-C5 correspond to the instant of the start of TESSC at each specific level; VA represents voluntary arm movement. Subjects were in the training machine at rest. Figure 2 After 30 seconds, TESSC was started at the level of T12-L1 vertebrae. After another 30 seconds, stimulation was increased at the level of L1-L2 vertebrae, and after another 30 seconds, stimulation was increased at the level of C4-C5 vertebrae. Stimulation continued at the three levels. After another 30 seconds, the subject began to perform voluntary arm movements under the instruction of the experimenter.

[0143] The effects of the nature of the movement and the TESSC condition on the kinematic parameters of leg movement and leg muscle activity were analyzed. Kinematic characteristics were calculated based on video recordings using coordinates of markers located on the joints, while step amplitude and velocity were calculated using coordinates of the big toe movement. Muscle activity was assessed using the integral characteristics of EMG for each stimulation mode. For this purpose, the EMG recordings were filtered to remove artifacts from the TESSC, inverted to the positive region, and the area under the curve was determined over 30 seconds. The changes in integral characteristics in each mode were assessed relative to the values ​​at the start condition (i.e., the first 30 seconds of the study). The relative values ​​calculated for all subjects were averaged, taking into account the results for both legs. Mathematical data processing was performed using the original program and Microsoft Excel spreadsheet.

[0144] result

[0145] Figure 3 This study record shows how arm movements obtained from subject BA affect the characteristics of involuntary leg movements induced by TESSC. 1-4 – EMG of the right leg muscles: tibialis anterior (1), gastrocnemius (2), biceps femoris (3), and rectus femoris (4). 5 – Angle changes in the right elbow joint. 6 – Changes in the position of the right thumb. 7, 8, and 9 – Activity markers of stimulation pathways at the levels of the T12-L1, L1-L2, and C5 vertebrae, respectively. The asterisk above line 6 indicates that movement of the right leg has been initiated.

[0146] Figure 4Records analyzing the effects of arm movements on the characteristics of movements induced by TESSC are shown. A – Changes in the angles of the right hip (H), knee (K), ankle (A), and elbow (E) joints at the initiation of TESSC at the levels of the T12-L1 (1ch), L1-L2 (2ch), and C4-C5 (3ch) vertebrae, and during voluntary arm movements; asterisks indicate the initiation of movement in the joints of the subject's BA. B – The reciprocity of movements in the hip joints of the left and right legs corresponds to the time intervals of the square assignments in part A. C – Changes in the overall characteristics of EMG activity of leg muscle activity; pattern sequence – on the horizontal axis: 1 – resting state, 2, 3, 4 – TESSC performed through channels 1 (at the level of the T12-L1 vertebrae), 2 (L1-L2), and 3 (C4-C5), respectively, 5 – voluntary arm movements. On the vertical axis – integral characteristics of 30-second EMG, with reference to their values ​​at rest, mean for all subjects, and relative values.

[0147] TESSC in the lumbar region of the spinal cord (with electrodes placed on the T12-L1 and L1-L2 vertebrae) did not induce any leg movement in any subject. Figure 3 , Figure 4 ), but increased muscle activity ( Figure 4 C). No movement during increased muscle activity was associated with insufficient muscle activity in relation to the heavy slide used to move the training machine. Additional stimulation in the neck region elicited low-amplitude leg movements in some subjects. Figure 4 A); When the slide of the training machine is stationary, the movement amplitude of the mark on the thumb is as high as 4-5cm. Figure 3 ).

[0148] Spontaneous rhythmic arm movements in the sagittal plane elicited rhythmic movements in the leg joints of all subjects during TESSC in the lumbar and cervical regions. Figure 4 A). Furthermore, the movements in the right and left leg joints are interactive ( Figure 4 B), meaning the resulting movement is similar to stepping. Muscle activity is greatest during voluntary arm movements. Figure 4 B).

[0149] in conclusion

[0150] In the presence of multi-stage TESSC, the voluntary arm movements in the rhythm of stepping increase the total activity of the leg muscles and help to initiate rhythmic, stepping leg movements.

[0151] Example 2. Spatiotemporal transcutaneous electrical stimulation of the spinal cord modulates the characteristics of human stepping movements.

[0152] This study was conducted to demonstrate that, based on the stepping phase, it is possible to modulate the swing phase of the stepping cycle (flexion) by periodically stimulating the spinal cord root at the level of the T11 vertebra, and based on the stepping phase, it is possible to modulate the standing phase (extension) by periodically stimulating the spinal cord root at the level of the L1 vertebra.

[0153] method

[0154] The study was conducted at the Velikie Luki State Academy of Physical Education and Sports (VLSAPEC). Healthy volunteers—young men, VLSAPEC employees, and students (N=9, aged 20–35)—participated in the study. Informed written consent was obtained from participants in accordance with the principles of the Declaration of Helsinki.

[0155] refer to Figure 5 This illustrates how periodic TESSC (spatiotemporal TESSC) applied to different roots of the spinal cord at different stages of stepping modulates the characteristics of human stepping movements during a study. Subjects walked on a treadmill of a training machine using canes intended for cross-country walking. Figure 5 The speed of the treadmill was selected individually, and for all test subjects, a comfortable speed was found to be in the range of 1.8–2.0 km / h. A microswitch is built into the support end of the walking stick used for cross-country walking. It closes when the stick is leaned against, and a sync signal from the closure is transmitted to the switch, which triggers a channel of a programmed electrical stimulator (e.g., Biostim-5™).

[0156] The TESSC method, the algorithm for selecting stimulus intensity, and the characteristics of the pulses are the same as in Example 1. The differences are listed below.

[0157] Figure 6 The cathode locations in the projection sites of the spinal cord and spinal cord roots are shown during the study of the effects of spatiotemporal TESSC on the characteristics of human stepping motion. Electrode numbers correspond to the stimulation channels during the study. All stimulation electrodes, five cathodes, were fixed in the lumbar region ( Figure 6 One cathode is located at the midline of the spine, above the projection point of the T11 vertebra. The remaining cathodes are fixed above the root of the T11 vertebra, and above the root of the L1 vertebra on the left and right sides. The anode is located above the iliac crest, a pair of anodes shared by all the cathodes.

[0158] The stimulation of electrode 1 is periodic, activated when leaning against the contralateral (left) walking stick and stopped when leaving the contralateral (left) walking stick.

[0159] The stimulation of electrode 2 is periodic, activating when the cane is removed from the contralateral (left) side and stopping when the cane is leaned against.

[0160] The stimulation of electrode 3 is periodic, activating when the electrode leaves the contralateral (right) walking stick and stopping when the electrode is leaned against the contralateral (right) walking stick.

[0161] The stimulation of electrode 4 is periodic, activating when leaning against the contralateral (right) walking stick and stopping when leaving the contralateral (right) walking stick.

[0162] The stimulation of electrode 5 is continuous.

[0163] Stimulation process:

[0164] 1. The subject walked on the treadmill for 15 seconds;

[0165] 2. At the level of the T11 vertebra during stepping ( Figure 6 Electrode 5) is continuously stimulated for 15 seconds;

[0166] 3. During stepping, apply pressure to the right root of the L1 vertebra ( Figure 6 Electrode 1) Periodically stimulated for 15 seconds and continuously stimulated at the level of T11 vertebra;

[0167] 4. During stepping, apply pressure to the right root of the T11 vertebra ( Figure 6 Electrode 2) Periodically stimulates for 15 seconds and continuously stimulates at the level of T11 and periodically stimulates the right root of the L1 vertebra.

[0168] 5. During stepping, apply pressure to the right root of the L1 vertebra ( Figure 6 Electrode 3) Periodically stimulates for 15 seconds and continuously stimulates at the level of T11 vertebra and periodically stimulates the right root of L1 and T11 vertebrae.

[0169] 6. During stepping, apply pressure to the right root of the T11 vertebra ( Figure 6 Electrode 4) Periodically stimulates for 15 seconds and continuously stimulates at the level of T11 vertebra, and periodically stimulates the right root of L1 and T11 vertebra and the left root of L1 vertebra.

[0170] 7. Step on the treadmill for 15 seconds without stimulation.

[0171] The recording of electromuscular activity and the recording of kinematics of the movement using video analysis were the same as in Example 1.

[0172] result

[0173] Figure 7The figures show changes in EMG activity of leg muscles and knee angle during the subject's DG's treading on a treadmill at 2 km / h and periodic stimulation of the spinal root according to the study protocol. Lines 1-4 – EMG of right-side muscles: tibialis anterior, gastrocnemius, biceps femoris, and rectus femoris. Lines 5 and 6 are readings from a biaxial goniometer fixed to the right knee. Lines 7-10 – EMG of left-side muscles: tibialis anterior, gastrocnemius, biceps femoris, and rectus femoris. Lines 11, 12, and 13 – respectively Figure 6 Stimulation markers on electrodes 1, 2 and 5.

[0174] Figure 7 The increase in total muscle activity in response to each stimulation level (lines 1–4 and 7–10) is shown. The increase in right knee angle (lines 5 and 6) is particularly pronounced during periodic stimulation on electrode 1 (line 11), which activates the extensors that provide the standing phase during stepping.

[0175] Figure 8 The figures illustrate the leg movement trajectory during stepping on a treadmill with and without continuous and periodic TESSC at different levels. A – Stepping on a treadmill without TESSC. B – Stepping on a treadmill with continuous stimulation at the level of the T11 vertebra. C – Stepping on a treadmill with continuous stimulation at the level of the T11 vertebra and periodic stimulation of the right root at the L1 vertebra. D – Stepping on a treadmill with continuous stimulation at the level of the T11 vertebra and periodic stimulation of the right root at both the L1 and T11 vertebrae. Within each section of the figure, a symbolic diagram reconstructing the standing and swinging phases is presented to the right of the active cathode scheme; the coordination of angles in the femoral, knee, and ankle joints is shown even further to the right, below which is the trajectory of the thumb in the sagittal plane; the dashed line perpendicular to the horizontal line equals the length of the big toe's trajectory during the standing phase of stepping without TESSC, and the vertical line shows the maximum elevation of the big toe during stepping without TESSC.

[0176] The results of the kinematic analysis of the motion are shown in Figure 8 In the study of the effects of continuous TESSC at the level of the T11 vertebra when healthy humans walked at a constant speed on a treadmill. Figure 8 B) It is actually undetectable.

[0177] The kinematic changes during the standing phase of periodic stimulation of the right spinal root at the L1 level (corresponding to the standing phase) are not immediately apparent, due to the fact that the treadmill sets the stepping rhythm. However, the effect can be observed even under such conditions.

[0178] exist Figure 8 The extreme values ​​and ranges of the angle changes of the right hip, knee and ankle joints under conditions A-D are shown in Table 1 (expressed in angles).

[0179] Table 1

[0180]

[0181] The range of knee angle changes during normal stepping ( Figure 8 A- Figure 8 C) The range of knee angle is 127-180 degrees; with continuous TESSC stimulation at the T11 level, it is 129-179 degrees; and with root stimulation at the L1 vertebra, it is 122-180 degrees. That is, the range of knee angle variation increases when the extensor muscles are activated during the standing phase. This increase is due to greater flexion within the knee joint. The range of ankle angle variation also increases. Figure 8 A- Figure 8 C) The knee angle ranged from 94 to 118 degrees during normal stepping, from 94 to 120 degrees during continuous TESSC stimulation at the T11 level, and from 91 to 121 degrees during root stimulation at the L1 vertebra. This recorded an increase in the range of knee angle variation when the extensor muscles were activated during the standing phase, at the cost of increased leg flexion. Stepping during stimulation of the right root at the L1 vertebra was presented as if the subject were squatting on the stimulated right side.

[0182] The height of the foot lift off the surface increased significantly with periodic stimulation (corresponding to the swing phase) at the level of the right root of the spinal cord at the T11 vertebra: the contour describing the trajectory of the right big toe was more pronounced than with all other stimulation choices (see the dashed triangles corresponding to the parameters during the standing and swing phases of movement without stimulation). This demonstrates the work of the flexor muscles that need to be activated during the swing phase. The range of variation at the knee joint increased more than with stimulation at the root of the L1 vertebra (111–180 degrees), and the range of variation at the ankle joint (90–124 degrees) also increased. Figure 8 With increased flexion of the knee and extension of the ankle on the outside, the step is characterized by an enhanced elevation of the right knee during walking.

[0183] The significant asymmetry in the dynamic characteristics of stepping performance became apparent during stimulation of the right root. The variations in maximum instantaneous stepping speed for the right and left legs when stepping on a treadmill at 2 km / h are shown in Table 2.

[0184] The measurements taken over all 15-second movement cycles, using marks on the thumb, were averaged. The maximum instantaneous stepping speed on the right side differed from that on the left side by 17-33% under asymmetrical stimulation, and by 8-9% under symmetrical TESSC or without stimulation.

[0185]

[0186]

[0187] in conclusion

[0188] It has been shown that TESSC applied above the spinal cord root activates the extensor kinetic pool during the standing phase of stepping and the flexor kinetic pool during the swing phase of stepping, which promotes the regulation of the kinematic and dynamic characteristics of stepping and controls the human gait.

[0189] Although the invention has been described with reference to the disclosed embodiments, it will be apparent to those skilled in the art that the specific details described are for illustrative purposes only and should not be construed as limiting the scope of the invention in any way. It should be understood that various modifications are possible without departing from the spirit of the invention.

Claims

1. A spinal nerve prosthesis for adjusting and restoring independent gait in patients with spinal cord and / or brain injuries and / or diseases, characterized in that, include - A multichannel stimulator for percutaneous electrical stimulation of the spinal cord and spinal cord roots, the multichannel stimulator comprising at least one microcontroller and one or more programs loaded into the at least one microcontroller. - An electrode or electrode array connected to the stimulator for transcutaneous stimulation, the electrode or electrode array being placed on the skin above the spine; - At least one recording device, said at least one recording device for detecting - During stepping, the walker, with the intact lower limb and / or slightly paralyzed lower limb or intact upper limb resting on it, makes contact with the surface and transmits the detected signal to the microcontroller of the stimulator. - During stepping, the walking aid on which the intact lower limb and / or slightly paralyzed lower limb or intact upper limb rests is removed from the surface, and the detected signal is transmitted to the microcontroller of the stimulator. - A device for triggering or terminating stimulation, configured to receive a signal characterizing one of the following external controls: movement of at least one complete upper or lower limb, head movement, shoulder elevation, trunk movement, and transmit the control signal to the microcontroller of the stimulator; The procedure includes instructions to apply transcutaneous electrical stimulation to the spinal cord, the instructions including performing two types of transcutaneous electrical stimulation simultaneously: 1) Continuous percutaneous stimulation of the spinal cord at least at the level of the T11-T12 vertebrae. 2) Spatiotemporally and spatially selective percutaneous stimulation of the spinal cord root at the level of the T11 and L1 vertebrae; The one or more procedures mentioned above include instructions for performing the following sequential steps: 1) Both types of transcutaneous electrical stimulation are triggered simultaneously based on control signals received from the device for triggering or terminating stimulation; 2) Based on the control signal received from the device for triggering or terminating stimulation, continuous stimulation is activated at least at the T11-T12 vertebral level by adjusting the current supply to the corresponding electrode; 3) When the intact lower limb leaves the surface and swings forward, stimulation of the root of the spinal cord on the injured side at the level of the L1 vertebra is activated by adjusting the current supply to the corresponding electrode according to the control signal received from at least one recording device. 4) When the intact lower limb is placed on the surface, the stimulation of the root of the spinal cord on the injured side at the level of the L1 vertebra is stopped by adjusting the current supply to the corresponding electrode by adjusting the control signal received from at least one recording device. 5) When the intact lower limb is placed on the surface or When the walking aid is lifted off the surface and moved forward due to the movement of the intact upper limb; and then the walking aid is placed on the surface, stimulation of the root of the spinal cord on the injured side at the level of the T11 vertebra is activated by adjusting the current supply to the corresponding electrode according to the control signal received from at least one recording device. 6) When the paralyzed lower limb leaves the surface and swings forward, according to the control signal received from at least one recording device, the root of the spinal cord on the injured side at the level of the T11 vertebra is stimulated by adjusting the current supply to the corresponding electrode. 7) When the paralyzed lower limb is placed on the surface, the stimulation of the root of the spinal cord on the injured side at the level of the T11 vertebra is stopped by adjusting the current supply to the corresponding electrode by adjusting the control signal received from at least one recording device. 8) Repeat steps 2) through 7) an arbitrary number of times. 9) Based on a control signal received from the device for triggering or terminating stimulation, the continuous stimulation of the spinal cord at the level of the T11-T12 vertebrae is stopped and terminated, and the spatiotemporal and spatial selective stimulation of the root of the spinal cord at the level of the T11 and L1 vertebrae is terminated, which stops the stimulation.

2. The spinal nerve prosthesis according to claim 1, characterized in that, The at least one recording device can be selected from: a surface contact sensor, or the surface contact sensor of the walking aid.

3. The spinal nerve prosthesis according to claim 1, characterized in that, The device used to trigger or stop stimulation can be made in the form of an electromechanical switch or a radio frequency switch.

4. The spinal nerve prosthesis according to claim 1, characterized in that, It can include an acceleration sensor and / or an angular velocity sensor and / or a joint angle sensor.

5. The spinal nerve prosthesis according to claim 1, characterized in that, The multichannel stimulator for transcutaneous electrical stimulation of the spinal cord and spinal cord root has a unipolar rectangular pulse or bipolar rectangular pulse with a modulation frequency in the range of 5 kHz to 10 kHz for transcutaneous electrical stimulation of the spinal cord, wherein the frequency for continuous stimulation of the spinal cord at the level of at least the T11-T12 vertebrae is selected in the range of 30 Hz to 45 Hz, the frequency for stimulation of the root of the spinal cord at the level of the L1 vertebra is selected in the range of 10 Hz to 30 Hz, and the frequency for stimulation of the root of the spinal cord at the level of the T11 vertebra is selected in the range of 30 Hz to 50 Hz.

6. The spinal nerve prosthesis according to claim 1, characterized in that, The multichannel stimulator is configured to provide continuous stimulation to the spinal cord and spatiotemporally selective stimulation to the root of the spinal cord, wherein the patient walks on the ground or on a mobile treadmill by resting the upper limbs on a fixed support or by partially compensating for body weight with the aid of a suspension system.

7. The spinal nerve prosthesis according to claim 1, characterized in that, The multichannel stimulator is configured to provide continuous stimulation of the spinal cord and spatiotemporally selective stimulation of the root of the spinal cord, wherein the patient is using a suspension system, using a walking aid to perform stepping movements on the ground, or using a mobile treadmill, with the patient's intact upper limb resting on the walking aid, which is selected from: walking sticks, canes, and crutches.

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