Cord Stimulation Research Articles

Study protocol for a prospective, randomized, multicenter trial to investigate the influence of peripheral nerve stimulation on patients with chronic sacroiliac joint syndrome (SILENCING)

BackgroundThe prevalence of sacroiliac joint pain (SIJP) is estimated to be 10–30% in patients with chronic low back pain. Numerous conservative and surgical treatment modalities for SIJP have been described with limited evidence regarding long-term pain relief.Spinal cord stimulation (SCS) is a well-established technique to treat patients with chronic low back pain. However, the effect on patients with SIJP is not consistent. Therefore, peripheral nerve stimulation (PNS) for chronic SIJP was implemented in experimental trials. Clinical data on PNS for SIJP is still lacking. The authors present a case series and a protocol for a prospective, multicenter study to determine the effect of PNS in patients with chronic intractable SIJP.MethodA multicenter, prospective randomized controlled trial was designed. Patients with chronic intractable SIJP will be recruited and randomized in a 4:3 ratio to either the peripheral nerve stimulation group or to the best medical treatment group. A total of 90 patients are planned to be enrolled (52 in the PNS group and 38 in the BMT group). Patients in the intervention group receive a percutaneous implantation of a unilateral or bilateral lead which is externalized for a trial phase for 3–14 days. After trial phase only patients with at least 50% reduction of pain receive an impulse generator for permanent stimulation. Regular visits for participants are planned on day 0, after 3 months (± 30 days), 6 months (± 30 days), and 12 months (± 60 days). The primary outcome measurements is the difference in Numeric Pain Rating Scale (NRS) between baseline and after 6 months. Secondary outcomes is improvement of pain associated disability (ODI) and improvement of health-related quality of life after 6 and 12 months.DiscussionWe have described the protocol for a prospective, multicenter, randomized trial evaluating the influence of PNS on patients with chronic sacroiliac joint syndrome. We believe that PNS on patients with chronic sacroiliac joint syndrome will show promising results regarding pain relief and quality of life in comparison to BMT after 12 months. The design of this trial promises high evidence in comparison to the data to date.Trial registrationClinicalTrials.gov, NCT05357300. Registered on April 26, 2022.

A wireless spinal stimulation system for ventral activation of the rat cervical spinal cord

Electrical stimulation of the cervical spinal cord is gaining traction as a therapy following spinal cord injury; however, it is difficult to target the cervical motor region in a rodent using a non-penetrating stimulus compared with direct placement of intraspinal wire electrodes. Penetrating wire electrodes have been explored in rodent and pig models and, while they have proven beneficial in the injured spinal cord, the negative aspects of spinal parenchymal penetration (e.g., gliosis, neural tissue damage, and obdurate inflammation) are of concern when considering therapeutic potential. We therefore designed a novel approach for epidural stimulation of the rat spinal cord using a wireless stimulation system and ventral electrode array. Our approach allowed for preservation of mobility following surgery and was suitable for long term stimulation strategies in awake, freely functioning animals. Further, electrophysiology mapping of the ventral spinal cord revealed the ventral approach was suitable to target muscle groups of the rat forelimb and, at a single electrode lead position, different stimulation protocols could be applied to achieve unique activation patterns of the muscles of the forelimb.

Muscle Coactivation Phenomenon in the Modulation of Walking by Electrical Stimulation of the Spinal Cord

Muscle Coactivation Phenomenon in the Modulation of Walking by Electrical Stimulation of the Spinal Cord

Application of the Mechanotherapy Devices Simulating Step-Like Movements in Combination with Electrical Stimulation in Spinal Cord Injury Patients

Summarizing the results of the world scientific data on this topic, the possibility to evoke step-like movements in the lower limbs of patients with spinal cord injury (SCI) below the level of damage was noted. That was verified during electrical stimulation in combination with mechanotherapy, the electrodes application to the definite areas of spinal cord. In addition, we stated that these measures led to reduction of muscle hypertonus in the lower limbs, improvement of neuromuscular junction and tolerance towards increasing stimulation that were instrumentally confirmed. We stated that it is impossible to achieve the same effect using only one of these methods isolated. The first studies were carried out by implantation of epidural electrodes in the spinal cord, and later by a combination of electrical stimulation and step-like movements with the same frequency setting manually. During further technology development, stimulation became percutaneous, and the movements were carried out using robotic mechanotherapy. The advantage of this method is obvious: the specialist needs to set the initial parameters which are selected individually for the patient,to monitor the progress of the procedure and to fix changes. These devices include robotic systems which perform movements in the lower extremities with full and partial axial load. Currently a study of the device for robotic therapy in horizontal unsupported state is ongoing in rehabilitation clinic of FSBI NMCC n. a. N.I. Pirogov. Its excellence is support absense, the training is held in conditions of complete body weight unloading. Multimodal electrical stimulation is performed simultaneously with robotic therapy: percutaneous electrical stimulation of the spinal cord and functional electrical stimulation (FES) of the legs, back and abdomen muscles. It was stated that parameters of neurological status were improved significantly. This article presents the results of unsupported robotic mechanotherapy`s clinical testing in the SCI patients rehabilitation.

Studies of Interactions between Limbs in Humans Subjected to Noninvasive Electrical Stimulation of the Spinal Cord

The effects of activation of spinal locomotor centers at the cervical and lumbar levels on interlimb synergies were studied in humans. Subjects were placed on a biomechanical trainer in the supine position and carried out voluntary rhythmic leg movements, moving the carriage of the walking device of the trainer, or performing voluntary arm movements moving the levers of the trainer, or making simultaneous leg and arm movements. In the resting state, sequential transcutaneous stimulation of the spinal cord at three levels (cathode positioned between vertebrae C4/C5, T12/L1, or L1/L2) did not induce leg movements in most subjects, though performance of arm movements in combination with stimulation initiated low-amplitude (less than 10°) movements in all the leg joints. Stimulation of the spinal cord and simultaneous arm movements induced facilitation of the performance of voluntary leg movements, which was apparent as an increase in the integral characteristic of muscle electrical activity and an increase in movement amplitude at the hip joint. The results obtained here may be useful for developing a neurorehabilitation method for patients with impaired motor function.

Neuromodulation in the treatment of symptoms of spinal cord injury

Introduction and purpose: Spinal cord injury may be associated with loss of motor and sensory functions, autonomic system functions and chronic pain. The development of technology has enabled the emergence of invasive and non-invasive methods of electrical and magnetic stimulation of the nervous system, which show a growing potential in the treatment of these symptoms in human and animal studies.The purpose of the study is a presentation of the most current studies about the selected methods of neuromodulation of the nervous system in the treatment of symptoms of spinal cord injury. Description of the state of knowledge: Neuromodulatory methods improve the functioning of patients affected by spinal cord injury. Studies on epidural stimulation of the spinal cord, transcranial magnetic stimulation, transcranial direct current stimulation transcutaneous spinal cord, and use of neuromodulation methods in combination with brain-machine interfaces stimulation show a reduction of chronic pain resistant to pharmacotherapy, improvement of motor limb function, respiratory function and bladder function. However, there are few large randomized studies with higher evidence strength.Conclusions: Neuromodulation is effective in the treatment of symptoms of spinal cord injury. Promising results should lead to further research to increase the strength of evidence for the effectiveness of these therapies, improve technology and a deeper understanding of the mechanisms behind their effectiveness.

Влияние неинвазивной электростимуляции спинного мозга и механостимуляции мышц ног на системную гемодинамику при сохранных и нарушенных супраспинальных связях

Влияние неинвазивной электростимуляции спинного мозга и механостимуляции мышц ног на системную гемодинамику при сохранных и нарушенных супраспинальных связях

Influence of Robotic Mechanotherapy in Various Combinations with Non-Invasive Electrostimulation of Muscles and Spinal Cord on the Postural Balance in Children with Severe Forms of Cerebral Palsy

Introduction. Postural disorders are significant in severe forms of cerebral palsy (CP). The aim of the work was to study the effect of locomotor training in combination with transcutaneous electrical stimulation of the spinal cord and functional electrical stimulation (FES) of the muscles of the lower extremities on the restoration of the function of maintaining a vertical posture in children with III level of limitation of motor activity according to the GMFCS classification. Materials and methods. 20 patients with CP at the age from 8 to 12 years old were examined. Patients of the main group (10 children) received 15 sessions of 45 minutes rehabilitation in the ≪Lokomat≫ robotic simulator in the sequence: 1) ≪Lokomat≫ in combination with FES, 2) ≪Lokomat≫ in combination with transcutaneous electrical stimulation of the spinal cord, 3) ≪Lokomat≫ in combination with FES and transcutaneous electrical stimulation of the spinal cord. The intervals between courses were 6 months. Patients from the control group (10 children) underwent only locomotor training. Results. The dynamics of regaining control of the upright posture in children was evaluated by the method of stabilometry, which revealed the active response of the musculoskeletal system in patients of the main group only in the case of combined robotic mechanotherapy and FES. This was manifested in a significant increase in the amplitude of oscillations A of the pressure center, a clear increase in the variance of the parameters of the LFS parameter, and a decrease in the strength of the correlation between the parameters LFS and A towards normalization. However, with a combination of locomotor training with FES and transcutaneous electrical stimulation of the spinal cord, there were no convincing signs of improving the regulation of the vertical posture. Conclusion. It is suggested that multilevel neurostimulation of patients with CP is necessary, which may be more effective, since it will affect the central components of motor activity.

Modulation of Blood Flow in the Skin of Human Legs during Transcutaneus Electrical Stimulation of the Spinal Cord

Changes in blood supply to the skin of the anterior-lateral surface of the shin of 12 healthy subjects were detected. The analysis was performed using laser Doppler flowmetry during transcutaneous electrical spinal cord stimulation (TSCS) by subthreshold bipolar pulses with a frequency of 30 Hz. The TSCS at T7 and L1 vertebrae level leads to a significant increase in cutaneous blood flow. With a stimulus intensity of 90% of the motor threshold, the increase in skin perfusion during stimulation at L1 was about 74%, and during stimulation at T7, 38%, relative to the baseline. We suggest that vasodilation and hyperemia of the skin during TSCS occur mainly due to the antidromic stimulation of sensory nerve fibers. Nitric oxide (NO) is an important modulator that promotes vasodilation in TSCS. It is released by the nerve endings and the layer of endothelial cells. Inhibition of cystathionine-γ-lyase significantly reduces the increase in skin blood flow during TSCS. Therefore, it was concluded that H2S, as well as NO, is also involved in the vasodilation in the skin during TSCS.

Complex Restorative Treatment of Patients with Post-Traumatic Tetraparesis

Summary. Despite the rapid development of medical technologies, the problem of restoration the functions of the spinal cord remains unsolved.
 Objective: to improve the quality of life of patients with the consequences of traumatic damage to the spinal cord.
 Materials and Methods. The study is based on an analysis of the treatment results of 95 patients with the consequences of traumatic damage to the cervical segments of the spinal cord. Depending on the severity of the spinal cord injury, the patients were distributed as follows: group ASIA A – 43 patients, group B – 37 patients, and group C – 15 patients. Reconstructive surgery was performed on patients from 6 months to 2 years after the injury. Among the methods of rehabilitation treatment, chronic epidural electrical stimulation of the spinal cord (as the first stage of rehabilitation treatment) was used in all patients, neurotization of the anterior interosseous nerve (anterior interosseous nerve AIN) by the branch of the muscular cutaneous nerve – in 38 patients, transposition of the tendon of the deltoid muscle to the tendon of the triceps of the shoulder – in 8 patients.
 Results. The ASIA impairment scale, SCIM (Spinal cord independence measure scale) and MRC (Medical Research Council scale) were used to evaluate treatment outcomes. The results were evaluated 18 months after reconstructive surgery. In the ASIA A group, the quality of life improved in 74.4% of patients, due to an improvement of the upper extremity function. In the ASIA B group, an improvement in the quality of life was noted in 83.7% of patients, both due to improved self-care and mobility, and due to improved control of the function of the pelvic organs. In the ASIA C group, improved quality of life was mainly due to improved mobility.
 Conclusions. Complex restorative treatment of patients with incomplete cervical spinal cord injury allowed to improve the quality of life due to correction of segmentary and conductive violations of the spinal cord. In patients with complete spinal cord injury, only segmentary violations are suitable for correction.

Quality of life indicators in assessing the results of various surgical treatment methods for cervical myelopathy

Quality of life indicators are widely used to determine the efficiency of various medical therapies for cervical myelopathy; however, but these have been insufficiently studied in assessing the results of surgical treatment for this pathology. In addition, the results of surgical treatment for cervical myelopathy are observed to be unsatisfactory in 15–20% of cases, which indicates the need to develop new techniques and to improve existing ones for its correction. Direct electrical stimulation of the spinal cord may become one of the promising areas. Objective: to comparatively analyze the efficiency of various surgical treatments for cervical myelopathy, by assessing the quality of life indicators in the patients. Patients and methods. The investigation enrolled 92 patients with cervical myelopathy: 29 (49.2%) patients underwent posterior spinal cord decompression via laminectomy; in 17 of them, that was supplemented with the electrodes placed on the posterior columns of the spinal cord for its postoperative direct electrical stimulation; 63 (50.8%) patients underwent anterior spinal cord decompression, 12 of them had electrodes placed on the anterior horns of the spinal cord. Results and discussion. After posterior spinal cord decompression with laminectomy, there were increases in physical functioning from 36.7±2.1 to 49.6±3.1 arbitrary units (arb. unit) (p<0.05) and in role physical functioning from 39.4±2.6 to 51.3±2.6 arb. unit (p<0.05) and a decrease in pain sensations from 51.6±2.6 to 30.2±0.8 arb. unit (p<0.05). Electric stimulation of the spinal cord caused increases in physical functioning from 40.3±3.6 to 61.3±2.8 arb. unit (p<0.05) and in role physical functioning from 36.7±1.6 to 69.4±1.6 arb. unit (p<0.05) and a reduction in pain sensations from 49.8±2.4 to 21.0±1.2 arb. unit (p<0.05). The similar trend as also observed in anterior spinal cord decompression concurrent with corporodesis at the cervical level after direct electrical stimulation of the spinal cord. Physical functioning increased from 42.0±3.1 to 57.6±1.4 arb. unit (by 26.4%; p<0.05) and mental health improved (only by 14.3%). After isolated anterior spinal cord decompression with corporodesis, physical functioning was 48.4±0.9 arb. unit by the end of the third month follow-up (p<0.05); following that in combination with electrical stimulation, physical functioning was 57.6±1.4 arb. unit (p<0.05). The posttreatment levels of viability, social functioning, role emotional functioning, and mental health were significantly lower in patients with a disease duration of more than 6 years than in those with that of less than 3 years. Conclusion. Posterior and anterior spinal cord decompression with laminectomy for cervical myelopathy increases the indicators of physical functioning and role physical functioning and reduces pain sensations. The additional use of electrical stimulation of the spinal cord allows one to increase role physical functioning.

Utilization of Spinal Cord and Peripheral Nerve Stimulation in Pain Patients: A Brief Review

Utilization of Spinal Cord and Peripheral Nerve Stimulation in Pain Patients: A Brief Review

Transcutaneous Direct Current Stimulation of the Spinal Cord for Treatment of Spasticity in Multiple Sclerosis

Transcutaneous Direct Current Stimulation of the Spinal Cord for Treatment of Spasticity in Multiple Sclerosis

Serotonergic Mechanisms in Locomotor Effects of Electrical Spinal Cord Stimulation

Electrical stimulation of the spinal cord (ESSC) is a method enabling researchers to confirm the existence of the stepping movement generator in humans. Currently, the ESSC-based technologies of motor rehabilitation of patients immobilized after spinal cord injury are actively developing. The impact of the serotonergic system in the organization of movement is intensively studied both at the systemic and the molecular–cellular level in a large number of researches. The aim of this review was to analyze the current experimental data on the participation of serotonergic system in the locomotor activity control at the spinal level with a focus on the processes related to electrical stimulation of spinal locomotor networks. Special interest is given to the serotonin-based regulation of human motor activity. The data on the use of serotonin-modulating pharmacotherapy for increasing the efficacy of the ESSC method in locomotor rehabilitation are presented in the final part of the review.

The Mechanistic Basis for Successful Spinal Cord Stimulation to Generate Steady Motor Outputs.

Electrical stimulation of the spinal cord is a promising rehabilitation intervention to restore/augment motor function after spinal cord injury (SCI). Combining sensory feedback with stimulation of remaining motor circuits has been shown to be a prerequisite for the functional improvement of SCI patients. However, little is known about the cellular mechanisms potentially underlying this functional benefit in the injured spinal cord. Here, we combine computer simulations with an isolated whole-tissue adult mouse spinal cord preparation to examine synaptic, cellular, and system potentials measured from single motoneurons and ventral roots. The stimulation protocol included separate and combined activation of the sensory inputs (evoked by dorsal root stimulation) and motor inputs (evoked by stimulation of spinal cord tissue) at different frequencies, intensities, and neuromodulatory states. Our data show that, while sensory inputs exhibit short-term depression in response to a train of stimulation, motor inputs exhibit short-term facilitation. However, the concurrent activation of both inputs elicits a stronger and steadier motor output. This effect is enhanced by the application of pharmacological neuromodulators. Furthermore, sensorimotor excitatory postsynaptic potentials (EPSPs) summate sublinearly (i.e., their combination produces an excitatory potential smaller than the sum of the excitatory potentials they would individually produce). However, ventral root compound action potentials (CoAPs) summate supralinearly generating much higher outputs. Computer simulations revealed that the contrasting summation and disproportionality in plasticity between the excitatory postsynaptic potentials (EPSPs) and CoAPs result from the motoneuronal firing threshold acting as an amplitude-selective filter. Together, these results provide the mechanistic basis for the cellular processes contributing to the generation of steady motor outputs using spinal stimulation. This data has great potential to guide the design of more effective stimulation protocols in SCI patients.

P1-12-03. The pathway of muscle evoked potentials after electrical stimulation of the spinal cord

P1-12-03. The pathway of muscle evoked potentials after electrical stimulation of the spinal cord

A Simulation Study of Light Propagation in the Spinal Cord for Optogenetic Surface Stimulation.

For utilizing optogenetics in neuroscience research, a proper setup is necessary, which delivers sufficient light to target cells and minimizes unexpected side effects caused by light exposure. In this study, we were interested in the area of influence of optical surface stimulation on a spinal cord tissue. We built a 3D spinal cord structure of rat and utilized the Monte-Carlo methods to simulate the light transport in it. We first evaluated light propagation in homogeneous nervous tissue models. For a 10-mW, 470-nm light source, light intensity of 1 mW=mm2 was detected at depths of 1:14 and 1:77 mm in white and grey matter, respectively. This indicated a narrower spreading pattern of light in the white matter than in the grey matter. Since the grey matter, which contains the somatosensory pathways, is an important target of spinal cord stimulation, we focused on investigating how much light could reach this area in a multi-layered structure. The results showed that when an optical fiber was positioned in the center line of the spinal cord dorsal surface, most of the light energy was absorbed before reaching the grey matter. In contrast, when we put the fiber on a lateral position, 0:8 mm away from the central line, relatively sufficient light intensity could be detected deep into the lamina 5 area. The experimental results obtained herein suggest that tissue type and the position of stimulation could greatly affect the area of influence of light stimulation in a 3D spinal cord. It is important to consider the location of the interested neural pathways and plan a proper stimulation site before conducting optogenetic surface stimulation of the spinal cord.

Dependence of Respiratory Reaction on the Intensity of Locomotor Response to Transcutaneous Electrical Stimulation of the Spinal Cord

We have studied the reaction of the respiratory system to transcutaneous spinal cord stimulation inducing stepping movements of large and small amplitudes. We have shown that the small amplitude of the generated stepping movements was associated with a reduction of the tidal volume, and generated movements with a large amplitude resulted in the elevation of the expiratory flow. We have compared the reactions of the respiratory system during stepping movements induced by spinal cord stimulation and by voluntary efforts. It has been found that, during stepping movements induced by the spinal cord stimulation, lung ventilation increased through reduction of the inspiration and expiration times, while the expiratory flow increased. During voluntary stepping movements, the inspiration time decreased, while the inspiratory and expiratory flows increased. These effects can ensue from tonic activation of abdominal muscles, as well as from the summation of the effects of spinal stimulation and working hyperpnoea.

Functional State of the Neuromotor Apparatus of the Gastrocnemius Muscle in Rat Under Microgravity: Effect of Spinal Cord Stimulation

The aim of this study was the evaluation of the functional state of the neuromotor apparatus of the gastrocnemius muscle in rat under conditions of gravitational unloading, as well as in conditions of gravitational unloading combined with magnetic stimulation of the spinal cord. The electrical potentials of gastrocnemius muscle of the rat evoked by the stimulation of the sciatic nerve were recorded after a week of exposure the animal in the experimental conditions. Parameters of motor response and H-reflex were evaluated. It was found that gravitational unloading caused an increase of the reflex excitability of the motor centers of gastrocnemius muscle of the rat and magnetic stimulation of the spinal cord combined with unloading increased the intensity of transformations. In addition, it was registered the changes of the functional state of the muscle under conditions of gravitational unloading combined with the stimulation of the spinal cord. The detected transformations were probably associated with the activation of adaptation processes in the new motor environment (simulation of the microgravity, restriction of peripheral afferentation including the support afferentation).

Mechanisms of Blood Flow Regulation in the Skin during Stimulation of the Spinal Cord in Humans

Changes in the blood flow in the shin skin were observed by laser Doppler flowmetry after transcutaneous electrical spinal cord stimulation (TSCS) by subthreshold bipolar pulses with a frequency of 30 Hz in 12 healthy subjects. It was found that TSCS in the area of the T11 and L1 vertebrae led to a significant increase in skin blood flow. The microcirculation rate increased by more than 85% relative to the baseline at a stimulus intensity of 90% of the motor threshold. Cutaneous blood flow activization by TSCS is implemented mainly through the antidromic stimulation of sensory nerve fibers. Nitric oxide (NO) is an important mediator that contributes to vasodilation and increase in cutaneous blood flow upon TSCS. NO is predominantly of endothelial origin.