Effects of a full-body electrostimulation garment application in a cohort of subjects with cerebral palsy, multiple sclerosis, and stroke on upper motor neuron syndrome symptoms.

OBJECTIVES: Dysfunction of the central nervous system may inflict spastic movement disorder (SMD). Electrical stimuli were identified as promising therapeutic option. Electrical stimulation provided by a 58-electrode full body garment was investigated based on data from regular trial fittings. METHODS: Data from 72 testees were investigated. Age averages 36.6 (19.8) ys with 44 females. The cohort spans infantile cerebral paresis (CP) (n=29), multiple sclerosis (MS) (n=23) and stroke (n=20). Data were stratified by etiology and an entry BBS Score<45. RESULTS: Effect sizes (Cohen`s d) related BBS, TUG, FGA, 10mWT, WMFT, EQ5D5L and Pain. Significance levels are indicated by *: p<0.05, **: p<0.01, ***: p<0.001, (t): p<0.1: CP: 1.64***, 0.29*, 1.59***, 0.76(t), 1.00***, 0.5*, 1.28***; MS: 1.83***, 0.83***, 1.28**, 1.07***, 0.93*, 1,11**, 0.78*; Stroke: 1.28**, 0.78**, 0.89, 0.92**, 0.71, 1.26*, 0.78*. CONCLUSIONS: Multi-site transcutaneous electrical stimulation may increase ambulation related skills in subjects with SMD stemming from CP, MS and stroke. The results indicate effects on static and dynamic balance, fall risk, mobility, upper extremity improvement and an overall increase in health utility and a reduction in spasticity related pain. Effects are immediate as well as sustained. These results may inspire individual trial fittings and inform further controlled trials.

Selective Electrical Surface Stimulation to Support Functional Recovery in the Early Phase After Unilateral Acute Facial Nerve or Vocal Fold Paralysis.

This article addresses the potential clinical value of surface electrical stimulation in the acute phase of denervation after the onset of facial nerve or recurrent laryngeal nerve paralysis. These two nerve lesions are the most frequent head and neck nerve lesions. In this review, we will work out several similarities concerning the pathophysiology features and the clinical scenario between both nerve lesions, which allow to develop some general rules for surface electrical stimulation applicable for both nerve lesions. The focus is on electrical stimulation in the phase between denervation and reinnervation of the target muscles. The aim of electrostimulation in this phase of denervation is to bridge the time until reinnervation is complete and to maintain facial or laryngeal function. In this phase, electrostimulation has to stimulate directly the denervated muscles, i.e. muscle stimulation and not nerve stimulation. There is preliminary data that early electrostimulation might also improve the functional outcome. Because there are still caveats against the use of electrostimulation, the neurophysiology of denervated facial and laryngeal muscles in comparison to innervated muscles is explained in detail. This is necessary to understand why the negative results published in several studies that used stimulation parameters are not suitable for denervated muscle fibers. Juxtaposed are studies using parameters adapted for the stimulation of denervated facial or laryngeal muscles. These studies used standardized outcome measure and show that an effective and tolerable electrostimulation of facial and laryngeal muscles without side effects in the early phase after onset of the lesions is feasible, does not hinder nerve regeneration and might even be able to improve the functional outcome. This has now to be proven in larger controlled trials. In our view, surface electrical stimulation has an unexploited potential to enrich the early therapy concepts for patients with unilateral facial or vocal fold paralysis.

Comparison of voice therapy and selective electrical stimulation of the larynx in early unilateral vocal fold paralysis after thyroid surgery: A retrospective data analysis.

OBJECTIVES: The goal of the retrospective study was to investigate the 3-month-outcome after treatment of patients with early unilateral vocal fold paralysis (UVFP) with either standard voice therapy (VT) or selective electrical stimulation of the larynx (SES). DESIGN: Non-randomised retrospective study. SETTING: 1519 patients who underwent thyroid surgery between 2015 and 2018 were analysed according vocal fold mobility; UVFP patients were treated either by VT or SES. PARTICIPANTS: 51 UVFP patients. MAIN OUTCOME MEASURES: 51 UVFP patients have been advised regarding treatment options like either VT (group 1) or SES (group 2). The patients of group 1 (n = 26) and 2 (n = 25) were re-assessed up to 3 months post-operatively regarding UVFP persistence/recovery and perceptive voice sound quality. At follow-ups, perceptual analysis of voice sound (using roughness=R/breathiness=B/hoarseness=H scale) and endoscopic laryngoscopy have been performed. Position of immobile vocal fold, shape of glottal closure and RBH parameters have been considered for statistical analyses. RESULTS: Restitution of UVFP with regular respiratory vocal fold mobility of both vocal folds occurred in 53.8% of group 1 (VT), and in 40.0% of group 2 (SES) after 3 months of therapy between both groups. No difference could be seen for RBH, type of glottal closure and position of ailing vocal folds in patients with persisting UVFP within both groups and between the groups. CONCLUSIONS: The study reveals that SES can achieve similar functional outcome in early UVFP. Thus, it should be considered as an equivalent therapy alternative to VT for treatment of early UVFP patients since no significant difference in vocal outcome and glottal configuration between the two groups could be demonstrated.

Functional Electrical Stimulation for Presbyphonia: A Prospective Randomized Trial.

OBJECTIVES: The aim of this prospective study was to examine the effects of transcutaneous functional electrical stimulation (FES) in a group of elderly women with presbyphonia. STUDY DESIGN: Prospective randomized study. METHODS: Fourteen participants were enrolled prospectively and attributed randomly to two different treatment groups, where one group (n = 7) received 8 weeks of training (5 days a week), whereas the other group (n = 7) received 4 weeks of ineffective stimulation, followed by 4 weeks of effective training. Stimulation protocols were established during baseline examination and confirmed with endoscopy to ensure a glottal reaction. Numerous acoustical, vocal, patient-centered, and respiratory parameters were obtained at several time points. RESULTS: Neither 4 weeks nor 8 weeks of functional electrical transcutaneous stimulation led to changes of vocal, acoustical, or respiratory parameters, apart from patient-centered items (Voice Handicap Index 12, Voice-Related Quality of Life), which improved over time. However, there were no differences between the two arms for both items. CONCLUSIONS: Transcutaneous FES over 4 weeks and 8 weeks did not lead to significantly improved objective voice and acoustical parameters, which could be caused by the fact that the muscles of interest cannot be targeted specifically enough. However, we found a significant improvement of subjective voice perception and voice-related quality of life in both groups. We explain this finding with an observer-expectancy effect secondary to the very time-consuming and elaborate study procedures. LEVEL OF EVIDENCE: 1b Laryngoscope, 130:E662-E666, 2020.

Sub-threshold depolarizing pre-pulses can enhance the efficiency of biphasic stimuli in transcutaneous neuromuscular electrical stimulation.

There is multiple evidence in the literature that a sub-threshold pre-pulse, delivered immediately prior to an electrical stimulation pulse, can alter the activation threshold of nerve fibers and motor unit recruitment characteristics. So far, previously published works combined monophasic stimuli with sub-threshold depolarizing pre-pulses (DPPs) with inconsistent findings-in some studies, the DPPs decreased the activation threshold, while in others it was increased. This work aimed to evaluate the effect of DPPs during biphasic transcutaneous electrical stimulation and to study the possible mechanism underlying those differences. Sub-threshold DPPs between 0.5 and 15 ms immediately followed by biphasic or monophasic pulses were administered to the tibial nerve; the electrophysiological muscular responses (motor-wave, M-wave) were monitored via electromyogram (EMG) recording from the soleus muscle. The data show that, under the specific studied conditions, DPPs tend to lower the threshold for nerve fiber activation rather than elevating it. DPPs with the same polarity as the leading phase of biphasic stimuli are more effective to increase the sensitivity. This work assesses for the first time the effect of DPPs on biphasic pulses, which are required to achieve charge-balanced stimulation, and it provides guidance on the effect of polarity and intensity to take full advantage of this feature. Graphical abstract In this work, the effect of sub-threshold depolarizing pre-pulses (DPP) is investigated in a setup with transcutaneous electrical stimulation. We found that, within the tested 0-15 ms DPP duration range, the DPPs administered immediately before biphasic pulses proportionally increase the nerve excitability as visible in the M-waves recorded from the soleus muscle. Interestingly, these findings oppose published results, where DPPs, administered immediately before monophasic stimuli via implanted electrodes, led to decrease of nerve excitability.

Optimization of Interphase Intervals to Enhance the Evoked Muscular Responses of Transcutaneous Neuromuscular Electrical Stimulation.

Neuromuscular electrical stimulation (NMES) is a widely used technique for clinical diagnostic, treatment, and research. Normally, it applies charge-balanced biphasic pulses, which several publications have reported to be less efficient than monophasic pulses. A good alternative is the use of interphase intervals (IPI) on biphasic pulses that allows to achieve similar responses than those evoked by monophasic stimulation. This study analyzes the enhancing mechanism of the IPI and provides guidelines on how to optimize the IPI in order to reduce secondary effects such as the electrode corrosion. The tibial nerve was excited by NMES biphasic pulses with different IPI durations and polarities. Then, the elicited responses were recorded on the soleus muscle via electromyography. When cathodic-first pulses were applied, the responses increased proportionally to the IPI until the duration of 250 µs, where the increase saturated at 30% of the original amplitude. The responses evoked during anodic-first were 6% to 30% smaller than those evoked during cathodic-first pulses and continuously increased until the IPI duration of 2500 µs, where the responses reached an increase of around 30%. The results suggest that when a cathodic-first pulse is used, the IPI could be optimized (based on the setup geometry) to allow the action potentials to travel out of the hyperpolarization zone induced by the anodic phase. When anodic-first stimuli are applied, the IPI duration allows the fiber to recover from an apparent insensitive state induced by the anodic phase. The use of IPI is a viable option to improve the efficiency of actual stimulation systems, since only small modifications are required to significantly reduce the electrical charge required and boost the stimulation efficiency.

Epidural and transcutaneous spinal electrical stimulation for restoration of movement after incomplete and complete spinal cord injury.

PURPOSE OF REVIEW: The Purpose of this review is to outline and explain the therapeutic use of electrical spinal cord stimulation (SCS) for modification of spinal motor output. Central functional stimulation provides afferent input to posterior root neurons and is applied to improve volitional movements, posture and their endurance, control spasticity, and improve bladder function or perfusion in the lower limbs. Clinical accomplishments strongly depend on each individual's physiological state and specific methodical adaptation to that physiological state. RECENT FINDINGS: Effectiveness of this neuromodulory technique for changing motor control after spinal cord injury (SCI) continues to be explored along with the underlying mechanisms of its effect in people with complete and incomplete spinal cord injuries. There are extensive studies of tonic and rhythmical activity elicited from the lumbar cord as well as data demonstrating augmentation of residual volitional activity. Recent studies have focused on verifying if and how SCS can modify features of neurocontrol in ambulatory spinal cord patients. SUMMARY: In this review, we emphasize recent publications of research revealing that SCS can substitute for the reduced brain drive for control of excitability in people with SCI. Artificially replacing diminished or lost brain control over the spinal cord has limitations. A fundamental requirement for successful SCS application is analysis of each individual's residual postinjury neural function. This will allow a better understanding of the physiological interactions between SCS and spinal cord motor control below injury and provide criteria for its application. Finally, the publication of both successful and failed applications of SCS will be crucial for gaining future progress.

Spinal Rhythm Generation by Step-Induced Feedback and Transcutaneous Posterior Root Stimulation in Complete Spinal Cord-Injured Individuals.

BACKGROUND: The human lumbosacral spinal circuitry can generate rhythmic motor output in response to different types of inputs after motor-complete spinal cord injury. OBJECTIVE: To explore spinal rhythm generating mechanisms recruited by phasic step-related sensory feedback and tonic posterior root stimulation when provided alone or in combination. METHODS: We studied stepping in 4 individuals with chronic, clinically complete spinal cord injury using a robotic-driven gait orthosis with body weight support over a treadmill. Electromyographic data were collected from thigh and lower leg muscles during stepping with 2 hip-movement conditions and 2 step frequencies, first without and then with tonic 30-Hz transcutaneous spinal cord stimulation (tSCS) over the lumbar posterior roots. RESULTS: Robotic-driven stepping alone generated rhythmic activity in a small number of muscles, mostly in hamstrings, coinciding with the stretch applied to the muscle, and in tibialis anterior as stance-phase synchronized clonus. Adding tonic 30-Hz tSCS increased the number of rhythmically responding muscles, augmented thigh muscle activity, and suppressed clonus. tSCS could also produce rhythmic activity without or independent of step-specific peripheral feedback. Changing stepping parameters could change the amount of activity generated but not the multimuscle activation patterns. CONCLUSIONS: The data suggest that the rhythmic motor patterns generated by the imposed stepping were responses of spinal reflex circuits to the cyclic sensory feedback. Tonic 30-Hz tSCS provided for additional excitation and engaged spinal rhythm-generating networks. The synergistic effects of these rhythm-generating mechanisms suggest that tSCS in combination with treadmill training might augment rehabilitation outcomes after severe spinal cord injury.

Neurocontrol of Movement in Humans With Spinal Cord Injury.

In this review of neurocontrol of movement after spinal cord injury, we discuss neurophysiological evidences of conducting and processing mechanisms of the spinal cord. We illustrate that external afferent inputs to the spinal cord below the level of the lesion can modify, initiate, and maintain execution of movement in absence or partial presence of brain motor control after chronic spinal cord injury. We review significant differences between spinal reflex activity elicited by single and repetitive stimulation. The spinal cord can respond with sensitization, habituation, and dis-habituation to regular repetitive stimulation. Therefore, repetitive spinal cord reflex activity can contribute to the functional configuration of the spinal network. Moreover, testing spinal reflex activity in individuals with motor complete spinal cord injury provided evidences for subclinical residual brain influence, suggesting the existence of axons traversing the injury site and influencing the activities below the level of lesion. Thus, there are two motor control models of chronic spinal cord injury in humans: "discomplete" and "reduced and altered volitional motor control." We outline accomplishments in modification and initiation of altered neurocontrol in chronic spinal cord injury people with epidural and functional electrical stimulation. By nonpatterned electrical stimulation of lumbar posterior roots, it is possible to evoke bilateral extension as well as rhythmic motor outputs. Epidural stimulation during treadmill stepping shows increased and/or modified motor activity. Finally, volitional efforts can alter epidurally induced rhythmic activities in incomplete spinal cord injury. Overall, we highlight that upper motor neuron paralysis does not entail complete absence of connectivity between cortex, brain stem, and spinal motor cells, but there can be altered anatomy and corresponding neurophysiological characteristics. With specific input to the spinal cord below the level of the lesion, the clinical status of upper motor neuron paralysis without structural modification can be modified, and movements can be initiated. Thus, external afferent input can partially replace brain control.

Multi-Electrode Array for Transcutaneous Lumbar Posterior Root Stimulation.

Interest in transcutaneous electrical stimulation of the lumbosacral spinal cord is increasing in human electrophysiological and clinical studies. The stimulation effects on lower limb muscles depend on the depolarization of segmentally organized posterior root afferents and, thus, the rostro-caudal stimulation site. In previous studies, selective stimulation was achieved by varying the positions of single self-adhesive electrodes over the thoracolumbar spine. Here, we developed a multi-electrode surface array consisting of 3 × 8 electrode pads and tested its stimulation-site specificity. The array was placed longitudinally over the spine covering the T10-L2 vertebrae. Two different hydrogel layer configurations were utilized: a single layer adhered to all electrode pads of the array and a configuration comprised of eight separate strips attached to the three transverse electrode pads of each level. Voltage measurements demonstrated that an effectively focused field distribution along the longitudinal extent of the array was not accomplished when using the single continuous hydrogel layer, and segmental selective stimulation of the posterior root afferents was not possible. The separate strips produced a focused electric field distribution at the rostro-caudal level of the electrode pads selected for stimulation. This configuration allowed for the preferential elicitation of posterior root-muscle reflexes in either the L2-L4 innervated quadriceps or the L5-S2 innervated triceps surae muscle groups. Such multi-electrode array for transcutaneous spinal cord stimulation shall allow for improved control of stimulation conditions in electrophysiological studies and time-dependent and site-specific stimulation patterns for neuromodulation applications.

Comparison of Twitch Responses During Current- or Voltage-Controlled Transcutaneous Neuromuscular Electrical Stimulation.

Neuromuscular electrical stimulation (NMES) is an established method for functional restoration of muscle function, rehabilitation, and diagnostics. In this work, NMES was applied with surface electrodes placed on the anterior thigh to identify the main differences between current-controlled (CC) and voltage-controlled (VC) modes. Measurements of the evoked knee extension force and the myoelectric signal of quadriceps and hamstrings were taken during stimulation with different amplitudes, pulse widths, and stimulation techniques. The stimulation pulses were rectangular and symmetric biphasic for both stimulation modes. The electrode-tissue impedance influences the differences between CC and VC stimulation. The main difference is that for CC stimulation, variation of pulse width and amplitude influences the amount of nerve depolarization, whereas VC stimulation is only dependent on amplitude variations for pulse widths longer than 150 µs. An important remark is that these findings are strongly dependent on the characteristics of the electrode-skin interface. In our case, we used large stimulation electrodes placed on the anterior thigh, which cause higher capacitive effects. The controllability, voltage compliance, and charge characteristics of each stimulation technique should be considered during the stimulators design. For applications that require the activation of a large amount of nerve fibers, VC is a more suitable option. In contrast, if the application requires a high controllability, then CC should be chosen prior to VC.

In Vitro Testing of an Implantable Wireless Telemetry System for Long-Term Electromyography Recordings in Large Animals.

Multichannel bio-signal recording in undisturbed in vivo conditions is a frequent demand in experimental work for development of methodology and associated equipment for functional electrical stimulation (FES) application, limb prosthesis, and diagnostic tools in contemporary rehabilitation efforts. Intramuscular electromyogram (EMG) recordings can provide comprehensive insight in complex interactions of agonistic and antagonistic muscles during movement tasks and in contrast act as reliable control signals for both neuroprosthesis and mechanical prosthesis. We fabricated a fully implantable device, which is capable of recording electromyography signals from inside a body and transmit these signals wirelessly to an external receiver. The developed analog front end uses only two electrodes per channel, provides a gain of 60 dB, and incorporates a band pass filter with lower cut-off frequency of 4 Hz and upper cut-off frequency of 480 Hz. The bidirectional wireless data link, which operates in the 2.4 GHz Industrial, Scientific and Medical band, is designed for transmission distances of 10 m using an application data rate of 1 kSps for each of the two channels. Performed in vitro tests with the devices coated in epoxy resin and inserted into a phantom with tissue-equivalent characteristics confirmed the functionality of our concept and the measurement results are consistent with those from preceding simulations.

Dynamic impedance model of the skin-electrode interface for transcutaneous electrical stimulation.

Transcutaneous electrical stimulation can depolarize nerve or muscle cells applying impulses through electrodes attached on the skin. For these applications, the electrode-skin impedance is an important factor which influences effectiveness. Various models describe the interface using constant or current-depending resistive-capacitive equivalent circuit. Here, we develop a dynamic impedance model valid for a wide range stimulation intensities. The model considers electroporation and charge-dependent effects to describe the impedance variation, which allows to describe high-charge pulses. The parameters were adjusted based on rectangular, biphasic stimulation pulses generated by a stimulator, providing optionally current or voltage-controlled impulses, and applied through electrodes of different sizes. Both control methods deliver a different electrical field to the tissue, which is constant throughout the impulse duration for current-controlled mode or have a very current peak for voltage-controlled. The results show a predominant dependence in the current intensity in the case of both stimulation techniques that allows to keep a simple model. A verification simulation using the proposed dynamic model shows coefficient of determination of around 0.99 in both stimulation types. The presented method for fitting electrode-skin impedance can be simple extended to other stimulation waveforms and electrode configuration. Therefore, it can be embedded in optimization algorithms for designing electrical stimulation applications even for pulses with high charges and high current spikes.

Modification of spasticity by transcutaneous spinal cord stimulation in individuals with incomplete spinal cord injury.

CONTEXT/OBJECTIVE: To examine the effects of transcutaneous spinal cord stimulation (tSCS) on lower-limb spasticity. DESIGN: Interventional pilot study to produce preliminary data. SETTING: Department of Physical Medicine and Rehabilitation, Wilhelminenspital, Vienna, Austria. PARTICIPANTS: Three subjects with chronic motor-incomplete spinal cord injury (SCI) who could walk ≥10 m. INTERVENTIONS: Two interconnected stimulating skin electrodes (Ø 5 cm) were placed paraspinally at the T11/T12 vertebral levels, and two rectangular electrodes (8 × 13 cm) on the abdomen for the reference. Biphasic 2 ms-width pulses were delivered at 50 Hz for 30 minutes at intensities producing paraesthesias but no motor responses in the lower limbs. OUTCOME MEASURES: The Wartenberg pendulum test and neurological recordings of surface-electromyography (EMG) were used to assess effects on exaggerated reflex excitability. Non-functional co-activation during volitional movement was evaluated. The timed 10-m walk test provided measures of clinical function. RESULTS: The index of spasticity derived from the pendulum test changed from 0.8 ± 0.4 pre- to 0.9 ± 0.3 post-stimulation, with an improvement in the subject with the lowest pre-stimulation index. Exaggerated reflex responsiveness was decreased after tSCS across all subjects, with the most profound effect on passive lower-limb movement (pre- to post-tSCS EMG ratio: 0.2 ± 0.1), as was non-functional co-activation during voluntary movement. Gait speed values increased in two subjects by 39%. CONCLUSION: These preliminary results suggest that tSCS, similar to epidurally delivered stimulation, may be used for spasticity control, without negatively impacting residual motor control in incomplete SCI. Further study in a larger population is warranted.

Neuromodulation of lower limb motor control in restorative neurology.

One consequence of central nervous system injury or disease is the impairment of neural control of movement, resulting in spasticity and paralysis. To enhance recovery, restorative neurology procedures modify altered, yet preserved nervous system function. This review focuses on functional electrical stimulation (FES) and spinal cord stimulation (SCS) that utilize remaining capabilities of the distal apparatus of spinal cord, peripheral nerves and muscles in upper motor neuron dysfunctions. FES for the immediate generation of lower limb movement along with current rehabilitative techniques is reviewed. The potential of SCS for controlling spinal spasticity and enhancing lower limb function in multiple sclerosis and spinal cord injury is discussed. The necessity for precise electrode placement and appropriate stimulation parameter settings to achieve therapeutic specificity is elaborated. This will lead to our human work of epidural and transcutaneous stimulation targeting the lumbar spinal cord for enhancing motor functions in spinal cord injured people, supplemented by pertinent human research of other investigators. We conclude that the concept of restorative neurology recently received new appreciation by accumulated evidence for locomotor circuits residing in the human spinal cord. Technological and clinical advancements need to follow for a major impact on the functional recovery in individuals with severe damage to their motor system.

Muscle, tendons, and bone: structural changes during denervation and FES treatment.

OBJECTIVES: This paper describes a novel approach to determine structural changes in bone, muscle, and tendons using medical imaging, finite element models, and processing techniques to evaluate and quantify: (1) progression of atrophy in permanently lower motor neuron (LMN) denervated human muscles, and tendons; (2) their recovery as induced by functional electrical stimulation (FES); and (3) changes in bone mineral density and bone strength as effect of FES treatment. METHODS: Briefly, we used three-dimensional reconstruction of muscle belly, tendons, and bone images to study the structural changes occurring in these tissues in paralysed subjects after complete lumbar-ischiadic spinal cord injury (SCI). These subjects were recruited through the European project RISE, an endeavour designed to establish a novel clinical rehabilitation method for patients who have permanent and non-recoverable muscle LMN denervation in the lower extremities. This paper describes the use of segmentation techniques to study muscles, tendons, and bone in several states: healthy, LMN denervated-degenerated but not stimulated, and LMN denervated-stimulated. Here, we have used medical images to develop three-dimensional models and advanced imaging, including computational tools to display tissue density. Different tissues are visualized associating proper Hounsfield intervals defined experimentally to fat, connective tissue, and muscle. Finite element techniques are used to calculate Young's modulus on the patella bone and to analyse correlation between muscle contraction and bone strength changes. RESULTS: These analyses show restoration of muscular structures, tendons, and bone after FES as well as decline of the same tissues when treatment is not performed. This study suggests also a correlation between muscle growth due to FES treatment and increase in density and strength in patella bone. CONCLUSION: Segmentation techniques and finite element analysis allow the study of the structural changes of human skeletal muscle, tendons, and bone in SCI patient with LMN injury and to monitor effects and changes in tissue composition due to FES treatment. This work demonstrates improved bone strength in the patella through the FES treatment applied on the quadriceps femur.