Exoskeleton-assisted Gait Training in Persons With Multiple Sclerosis: A Single-Group Pilot Study.

OBJECTIVE: To investigate the feasibility of conducting exoskeleton-assisted gait training (EGT) and the effects of EGT on gait, metabolic expenditure, and physical function in persons with multiple sclerosis (MS). DESIGN: Single-group pilot study. SETTING: Research laboratory in a rehabilitation hospital. PARTICIPANTS: Individuals with MS (N=10; mean age, 54.3±12.4y) and Expanded Disability Status Scale 6.0-7.5. INTERVENTIONS: All participants completed up to 15 sessions of EGT. MAIN OUTCOME MEASURES: Timed 25-foot walk test at self-selected and fast speed, 6-minute walk test, metabolic expenditure of walking and timed Up and Go test were assessed during walking without the exoskeleton at baseline and immediate post training. RESULTS: All participants tolerated the training intensity and completed training without adverse events. After training, gait speed was improved and metabolic expenditure was reduced significantly during the timed 25-foot walk test at self-selected speed. CONCLUSIONS: EGT is not only feasible but may also improve gait efficiency for persons with MS. Our observed improvement in gait speed was associated with reduced metabolic expenditure, which was likely because of improved neuromotor coordination. Further studies are required to investigate the effectiveness and integration of EGT in the continuum of MS rehabilitation.

Stretch reflex excitability in contralateral limbs of stroke survivors is higher than in matched controls.

BACKGROUND: Spasticity, characterized by hyperreflexia, is a motor impairment that can arise following a hemispheric stroke. While the neural mechanisms underlying spasticity in chronic stroke survivors are unknown, one probable cause of hyperreflexia is increased motoneuron (MN) excitability. Potential sources of increased spinal MN excitability after a stroke include increased vestibulospinal (VS) and/or reticulospinal (RS) drive. Spasticity, as clinically assessed in stroke survivors, is highly lateralized, thus RS contributions to stroke-induced spasticity are more difficult to reconcile, as RS nuclei routinely project bilaterally to the spinal cord. Yet studies in stroke survivors suggest that there may also be changes in neuromodulation at the spinal level, indicative of RS tract influence. We hypothesize that after hemispheric stroke, alterations in the excitability of the RS nuclei affect both sides of the spinal cord, and thereby contribute to increased MN excitability on both paretic/spastic and contralateral sides of stroke survivors, as compared to neurologically intact subjects. METHODS: We estimated stretch reflex thresholds of the biceps brachii (BB) muscle using a position-feedback controlled linear motor to progressively indent the BB distal tendon in both spastic and contralateral limbs of hemispheric stroke survivors and in age-matched intact subjects. RESULTS: Our previously reported results show a significant difference between reflex thresholds of spastic and contralateral limbs of stroke survivors recorded from BB-medial (p < 0.005) and BB-lateral (p < 0.001). For this study, we report that there is also a significant difference between the reflex thresholds in the contralateral limb of stroke subjects and the dominant arm of intact subjects, again measured from both BB-medial (p < 0.05) and BB-lateral (p < 0.05). CONCLUSION: The reduction in stretch reflex thresholds in the contralateral limb of stroke survivors, based here on comparisons with thresholds of intact subjects, suggests an increased MN excitability on contralateral sides of stroke survivors as compared to intact subjects. This in turn supports our contention that RS tract activation, which has bilateral descending influences, is at least partially responsible for increased stretch reflex excitability, post-stroke, as both contralateral and affected sides show increased MN excitability as compared to intact subjects. Still, spasticity, presently diagnosed only on the affected side, with increased MN excitability on the affected side as compared to the contralateral side (our previous study), may be due to a different strongly lateralized pathway, such as the VS tract, which has not been directly tested here. Currently available clinical methods of spasticity assessment, such as the Modified Ashworth Scale, lack the resolution to quantify this phenomenon of a bilateral increase in MN excitability.

Green synthesis and characterization of silver nanoparticles through the Piper cubeba ethanolic extract and their enzyme inhibitory activities.

Introduction: The area of "Green Synthesis of Nano-medicine," as compared to its synthetic counterparts, is a relatively safer research technology for various biomedical applications, including identification, therapeutic application, and prevention of pathological conditions, pain control, safety, and development of human wellness. The present study explored the synthesis and characterization of AgNPs using the ethanolic extract of Piper cubeba fruit as a reducing and stabilizing agent and its potential as an enzyme inhibitory agent. Urease inhibitors are helpful against many severe diseases, including gastric ulcers induced by Helicobacter pylori. Method: The fruits of the Piper cubeba plant were taken and ground to a fine powder. Plant material was added to 500 ml ethanol, and the mixture was filtered. The solvent of the filtrate was evaporated, and a thick, gummy extract was obtained and stored at 4°C in the refrigerator. AgNPs were green synthesized from solutions of AgNO3 using the P. cubeba extract, which was indicated by a change in the color from light brown to deep brown. The synthesized AgNPs were characterized via Ultraviolet-visible (UV-Vis) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy (SEM). Results and Discussion: Analysis showed the reduction of Ag+ to Ag0 at room temperature (25°C), and the average particle size of AgNPs was in the range of 40-80 nm. Consequently, the synthesized AgNPs were evaluated for their anti-urease activity. The maximum urease inhibition of the Piper cubeba ethanolic extract was 88.5% at 5 mg conc., and of derived nanoparticles was 78.6% at 0.05 mg conc. The results were nearly similar to the control drug, i.e., thiourea (0.5 and 0.6 mM conc., respectively). Conclusion: The study concluded that the P. cubeba extract, as well as its green-derived AgNPs, might prove to be a better and safer substitute for their enzyme inhibitory potential in emerging medicine and novel drug delivery techniques to improve and maintain human health.

Evaluation of Muscle Synergy During Exoskeleton-Assisted Walking in Persons With Multiple Sclerosis.

OBJECTIVE: Gait deficit after multiple sclerosis (MS) can be characterized by altered muscle activation patterns. There is preliminary evidence of improved walking with a lower limb exoskeleton in persons with MS. However, the effects of exoskeleton-assisted walking on neuromuscular modifications are relatively unclear. The objective of this study was to investigate the muscle synergies, their activation patterns and the differences in neural strategies during walking with (EXO) and without (No-EXO) an exoskeleton. METHODS: Ten subjects with MS performed walking during EXO and No-EXO conditions. Electromyography signals from seven leg muscles were recorded. Muscle synergies and the activation profiles were extracted using non-negative matrix factorization. RESULTS: The stance phase duration was significantly shorter during EXO compared to the No-EXO condition (p<0.05). Moreover, typically 3-5 modules were extracted in each condition. The module-1 (comprising Vastus Medialis and Rectus Femoris muscles), module-2 (comprising Soleus and Medial Gastrocnemius muscles), module-3 (Tibialis Anterior muscle) and module-4 (comprising Biceps Femoris and Semitendinosus muscles) were comparable between conditions. During EXO condition, Semitendinosus and Vastus Medialis emerged in module-5 in 7/10 subjects. Compared to No-EXO, average activation amplitude was significantly reduced corresponding to module-2 during the stance phase and module-3 during the swing phase during EXO. CONCLUSION: Exoskeleton-assistance does not alter the existing synergy modules, but could induce a new module to emerge, and alters the control of these modules, i.e., modifies the neural commands indicated by the reduced amplitude of the activation profiles. SIGNIFICANCE: The work provides insights on the potential underlying mechanism of improving gait functions after exoskeleton-assisted locomotor training.

Effects of an exoskeleton-assisted gait training on post-stroke lower-limb muscle coordination.

Objective.Powered exoskeletons have been used to help persons with gait impairment regain some walking ability. However, little is known about its impact on neuromuscular coordination in persons with stroke. The objective of this study is to investigate how a powered exoskeleton could affect the neuromuscular coordination of persons with post-stroke hemiparesis.Approach.Eleven able-bodied subjects and ten stroke subjects participated in a single-visit treadmill walking assessment, in which their motion and lower-limb muscle activities were captured. By comparing spatiotemporal parameters, kinematics, and muscle synergy pattern between two groups, we characterized the normal gait pattern and the post-stroke motor deficits. Five eligible stroke subjects received exoskeleton-assisted gait trainings and walking assessments were conducted pre-intervention (Pre) and post-intervention (Post), without (WO) and with (WT) the exoskeleton. We compared their gait performance between (a) Pre and Post to investigate the effect of exoskeleton-assisted gait training and, (b) WO and WT the exoskeleton to investigate the effect of exoskeleton wearing on stroke subjects.Main results.While four distinct motor modules were needed to describe lower-extremity activities during stead-speed walking among able-bodied subjects, three modules were sufficient for the paretic leg from the stroke subjects. Muscle coordination complexity, module composition and activation timing were preserved after the training, indicating the intervention did not significantly change the neuromuscular coordination. In contrast, walking WT the exoskeleton altered the stroke subjects' synergy pattern, especially on the paretic side. The changes were dominated by the activation profile modulation towards the normal pattern observed from the able-bodied group.Significance.This study gave us some critical insight into how a powered exoskeleton affects the stroke subjects' neuromuscular coordination during gait and demonstrated the potential to use muscle synergy as a method to evaluate the effect of the exoskeleton training.This study was registered at ClinicalTrials.gov (identifier: NCT03057652).

Combining robotic exoskeleton and body weight unweighing technology to promote walking activity in tetraplegia following SCI: A case study.

Context: To investigate the feasibility of combining the lower-limb exoskeleton and body weight unweighing technology for assisted walking in tetraplegia following spinal cord injury (SCI).Findings: A 66-year-old participant with a complete SCI at the C7 level, graded on the American Spinal Injury Association Impairment Scale (AIS) as AIS A, participated in nine sessions of overground walking with the assistance from exoskeleton and body weight unweighing system. The participant could tolerate the intensity and ambulate with exoskeleton assistance for a short distance with acceptable and appropriate gait kinematics after training.Conclusion: This report showed that using technology can assist non-ambulatory individuals following SCI to stand and ambulate with assistance which may promote general physical and psychological health if used in the long term.

Quantifying the Peak Amplitude Distributions of Electromyogram in Bicep Brachii muscle after Stroke.

The objective of this study was to quantify the differences in surface electromyogram (EMG) signal characteristics between affected and contralateral arm muscles of hemispheric stroke survivors. EMG signals were recorded from the biceps brachii muscles using single differential electrodes. Four chronic stroke subjects performed isometric elbow flexions at sub-maximal voluntary contraction levels on both the affected and contralateral limbs. The force generated on the contralateral side was matched to the force generated on the affected side. We observed different types of EMG activation on the affected side compared to the contralateral side.Specifically, two subjects showed lower RMS EMG activity on the affected side whereas two subjects showed greater EMG activity on the affected side compared to the contralateral side. Analysis of the peak amplitudes of the EMG activity showed greater number of peaks in the EMG on affected side compared to the contralateral side in all subjects. The histogram of the peak amplitudes showed greater number of smaller peak amplitudes in subjects with lower EMG activity on the affected side suggesting a reliance on smaller motor units. Our combined EMG signal analysis techniques on one set of recorded signals provides insight regarding potential mechanisms of weakness.Clinical Relevance- Decoding neural information from surface EMG signals without decomposition into individual motor units could provide clinicians with quick insight about disease progress and potential treatment.

A Tendon Indentation Method to Quantify Velocity-Dependent Reflex Responses after Hemispheric Stroke.

Stretch reflex responses in passive muscle can be utilized to assess spasticity in chronic stroke survivors. In this study, we present a different method of eliciting the reflex response by imposing tendon indentation using a linear motor. Specifically, we test a "Ramp-and-hold" protocol, utilizing a linear motor controlled by a position-controlled feedback loop (Linmot, Inc), to indent the biceps brachii distal tendon at different velocities. The protocol was tested on the affected arm of three stroke subjects. We also utilized a tendon indentation combined with tendon-tapping method to quantify the reflex threshold. Our results indicate that the reflex response was elicited at velocities equal to or above 50 mm/s in 2/3 subjects. No reflex response was detected in one subject. All subjects showed a distinct reflex threshold using the indentation/tapping method. Furthermore, the presence of a reflex response during tendon-tapping was not necessarily accompanied by the elicitation of a reflex response during the ramp-and-hold. However, our data suggests that the indentation threshold during tapping is correlated to the presence of a reflex response at the velocities tested during the ramp-and-hold. Though more time consuming, tendon indentation using ramp-and-hold could provide greater resolution of the reflex response to quantify spasticity than the current clinically employed ballistic tapping method using a reflex hammer.

Exoskeleton-assisted gait training to improve gait in individuals with spinal cord injury: a pilot randomized study.

BACKGROUND: Robotic wearable exoskeletons have been utilized as a gait training device in persons with spinal cord injury. This pilot study investigated the feasibility of offering exoskeleton-assisted gait training (EGT) on gait in individuals with incomplete spinal cord injury (iSCI) in preparation for a phase III RCT. The objective was to assess treatment reliability and potential efficacy of EGT and conventional physical therapy (CPT). METHODS: Forty-four individuals were screened, and 13 were eligible to participate in the study. Nine participants consented and were randomly assigned to receive either EGT or CPT with focus on gait. Subjects received EGT or CPT, five sessions a week (1 h/session daily) for 3 weeks. American Spinal Injury Association (ASIA) Lower Extremity Motor Score (LEMS), 10-Meter Walk Test (10MWT), 6-Minute Walk Test (6MWT), Timed Up and Go (TUG) test, and gait characteristics including stride and step length, cadence and stance, and swing phase durations were assessed at the pre- and immediate post- training. Mean difference estimates with 95% confidence intervals were used to analyze the differences. RESULTS: After training, improvement was observed in the 6MWT for the EGT group. The CPT group showed significant improvement in the TUG test. Both the EGT and the CPT groups showed significant increase in the right step length. EGT group also showed improvement in the stride length. CONCLUSION: EGT could be applied to individuals with iSCI to facilitate gait recovery. The subjects were able to tolerate the treatment; however, exoskeleton size range may be a limiting factor in recruiting larger cohort of patients. Future studies with larger sample size are needed to investigate the effectiveness and efficacy of exoskeleton-assisted gait training as single gait training and combined with other gait training strategies. TRIAL REGISTRATION: Clinicaltrials.org, NCT03011099, retrospectively registered on January 3, 2017.

A Method for Locomotion Mode Identification Using Muscle Synergies.

Active lower limb transfemoral prostheses have enabled amputees to perform different locomotion modes such as walking, stair ascent, stair descent, ramp ascent and ramp descent. To achieve seamless mode transitions, these devices either rely on neural information from the amputee's residual limbs or sensors attached to the prosthesis to identify the intended locomotion modes or both. We present an approach for classification of locomotion modes based on the framework of muscle synergies underlying electromyography signals. Neural information at the critical instances (e.g., heel contact and toe-off) was decoded for this purpose. Non-negative matrix factorization was used to extract the muscles synergies from the muscle feature matrix. The estimation of the neural command was done using non-negative least squares. The muscle synergy approach was compared with linear discriminant analysis (LDA), support vector machine (SVM), and neural network (NN) and was tested on seven able-bodied subjects. There was no significant difference ( p > 0.05 ) in transitional and steady state classification errors during stance phase. The muscle synergy approach performed significantly better ( ) than NN and LDA during swing phase while results were similar to SVM. These results suggest that the muscle synergy approach can be used to discriminate between locomotion modes involving transitions.