Changes in walking function and neural control following pelvic cancer surgery with reconstruction.

Introduction: Surgical planning and custom prosthesis design for pelvic cancer patients are challenging due to the unique clinical characteristics of each patient and the significant amount of pelvic bone and hip musculature often removed. Limb-sparing internal hemipelvectomy surgery with custom prosthesis reconstruction has become a viable option for this patient population. However, little is known about how post-surgery walking function and neural control change from pre-surgery conditions. Methods: This case study combined comprehensive walking data (video motion capture, ground reaction, and electromyography) with personalized neuromusculoskeletal computer models to provide a thorough assessment of pre- to post-surgery changes in walking function (ground reactions, joint motions, and joint moments) and neural control (muscle synergies) for a single pelvic sarcoma patient who received internal hemipelvectomy surgery with custom prosthesis reconstruction. Pre- and post-surgery walking function and neural control were quantified using pre- and post-surgery neuromusculoskeletal models, respectively, whose pelvic anatomy, joint functional axes, muscle-tendon properties, and muscle synergy controls were personalized using the participant's pre-and post-surgery walking and imaging data. For the post-surgery model, virtual surgery was performed to emulate the implemented surgical decisions, including removal of hip muscles and implantation of a custom prosthesis with total hip replacement. Results: The participant's post-surgery walking function was marked by a slower self-selected walking speed coupled with several compensatory mechanisms necessitated by lost or impaired hip muscle function, while the participant's post-surgery neural control demonstrated a dramatic change in coordination strategy (as evidenced by modified time-invariant synergy vectors) with little change in recruitment timing (as evidenced by conserved time-varying synergy activations). Furthermore, the participant's post-surgery muscle activations were fitted accurately using his pre-surgery synergy activations but fitted poorly using his pre-surgery synergy vectors. Discussion: These results provide valuable information about which aspects of post-surgery walking function could potentially be improved through modifications to surgical decisions, custom prosthesis design, or rehabilitation protocol, as well as how computational simulations could be formulated to predict post-surgery walking function reliably given a patient's pre-surgery walking data and the planned surgical decisions and custom prosthesis design.

Proportional sway-based electrotactile feedback improves lateral standing balance.

Introduction: Plantar cutaneous augmentation is a promising approach in balance rehabilitation by enhancing motion-dependent sensory feedback. The effect of plantar cutaneous augmentation on balance has been mainly investigated in its passive form (e.g., textured insole) or on lower-limb amputees. In this study, we tested the effect of plantar cutaneous augmentation on balance in its active form (i.e., electrical stimulation) for individuals with intact limbs. Methods: Ten healthy subjects participated in the study and were instructed to maintain their balance as long as possible on the balance board, with or without electrotactile feedback evoked on the medial side of the heel, synched with the lateral board sway. Electrotactile feedback was given in two different modes: 1) Discrete-mode E-stim as the stimulation on/off by a predefined threshold of lateral board sway and 2) Proportional-mode E-stim as the stimulation frequency proportional to the amount of lateral board sway. All subjects were distracted from the balancing task by the n-back counting task, to test subjects' balancing capability with minimal cognitive involvement. Results: Proportional-mode E-stim, along with the n-back counting task, increased the balance time from 1.86 ± 0.03 s to 1.98 ± 0.04 s (p = 0.010). However, discrete-mode E-stim did not change the balance time (p = 0.669). Proportional-mode E-stim also increased the time duration per each swayed state (p = 0.035) while discrete-mode E-stim did not (p = 0.053). Discussion: These results suggest that proportional-mode E-stim is more effective than discrete-mode E-stim on improving standing balance. It is perhaps because the proportional electrotactile feedback better mimics the natural tactile sensation of foot pressure than its discrete counterpart.

The effects of combined transcranial brain stimulation and a 4-week visuomotor stepping training on voluntary step initiation in persons with chronic stroke-a pilot study.

Purpose: Evidence suggests that transcranial direct current stimulation (tDCS) can enhance motor performance and learning of hand tasks in persons with chronic stroke (PCS). However, the effects of tDCS on the locomotor tasks in PCS are unclear. This pilot study aimed to: (1) determine aggregate effects of anodal tDCS combined with step training on improvements of the neural and biomechanical attributes of stepping initiation in a small cohort of persons with chronic stroke (PCS) over a 4-week training program; and (2) assess the feasibility and efficacy of this novel approach for improving voluntary stepping initiation in PCS. Methods: A total of 10 PCS were randomly assigned to one of two training groups, consisting of either 12 sessions of VST paired with a-tDCS (n = 6) or sham tDCS (s-tDCS, n = 4) over 4 weeks, with step initiation (SI) tests at pre-training, post-training, 1-week and 1-month follow-ups. Primary outcomes were: baseline vertical ground reaction force (B-vGRF), response time (RT) to initiate anticipatory postural adjustment (APA), and the retention of B-VGRF and RT. Results: a-tDCS paired with a 4-week VST program results in a significant increase in paretic weight loading at 1-week follow up. Furthermore, a-tDCS in combination with VST led to significantly greater retention of paretic BWB compared with the sham group at 1 week post-training. Clinical implications: The preliminary findings suggest a 4-week VST results in improved paretic limb weight bearing (WB) during SI in PCS. Furthermore, VST combined with a-tDCS may lead to better retention of gait improvements (NCT04437251) (https://classic.clinicaltrials.gov/ct2/show/NCT04437251).

Cost-effectiveness analysis of overground robotic training versus conventional locomotor training in people with spinal cord injury.

BACKGROUND: Few, if any estimates of cost-effectiveness for locomotor training strategies following spinal cord injury (SCI) are available. The purpose of this study was to estimate the cost-effectiveness of locomotor training strategies following spinal cord injury (overground robotic locomotor training versus conventional locomotor training) by injury status (complete versus incomplete) using a practice-based cohort. METHODS: A probabilistic cost-effectiveness analysis was conducted using a prospective, practice-based cohort from four participating Spinal Cord Injury Model System sites. Conventional locomotor training strategies (conventional training) were compared to overground robotic locomotor training (overground robotic training). Conventional locomotor training included treadmill-based training with body weight support, overground training, and stationary robotic systems. The outcome measures included the calculation of quality adjusted life years (QALYs) using the EQ-5D and therapy costs. We estimate cost-effectiveness using the incremental cost utility ratio and present results on the cost-effectiveness plane and on cost-effectiveness acceptability curves. RESULTS: Participants in the prospective, practice-based cohort with complete EQ-5D data (n = 99) qualified for the analysis. Both conventional training and overground robotic training experienced an improvement in QALYs. Only people with incomplete SCI improved with conventional locomotor training, 0.045 (SD 0.28), and only people with complete SCI improved with overground robotic training, 0.097 (SD 0.20). Costs were lower for conventional training, $1758 (SD $1697) versus overground robotic training $3952 (SD $3989), and lower for those with incomplete versus complete injury. Conventional overground training was more effective and cost less than robotic therapy for people with incomplete SCI. Overground robotic training was more effective and cost more than conventional training for people with complete SCI. The incremental cost utility ratio for overground robotic training for people with complete spinal cord injury was $12,353/QALY. CONCLUSIONS: The most cost-effective locomotor training strategy for people with SCI differed based on injury completeness. Conventional training was more cost-effective than overground robotic training for people with incomplete SCI. Overground robotic training was more cost-effective than conventional training for people with complete SCI. The effect estimates may be subject to limitations associated with small sample sizes and practice-based evidence methodology. These estimates provide a baseline for future research.

A computational method for estimating trunk muscle activations during gait using lower extremity muscle synergies.

One of the surgical treatments for pelvic sarcoma is the restoration of hip function with a custom pelvic prosthesis after cancerous tumor removal. The orthopedic oncologist and orthopedic implant company must make numerous often subjective decisions regarding the design of the pelvic surgery and custom pelvic prosthesis. Using personalized musculoskeletal computer models to predict post-surgery walking function and custom pelvic prosthesis loading is an emerging method for making surgical and custom prosthesis design decisions in a more objective manner. Such predictions would necessitate the estimation of forces generated by muscles spanning the lower trunk and all joints of the lower extremities. However, estimating trunk and leg muscle forces simultaneously during walking based on electromyography (EMG) data remains challenging due to the limited number of EMG channels typically used for measurement of leg muscle activity. This study developed a computational method for estimating unmeasured trunk muscle activations during walking using lower extremity muscle synergies. To facilitate the calibration of an EMG-driven model and the estimation of leg muscle activations, EMG data were collected from each leg. Using non-negative matrix factorization, muscle synergies were extracted from activations of leg muscles. On the basis of previous studies, it was hypothesized that the time-varying synergy activations were shared between the trunk and leg muscles. The synergy weights required to reconstruct the trunk muscle activations were determined through optimization. The accuracy of the synergy-based method was dependent on the number of synergies and optimization formulation. With seven synergies and an increased level of activation minimization, the estimated activations of the erector spinae were strongly correlated with their measured activity. This study created a custom full-body model by combining two existing musculoskeletal models. The model was further modified and heavily personalized to represent various aspects of the pelvic sarcoma patient, all of which contributed to the estimation of trunk muscle activations. This proposed method can facilitate the prediction of post-surgery walking function and pelvic prosthesis loading, as well as provide objective evaluations for surgical and prosthesis design decisions.

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.

Walking improvement in chronic incomplete spinal cord injury with exoskeleton robotic training (WISE): a randomized controlled trial.

STUDY DESIGN: Clinical trial. OBJECTIVE: To demonstrate that a 12-week exoskeleton-based robotic gait training regimen can lead to a clinically meaningful improvement in independent gait speed, in community-dwelling participants with chronic incomplete spinal cord injury (iSCI). SETTING: Outpatient rehabilitation or research institute. METHODS: Multi-site (United States), randomized, controlled trial, comparing exoskeleton gait training (12 weeks, 36 sessions) with standard gait training or no gait training (2:2:1 randomization) in chronic iSCI (>1 year post injury, AIS-C, and D), with residual stepping ability. The primary outcome measure was change in robot-independent gait speed (10-meter walk test, 10MWT) post 12-week intervention. Secondary outcomes included: Timed-Up-and-Go (TUG), 6-min walk test (6MWT), Walking Index for Spinal Cord Injury (WISCI-II) (assistance and devices), and treating therapist NASA-Task Load Index. RESULTS: Twenty-five participants completed the assessments and training as assigned (9 Ekso, 10 Active Control, 6 Passive Control). Mean change in gait speed at the primary endpoint was not statistically significant. The proportion of participants with improvement in clinical ambulation category from home to community speed post-intervention was greatest in the Ekso group (>1/2 Ekso, 1/3 Active Control, 0 Passive Control, p < 0.05). Improvements in secondary outcome measures were not significant. CONCLUSIONS: Twelve weeks of exoskeleton robotic training in chronic SCI participants with independent stepping ability at baseline can improve clinical ambulatory status. Improvements in raw gait speed were not statistically significant at the group level, which may guide future trials for participant inclusion criteria. While generally safe and tolerable, larger gains in ambulation might be associated with higher risk for non-serious adverse events.

Predicting Duration of Outpatient Physical Therapy Episodes for Individuals with Spinal Cord Injury Based on Locomotor Training Strategy.

OBJECTIVE: To characterize individuals with spinal cord injuries (SCI) who use outpatient physical therapy or community wellness services for locomotor training and predict the duration of services, controlling for demographic, injury, quality of life, and service and financial characteristics. We explore how the duration of services is related to locomotor strategy. DESIGN: Observational study of participants at 4 SCI Model Systems centers with survival. Weibull regression model to predict the duration of services. SETTING: Rehabilitation and community wellness facilities at 4 SCI Model Systems centers. PARTICIPANTS: Eligibility criteria were SCI or dysfunction resulting in motor impairment and the use of physical therapy or community wellness programs for locomotor/gait training. We excluded those who did not complete training or who experienced a disruption in training greater than 45 days. Our sample included 62 participants in conventional therapy and 37 participants in robotic exoskeleton training. INTERVENTIONS: Outpatient physical therapy or community wellness services for locomotor/gait training. MAIN OUTCOME MEASURES: SCI characteristics (level and completeness of injury) and the duration of services from medical records. Self-reported perceptions of SCI consequences using the SCI-Functional Index for basic mobility and SCI-Quality of Life measurement system for bowel difficulties, bladder difficulties, and pain interference. RESULTS: After controlling for predictors, the duration of services for the conventional therapy group was an average of 63% longer than for the robotic exoskeleton group, however each visit was 50% shorter in total time. Men had an 11% longer duration of services than women had. Participants with complete injuries had a duration of services that was approximately 1.72 times longer than participants with incomplete injuries. Perceived improvement was larger in the conventional group. CONCLUSIONS: Locomotor/gait training strategies are distinctive for individuals with SCI using a robotic exoskeleton in a community wellness facility as episodes are shorter but individual sessions are longer. Participants' preferences and the ability to pay for ongoing services may be critical factors associated with the duration of outpatient services.

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).

Plantar or Palmar Tactile Augmentation Improves Lateral Postural Balance With Significant Influence from Cognitive Load.

Although it seems intuitive to address the issue of reduced plantar cutaneous feedback by augmenting it, many approaches have adopted compensatory sensory cues, such as tactile input from another part of the body, for multiple reasons including easiness and accessibility. The efficacy of the compensatory approaches might be limited due to the cognitive involvement to interpret such compensatory sensory cues. The objective of this study is to test the hypothesis that the plantar cutaneous augmentation is more effective than providing compensatory sensory cues on improving postural regulation, when plantar cutaneous feedback is reduced. In our experiments, six healthy human subjects were asked to maintain their balance on a lateral balance board for as long as possible, until the balance board contacted the ground, for 240 trials with five interventions. During these experiments, subjects were instructed to close their eyes to increase dependency on plantar cutaneous feedback for balancing. Foam pad was also added on the board to emulate the condition of reduced plantar cutaneous feedback. The effects of tactile augmentation from the foot sole or the palm on standing balance were tested by applying transcutaneous electrical stimulation on calcaneal or ulnar nerve during the balance board tests, with and without a cognitively-challenging counting task. Experimental results indicate that the plantar cutaneous augmentation was effective on improving balance only with cognitive load, while the palmar cutaneous augmentation was effective only without cognitive load. This result suggests that the location of sensory augmentation should be carefully determined according to the attentional demands.

Anodal Transcranial Direct Current Stimulation Enhances Retention of Visuomotor Stepping Skills in Healthy Adults.

Transcranial direct current stimulation (tDCS) paired with exercise training can enhance learning and retention of hand tasks; however, there have been few investigations of the effects of tDCS on leg skill improvements. The purpose of this study was to investigate whether tDCS paired with visuomotor step training can promote skill learning and retention. We hypothesized that pairing step training with anodal tDCS would improve skill learning and retention, evidenced by decreased step reaction times (RTs), both immediately (online skill gains) and 30 min after training (offline skill gains). Twenty healthy adults were randomly assigned to one of two groups, in which 20-min anodal or sham tDCS was applied to the lower limb motor cortex and paired with visuomotor step training. Step RTs were determined across three time points: (1) before brain stimulation (baseline); (2) immediately after brain stimulation (P0); and (3) 30 min after brain stimulation (P3). A continuous decline in RT was observed in the anodal tDCS group at both P0 and P3, with a significant decrease in RT at P3; whereas there were no improvements in RT at P0 and P3 in the sham group. These findings do not support our hypothesis that anodal tDCS enhances online learning, as RT was not decreased significantly immediately after stimulation. Nevertheless, the results indicate that anodal tDCS enhances offline learning, as RT was significantly decreased 30 min after stimulation, likely because of tDCS-induced neural modulation of cortical and subcortical excitability, synaptic efficacy, and spinal neuronal activity.

Classifying Major Depressive Disorder Using fNIRS During Motor Rehabilitation.

Major depressive disorder (MDD) has shown to negatively impact physical recovery in a variety of medical events (e.g., stroke and spinal cord injuries). Yet depression assessments, which are typically subjective in nature, are seldom considered to develop or guide rehabilitation strategies. The present study developed a predictive depression assessment technique using functional near-infrared spectroscopy (fNIRS) that can be rapidly integrated or performed concurrently with existing physical rehabilitation tasks. Thirty-one volunteers, including 14 adults clinically diagnosed with MDD and 17 healthy adults, participated in the study. Brain oxy-hemodynamic (HbO) responses were recorded using a 16-channel wearable continuous-wave fNIRS device while the volunteers performed the Grasp and Release Test in four 16-minute blocks. Ten features, extracted from HbO signals, from each channel served as inputs to XGBoost and Random Forest algorithms developed for each block and combination of successive blocks. Top 5 common features resulted in a classification accuracy of 92.6%, sensitivity of 84.8%, and specificity of 91.7% using the XGBoost classifier. This study identified mean HbO, full width half maximum and kurtosis, as specific neuromarkers, for predicting MDD across specific depression-related regions of interests (i.e., dorsolateral and ventrolateral prefrontal cortex). Our results suggest that a wearable fNIRS head probe monitoring specific brain regions, and limiting extraction to few features, can enable quick setup and rapid assessment of depression in patients. The overarching goal is to embed predictive neurotechnology during post-stroke and post-spinal-cord-injury rehabilitation sessions to monitor patients' depression symptomology so as to actively guide decisions about motor therapies.

Budget impact analysis of robotic exoskeleton use for locomotor training following spinal cord injury in four SCI Model Systems.

BACKGROUND: We know little about the budget impact of integrating robotic exoskeleton over-ground training into therapy services for locomotor training. The purpose of this study was to estimate the budget impact of adding robotic exoskeleton over-ground training to existing locomotor training strategies in the rehabilitation of people with spinal cord injury. METHODS: A Budget Impact Analysis (BIA) was conducted using data provided by four Spinal Cord Injury (SCI) Model Systems rehabilitation hospitals. Hospitals provided estimates of therapy utilization and costs about people with spinal cord injury who participated in locomotor training in the calendar year 2017. Interventions were standard of care walking training including body-weight supported treadmill training, overground training, stationary robotic systems (i.e., treadmill-based robotic gait orthoses), and overground robotic exoskeleton training. The main outcome measures included device costs, training costs for personnel to use the device, human capital costs of locomotor training, device demand, and the number of training sessions per person with SCI. RESULTS: Robotic exoskeletons for over-ground training decreased hospital costs associated with delivering locomotor training in the base case analysis. This analysis assumed no difference in intervention effectiveness across locomotor training strategies. Providing robotic exoskeleton overground training for 10% of locomotor training sessions over the course of the year (range 226-397 sessions) results in decreased annual locomotor training costs (i.e., net savings) between $1114 to $4784 per annum. The base case shows small savings that are sensitive to parameters of the BIA model which were tested in one-way sensitivity analyses, scenarios analyses, and probability sensitivity analyses. The base case scenario was more sensitive to clinical utilization parameters (e.g., how often devices sit idle and the substitution of high cost training) than device-specific parameters (e.g., robotic exoskeleton device cost or device life). Probabilistic sensitivity analysis simultaneously considered human capital cost, device cost, and locomotor device substitution. With probabilistic sensitivity analysis, the introduction of a robotic exoskeleton only remained cost saving for one facility. CONCLUSIONS: Providing robotic exoskeleton for over-ground training was associated with lower costs for the locomotor training of people with SCI in the base case analyses. The analysis was sensitive to parameter assumptions.

User satisfaction with lower limb wearable robotic exoskeletons.

Objective: To provide the results of a robotic exoskeleton user satisfaction questionnaire completed by participants utilizing two robotic exoskeletons.Method: Seven individuals with physical disabilities engaged in two exoskeleton-assisted training phases with the REX and the Ekso 1.1 (Ekso), after which they completed a user satisfaction questionnaire. The questionnaire consisted of structured items with a Likert scale, which were averaged and compared, as well as free response questions, which were interpreted thematically.Results: Participants reported some differences in user satisfaction between the two exoskeletons. They indicated higher satisfaction with transferring in and out of the REX and with its appearance and higher satisfaction with the transportability of the Ekso. Expectations for exoskeleton use were relatively similar for the two devices, with some exceptions. Whereas participants indicated that many changes should be made to both exoskeletons, they reported that some were more necessary for the REX and others were more necessary for the Ekso. Participants reported that they would be somewhat likely to use both exoskeletons at home and in the community if they were available.Conclusions: This brief report provides an initial comparison of user satisfaction with two exoskeletons, thereby contributing to the growing body of literature in this area.Implications for rehabiliationContributes to the literature on user satisfaction with robotic exoskeletons Implications for rehabilitationEmphasizes the role of user/participant/patient feedback in rehabilitation researchProvides user satisfaction questionnaire items that can be used in future studies.

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.

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.

Experience of Robotic Exoskeleton Use at Four Spinal Cord Injury Model Systems Centers.

BACKGROUND AND PURPOSE: Refinement of robotic exoskeletons for overground walking is progressing rapidly. We describe clinicians' experiences, evaluations, and training strategies using robotic exoskeletons in spinal cord injury rehabilitation and wellness settings and describe clinicians' perceptions of exoskeleton benefits and risks and developments that would enhance utility. METHODS: We convened focus groups at 4 spinal cord injury model system centers. A court reporter took verbatim notes and provided a transcript. Research staff used a thematic coding approach to summarize discussions. RESULTS: Thirty clinicians participated in focus groups. They reported using exoskeletons primarily in outpatient and wellness settings; 1 center used exoskeletons during inpatient rehabilitation. A typical episode of outpatient exoskeleton therapy comprises 20 to 30 sessions and at least 2 staff members are involved in each session. Treatment focuses on standing, stepping, and gait training; therapists measure progress with standardized assessments. Beyond improved gait, participants attributed physiological, psychological, and social benefits to exoskeleton use. Potential risks included falls, skin irritation, and disappointed expectations. Participants identified enhancements that would be of value including greater durability and adjustability, lighter weight, 1-hand controls, ability to navigate stairs and uneven surfaces, and ability to balance without upper extremity support. DISCUSSION AND CONCLUSIONS: Each spinal cord injury model system center had shared and distinct practices in terms of how it integrates robotic exoskeletons into physical therapy services. There is currently little evidence to guide integration of exoskeletons into rehabilitation therapy services and a pressing need to generate evidence to guide practice and to inform patients' expectations as more devices enter the market.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A231).

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.

RBM4 promotes neuronal differentiation and neurite outgrowth by modulating Numb isoform expression.

RBM4 participates in cell differentiation by regulating tissue-specific alternative pre-mRNA splicing. RBM4 also has been implicated in neurogenesis in the mouse embryonic brain. Using mouse embryonal carcinoma P19 cells as a neural differentiation model, we observed a temporal correlation between RBM4 expression and a change in splicing isoforms of Numb, a cell-fate determination gene. Knockdown of RBM4 affected the inclusion/exclusion of exons 3 and 9 of Numb in P19 cells. RBM4-deficient embryonic mouse brain also exhibited aberrant splicing of Numb pre-mRNA. Using a splicing reporter minigene assay, we demonstrated that RBM4 promoted exon 3 inclusion and exon 9 exclusion. Moreover, we found that RBM4 depletion reduced the expression of the proneural gene Mash1, and such reduction was reversed by an RBM4-induced Numb isoform containing exon 3 but lacking exon 9. Accordingly, induction of ectopic RBM4 expression in neuronal progenitor cells increased Mash1 expression and promoted cell differentiation. Finally, we found that RBM4 was also essential for neurite outgrowth from cortical neurons in vitro. Neurite outgrowth defects of RBM4-depleted neurons were rescued by RBM4-induced exon 9-lacking Numb isoforms. Therefore our findings indicate that RBM4 modulates exon selection of Numb to generate isoforms that promote neuronal cell differentiation and neurite outgrowth.