Robotic Postural Training With Epidural Stimulation for the Recovery of Upright Postural Control in Individuals With Motor Complete Spinal Cord Injury: A Pilot Study.

Activity-based training and lumbosacral spinal cord epidural stimulation (scES) have the potential to restore standing and walking with self-balance assistance after motor complete spinal cord injury (SCI). However, improvements in upright postural control have not previously been addressed in this population. Here, we implemented a novel robotic postural training with scES, performed with free hands, to restore upright postural control in individuals with chronic, cervical (n = 5) or high-thoracic (n = 1) motor complete SCI, who had previously undergone stand training with scES using a walker or a standing frame for self-balance assistance. Robotic postural training re-enabled and/or largely improved the participants' ability to control steady standing, self-initiated trunk movements and upper limb reaching movements while standing with free hands, receiving only external assistance for pelvic control. These improvements were associated with neuromuscular activation pattern adaptations above and below the lesion. These findings suggest that the human spinal cord below the level of injury can generate meaningful postural responses when its excitability is modulated by scES, and can learn to improve these responses. Upright postural control improvements can enhance functional motor recovery promoted by scES after severe SCI.

Corticospinal inhibition investigated in relation to upper extremity motor function in cervical spinal cord injury.

OBJECTIVE: Corticospinal inhibitory mechanisms are relevant to functional recovery but remain poorly understood after spinal cord injury (SCI). Post-injury characteristics of contralateral silent period (CSP), a measure of corticospinal inhibition evaluated using transcranial magnetic stimulation (TMS), is inconsistent in literature. We envisioned that investigating CSP across muscles with varying degrees of weakness may be a reasonable approach to resolve inconsistencies and elucidate the relevance of corticospinal inhibition for upper extremity function following SCI. METHODS: We studied 27 adults with chronic C1-C8 SCI (age 48.8 ± 16.1 years, 3 females) and 16 able-bodied participants (age 33.2 ± 11.8 years, 9 females). CSP characteristics were assessed across biceps (muscle power = 3-5) and triceps (muscle power = 1-3) representing stronger and weaker muscles, respectively. We assessed functional abilities using the Capabilities of the Upper Extremity Test (CUE-T). RESULTS: Participants with chronic SCI had prolonged CSPs for biceps but delayed and diminished CSPs for triceps compared to able-bodied participants. Early-onset CSPs for biceps and longer, deeper CSPs for triceps correlated with better CUE-T scores. CONCLUSIONS: Corticospinal inhibition is pronounced for stronger biceps but diminished for weaker triceps muscle in SCI indicating innervation relative to the level of injury matters in the study of CSP. SIGNIFICANCE: Nevertheless, corticospinal inhibition or CSP holds relevance for upper extremity function following SCI.

Combining Spinal Cord Transcutaneous Stimulation with Activity-based Training to Improve Upper Extremity Function Following Cervical Spinal Cord Injury.

Recovery of upper extremity (UE) function is the top priority following cervical spinal cord injury (SCI); even partial function restoration would greatly improve the quality of their life and thus remains an important goal in SCI rehabilitation. Current clinical therapies focus on promoting neuroplasticity by performing task-specific activities with high intensity and high repetition. Repetitive training, paired with functional electrical, somatosensory, or transcranial magnetic stimulation, has been evaluated to augment functional recovery in chronic SCI, but improvements were modest. Evidence has demonstrated that the non-invasive spinal cord transcutaneous stimulation (scTS) can increase the excitability of spinal circuits and facilitate the weak or silent descending drive for restoration of sensorimotor function. Currently, we are conducting a multicenter randomized clinical trial to investigate the efficacy and potential mechanisms of scTS combined with activity-based training (ABT) to facilitate UE function recovery in individuals with tetraplegia. The preliminary outcomes from our four individuals with complete and incomplete injury demonstrated that the combination of scTS and ABT led to immediate and sustained (for up to 1-month follow-up) UE function recovery. Notably, one individual with motor complete injury showed a 5-fold improvement in UE function quantified by the Graded Redefined Assessment of Strength, Sensibility, and Prehension following scTS+ABT, as compared to receiving ABT alone. These functional gains were also reflected in the increased spinal excitability by measuring the scTS-evoked muscle response of UE motor pools, suggesting physiological evidence of reorganization of the non-functional, but surviving spinal networks after spinal transcutaneous stimulation.Clinical Relevance-This study offered the preliminary efficacy of combining scTS and ABT to facilitate UE function recovery following cervical SCI.

Spinal Cord Stimulation with Activity-Based Training: Effect on Spasticity.

Spasticity is common after a spinal cord injury (SCI). Pharmacological treatments for spasticity often have adverse effects on neurorehabilitation. Spinal cord transcutaneous stimulation (scTS) and activity-based training (ABT) have been shown to be useful tools for neurorehabilitation which can lead to improved function for people with SCI. Our preliminary data suggests that neuromodulation of the spinal circuitry may result in attenuating spasticity.Clinical Relevance- Spasticity effects 65-70% of individuals following SCI, this technique of using ABT with scTS may allow for improvements in limiting spasticity.

Standing Reactive Postural Responses of Lower Limbs With and Without Self-Balance Assistance in Individuals With Spinal Cord Injury Receiving Epidural Stimulation.

Spinal cord epidural stimulation can promote the recovery of motor function in individuals with severe spinal cord injury (SCI) by enabling the spinal circuitry to interpret sensory information and generate related neuromuscular responses. This approach enables the spinal cord to generate lower limb extension patterns during weight bearing, allowing individuals with SCI to achieve upright standing. We have shown that the human spinal cord can generate some standing postural responses during self-initiated body weight shifting. In this study, we investigated the ability of individuals with motor complete SCI receiving epidural stimulation to generate standing reactive postural responses after external perturbations were applied at the trunk. A cable-driven robotic device was used to provide constant assistance for pelvic control and to deliver precise trunk perturbations while participants used their hands to grasp onto handlebars for self-balance support (hands-on) as well as when participants were without support (free-hands). Five individuals with motor complete SCI receiving lumbosacral spinal cord epidural stimulation parameters specific for standing (Stand-scES) participated in this study. Trunk perturbations (average magnitude: 17 ± 3% body weight) were delivered randomly in the four cardinal directions. Participants attempted to control each perturbation such that upright standing was maintained and no additional external assistance was needed. Lower limb postural responses were generally more frequent, larger in magnitude, and appropriately modulated during the free-hands condition. This was associated with trunk displacement and lower limb loading modulation that were larger in the free-hands condition. Further, we observed discernible lower limb muscle synergies that were similar between the two perturbed standing conditions. These findings suggest that the human spinal circuitry involved in postural control retains the ability to generate meaningful lower limb postural responses after SCI when its excitability is properly modulated. Moreover, lower limb postural responses appear enhanced by a standing environment without upper limb stabilization that promotes afferent inputs associated with a larger modulation of ground reaction forces and trunk kinematics. These findings should be considered when developing future experimental frameworks aimed at studying upright postural control and activity-based recovery training protocols aimed at promoting neural plasticity and sensory-motor recovery.

Multi-Site Spinal Cord Transcutaneous Stimulation Facilitates Upper Limb Sensory and Motor Recovery in Severe Cervical Spinal Cord Injury: A Case Study.

Individuals with cervical spinal cord injury (SCI) rank regaining arm and hand function as their top rehabilitation priority post-injury. Cervical spinal cord transcutaneous stimulation (scTS) combined with activity-based recovery training (ABRT) is known to effectively facilitate upper extremity sensorimotor recovery in individuals with residual arm and hand function post SCI. However, scTS effectiveness in facilitating upper extremity recovery in individuals with severe SCI with minimal to no sensory and motor preservation below injury level remains largely unknown. We herein introduced a multimodal neuro-rehabilitative approach involving scTS targeting systematically identified various spinal segments combined with ABRT. We hypothesized that multi-site scTS combined with ABRT will effectively neuromodulate the spinal networks, resulting in improved integration of ascending and descending neural information required for sensory and motor recovery in individuals with severe cervical SCI. To test the hypothesis, a 53-year-old male (C2, AIS A, 8 years post-injury) received 60 ABRT sessions combined with continuous multi-site scTS. Post-training assessments revealed improved activation of previously paralyzed upper extremity muscles and sensory improvements over the dorsal and volar aspects of the hand. Most likely, altered spinal cord excitability and improved muscle activation and sensations resulted in observed sensorimotor recovery. However, despite promising neurophysiological evidence pertaining to motor re-activation, we did not observe visually appreciable functional recovery on obtained upper extremity motor assessments.

Targeted Selection of Stimulation Parameters for Restoration of Motor and Autonomic Function in Individuals With Spinal Cord Injury.

STUDY DESIGN: This is a report of methods and tools for selection of task and individual configurations targeted for voluntary movement, standing, stepping, blood pressure stabilization, and facilitation of bladder storage and emptying using tonic-interleaved excitation of the lumbosacral spinal cord. OBJECTIVES: This study aimed to present strategies used for selection of stimulation parameters for various motor and autonomic functions. CONCLUSIONS: Tonic-interleaved functionally focused neuromodulation targets a myriad of consequences from spinal cord injury with surgical implantation of the epidural electrode at a single location. This approach indicates the sophistication of the human spinal cord circuitry and its important role in the regulation of motor and autonomic functions in humans.

Profiling Immunological Phenotypes in Individuals During the First Year After Traumatic Spinal Cord Injury: A Longitudinal Analysis.

Abstract Individuals with SCI are severely affected by immune system changes, resulting in increased risk of infections and persistent systemic inflammation. While recent data support that immunological changes after SCI differ in the acute and chronic phases of living with SCI, only limited immunological phenotyping in humans is available. To characterize dynamic molecular and cellular immune phenotypes over the first year, we assess RNA (bulk-RNA sequencing), protein, and flow cytometry (FACS) profiles of blood samples from 12 individuals with SCI at 0-3 days and at 3, 6, and 12 months post injury (MPI) compared to 23 uninjured individuals (controls). We identified 967 differentially expressed (DE) genes in individuals with SCI (FDR <0.001) compared to controls. Within the first 6 MPI we detected a reduced expression of NK cell genes, consistent with reduced frequencies of CD56bright, CD56dim NK cells present at 12 MPI. Over 6MPI, we observed increased and prolonged expression of genes associated with inflammation (e.g. HMGB1, Toll-like receptor signaling) and expanded frequencies of monocytes acutely. Canonical T-cell related DE genes (e.g. FOXP3, TCF7, CD4) were upregulated during the first 6 MPI and increased frequencies of activated T cells at 3-12 MPI. Neurological injury severity was reflected in distinct whole blood gene expression profiles at any time after SCI, verifying a persistent 'neurogenic' imprint. Overall, 2876 DE genes emerge when comparing motor complete to motor incomplete SCI (ANOVA, FDR <0.05), including those related to neutrophils, inflammation, and infection. In summary, we identify a dynamic immunological phenotype in humans, including molecular and cellular changes which may provide potential targets to reduce inflammation, improve immunity, or serve as candidate biomarkers of injury severity.

Spinal cord epidural stimulation for motor and autonomic function recovery after chronic spinal cord injury: A case series and technical note.

Background: Traumatic spinal cord injury (tSCI) is a debilitating condition, leading to chronic morbidity and mortality. In recent peer-reviewed studies, spinal cord epidural stimulation (scES) enabled voluntary movement and return of over-ground walking in a small number of patients with motor complete SCI. Using the most extensive case series (n = 25) for chronic SCI, the present report describes our motor and cardiovascular and functional outcomes, surgical and training complication rates, quality of life (QOL) improvements, and patient satisfaction results after scES. Methods: This prospective study occurred at the University of Louisville from 2009 to 2020. scES interventions began 2-3 weeks after surgical implantation of the scES device. Perioperative complications were recorded as well as long-term complications during training and device related events. QOL outcomes and patient satisfaction were evaluated using the impairment domains model and a global patient satisfaction scale, respectively. Results: Twenty-five patients (80% male, mean age of 30.9 ± 9.4 years) with chronic motor complete tSCI underwent scES using an epidural paddle electrode and internal pulse generator. The interval from SCI to scES implantation was 5.9 ± 3.4 years. Two participants (8%) developed infections, and three additional patients required washouts (12%). All participants achieved voluntary movement after implantation. A total of 17 research participants (85%) reported that the procedure either met (n = 9) or exceeded (n = 8) their expectations, and 100% would undergo the operation again. Conclusion: scES in this series was safe and achieved numerous benefits on motor and cardiovascular regulation and improved patient-reported QOL in multiple domains, with a high degree of patient satisfaction. The multiple previously unreported benefits beyond improvements in motor function render scES a promising option for improving QOL after motor complete SCI. Further studies may quantify these other benefits and clarify scES's role in SCI patients.

Development of a Remote Version of the Graded Redefined Assessment of Strength, Sensation, and Prehension (GRASSP): Validity and Reliability.

BACKGROUND: The Graded Redefined Assessment of Strength, Sensation, and Prehension (GRASSP V1.0) was developed in 2010 as a 3-domain assessment for upper extremity function after tetraplegia (domains: Strength, Sensibility, and Prehension). A remote version (rGRASSP) was created in response to the growing needs of the field of Telemedicine. OBJECTIVE: The purpose of this study was to assess the psychometric properties of rGRASSP, establishing concurrent validity and inter-rater reliability. METHODS: Individuals with tetraplegia (n = 61) completed 2 visits: 1 in-person and 1 remote. The first visit was completed in-person to administer the GRASSP, and the second visit was conducted remotely to administer the rGRASSP. The rGRASSP was scored both by the administrator of the rGRASSP (Examiner 1), and a second assessor (Examiner 2) to establish inter-rater reliability. Agreement between the in-person and remote GRASSP evaluations was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman agreement plots. RESULTS: The remote GRASSP demonstrated excellent concurrent validity with the GRASSP (left hand intraclass correlation coefficient (ICC) = .96, right ICC = .96). Concurrent validity for the domains was excellent for strength (left ICC = .96, right ICC = .95), prehension ability (left ICC = .94, right ICC = .95), and prehension performance (left ICC = .92, right ICC = .93), and moderate for sensibility (left ICC = .59, right ICC = .68). Inter-rater reliability for rGRASSP total score was high (ICC = .99), and remained high for all 4 domains. Bland-Altman plots and limits of agreements support these findings. CONCLUSIONS: The rGRASSP shows strong concurrent validity and inter-rater reliability, providing a psychometrically sound remote assessment for the upper extremity in individuals with tetraplegia.

Aging-induced alterations in EEG spectral power associated with graded force motor tasks.

BACKGROUND: It has been demonstrated that in young and healthy individuals, there is a strong association between the amplitude of EEG-derived motor activity-related cortical potential or EEG spectral power (ESP) and voluntary muscle force. This association suggests that the motor-related ESP may serve as an index of central nervous system function in controlling voluntary muscle activation Therefore, it may potentially be used as an objective marker to track changes in functional neuroplasticity due to neurological disorders, aging, and following rehabilitation therapies. To this end, the relationship between the band-specific ESP-combined spectral power of EEG oscillatory and aperiodic (noise) components-and voluntary elbow flexion (EF) force has been analyzed in elder and young individuals. METHODS: 20 young (22.6 ± 0.87 year) and 28 elderly (74.79 ± 1.37 year) participants performed EF contractions at 20%, 50%, and 80% of maximum voluntary contraction (MVC) while high-density EEG signals were recorded. Both the absolute and relative ESPs were computed for the EEG frequency bands of interest. RESULTS: The MVC force generated by the elderly was foreseeably lower than that of the young participants. Compared to young, the elderly cohort's (1) total ESP was significantly lower for the high (80% MVC) force task; (2) relative ESP in beta band was significantly elevated for the low and moderate (20% MVC and 50% MVC) force tasks; (3) absolute ESP failed to have a positive trend with force for EEG frequency bands of interest; and (4) beta-band relative ESP did not exhibit a significant decrease with increasing force levels. CONCLUSIONS: As opposed to young subjects, the beta-band relative ESP in elderly did not significantly decrease with increasing EF force values. This observation suggests the use of beta-band relative ESP as a potential biomarker for age-related motor control degeneration.

Australian statewide virtual care competency-based education framework for the healthcare workforce: a Delphi study.

This study aimed to establish shared interprofessional competencies across health professions that promote education, communication, and teamwork, preparing the virtual care workforce to work collaboratively with the patient and their carers, family members, and communities to improve health outcomes. A modified, two-round Delphi process was undertaken with an interprofessional panel selected from the public health sector workforce across one Australian state. Sixty-nine panelists participated in Round 1 and 40 panelists participated in Round 2. Fifty-eight competencies across seven domains were established to support an interprofessional approach to virtual care provision: compliance, professional practice, patient safety, communication, interprofessional collaboration, patient assessment and care planning/delivery/coordination. This virtual care education framework may assist different health disciplines to develop, revise or map new or existing undergraduate or postgraduate education programs or design professional development activities. Drawing upon the expertise of a broad range of health professionals in its development, this education framework focuses on improving interprofessional collaboration in virtual care settings.

Education guidelines, frameworks and resources for building virtual care capacity: An integrative review.

INTRODUCTION: Despite its reported benefits, the accelerated adoption of virtual care since the COVID-19 pandemic has occurred without critical consideration of clinician education and training. This integrative review aims to better understand the necessary education guidelines, frameworks and resources for building the confidence and capability of the workforce for virtual care delivery. METHODS: Whittemore and Knafl's (2005) five-stage methodological framework informed this review. Using a clearly articulated search strategy and reporting process, over 8000 pieces of literature were analysed. A final 46 publications comprising 26 scholarly papers and 20 pieces of grey literature were included for review. RESULTS: A set of key curriculum inclusions under three domains: clinical, administrative and technical are proposed. Many publications emphasise a domain-specific approach as the most effective means of translating virtual care knowledge and skills to practice. A number of new domain frameworks have been tailormade for specific disciplines, while well-established frameworks such as the ACGME, CanMEDS, AAMC and IPEC have been adapted for virtual care education. Virtual care checklists, clinical champions and models that involve frontline clinicians, content experts and care recipients are considered useful resources for virtual care education. DISCUSSION: Moving beyond the COVID-19 pandemic, virtual care education for current and future clinicians requires a cohesive, interprofessional approach. This approach should be rigorously evaluated as part of a continuous quality improvement process.

A comparison of one year outcomes between standardized locomotor training and usual care after motor incomplete spinal cord injury: Community participation, quality of life and re-hospitalization.

CONTEXT/OBJECTIVE: Spinal cord injury (SCI) often results in a significant loss of mobility and independence coinciding with reports of decreased quality of life (QOL), community participation, and medical complications often requiring re-hospitalization. Locomotor training (LT), the repetition of stepping-like patterning has shown beneficial effects for improving walking ability after motor incomplete SCI, but the potential impact of LT on psychosocial outcomes has not been well-established. The purpose of this study was to evaluate one year QOL, community participation and re-hospitalization outcomes between individuals who participated in a standardized LT program and those who received usual care (UC). DESIGN/SETTING/PARTICIPANTS: A retrospective (nested case/control) analysis was completed using SCI Model Systems (SCIMS) data comparing one year post-injury outcomes between individuals with traumatic motor incomplete SCI who participated in standardized LT to those who received UC. OUTCOME MEASURES: Outcomes compared include the following: Satisfaction with Life Scale (SWLS™), Craig Handicap Assessment and Reporting Technique-Short Form (CHART-SF™), and whether or not an individual was re-hospitalized during the first year of injury. RESULTS: Statistically significant improvements for the LT group were found in the following outcomes: SWLS (P = 0.019); and CHART subscales [mobility (P = <0.001)]; occupation (P = 0.028); with small to medium effects sizes. CONCLUSION: Individuals who completed a standardized LT intervention reported greater improvements in satisfaction with life, community participation, and fewer re-hospitalizations at one year post-injury in comparison to those who received UC. Future randomized controlled trials are needed to verify these findings.

Safety and effects of a therapeutic 15 Hz rTMS protocol administered at different suprathreshold intensities in able-bodied individuals.

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) remains a promising strategy for neurorehabilitation. The stimulation intensity (SI) influences the aftereffects observed. Here, we examined whether single sessions of a 15 Hz rTMS protocol, administered at suprathreshold SI, can be safely administered to able-bodied (AB) individuals. Six right-handed men were included in this pilot study. HF-rTMS was delivered over the right M1, in 10 trains of 75 biphasic stimuli at 15 Hz, at 105-120% of the individual resting motor threshold (RMT). To assess safety, electromyography (EMG) was monitored to control for signs of spread of excitation and brief EMG burst (BEB) after stimulation. Additionally, TMS side effects questionnaires and the numeric rating scale (NRS) were administered during each session. We assessed corticospinal excitability (CSE) and motor performance changes with measures of resting (rMEP) and active (aMEP) motor evoked potential and grip strength and box and blocks test (BBT) scores, respectively. Overall, the sessions were tolerated and feasible without any pain development. However, EMG analysis during 15 Hz rTMS administration revealed increased BEB frequency with SI. Statistical models revealed an increase of CSE at rest (rMEP) but not during active muscle contraction (aMEP). No linear relationship was observed between 15 Hz rTMS SI and rMEP increase. No significant changes were highlighted for motor performance measures. Although feasible and tolerable by the AB individuals tested, the results demonstrate that when administered at suprathreshold intensities (≥ 105% RMT) the 15 Hz rTMS protocol reveals signs of persistent excitation, suggesting that safety precautions and close monitoring of participants should be performed when testing such combinations of high-intensity and high-frequency stimulation protocols. The results also give insight into the nonlinear existent relationship between the SI and HF-rTMS effects on CSE.NEW & NOTEWORTHY The results of this pilot study show the effects of a therapeutically promising 15 Hz repetitive transcranial magnetic stimulation (rTMS) protocol, administered at different suprathreshold intensities in able-bodied individuals. Although tolerable and feasible with a neuromodulatory potential, 15 Hz rTMS might result in persistent excitability that needs to be closely monitored if administered at suprathreshold stimulation intensity. These results reaffirm the importance of feasibility studies, especially in translational animal-to-human research.

Spinal Cord Transcutaneous Stimulation Enables Volitional Knee Extension in Motor-complete SCI.

Non-invasive spinal cord transcutaneous stimulation (scTS) is often applied to one or multiple spinal segments and may improve motor control after spinal cord injury (SCI). The purpose of this pilot study was to apply tonic scTS to an individual with motor-complete spinal cord injury (SCI) in order to initiate and maintain volitional control during a specific lower-extremity motor task. The participant's legs were placed in a gravity-neutral position, and he was asked to extend his knee, with and without the presence of tonic scTS. Our results show intentional voluntary control of knee extension with scTS (with no assistance). Our preliminary findings highlight how scTS neuromodulation of the spinal circuitry has the potential to restore motor function for people with motor-complete SCI. Clinical Relevance- This investigation is critical to better understand the neuromodulatory effects of tonic scTS for augmentation of voluntary-induced muscle activations in individuals with motor-complete SCI.

High-Frequency rTMS Combined with Task-Specific Hand Motor Training Modulates Corticospinal Plasticity in Motor Complete Spinal Cord Injury: A case report.

Since its first use in spinal cord injury (SCI) in the early 2000s [1], high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) demonstrated a capacity to modulate corticospinal excitability (CSE) and motor performance. Studies focused on individuals with incomplete SCI. Here, we examined the feasibility of a 15-day therapeutic stimulation protocol combining HF-rTMS with task-specific motor training targeting the weaker hand in an individual with early chronic complete SCI. In this case report, we present evidence of progressive increase of CSE at rest and during muscle activation, and decreased cortical inhibition, associated with a trend toward improvement in pinch function of the weaker hand. These promising findings need to be confirmed in a larger population. Clinical Relevance- These preliminary results are promising and demonstrate the importance of a large number of training session repetitions to induce consistent changes relevant to the recovery after a complete SCI.

Corticomuscular Connectivity during Walking in Able Bodied and Individuals with Incomplete Spinal Cord Injury.

This exploratory study used EEG as mobile imaging method to study cortico-muscular connectivity (CMC) during walking in able-bodied individuals (AB) and individuals with spinal cord injury (iSCI), while walking with and without exoskeleton walking robot (EWR) assistance. We also explored change in CMC after intensive training using EWR assistance in iSCI. Results showed no different in CMC within the AB group during walking with and without robot assistance. However, before training the iSCI subjects showed lower CMC during walking with robot assistance. The intensive 40 hours of walking training with EWR improved the walking function in iSCI participants allowing them to walk with robot assistance set to lower assistance level. This decrease in assistance level and improvement in walking function correlated with increase in CMC, reducing the difference in CMC during walking with and without EWR assistance. The findings suggest that high level of robot assistance and low walking function in iSCI correlates with weaker connectivity between primary motor cortices and lower extremity muscles. Further research is needed to better understand the importance of intention and cortical involvement in training of walking function using EWRs. Clinical Relevance - This study provides innovative data on CMC during walking and how it changes with EWR assistance and with training. This research is important to the clinical field to provide recommendations of how training of walking function can be delivered to maximize cortical engagement and improve rehabilitation outcomes.

Stimulation Parameters Used During Repetitive Transcranial Magnetic Stimulation for Motor Recovery and Corticospinal Excitability Modulation in SCI: A Scoping Review.

There is a growing interest in non-invasive stimulation interventions as treatment strategies to improve functional outcomes and recovery after spinal cord injury (SCI). Repetitive transcranial magnetic stimulation (rTMS) is a neuromodulatory intervention which has the potential to reinforce the residual spinal and supraspinal pathways and induce plasticity. Recent reviews have highlighted the therapeutic potential and the beneficial effects of rTMS on motor function, spasticity, and corticospinal excitability modulation in SCI individuals. For this scoping review, we focus on the stimulation parameters used in 20 rTMS protocols. We extracted the rTMS parameters from 16 published rTMS studies involving SCI individuals and were able to infer preliminary associations between specific parameters and the effects observed. Future investigations will need to consider timing, intervention duration and dosage (in terms of number of sessions and number of pulses) that may depend on the stage, the level, and the severity of the injury. There is a need for more real vs. sham rTMS studies, reporting similar designs with sufficient information for replication, to achieve a significant level of evidence regarding the use of rTMS in SCI.

Safety and efficacy of transcranial direct current stimulation in upper extremity rehabilitation after tetraplegia: protocol of a multicenter randomized, clinical trial.

STUDY DESIGN: A multisite, randomized, controlled, double-blinded phase I/II clinical trial. OBJECTIVE: The purpose of this clinical trial is to evaluate the safety, feasibility and efficacy of pairing noninvasive transcranial direct current stimulation (tDCS) with rehabilitation to promote paretic upper extremity recovery and functional independence in persons living with chronic cervical spinal cord injury (SCI). SETTING: Four-site trial conducted across Cleveland Clinic, Louis Stokes Veterans Affairs Medical Center of Cleveland and MetroHealth Rehabilitation Rehabilitation Institute of Ohio, and Kessler Foundation of New Jersey. METHODS: Forty-four adults (age ≥18 years) with tetraplegia following cervical SCI that occurred ≥1-year ago will participate. Participants will be randomly assigned to receive anodal tDCS or sham tDCS given in combination with upper extremity rehabilitation for 15 sessions each over 3-5 weeks. Assessments will be made twice at baseline separated by at least a 3-week interval, once at end-of-intervention, and once at 3-month follow-up. PRIMARY OUTCOME MEASURE(S): Primary outcome measure is upper extremity motor impairment assessed using the Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) scale. Functional abilities will be assessed using Capabilities of Upper Extremity-Test (CUE-T), while functional independence and participation restrictions will be evaluated using the self-care domain of Spinal Cord Independent Measure (SCIM), and Canadian Occupational Performance Measure (COPM). SECONDARY OUTCOME MEASURES: Treatment-associated change in corticospinal excitability and output will also be studied using transcranial magnetic stimulation (TMS) and safety (reports of adverse events) and feasibility (attrition, adherence etc.) will also be evaluated. TRIAL REGISTRATION: ClincalTrials.gov identifier NCT03892746. This clinical trial is being performed at four sites within the United States: Cleveland Clinic (lead site), Louis Stokes Cleveland Veterans Affairs Medical Center (VAMC) and MetroHealth Rehabilitation Institute in Ohio, and Kessler Foundation in New Jersey. The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office.