Effects of Robotic Postural Stand Training with Epidural Stimulation on Sitting Postural Control in Individuals with Spinal Cord Injury: A Pilot Study.

(1) Background. High-level spinal cord injury (SCI) disrupts trunk control, leading to an impaired performance of upright postural tasks in sitting and standing. We previously showed that a novel robotic postural stand training with spinal cord epidural stimulation targeted at facilitating standing (Stand-scES) largely improved standing trunk control in individuals with high-level motor complete SCI. Here, we aimed at assessing the effects of robotic postural stand training with Stand-scES on sitting postural control in the same population. (2) Methods. Individuals with cervical (n = 5) or high-thoracic (n = 1) motor complete SCI underwent approximately 80 sessions (1 h/day; 5 days/week) of robotic postural stand training with Stand-scES, which was performed with free hands (i.e., without using handlebars) and included periods of standing with steady trunk control, self-initiated trunk and arm movements, and trunk perturbations. Sitting postural control was assessed on a standard therapy mat, with and without scES targeted at facilitating sitting (Sit-scES), before and after robotic postural stand training. Independent sit time and trunk center of mass (CM) displacement were assessed during a 5 min time window to evaluate steady sitting control. Self-initiated antero-posterior and medial-lateral trunk movements were also attempted from a sitting position, with the goal of covering the largest distance in the respective cardinal directions. Finally, the four Neuromuscular Recovery Scale items focused on sitting trunk control (Sit, Sit-up, Trunk extension in sitting, Reverse sit-up) were assessed. (3) Results. In summary, neither statistically significant differences nor large Effect Size were promoted by robotic postural stand training for the sitting outcomes considered for analysis. (4) Conclusions. The findings of the present study, together with previous observations, may suggest that robotic postural stand training with Stand-scES promoted trunk motor learning that was posture- and/or task-specific and, by itself, was not sufficient to significantly impact sitting postural control.

Spinal Cord Transcutaneous Stimulation in Cervical Spinal Cord Injury: A Review Examining Upper Extremity Neuromotor Control, Recovery Mechanisms, and Future Directions.

Cervical spinal cord injury (SCI) results in significant sensorimotor impairments below the injury level, notably in the upper extremities (UEs), impacting daily activities and quality of life. Regaining UE function remains the top priority for individuals post-cervical SCI. Recent advances in understanding adaptive plasticity within the sensorimotor system have led to the development of novel non-invasive neurostimulation strategies, such as spinal cord transcutaneous stimulation (scTS), to facilitate UE motor recovery after SCI. This comprehensive review investigates the neuromotor control of UE, the typical recovery trajectories following SCI, and the therapeutic potential of scTS to enhance UE motor function in individuals with cervical SCI. Although limited in number with smaller sample sizes, the included research articles consistently suggest that scTS, when combined with task-specific training, improves voluntary control of arm and hand function and sensation. Further, the reported improvements translate to the recovery of various UE functional tasks and positively impact the quality of life in individuals with cervical SCI. Several methodological limitations, including stimulation site selection and parameters, training strategies, and sensitive outcome measures, require further advancements to allow successful translation of scTS from research to clinical settings. This review also summarizes the current literature and proposes future directions to support establishing approaches for scTS as a viable neuro-rehabilitative tool.

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.

Sensory Information Modulates Voluntary Movement in an Individual with a Clinically Motor- and Sensory-Complete Spinal Cord Injury: A Case Report.

Motor recovery following a complete spinal cord injury is not likely. This is partially due to insurance limitations. Rehabilitation strategies for individuals with this type of severe injury focus on the compensation for the activities of daily living in the home and community and not on the restoration of function. With limited time in therapies, the initial goals must focus on getting the patient home safely without the expectation of recovery of voluntary movement below the level of injury. In this study, we report a case of an individual with a chronic, cervical (C3)-level clinically motor- and sensory-complete injury who was able to perform voluntary movements with both upper and lower extremities when positioned in a sensory-rich environment conducive to the specific motor task. We show how he is able to intentionally perform push-ups, trunk extensions and leg presses only when appropriate sensory information is available to the spinal circuitry. These data show that the human spinal circuitry, even in the absence of clinically detectable supraspinal input, can generate motor patterns effective for the execution of various upper and lower extremity tasks, only when appropriate sensory information is present. Neurorehabilitation in the right sensory-motor environment that can promote partial recovery of voluntary movements below the level of injury, even in individuals diagnosed with a clinically motor-complete spinal cord injury.

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.

Spinal Cord Epidural Stimulation Improves Lower Spine Sitting Posture Following Severe Cervical Spinal Cord Injury.

Cervical spinal cord injury (SCI) leads to impaired trunk motor control, negatively impacting the performance of activities of daily living in the affected individuals. Improved trunk control with better sitting posture has been previously observed due to neuromuscular electrical stimulation and transcutaneous spinal stimulation, while improved postural stability has been observed with spinal cord epidural stimulation (scES). Hence, we studied how trunk-specific scES impacts sitting independence and posture. Fourteen individuals with chronic, severe cervical SCI with an implanted neurostimulator performed a 5-min tall-sit task without and with trunk-specific scES. Spine posture was assessed by placing markers on five spine levels and evaluating vertical spine inclination angles. Duration of trunk manual assistance was used to assess independence along with the number of independence changes and average independence score across those changes. With scES, the sacrum-L1 inclination and number of independence changes tended to decrease by 1.64 ± 3.16° (p = 0.07; Cohen's d = 0.53) and 9.86 ± 16.8 (p = 0.047; Cohen's d = 0.59), respectively. Additionally, for the participants who had poor sitting independence without scES, level of independence tended to increase by 12.91% [0%, 31.52%] (p = 0.38; Cohen's d = 0.96) when scES was present. Hence, trunk-specific scES promoted improvements in lower spine posture and lower levels of trunk assistance.

Case study: persistent recovery of hand movement and tactile sensation in peripheral nerve injury using targeted transcutaneous spinal cord stimulation.

Peripheral nerve injury can lead to chronic pain, paralysis, and loss of sensation, severely affecting quality of life. Spinal cord stimulation has been used in the clinic to provide pain relief arising from peripheral nerve injuries, however, its ability to restore function after peripheral nerve injury have not been explored. Neuromodulation of the spinal cord through transcutaneous spinal cord stimulation (tSCS), when paired with activity-based training, has shown promising results towards restoring volitional limb control in people with spinal cord injury. We show, for the first time, the effectiveness of targeted tSCS in restoring strength (407% increase from 1.79 ± 1.24 N to up to 7.3 ± 0.93 N) and significantly increasing hand dexterity in an individual with paralysis due to a peripheral nerve injury (PNI). Furthermore, this is the first study to document a persisting 3-point improvement during clinical assessment of tactile sensation in peripheral injury after receiving 6 weeks of tSCS. Lastly, the motor and sensory gains persisted for several months after stimulation was received, suggesting tSCS may lead to long-lasting benefits, even in PNI. Non-invasive spinal cord stimulation shows tremendous promise as a safe and effective therapeutic approach with broad applications in functional recovery after debilitating injuries.

Artifact Adaptive Ideal Filtering of EMG Signals Contaminated by Spinal Cord Transcutaneous Stimulation.

The aims of this study are to characterize the contamination of EMG signals by artifacts generated by the delivery of spinal cord transcutaneous stimulation (scTS) and to evaluate the performance of an Artifact Adaptive Ideal Filtering (AA-IF) technique to remove scTS artifacts from EMG signals. METHODS: In five participants with spinal cord injury (SCI), scTS was delivered at different combinations of intensity (from 20 to 55 mA) and frequencies (from 30 to 60 Hz) while Biceps Brachii (BB) and Triceps Brachii (TB) muscles were at rest or voluntarily activated. Using a Fast Fourier Transform (FFT), we characterized peak amplitude of scTS artifacts and boundaries of contaminated frequency bands in the EMG signals recorded from BB and TB muscles. Then, we applied the AA-IF technique and the empirical mode decomposition Butterworth filtering method (EMD-BF) to identify and remove scTS artifacts. Finally, we compared the content of the FFT that was preserved and the root mean square of the EMG signals (EMGrms) following application of the AA-IF and EMD-BF techniques. RESULTS: Frequency bands of ~2Hz width were contaminated by scTS artifact at frequencies nearby the main frequency set for the stimulator and its harmonics. The width of the frequency bands contaminated by scTS artifacts increased with current intensity delivered using scTS ( [Formula: see text]), was lower when EMG signals were recorded during voluntary contractions compared to rest ( [Formula: see text]), and was larger in BB muscle compared to TB muscle ( [Formula: see text]). A larger portion of the FFT was preserved using the AA-IF technique compared to the EMD-BF technique (96±5% vs. 75±6%, [Formula: see text]). CONCLUSION: The AA-IF technique allows for a precise identification of the frequency bands contaminated by scTS artifacts and ultimately preserves a larger amount of uncontaminated content from the EMG signals.

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 transcutaneous spinal cord stimulation promotes persistent recovery of upper limb strength and tactile sensation in spinal cord injury: a pilot study.

Long-term recovery of limb function is a significant unmet need in people with paralysis. Neuromodulation of the spinal cord through epidural stimulation, when paired with intense activity-based training, has shown promising results toward restoring volitional limb control in people with spinal cord injury. Non-invasive neuromodulation of the cervical spinal cord using transcutaneous spinal cord stimulation (tSCS) has shown similar improvements in upper-limb motor control rehabilitation. However, the motor and sensory rehabilitative effects of activating specific cervical spinal segments using tSCS have largely remained unexplored. We show in two individuals with motor-complete SCI that targeted stimulation of the cervical spinal cord resulted in up to a 1,136% increase in exerted force, with weekly activity-based training. Furthermore, this is the first study to document up to a 2-point improvement in clinical assessment of tactile sensation in SCI after receiving tSCS. Lastly, participant gains persisted after a one-month period void of stimulation, suggesting that targeted tSCS may lead to persistent recovery of motor and sensory function.

Mid-lumbar (L3) epidural stimulation effects on bladder and external urethral sphincter in non-injured and chronically transected urethane-anesthetized rats.

Recent pre-clinical and clinical spinal cord epidural stimulation (scES) experiments specifically targeting the thoracolumbar and lumbosacral circuitries mediating lower urinary tract (LUT) function have shown improvements in storage, detrusor pressure, and emptying. With the existence of a lumbar spinal coordinating center in rats that is involved with external urethral sphincter (EUS) functionality during micturition, the mid-lumbar spinal cord (specifically L3) was targeted in the current study with scES to determine if the EUS and thus the void pattern could be modulated, using both intact and chronic complete spinal cord injured female rats under urethane anesthesia. L3 scES at select frequencies and intensities of stimulation produced a reduction in void volumes and EUS burst duration in intact rats. After chronic transection, three different subgroups of LUT dysfunction were identified and the response to L3 scES promoted different cystometry outcomes, including changes in EUS bursting. The current findings suggest that scES at the L3 level can generate functional neuromodulation of both the urinary bladder and the EUS in intact and SCI rats to enhance voiding in a variety of clinical scenarios.

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.

Preservation of functional descending input to paralyzed upper extremity muscles in motor complete cervical spinal cord injury.

OBJECTIVE: Spinal cord injury (SCI) is classified as complete or incomplete depending on the extent of sensorimotor preservation below the injury level. However, individuals with complete SCIs can voluntarily activate paralyzed lower limb muscles alone or by engaging non-paralyzed muscles during neurophysiological assessments, indicating presence of residual pathways across the injury. However, similar phenomena have not been explored for the upper extremity (UE) muscles following cervical SCIs. METHODS: Eighteen individuals with motor complete cervical SCI (AIS A or B) and five age-matched non-injured (NI) individuals performed various UE events against manual resistance during functional neurophysiological assessment (FNPA), and electromyographic (EMG) activity was recorded from UE muscles. RESULTS: Our findings demonstrated i) voluntary activation of clinically paralyzed muscles as evident from EMG readouts, ii) increased activity in these muscles during events engaging muscles above the injury level, iii) reduced spectral properties of paralyzed muscles in SCI compared to NI participants. CONCLUSIONS: Functional EMG activity in clinically paralyzed muscles indicate presence of residual pathways across the injury establishing supralesional control over the sublesional neural circuitry. SIGNIFICANCE: The findings may help explain the neurophysiological basis for UE recovery and can be exploited in designing rehabilitation techniques to facilitate UE recovery following cervical SCIs.

Neuroanatomical mapping of the lumbosacral spinal cord in individuals with chronic spinal cord injury.

With emerging applications of spinal cord electrical stimulation in restoring autonomic and motor function after spinal cord injury, understanding the neuroanatomical substrates of the human spinal cord after spinal cord injury using neuroimaging techniques can play a critical role in optimizing the outcomes of these stimulation-based interventions. In this study, we have introduced a neuroimaging acquisition and analysis protocol of the spinal cord in order to identify: (i) spinal cord levels at the lumbosacral enlargement using nerve root tracing; (ii) variability in the neuroanatomical characteristics of the spinal cord among individuals; (iii) location of the epidural stimulation paddle electrode and contacts with respect to the spinal cord levels at lumbosacral enlargement; and (iv) the links between the anatomical levels of stimulation and the corresponding neurophysiological motor responses. Twelve individuals with chronic, motor complete spinal cord injury implanted with a spinal cord epidural stimulator were included in the study (age: 34 ± 10.9 years, sex: 10 males, 2 females, time since injury: 8.2 ± 9.9 years, American Spinal Injury Association Impairment Scale: 6 A, 6 B). High-resolution MRI scans of the spinal cord were recorded pre-implant. An analysis of neuroanatomical substrates indicates that the length of the spinal column and spinal cord, location of the conus tip and the relationship between the spinal cord levels and vertebral levels, particularly at the lumbosacral enlargement, are variable across individuals. There is no statistically significant correlation between the length of the spinal column and the length of the spinal cord. The percentage of volumetric coverage of the lumbosacral spinal cord by the epidural stimulation paddle electrode ranges from 33.4 to 90.4% across participants. The location of the spinal cord levels with respect to the electrode contacts varies across individuals and impacts the recruitment patterns of neurophysiological responses. Finally, MRI-based spinal cord modelling can be used as a guide for the prediction and preplanning of optimum epidural stimulation paddle placement prior to the implant surgery to ensure maximizing functional outcomes. These findings highlight the crucial role that the neuroanatomical characteristics of the spinal cord specific to each individual play in achieving maximum functional benefits with spinal cord electrical stimulation.

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.

Robotic upright stand trainer (RobUST) and postural control in individuals with spinal cord injury.

CONTEXT/OBJECTIVE: Assessed feasibility and potential effectiveness of using a novel robotic upright stand trainer (RobUST) to deliver postural perturbations or provide assistance-as-needed at the trunk while individuals with spinal cord injury (SCI) performed stable standing and self-initiated trunk movements. These tasks were assessed with research participants' hands on handlebars for self-balance assistance (hands on) and with hands off (free hands). DESIGN: Proof of concept study. PARTICIPANTS: Four individuals with motor complete (n = 3) or incomplete (n = 1) SCI who were not able to achieve independent standing and presented a neurological lesion level ranging from cervical 4 to thoracic 2. OUTCOME MEASURES: Ground reaction forces, trunk displacement, and electromyography activity of trunk and lower limb muscles. RESULTS: Research participants received continuous pelvic assistance via RobUST, and manual trainer assistance at the knees to maintain standing. Participants were able to attempt all tasks. Free hands trunk perturbations resulted in greater load bearing-related sensory information (73% ipsilateral vertical loading), trunk displacement (57%), and muscle activation compared to hands on. Similarly, free hands stable standing with RobUST assistance-as-needed resulted in 8.5% larger bodyweight bearing, 112% larger trunk movement velocity, and higher trunk muscles activation compared to standing with hands on. Self-initiated trunk movements controlled by hands on showed 116% greater trunk displacement, 10% greater vertical ground reaction force, and greater ankle muscle activation compared to free hands. CONCLUSION: RobUST established a safe and challenging standing environment for individuals with SCI and has the potential to improve training paradigms and assessments of standing postural control.

Intrathecal and Oral Baclofen Use in Adults With Spinal Cord Injury: A Systematic Review of Efficacy in Spasticity Reduction, Functional Changes, Dosing, and Adverse Events.

OBJECTIVE: To examine the efficacy, dosing, and safety profiles of intrathecal and oral baclofen in treating spasticity after spinal cord injury (SCI). DATA SOURCES: PubMed and Cochrane Databases were searched from 1970-2018 with keywords baclofen, spinal cord injury, and efficacy. STUDY SELECTION: The database search yielded 588 sources and 10 additional relevant publications. After removal of duplicates, 398 publications were screened. DATA EXTRACTION: Data were extracted using the following population, intervention, comparator, outcomes, and study designs criteria: studies including adult patients with SCI with spasticity; the intervention could be oral or intrathecal administration of baclofen; selection was inclusive for control groups, surgical management, rehabilitation, and alternative pharmaceutical agents; outcomes were efficacy, dosing, and adverse events. Randomized controlled trials, observational studies, and case reports were included. Meta-analyses and systematic reviews were excluded. DATA SYNTHESIS: A total of 98 studies were included with 1943 patients. Only 4 randomized, double-blinded, and placebo-controlled trials were reported. Thirty-nine studies examined changes in the Modified Ashworth Scale (MAS; 34 studies) and Penn Spasm scores (Penn Spasm Frequency; 19 studies), with average reductions of 1.7±1.3 and 1.6±1.4 in individuals with SCI, respectively. Of these data, a total of 6 of the 34 studies (MAS) and 2 of the 19 studies (Penn Spasm Frequency) analyzed oral baclofen. Forty-three studies addressed adverse events with muscle weakness and fatigue frequently reported. CONCLUSIONS: Baclofen is the most commonly-prescribed antispasmodic after SCI. Surprisingly, there remains a significant lack of large, placebo-controlled, double-blinded clinical trials, with most efficacy data arising from small studies examining treatment across different etiologies. In the studies reviewed, baclofen effectively improved spasticity outcome measures, with increased efficacy through intrathecal administration. Few studies assessed how reduced neural excitability affected residual motor function and activities of daily living. A host of adverse events were reported that may negatively affect quality of life. Comparative randomized controlled trials of baclofen and alternative treatments are warranted because these have demonstrated promise in relieving spasticity with reduced adverse events and without negatively affecting residual motor function.

Modular organization of locomotor networks in people with severe spinal cord injury.

Introduction: Previous studies support modular organization of locomotor circuitry contributing to the activation of muscles in a spatially and temporally organized manner during locomotion. Human spinal circuitry may reorganize after spinal cord injury; however, it is unclear if reorganization of spinal circuitry post-injury affects the modular organization. Here we characterize the modular synergy organization of locomotor muscle activity expressed during assisted stepping in subjects with complete and incomplete spinal cord injury (SCI) of varying chronicity, before any explicit training regimen. We also investigated whether the synergy characteristics changed in two subjects who achieved independent walking after training with spinal cord epidural stimulation. Methods: To capture synergy structures during stepping, individuals with SCI were stepped on a body-weight supported treadmill with manual facilitation, while electromyography (EMGs) were recorded from bilateral leg muscles. EMGs were analyzed using non-negative matrix factorization (NMF) and independent component analysis (ICA) to identify synergy patterns. Synergy patterns from the SCI subjects were compared across different clinical characteristics and to non-disabled subjects (NDs). Results: Results for both NMF and ICA indicated that the subjects with SCI were similar among themselves, but expressed a greater variability in the number of synergies for criterion variance capture compared to NDs, and weaker correlation to NDs. ICA yielded a greater number of muscle synergies than NMF. Further, the clinical characteristics of SCI subjects and chronicity did not predict any significant differences in the spatial synergy structures despite any neuroplastic changes. Further, post-training synergies did not become closer to ND synergies in two individuals. Discussion: These findings suggest fundamental differences between motor modules expressed in SCIs and NDs, as well as a striking level of spatial and temporal synergy stability in motor modules in the SCI population, absent the application of specific interventions.