Amplify Gait to Improve Locomotor Engagement in Spinal Cord Injury (AGILE SCI) trial: study protocol for an assessor blinded randomized controlled trial.

BACKGROUND: Among ambulatory people with incomplete spinal cord injury (iSCI), balance deficits are a primary factor limiting participation in walking activities. There is broad recognition that effective interventions are needed to enhance walking balance following iSCI. Interventions that amplify self-generated movements (e.g., error augmentation) can accelerate motor learning by intensifying sensorimotor feedback and facilitating exploration of motor control strategies. These features may be beneficial for retraining walking balance after iSCI. We have developed a cable-driven robot that creates a movement amplification environment during treadmill walking. The robot applies a continuous, laterally-directed, force to the pelvis that is proportional in magnitude to real-time lateral velocity. Our purpose is to investigate the effects of locomotor training in this movement amplification environment on walking balance. We hypothesize that for ambulatory people with iSCI, locomotor training in a movement amplification environment will be more effective for improving walking balance and participation in walking activities than locomotor training in a natural environment (no applied external forces). METHODS: We are conducting a two-arm parallel-assignment intervention. We will enroll 36 ambulatory participants with chronic iSCI. Participants will be randomized into either a control or experimental group. Each group will receive 20 locomotor training sessions. Training will be performed in either a traditional treadmill environment (control) or in a movement amplification environment (experimental). We will assess changes using measures that span the International Classification of Functioning, Disability and Health (ICF) framework including 1) clinical outcome measures of gait, balance, and quality of life, 2) biomechanical assessments of walking balance, and 3) participation in walking activities quantified by number of steps taken per day. DISCUSSION: Training walking balance in people with iSCI by amplifying the individual's own movement during walking is a radical departure from current practice and may result in new strategies for addressing balance impairments. Knowledge gained from this study will expand our understanding of how people with iSCI improve walking balance and how an intervention targeting walking balance affects participation in walking activities. Successful outcomes could motivate development of clinically feasible tools to replicate the movement amplification environment within clinical settings. TRIAL REGISTRATION: NCT04340063.

Reliability and Validity of the Functional Gait Assessment in Incomplete Spinal Cord Injury.

BACKGROUND: There are limited psychometrically sound measures to assess higher level balance in individuals with incomplete spinal cord injury (iSCI). OBJECTIVES: To evaluate interrater and intrarater reliability and convergent validity of the Functional Gait Assessment (FGA) in individuals with iSCI. METHODS: Twelve participants (11 male, 1 female) 32 to 73 years old with chronic motor iSCI, American Spinal Injury Association Impairment Scale C (n = 2) or D (n = 10), were included. Participants completed five outcome measures during a single test session including lower extremity motor scores from the International Standards for the Neurological Classification of Spinal Cord Injury, FGA, 10-Meter Walk Test (10MWT), Walking Index for Spinal Cord Injury (WISCI-II), and the Spinal Cord Injury Functional Ambulation Profile (SCI-FAP). RESULTS: Inter- and intrarater reliability for the FGA were excellent. Interrater reliability was excellent with intraclass correlation coefficient (ICC) scores greater than 0.92 (p < .001). Interrater reliability against an expert was also excellent for all raters, with an ICC greater than or equal to 0.92 (p < .01). Intrarater reliability was excellent with an ICC score of greater than 0.91 (p < .002) for all raters. Validity of the FGA with 10MWT was -0.90 (p = .000), FGA with WISCI-II was 0.74 (p = .006), and FGA with SCI-FAP was -0.83 (p = .001). CONCLUSION: The FGA is a reliable and valid outcome measure to use when assessing gait and balance in individuals with motor iSCI. The FGA provides clinicians with a single tool to utilize across a variety of neurologic diagnoses.

Effect of sensory feedback from the proximal upper limb on voluntary isometric finger flexion and extension in hemiparetic stroke subjects.

This study investigated the potential influence of proximal sensory feedback on voluntary distal motor activity in the paretic upper limb of hemiparetic stroke survivors and the potential effect of voluntary distal motor activity on proximal muscle activity. Ten stroke subjects and 10 neurologically intact control subjects performed maximum voluntary isometric flexion and extension, respectively, at the metacarpophalangeal (MCP) joints of the fingers in two static arm postures and under three conditions of electrical stimulation of the arm. The tasks were quantified in terms of maximum MCP torque [MCP flexion (MCP(flex)) or MCP extension (MCP(ext))] and activity of targeted (flexor digitorum superficialis or extensor digitorum communis) and nontargeted upper limb muscles. From a previous study on the MCP stretch reflex poststroke, we expected stroke subjects to exhibit a modulation of voluntary MCP torque production by arm posture and electrical stimulation and increased nontargeted muscle activity. Posture 1 (flexed elbow, neutral shoulder) led to greater MCP(flex) in stroke subjects than posture 2 (extended elbow, flexed shoulder). Electrical stimulation did not influence MCP(flex) or MCP(ext) in either subject group. In stroke subjects, posture 1 led to greater nontargeted upper limb flexor activity during MCP(flex) and to greater elbow flexor and extensor activity during MCP(ext). Stroke subjects exhibited greater elbow flexor activity during MCP(flex) and greater elbow flexor and extensor activity during MCP(ext) than control subjects. The results suggest that static arm posture can modulate voluntary distal motor activity and accompanying muscle activity in the paretic upper limb poststroke.

Prolonged electrical stimulation over hip flexors increases locomotor output in human SCI.

OBJECTIVES: The objective of this study was to determine whether enhanced feedback from thigh afferents improves locomotor output in human spinal cord injury (SCI). METHODS: The effects of afferent feedback originating from the upper thigh muscles on locomotion was examined using electrical stimulation in 10 subjects with incomplete SCI and three neurologically intact controls during robotic-assisted treadmill walking. Electrical stimulation consisted of 20 pulses at 30 Hz, applied bilaterally to the skin of the medial thigh, approximately over the sartorius muscle. The stimulation was applied at four different phases of the gait cycle. Torque responses of hip and knee joints and electromyograms of both legs were recorded during baseline with no stimulation, stimulation, and post-stimulation. RESULTS: During stimulation, enhanced hip and knee extension and flexion torque responses were observed during the stance and swing phases, respectively, for all four different stimulation conditions. Larger hip extension torque was observed when the stimulation was applied during the stance phase and the transition from stance to swing. CONCLUSIONS: Enhanced afferent feedback produced by electrical stimulation may increase the excitability of the spinal cord locomotor circuits in human SCI. SIGNIFICANCE: Results from this study emphasize the contribution of sensory information from thigh muscles, particularly the sartorius muscle afferents, to locomotor control in human SCI during treadmill walking.

Feedback and feedforward locomotor adaptations to ankle-foot load in people with incomplete spinal cord injury.

Humans with spinal cord injury (SCI) modulate locomotor output in response to limb load. Understanding the neural control mechanisms responsible for locomotor adaptation could provide a framework for selecting effective interventions. We quantified feedback and feedforward locomotor adaptations to limb load modulations in people with incomplete SCI. While subjects airstepped (stepping performed with kinematic assistance and 100% bodyweight support), a powered-orthosis created a dorisflexor torque during the "stance phase" of select steps producing highly controlled ankle-load perturbations. When given repetitive, stance phase ankle-load, the increase in hip extension work, 0.27 J/kg above baseline (no ankle-load airstepping), was greater than the response to ankle-load applied during a single step, 0.14 J/kg (P = 0.029). This finding suggests that, at the hip, subjects produced both feedforward and feedback locomotor modulations. We estimate that, at the hip, the locomotor response to repetitive ankle-load was modulated almost equally by ongoing feedback and feedforward adaptations. The majority of subjects also showed after-effects in hip kinetic patterns that lasted 3 min in response to repetitive loading, providing additional evidence of feedforward locomotor adaptations. The magnitude of the after-effect was proportional to the response to repetitive ankle-foot load (R(2) = 0.92). In contrast, increases in soleus EMG amplitude were not different during repetitive and single-step ankle-load exposure, suggesting that ankle locomotor modulations were predominately feedback-based. Although subjects made both feedback and feedforward locomotor adaptations to changes in ankle-load, between-subject variations suggest that walking function may be related to the ability to make feedforward adaptations.

Daily stepping in individuals with motor incomplete spinal cord injury.

BACKGROUND: In individuals with motor incomplete spinal cord injury (SCI), ambulatory function determined in the clinical setting is related to specific measures of body structure and function and activity limitations, although few studies have quantified the relationship of these variables with daily stepping (steps/day). OBJECTIVE: The aim of this study was to quantify daily stepping in ambulatory individuals with SCI and its relationship with clinical walking performance measures and specific demographics, impairments, and activity limitations. DESIGN: A cross-sectional study was performed to estimate relationships among clinical variables to daily stepping in self-identified community versus non-community (household) walkers. METHODS: Average daily stepping was determined in 50 people with chronic, motor incomplete SCI. Data for clinical and self-report measures of walking performance also were collected, and their associations with daily stepping were analyzed using correlation and receiver operating characteristic (ROC) analyses. Relationships between daily stepping and the measures of demographics, impairments, and activity limitations were identified using correlation and regression analyses. RESULTS: The ROC analyses revealed a significant discriminative ability between self-reported community and non-community walkers using clinical gait measures and daily stepping. Stepping activity generally was low throughout the sample tested, however, with an average of approximately 2,600 steps/day. Knee extension strength (force-generating capacity) and static balance were the primary variables related to daily stepping, with metabolic efficiency and capacity and balance confidence contributing to a lesser extent. LIMITATIONS: The small sample size and use of specific impairment-related measures were potential limitations of the study. CONCLUSIONS: Daily stepping is extremely limited in individuals with incomplete SCI, with a potentially substantial contribution of impairments in knee extension strength and balance.

Modulation of stretch reflexes of the finger flexors by sensory feedback from the proximal upper limb poststroke.

Neural coupling of proximal and distal upper limb segments may have functional implications in the recovery of hemiparesis after stroke. The goal of the present study was to investigate whether the stretch reflex response magnitude of spastic finger flexor muscles poststroke is influenced by sensory input from the shoulder and the elbow and whether reflex coupling of muscles throughout the upper limb is altered in spastic stroke survivors. Through imposed extension of the metacarpophalangeal (MCP) joints, stretch of the relaxed finger flexors of the four fingers was imposed in 10 relaxed stroke subjects under different conditions of proximal sensory input, namely static arm posture (3 different shoulder/elbow postures) and electrical stimulation (surface stimulation of biceps brachii or triceps brachii, or none). Fast (300 degrees/s) imposed stretch elicited stretch reflex flexion torque at the MCP joints and reflex electromyographic (EMG) activity in flexor digitorum superficialis. Both measures were greatest in an arm posture of 90 degrees of elbow flexion and neutral shoulder position. Biceps stimulation resulted in greater MCP stretch reflex flexion torque. Fast imposed stretch also elicited reflex EMG activity in nonstretched heteronymous upper limb muscles, both proximal and distal. These results suggest that in the spastic hemiparetic upper limb poststroke, sensorimotor coupling of proximal and distal upper limb segments is involved in both the increased stretch reflex response of the finger flexors and an increased reflex coupling of heteronymous muscles. Both phenomena may be mediated through changes poststroke in the spinal reflex circuits and/or in the descending influence of supraspinal pathways.

Rapid and long-term adaptations in gait symmetry following unilateral step training in people with hemiparesis.

BACKGROUND AND OBJECTIVE: Evidence for specific physical interventions that improve walking symmetry in individuals with hemiparesis poststroke is limited. The aim of this study was to investigate the rapid and prolonged effects of unilateral step training (UST) on step length asymmetry (SLA) in people with hemiparesis. SUBJECTS AND DESIGN: Eighteen individuals with chronic hemiparesis and substantial SLA during overground walking participated in a single-group, pretest-posttest study. The study consisted of 2 phases, with 10 subjects participating in each phase; 2 subjects participated in both phases. INTERVENTIONS AND MEASUREMENTS: To investigate rapid effects of UST, the participants completed a 20-minute session of UST on a treadmill with their unimpaired limb, with the impaired limb held stationary off the treadmill. Data for spatiotemporal gait parameters during overground walking at self-selected and fastest speeds were collected prior to and following UST, with follow-up measurements at 1 day and 1 week. To investigate the prolonged effects, the participants completed ten 20-minute sessions of UST. Data for spatiotemporal gait parameters were collected prior to training as well as after every third session, with follow-up measurements at 1 and 2 weeks. RESULTS: Immediately following UST, SLA tested during fast-paced overground walking improved by up to 13% (49% reduced to a 36% SLA), with changes retained for up to 24 hours. Following 10 sessions of UST, SLA improved significantly, with changes retained for up to 2 weeks. LIMITATIONS: Despite repeated baseline measurements, the absence of a control group was a limitation. Furthermore, stepping characteristics during UST were not quantified. CONCLUSION: Unilateral step training may improve spatiotemporal patterns in people with substantial gait asymmetry poststroke. Repeated training may be necessary for maintenance of adaptations.

Ankle load modulates hip kinetics and EMG during human locomotion.

The purpose of this research was to examine the role of isolated ankle-foot load in regulating locomotor patterns in humans with and without spinal cord injury (SCI). We used a powered ankle-foot orthosis to unilaterally load the ankle and foot during robotically assisted airstepping. The load perturbation consisted of an applied dorsiflexion torque designed to stimulate physiological load sensors originating from the ankle plantar flexor muscles and pressure receptors on the sole of the foot. We hypothesized that 1) the response to load would be phase specific with enhanced ipsilateral extensor muscle activity and joint torque occurring when unilateral ankle-foot load was provided during the stance phase of walking and 2) that the phasing of subject produced hip moments would be modulated by varying the timing of the applied ankle-foot load within the gait cycle. As expected, both SCI and nondisabled subjects demonstrated a significant increase (P < 0.05) in peak hip extension moments (142 and 43% increase, respectively) when given ankle-foot load during the stance phase compared with no ankle-foot load. In SCI subjects, this enhanced hip extension response was accompanied by significant increases (P < 0.05) in stance phase gluteus maximus activity (27% increase). In addition, when ankle-foot load was applied either 200 ms earlier or later within the gait cycle, SCI subjects demonstrated significant phase shifts ( approximately 100 ms) in hip moment profile (P < 0.05; i.e., the onset of hip extension moments occurred earlier when ankle-foot load was applied earlier). This study provides new insights into how individuals with spinal cord injury use sensory feedback from ankle-foot load afferents to regulate hip joint moments and muscle activity during gait.

Multicenter randomized clinical trial evaluating the effectiveness of the Lokomat in subacute stroke.

OBJECTIVE: To compare the efficacy of robotic-assisted gait training with the Lokomat to conventional gait training in individuals with subacute stroke. METHODS: A total of 63 participants<6 months poststroke with an initial walking speed between 0.1 to 0.6 m/s completed the multicenter, randomized clinical trial. All participants received twenty-four 1-hour sessions of either Lokomat or conventional gait training. Outcome measures were evaluated prior to training, after 12 and 24 sessions, and at a 3-month follow-up exam. Self-selected overground walking speed and distance walked in 6 minutes were the primary outcome measures, whereas secondary outcome measures included balance, mobility and function, cadence and symmetry, level of disability, and quality of life measures. RESULTS: Participants who received conventional gait training experienced significantly greater gains in walking speed (P=.002) and distance (P=.03) than those trained on the Lokomat. These differences were maintained at the 3-month follow-up evaluation. Secondary measures were not different between the 2 groups, although a 2-fold greater improvement in cadence was observed in the conventional versus Lokomat group. CONCLUSIONS: For subacute stroke participants with moderate to severe gait impairments, the diversity of conventional gait training interventions appears to be more effective than robotic-assisted gait training for facilitating returns in walking ability.

Rebound responses to prolonged flexor reflex stimuli in human spinal cord injury.

The purpose of this study was to examine the reflex effects of electrical stimulation applied to the thigh using skin electrodes, targeting the sensory fibers of the rectus femoris and sartorius, in people with spinal cord injury (SCI). Thirteen individuals with SCI were recruited to participate in experiments using prolonged electrical stimuli on the right medial thigh over the regions of the sartorius and rectus femoris muscles. Three stimuli, spaced 20 s apart, were applied at 30 Hz for 1 s at four different intensities (15-60 mA) while subjects rested in a seated position. Isometric joint torques of the hip, knee and ankle, and electromyograms (EMGs) from six muscles of the leg were recorded during the stimulation. Early in the stimulation, a flexion response was observed at the hip and ankle, analogous to a flexor reflex; however, this response was usually followed by a "rebound" response consisting of hip extension, knee flexion and ankle plantarflexion, occurring in 10/13 subjects. Stimuli applied in a more lateral (mid thigh) electrode position (i.e. over the rectus femoris) were less effective in producing the response than medial placement, despite vigorous quadriceps activation. This complex reflex response is consistent with activation of a coordinating spinal circuit that could play a role in motor function. The reversal of the reflex pattern emphasizes the potential connection between skin/muscle afferents of the thigh, possibly including sartorius muscle afferents and locomotor reflex centers. This knowledge may be helpful in identifying rehabilitation strategies for enhancing gait training in human SCI.

Enhanced gait-related improvements after therapist- versus robotic-assisted locomotor training in subjects with chronic stroke: a randomized controlled study.

BACKGROUND AND PURPOSE: Locomotor training (LT) using a treadmill can improve walking ability over conventional rehabilitation in individuals with hemiparesis, although the personnel requirements often necessary to provide LT may limit its application. Robotic devices that provide consistent symmetrical assistance have been developed to facilitate LT, although their effectiveness in improving locomotor ability has not been well established. METHODS: Forty-eight ambulatory chronic stroke survivors stratified by severity of locomotor deficits completed a randomized controlled study on the effects of robotic- versus therapist-assisted LT. Both groups received 12 LT sessions for 30 minutes at similar speeds, with guided symmetrical locomotor assistance using a robotic orthosis versus manual facilitation from a single therapist using an assist-as-needed paradigm. Outcome measures included gait speed and symmetry, and clinical measures of activity and participation. RESULTS: Greater improvements in speed and single limb stance time on the impaired leg were observed in subjects who received therapist-assisted LT, with larger speed improvements in those with less severe gait deficits. Perceived rating of the effects of physical limitations on quality of life improved only in subjects with severe gait deficits who received therapist-assisted LT. CONCLUSIONS: Therapist-assisted LT facilitates greater improvements in walking ability in ambulatory stroke survivors as compared to a similar dosage of robotic-assisted LT.

Metabolic costs and muscle activity patterns during robotic- and therapist-assisted treadmill walking in individuals with incomplete spinal cord injury.

BACKGROUND AND PURPOSE: Robotic devices that provide passive guidance and stabilization of the legs and trunk during treadmill stepping may increase the delivery of locomotor training to subjects with neurological injury. Lower-extremity guidance also may reduce voluntary muscle activity as compared with compliant assistance provided by therapists. The purpose of this study was to investigate differences in metabolic costs and lower-limb muscle activity patterns during robotic- and therapist-assisted treadmill walking. SUBJECTS: Twelve ambulatory subjects with motor incomplete spinal cord injury participated. METHODS: In 2 separate protocols, metabolic and electromyographic (EMG) data were collected during standing and stepping on a treadmill with therapist and robotic assistance. During robotic-assisted walking, subjects were asked to match the kinematic trajectories of the device and maximize their effort. During therapist-assisted walking, subjects walked on the treadmill with manual assistance provided as necessary. RESULTS: Metabolic costs and swing-phase hip flexor EMG activity were significantly lower when subjects were asked to match the robotic device trajectories than with therapist-assisted walking. These differences were reduced when subjects were asked to maximize their effort during robotic-assisted stepping, although swing-phase plantar-flexor EMG activity was increased. In addition, during standing prior to therapist- or robotic-assisted stepping, metabolic costs were higher without stabilization from the robotic device. DISCUSSION AND CONCLUSION: Differences in metabolic costs and muscle activity patterns between therapist- and robotic-assisted standing and stepping illustrate the importance of minimizing passive guidance and stabilization provided during step training protocols.

Temporal facilitation of spastic stretch reflexes following human spinal cord injury.

Recent evidence suggests that alterations in ionic conductances in spinal motoneurones, specifically the manifestation of persistent inward currents, may be partly responsible for the appearance of hyperexcitable reflexes following spinal cord injury (SCI). We hypothesized that such alterations would manifest as temporal facilitation of stretch reflexes in human SCI. Controlled, triangular wave, ankle joint rotations applied at variable velocities (30-120 deg s(-1)) and intervals between stretches (0.25-5.0 s) were performed on 14 SCI subjects with velocity-dependent, hyperexcitable plantarflexors. Repeated stretch elicited significant increases in plantarflexion torques and electromyographic (EMG) activity from the soleus (SOL) and medial gastrocnemius (MG). At higher velocities (> or = 90 deg s(-1)), reflex torques declined initially, but subsequently increased to levels exceeding the initial response, while mean EMG responses increased throughout the joint perturbations. At lower velocities (< or = 60 deg s(-1)), both joint torques and EMGs increased gradually. Throughout a range of angular velocities, reflex responses increased significantly only at intervals < or = 1 s between stretches and following at least four rotations. Ramp-and-hold perturbations used to elicit tonic stretch reflexes revealed significantly prolonged EMG responses following one or two triangular stretches, as compared to single ramp-and-hold excursions. Post hoc analyses revealed reduced reflex facilitation in subjects using baclofen to control spastic behaviours. Evidence of stretch reflex facilitation post-SCI may reflect changes in underlying neuronal properties and provide insight into the mechanisms underlying spastic reflexes.

Flexor reflex responses triggered by imposed knee extension in chronic human spinal cord injury.

Hypersensitivity of the flexor reflex pathways to input from force-sensitive muscle afferents may contribute to the prevalence and severity of muscle spasms in patients with spinal cord injury (SCI). In this study, we triggered flexor reflexes with constant velocity knee movements in 15 subjects with SCI. Ramp and hold knee extension perturbations were imposed on one leg while the hip and ankle were held in an isometric position using an instrumented leg brace. Knee, ankle and hip torque responses and electromyograms from six muscles of the leg were recorded following controlled knee extension at four different velocities. Tests were conducted with the hip in both flexed and extended positions. During the movement into knee extension, a velocity-dependent stretch reflex, represented by a progressively increasing knee flexion torque, was observed. In addition, another type of reflex that resembled a flexor reflex (flexion of the hip and ankle) was also triggered by the imposed knee extension. The magnitude of the ankle dorsiflexion torque responses was significantly correlated to the stretch reflex torque at the knee in 9 of the 15 subjects. We concluded that stretch reflexes initiate a muscle contraction that then can contribute to a flexor reflex response, possibly through muscle group III/IV afferent pathways. These results suggest that spasticity in SCI consists of a myriad of complex reflex responses that extend beyond stretch reflexes.