Locomotor Training Interventions to Improve Neurological Outcomes after SCI Summary of a Research Synthesis Shepherd Center Study Group 1 Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Shepherd Center Systematic Review Group Leadership team: Lesley Hudson, MS, David Apple, MD, Deborah Backus, PhD, PT Neural Reviewers: David Apple, MD Lesley Hudson, MA Jennith Bernstein, PT Amanda Gillot, PT Jennifer Huggins, OT Ashley Kim, OT Data coordinator: Rebecca Acevedo 2 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Table of Contents Background and purpose of reviewpp. 4 Overview of methodspp. 10 Experimental design studiespp. 16 Quasi-Experimental design studiespp. 39 Descriptive design studiespp. 49 Case Studies and Reportspp. 50 Acknowledgementspp. 81 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 3

Rationale for Review Tremendous advances in neuroscience research, as well as the development of new technology geared toward spinal cord injury (SCI) have led to the expectation of cure and "lifetime recovery" after SCI Enter the term spinal cord injury on the web and you will find multiple sites dedicated to the pursuit of the cure or neurorecovery Much focus on activity-based programs Little evidence related to neural recovery after participation in activity-based programs 4 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Rationale for Review Evidence from animal models of SCI suggests that the use of intense and repeated sensory stimulation, and intense motor practice, or exercise, can elicit plastic changes throughout the neural axis (Hutchinson et al 2004;Ying wt al. 2008;Gazula et al. 2004;Goldschmidt et al. 2008; McDonald et al, 2002; Perez et al 2004) 5 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Rationale for Review Evidence from other patient populations (eg. Stroke) suggests that intense, focused, repeated active movement of impaired limbs, especially when combined with sensory augmentation, is beneficial for improving function, and inducing neural changes in the cerebral cortex 6 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Rationale for Review The assumption: Intense activity, in the form of repeated active movement, often combined with augmented sensory stimulation, can lead to neural or functional improvements, or both, in humans with any level of injury, with any degree of completeness of injury Has led to the development of activity-based programs around the globe, inviting individuals with complete or incomplete tetraplegia or paraplegia, at any age to participate in order to achieve their maximal potential, and perhaps even full recovery of walking! 7 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Rationale for Review Several questions remain unanswered: Do the findings in animal models of SCI translate to humans with SCI? Which individuals with SCI (i.e. age, gender, level of injury, completeness of injury) actually improve in function? Is there neural recovery that can explain improvements in function in humans? Is neural recovery necessary, or sufficient, for substantial and meaningful functional recovery after SCI? 8 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Purpose of Review Main objective: To evaluate all literature between 1998 and 2008 related to the efficacy for improving neural activity and function with the use of intense therapies, often referred to as activity-based interventions, in individuals with paralysis and sensory loss due to spinal cord injury (SCI) Activity-based interventions: Include any therapy activity, or intervention, that is focused on improving muscle function and sensory perception below the level of injury, and not simply accommodation or compensation for the paralysis and sensory loss due to the SCI, in order to improve overall function after SCI 9 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Methods Employed: Important Consideration ABints do NOT include the use of electrical stimulation or robotics as neuroprosthetics, or tools to replace the lost function below the level of injury 10 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Methods Employed Definitions and Focus Overall study included any study describing the effects of activity-based interventions on neural and/or functional recovery after spinal cord injury (SCI), and includes interventions that combine intense active movement with one or more of the following: Facilitation techniques to activate muscles below the level of injury (such as the use of tactile or vibratory stimulation) Electrical stimulation (surface or indwelling) Upper extremity robotics; and intense strength training Locomotor training (manual or robotic) – this presentation presents evidence related to locomotor training interventions 11 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Methods Employed: More Definitions Neural recovery or changes in neural function: Measurable changes in neural circuitry or neuronal activity at any level of the neural axis in response to injury or learning Given that AIS and the ASIA motor scores are often used as markers for neural recovery at this time, studies that include AIS classification, ASIA sensory or motor scores, or muscle strength changes, will be included in the classification of neural outcomes for the purpose of this review Other measures of neurological changes include: Measurement of activity in a neural circuit, such as via a reflex Increases in neural factors, such as BDNF Demonstrations of supraspinal activity with imaging tools or stimulation, such as functional magnetic resonance or transcranial magnetic stimulation, respectively. 12 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Methods Employed: Definitions Functional ability: Includes any skill that leads to improved mobility (locomotion, bed mobility, transfers) or activities of daily living: Typical outcome measures include, but are not limited to, the: Functional Independence Measure (FIM) Spinal Cord Independence Measure (SCIM) Walking Index for Spinal Cord Injury (WISCI) Jebsen Hand Function Test (JHFT) Action Research Arm Test 13 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Methods Employed: Study Designs Included Experimental: Employed methods including a random assignment and a control group or a reasonably constructed comparison group Quasi-experimental: No random assignment, but either with a control group or a reasonably constructed comparison group Descriptive: Neither a control group, nor randomization, is used. These included case studies and reports, studies employing repeated measures, and Pre-post designs. 14 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Methods Employed: Study Designs Included 40 articles pulled from the literature and 21 articles met rigor and meaningfulness criteria: Descriptive (n=16) Experimental (n=3) Quasi-experimental (n=2) 15 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Studies Using Experimental Design 16 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Dobkin et al Study Design Single-blinded, randomized, multi-center clinical trial Compared the efficacy of manual locomotor training (LT) with overground gait (OG) training to overground training in adults with acute spinal cord injury (SCI) 17 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Dobkin et al Participants n=146 subjects From 6 regional centers Receiving inpatient rehabilitation for the first time Classified with an incomplete injury (American Spinal Injury Association Impairment Scale (AIS) score of B, C, or D), between spinal level and L3 18 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Dobkin et al Participants The level of injury was further delineated: Those with injuries between C5 and T10/11 were classified as upper motor neuron injuries Those with injuries T12 to L3 were classified as lower motor neuron injuries Those with lower motor neuron injury on one side and upper motor neuron injury on the other were classified with upper motor neuron injury All were within 8 weeks of their SCI when enrolled All were between 16 and 69 years old. 19 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Dobkin et al Methods Subjects in both groups (locomotor training (LT) and overground (OG)) received the standard rehabilitation interventions provided in inpatient and outpatient therapy for mobility and activities of daily living training at their respective centers Each group also received some form of LT The LT group received manual locomotor training on the treadmill, followed by overground walking training The OG group received overground walking training only Neither group received any other form of specified walking training other than these specific interventions 20 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Dobkin et al LT Group Stretched for up to 10 minutes Followed by walking on the treadmill with harness support and manual assistance for 20 to 30 minutes (3 to 10 minute increments) Amount of body weight support (BWS) and speed were adjusted so that the individual was able to walk at least 0.72 m/s, with the goal of walking at 1.07 m/s Treadmill walking followed by 10 to 20 minutes of overground walking with assistance 21 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Dobkin et al OG Group Spent their walking training time either standing or stepping, depending on their individual fatigue, and followed essentially the same order as those in the LM group: stretching (10 minutes) followed by standing or walking for 30 to 45 minutes Those who could walk practiced in the parallel bars or overground with therapist assistance, assistive devices and orthotics as necessary Not allowed to use the treadmill or harness at all during this 12-week training period 22 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Dobkin et al Both Groups Trained for 12 weeks Specific order of activities followed for all training, BUT the amount of time spent on each activity during a given session was tailored to the individuals needs Training 1 hr/day Permitted to walk at other times during therapy, and to perform trunk and lower extremity strengthening exercises Number of training sessions for individuals in both groups varied between 45 and 60 sessions depending on how quickly they reached the highest functional walking speed (0.98 m/s) 23 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Dobkin et al Methods: Outcome Measures Primary obtained: pre-intervention every 2 weeks for 12 weeks at the end of the training intervention at 6 months and 12 months after enrollment Secondary obtained 3, 6, and 12 months post- enrollment 24 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Dobkin et al Methods: Outcome Measures No neural-related primary outcome measures, only secondary outcome measures of neural changes: ASIA lower extremity motor score (LEMS) Ashworth scale Functional outcome measures: Primary: FIM lower extremity score and overground walking speed Secondary: Distance walked 6-minute walk test Berg Balance Scale Walking Index for Spinal Cord injury (WISCI SF Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Dobkin et al Outcomes No significant differences between the LT and OG groups in terms of most of the outcome measures, and specifically in terms of the neural outcome measures Neither group experienced any significant change in Ashworth scores, or in frequency of spasms No differences were found in adverse events, and neither group reported excess muscle strain, or joint pain. 26 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Dobkin et al Outcomes The majority of subjects with AIS C classification in both the LT and OG groups achieved independent walking The majority of those classified as AIS C had a FIM lower extremity score >/= 6 at 6 months post-enrollment Individuals in both groups with AIS C or D classification demonstrated a significant increase in walking velocity, consistent with functional community ambulation Speed continued to increase between 3 and 6 months, in both groups For persons classified as AIS B, neither intervention led to improvements in overground walking 27 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Dobkin et al Methodological Considerations Earlier LT studies were conducted in persons with chronic SCI, while this study was conducted in those with acute SCI There may not have been enough of a contrast between the LT and OG groups Both interventions were more intense and more task-specific than that which may be generally provided in traditional therapy, which may have lead to the lack of significant differences in outcomes between the two groups 28 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Field-Fote et al Overview Compared different LT approaches in an RCT using functional outcome measures only (no neural) Participants: 27 adults with chronic (> 1 year post-SCI) motor-incomplete SCI Randomly assigned, based LEMS, to one of four groups: Treadmill training with manual assistance (similar Dobkin et al) (TM) Treadmill training with stimulation (TS) Over-ground walking with stimulation (OG) Treadmill training with robotic assistance (LR) 29 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Field-Fote et al Methods: Training All subjects/all groups trained with body-weight support (BWS) modified based on the amount of knee flexion during the stance phase or toe dragging during swing phase Always </= 30% All participated in training for: 60-minute periods 5 days/week 12 weeks Allowed to rest during each session as needed 30 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Field-Fote et al Methods: Training Subjects in the treadmill training groups (TM, TS) were: Allowed to use the handrails, but bear full weight through their arm Encouraged to walk at their maximum walking speeds, as long as walking quality was maintained Those in the treadmill training with robotic assistance (LR) were: Progressed in walking speed based on a pre-determined algorithm until they could reach the maximum speed of 3.2 km/hr, or 2 miles/hr by 5 weeks 31 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Field-Fote et al Methods: Training Subjects in the overground group (OS) were: instructed to walk as fast as possible around the 80-foot track, and were allowed to use both the upper extremity assistive device and lower extremity orthotic with which they were most comfortable. There was no attempt to advance either device with training. 32 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Field-Fote et al Methods: Training Subjects who performed training with electrical stimulation (TS, OS), all had the same relative placement of electrodes, positioned to get the most robust flexion withdrawal response. Stimulation parameters were 300 to 600 ms train, 50 Hz, 5 to 20 mA. These parameters were adjusted throughout the training sessions to prevent habituation. Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 33

Field-Fote et al Methods: Outcome Measures Assessed function only (no neural-related outcome measures): 6-meter walk 2-minute walking test For all walking tests, the subjects were: Allowed to walk at self-selected walking speeds Videotaped for evaluation of walking performance Allowed to use whichever assistive and/or orthotic devices to which they were accustomed Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 34

Field-Fote et al Outcomes n=7 in each group, except for the LR group (n=6) # of training sessions over the 12-week training= 27 to 54 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 35

Field-Fote et al Outcomes Subjects in all four groups: Improved in walking performance AND there was no significant difference between groups. Subjects in each of the four groups demonstrated improvements in walking speed Those with the most impairment in walking function showed the greatest improvements Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 36

Field-Fote et al Conclusion Power analysis suggested that more subjects would be required in each group in order to detect a significant difference HOWEVER, there was a trend for greater improvement in walking in the electrical stimulation groups (TS, OS) Although subjects did improve, none were able to discard their wheelchairs and walk independently or in the community Further study is required Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 37

Studies Using Quasi-experimental Design 38 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Grasso et al Overview Evaluated the neural and functional outcomes in 22 adults: 17 to 60 years old Half with acute SCI (1 to 6 months post-SCI) The injury levels ranged from C7 to L2 Classified clinically as AIS A (n=5), AIS B (n=2), AIS C (n=4) Half age-matched controls with no neurological impairment All performed daily manual assisted locomotor training sessions Worked on increasing speed and decreasing the amount of body-weight support and manual assistance required Training time ranged from one to three months Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 39

Grasso et al Methods: Outcome Measures Neural: Modified Ashworth Scale (MAS) Kinematic data and electromyography (EMG) data collected during stepping attempts on the first day of training, and every 15 days thereafter Functional The Rivermeade Mobility Index (RMI) The Walking Index of Spinal Cord Injury (WISCI) The Garrett Scale (Garrett et al. 1987). Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 40

Grasso et al Outcomes: Neural I n subjects with SCI who were able to step in the first session, stepping started very irregularly The trajectory of the foot during stepping in these individuals progressed to the shape typically found in able-bodied individuals The majority of these subjects (n = 8) also demonstrated a significantly greater end-point path, indicating a longer step length and greater foot clearance during stepping Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 41

Grasso et al Outcomes: Neural (Kinematic) Subjects with SCI demonstrated an increase in amplitude and decrease in variability, suggesting alterations in inter-segmental kinematic coordination, when compared to the able bodied subjects The phase-relationship between limb segments remained abnormal Most likely due to different muscle activation patterns from what is available in able-bodies individuals Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 42

Grasso et al Outcomes: Neural (Kinematic) Suggests that although the end-point was changed in persons with SCI and approximated normal (i.e. the foot position in space closely approximated that of the able-bodied subjects during stepping on the treadmill), the muscle activity deviated from that of the able-bodied subjects, and continued to deviate with training Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 43

Grasso et al Outcomes: Neural (EMG) The averaged and normalized EMG waveforms were mapped on published charts to determine segmental localization In subjects classified with AIS C SCI: Activity in the upper lumbar (L2 to 4) segments of the cord started later and lasted longer than in able-bodied subjects Activity in the lower lumbar cord (L5 to S2) lasted for a shorter duration in those with SCI than those that were able-bodied subjects This activation in L5 to S2 corresponds to weight acceptance and activation of the hip extensors and ankle plantarflexors. Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 44

Grasso et al Outcomes: Neural (EMG) Suggests that the control of stepping in persons with motor incomplete SCI had changed its distribution after training, and was different from that in the able-bodied population Thus, neural plasticity was evident, but did not resemble that in able-bodied individuals Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 45

Grasso et al Outcomes: Functional Similar to what had already been reported Those who could not walk before training (n=5) could walk within the treadmill environment post-training, but not overground Three subjects were able to walk independently in the community post-training The remainder maintained some degree of disability in walking overground Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 46

Grasso et al Conclusion Although some subjects demonstrated neural changes with LT training: These changes were not identical to the patterns that are seen in the able bodied population These changes appear to be correlated with functional changes in walking overground Further study is required to gain a greater understanding of the neural effects of LT and to determine the relationship between such neural effects and functional outcomes in order to better understand and define the goals of interventions for persons with SCI Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 47

Studies Using Descriptive Design 48 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Case Studies and Reports 49 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation

Behrman & Harkema 2000 Methods Training procedures were similar to those described previously in the Dobkin et al. study: Subjects walked with BWS on a treadmill with manual assistance Over-ground training was initiated when an individual could: Maintain independent standing while supporting at least 80% of their body weight Initiate stepping with appropriate kinematics in at least one leg n=3 Two with AIS C or D classification trained 3 times per week One with AIS A trained 5 times per week Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 50

Behrman & Harkema 2000 Outcomes Neural ASIA lower extremity motor score (LEMS) Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 51

Behrman & Harkema 2000 Outcomes Reported that three adults with motor incomplete SCI (AIS C or D), and one subject with complete (AIS A) SCI, improved walking over the treadmill The subject classified with an AIS A paraplegia: Did not improve in ASIA LEMS BUT did improve in stepping on the treadmill Did not receive overground training and was not evaluated for overground walking Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 52

Behrman & Harkema 2000 Outcomes Both subjects with AIS C SCI, improved in ASIA LEMS, as well as stepping on the treadmill Subject with AIS D SCI did not show improvements in LEMS that corresponded with improvements in walking, not only on the treadmill but overground as well Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 53

Behrman & Harkema 2000 Important Considerations Time post-injury and the AIS varied Three subjects with motor incomplete SCI injured < 1 year Subjects that were motor incomplete were also all males, whereas the one with complete SCI was a female Ages varied between 20 years old for two subjects, 43 and 45 for the other two Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 54

Behrman et al Summary of one case study Reported that a 55-year-old man with an acute SCI and incomplete (AIS D) tetraplegia at C6/7 who particpated in manual LT (same protocol as defined previously) Did not demonstrate significant changes in neural function (i.e., improvements in LEMS) HOWEVER, did demonstrate improvements in walking function After 45 sessions of manual locomotor training, 5 times a week for 9 weeks, he demonstrated improvements in walking speed, distance, and kinematics overground Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 55

Behrman et al Case Report: Methods Evaluated neural and functional outcomes following LT in a pediatric subject 4.5-year-old child with AIS C tetraplegia (C6/7) One year post-SCI Intervention: Manual LT and overground walking each session 16 months Neural outcome measures: ASIA LEMS ASIA somatosensory scores Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 56

Behrman et al Methods: Outcomes Evaluations were performed 5 days prior to initiation of training, and upon completion of training At the completion of 76 sessions: Demonstrated no significant increases in LEMS or sensory scores on the ASIA exam HOWEVER, demonstrated improvement in walking independence Could ambulate in the community with a rolling walker and with a self-selected gait speed of 0.29 m/s and maximum speed of 0.48 m/s Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 57

Behrman et al Summary of case study in a child Suggests that the methods most appropriate for improving walking function after SCI in children may be similar to those utilized in adults Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 58

Prosser 2007 Overview Reported similar findings to those of Behrman et al. Subject 5-year old girl with SCI at C4, AIS C Brown-Sequard pattern Mild head injury as well LT was added to her inpatient PT program Approximately one month after her injury Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 59

Prosser 2007 Methods: Training BWS system slightly different from the system used by Behrman and colleagues: BWS was measured with the subject standing over a scale and bearing down with her weight The weight on the scale was subtracted from her body-weight to determine the percent of support she was receiving Overground training was initiated 10 weeks after her injury when she was able to independently step with her right leg on the treadmill Initially, the subject used a rolling walker and an articulating ankle-foot orthosis (AFO) on her left leg, and walked with assistance of two people overground. Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 60

Prosser 2007 Methods: Training The focus, throughout both treadmill and overground training was on kinematics of gait LT performed 3 to 4 times per week, for a total of 6 months Ranged form 10 minutes for the first three sessions to 20 minutes for the remainder of the sessions Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 61

Prosser 2007 Methods: Outcome Measures Primary outcome measures ASIA Impairment Scale The Functional Independence Measure for Children (WeeFIM II) mobility score The WISCI II Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 62

Prosser 2007 Outcomes During 6 months of training, the subject was able to: Decrease BWS over the duration of the locomotor intervention, from 80% support to 10% support Increase her speed from 0.27 m/s to 0.98 to 1.12 m/s Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 63

Prosser 2007 Outcomes At the completion of training: Neural: LEMS increased from 4/50 to 29/50 Functional She progressed from the rolling walker, AFO, and assistance of two people, to walking with bilateral Loftstrand crutches, the AFO, and supervision only overground The WeeFIM II scores improved from 5/35 to 21/35 in mobility The WISCI II from 0 to 12 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 64

Prosser 2007 Important Considerations This is a case study During the acute phase of recovery The subject also received concurrent inpatient therapy THEREFORE, it is not possible to determine causality between locomotor training and improvements in walking function HOWEVER, this report does demonstrate that manual LT can be used in at least some clients in the pediatric population with no harm to the subject and further study is warranted Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 65

Wirz et al Overview Multicenter case series Functional (primary outcome measures) and neural (secondary outcome measures) outcomes Pre- and post-training with robotic LT Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 66

Wirz et al Methods 20 adults 16 to 64 years old Motor incomplete (AIS C or D) tetraplegia (n = 11) and paraplegia (n = 9) Levels of injury ranged from C5 to L1 Including subjects with lower motor neuron injury, unlike the locomotor training studies already reported All 2 to 17 years post-SCI Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 67

Wirz et al Methods Similar to the manual LT that was described previously, BUT used a robotic system Subjects were provided with BWS and robotic assistance while walking on a treadmill For robotic assistance, the legs were positioned in the orthoses of a Driven Gait Orthosis that was powered by a computer while subjects walked on the treadmill, which assisted them in their stepping motion Subjects trained: In approximately 45-minute sessions 3 to 5 times per week For 8 weeks Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 68

Wirz et al Outcome Measures: Functional The WISCI II The 10-Meter Walk Test (10MWT) 6-Minute Walk Test (6MWT) Timed Up & Go (TUG) Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 69

Wirz et al Outcome Measures: Neural ASIA LEMS The Ashworth Scale The Spinal Cord Assessment Tools for Spasticity (SCATS) Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 70

Wirz et al Outcomes: Functional All of the subjects who were unable to walk prior to the intervention were able to walk overground after the intervention Only two of those who could ambulate prior to the intervention demonstrated functional improvements on the WSICI II Subjects who were able to walk overground demonstrated significant increases in gait speed and distance walked, and there was no difference in rate of improvement between the first 4 weeks and the final 4 weeks of training Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 71

Wirz et al Outcomes: Functional All but two of the subjects tested in the TUG demonstrated improvements in balance As measured by a decrease in the time to perform the test, with the greatest change during the first four weeks of training There was less improvement in persons with injuries above T11, and in those who were not taking anti-spasticity medications There was a significant correlation between the pre- training performance and the magnitude of improvements for the 10MWT and the 6MWT Slower walkers had the greatest improvements in gait speed and distance Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 72

Wirz et al Outcomes: Neural Only 10 subjects were tested in relation to neural outcomes, and only at one of the centers The only significant increase in LEMS was between the 4 and 8-week assessments In the majority of the subjects (90%), the changes in LEMS did not correlate with the changes in performance on the walking function tests (10MWT, 6MWT, TUG) There was also a significant decrease in spasticity, but only in the extensor spasm score as measured with the SCATS Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 73

Wirz et al Conclusions Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 74

Protas et al Overview Increased number of neural measures, including not simply ASIA and Ashworth outcome measures, but also: Added the Brain Motor Control Assessment (BMCA) (Sherwood, McKay & Dimitrijevic 1996, Sherwood, Priebe & Graves 1997) Employs surface EMG during a standardized protocol to assess changes in EMG activity as an indirect measure of motor control Involves having the subject perform voluntary movements, reinforcement maneuvers, and reflex stimulation while EMG is recorded at multiple muscles Three subjects with chronic, motor incomplete, thoracic SCI were enrolled to train on a treadmill 1 hour per day, 5 days per week, for 12 weeks Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 75

Protas et al Methods Manual LT training was similar to those studies reported earlier Subjects walked with BWS on the treadmill, with trainers providing manual assistance and verbal cueing to facilitate optimal kinematics during stepping Subjects walked until they reported fatigue, and then were allowed to rest before continuing Over-ground walking in this study, however, was initiated in all subjects after 3 weeks of training, regardless of the amount of BWS, walking speed, or stepping kinematics. Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 76

Protas et al Outcomes All 3 subjects tripled their gait speed and endurance s a result of training, and that these changes are independent of the neural outcomes, reflecting functional changes Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 77

Protas et al Outcomes Neural changes included: Changes reflected on the BMCA: Shift in EMG activity toward that which is seen in able bodied subjects in two of the subjects No other consistent findings related to neural function across all three subjects No significant changes in motor function, and no significant changes in Ashworth scores One subject reported a reduction in his clonus as training progressed Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation 78

Thank you! National Institute Disability Rehabilitation Research Shepherd Center Lesley Hudson, MS David Apple, MD Jennith Bernstein, PT Amanda Gillot, PT Ashley Kim, OT Elizabeth Sasso, PT Kristen Casperson, PT Brian Smith, PT Anna Berry, PT Angela Cooke, RN 79 Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation