Interlimb conditioning of lumbosacral spinally evoked motor responses after spinal cord injury.

OBJECTIVE: The importance of subcortical pathways to functional motor recovery after spinal cord injury (SCI) has been demonstrated in multiple animal models. The current study evaluated descending interlimb influence on lumbosacral motor excitability after chronic SCI in humans. METHODS: Ulnar nerve stimulation and transcutaneous electrical spinal stimulation were used in a condition-test paradigm to evaluate the presence of interlimb connections linking the cervical and lumbosacral spinal segments in non-injured (n=15) and spinal cord injured (SCI) (n=18) participants. RESULTS: Potentiation of spinally evoked motor responses (sEMRs) by ulnar nerve conditioning was observed in 7/7 SCI participants with volitional leg muscle activation, and in 6/11 SCI participants with no volitional activation. Of these six, conditioning of sEMRs was present only when the neurological level of injury was rostral to the ulnar innervation entry zones. CONCLUSIONS: Descending modulation of lumbosacral motor pools via interlimb projections may exist in SCI participants despite the absence of volitional leg muscle activation. SIGNIFICANCE: Evaluation of sub-clinical, spared pathways within the spinal cord after SCI may provide an improved understanding of both the contributions of different pathways to residual function, and the mechanisms of plasticity and functional motor recovery following rehabilitation..

Lumbosacral spinal cord epidural stimulation improves voiding function after human spinal cord injury.

Deficits in urologic function after spinal cord injury (SCI) manifest both as a failure to store and empty, greatly impacting daily life. While current management strategies are necessary for urological maintenance, they oftentimes are associated with life-long side effects. Our objective was to investigate the efficacy of spinal cord epidural stimulation (scES) as a promising therapy to improve bladder control after SCI. A bladder mapping study was undertaken for sixteen sessions over the course of four months in an individual with chronic, motor complete SCI. Varying combinations of stimulating cathode electrodes were initially tested during filling cystometry resulting in the identification of an effective configuration for reflexive bladder emptying at the caudal end of the electrode array. Subsequent systematic testing of different frequencies at a fixed stimulus intensity and pulse width yielded lowest post-void residual volumes at 30 Hz. These stimulation parameters were then tested in four additional research participants and found to also improve reflexive voiding efficiency. Taken together with SCI studies on step, stand, voluntary motor control and cardiovascular regulation, these findings further corroborate that scES has an all-encompassing potential to increase the central state of excitability, allowing for the control of multiple body functions, including the urological system.

Training-Induced Functional Gains following SCI.

We previously demonstrated that daily, hour-long training sessions significantly improved both locomotor (limb kinematics, gait, and hindlimb flexor-extensor bursting patterns) and nonlocomotor (bladder function and at-level mechanical allodynia) functions following a moderate contusive spinal cord injury. The amount of training needed to achieve this recovery is unknown. Furthermore, whether this recovery is induced primarily by neuronal activity below the lesion or other aspects related to general exercise is unclear. Therefore, the current study objectives were to (1) test the efficacy of 30 minutes of step training for recovery following a clinically relevant contusion injury in male Wistar rats and (2) test the efficacy of training without hindlimb engagement. The results indicate that as little as 30 minutes of step training six days per week enhances overground locomotion in male rats with contusive spinal cord injury but does not alter allodynia or bladder function. Thirty minutes of forelimb-only exercise did not alter locomotion, allodynia, or bladder function, and neither training protocol altered the amount of in-cage activity. Taken together, locomotor improvements were facilitated by hindlimb step training for 30 minutes, but longer durations of training are required to affect nonlocomotor systems.

Effects of chronic baclofen use on active movement in an individual with a spinal cord injury.

STUDY DESIGN: Case report. OBJECTIVES: To describe a case of chronic use of oral baclofen in a patient with spinal cord injury limiting lower extremity movements. SETTING: Frazier Rehab Institute, Louisville, Kentucky and University of Louisville. REPORT: A 24-year-old male with a C5 AIS-B spinal cord injury received a neurophysiological examination pre and post cessation of the use of oral baclofen. The initial results revealed no motor activity below the level of the lesion during reinforcement maneuvers or active movements. Following discontinuance of baclofen, motor activity was detected in upper and lower extremity muscles during some tasks. Locomotor patterns during stepping on a treadmill with body weight support did not reveal excessive overactivity of the lower extremity muscles. The patient was also able to perform squats independently at 35-40% body weight support when standing on a treadmill. CONCLUSION: Baclofen is typically prescribed for the management of spasticity in individuals with spinal cord injury. The interaction of reduced spasticity on functional tasks is not well understood, raising an important limitation of neurological exams and classifications done under heavy dosages of medication.

United States (US) multi-center study to assess the validity and reliability of the Spinal Cord Independence Measure (SCIM III).

STUDY DESIGN: Multi-center, prospective, cohort study. OBJECTIVES: To assess the validity and reliability of the Spinal Cord Independence Measure (SCIM III) in measuring functional ability in persons with spinal cord injury (SCI). SETTING: Inpatient rehabilitation hospitals in the United States (US). METHODS: Functional ability was measured with the SCIM III during the first week of admittance into inpatient acute rehabilitation and within one week of discharge from the same rehabilitation program. Motor and sensory neurologic impairment was measured with the American Spinal Injury Association Impairment Scale. The Functional Independence Measure (FIM), the default functional measure currently used in most US hospitals, was used as a comparison standard for the SCIM III. Statistical analyses were used to test the validity and reliability of the SCIM III. RESULTS: Total agreement between raters was above 70% on most SCIM III tasks and all κ-coefficients were statistically significant (P<0.001). The coefficients of Pearson correlation between the paired raters were above 0.81 and intraclass correlation coefficients were above 0.81. Cronbach's-α was above 0.7, with the exception of the respiration task. The coefficient of Pearson correlation between the FIM and SCIM III was 0.8 (P<0.001). For the respiration and sphincter management subscale, the SCIM III was more responsive to change, than the FIM (P<0.0001). CONCLUSION: Overall, the SCIM III is a reliable and valid measure of functional change in SCI. However, improved scoring instructions and a few modifications to the scoring categories may reduce variability between raters and enhance clinical utility.

Long-lasting involuntary motor activity after spinal cord injury.

STUDY DESIGN: The study design used is prospective cohort study. OBJECTIVES: This study was designed to neurophysiologically characterize spinal motor activity during recovery from spinal cord injury (SCI). SETTING: University of Louisville, Louisville, Kentucky, USA. METHODS: Twenty-five consecutive acute SCI admissions were recruited for this study. The American Spinal Injury Association Impairment Scale (AIS) was used to categorize injury level and severity at onset. Surface EMG recording was carried out initially between the day of admission and 17 days post-onset (6.0 ± 4.3, mean ± s.d. days). Follow-up recordings were performed for up to 9 months after injury. Initial AIS distribution was 7 AIS-A; 3 AIS-B; 2 AIS-C; 13 AIS-D. RESULTS: Twelve subjects (48%) showed long-duration involuntary motor-unit activation during relaxation. This activity was seen on initial examination in nine and on follow-up by 3 months post-injury in three others. It was seen in muscles innervated from the injury zone in 11 and caudal to the lesion in 9 subjects. This activity was independent of the presence or absence of tendon reflexes and the ability to volitionally suppress plantar stimulation elicited reflex withdrawal. CONCLUSION: The form of involuntary activity described here is the likely result of the altered balance of excitation and inhibition reaching spinal motor neurons because of the loss of inhibitory interneurons or their reduced activation by damaged supraspinal drive and the synaptic reorganization that follows SCI. As such, this activity may be useful for monitoring the effects of neuroprotective and restorative intervention strategies in persons with SCI.

Neurophysiological characterization of motor recovery in acute spinal cord injury.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: This study was designed to neurophysiologically characterize motor control recovery after spinal cord injury (SCI). SETTING: University of Louisville, Louisville, Kentucky, USA. MATERIAL: Eleven acute SCI admissions and five non-injured subjects were recruited for this study. METHODS: The American Spinal Injury Association Impairment Scale (AIS) was used to categorize injury level and severity at onset. Multimuscle surface electromyography (sEMG) recording protocol of reflex and volitional motor tasks was initially performed between the day of injury and 11 days post onset (6.4±3.6, mean±s.d. days). Follow-up data were recorded for up to 17 months after injury. Initial AIS distribution was as follows: 4 AIS-A; 2 AIS-C; 5 AIS-D. Multimuscle activation patterns were quantified from the sEMG amplitudes of selected muscles using a vector-based calculation that produces separate values for the magnitude and similarity of SCI test-subject patterns to those of non-injured subjects for each task. RESULTS: In SCI subjects, overall sEMG amplitudes were lower after SCI. Prime mover muscle voluntary recruitment was slower and multimuscle patterns were disrupted by SCI. Recovery occurred in 9 of the 11 subjects, showing an increase in sEMG amplitudes, more rapid prime mover muscle recruitment rates and the progressive normalization of the multimuscle activation patterns. The rate of increase was highly individualized, differing over time by limb and proximal or distal joint within each subject and across the SCI group. CONCLUSIONS: Recovery of voluntary motor function can be quantitatively tracked using neurophysiological methods in the domains of time and multimuscle motor unit activation.

The evolution of walking-related outcomes over the first 12 weeks of rehabilitation for incomplete traumatic spinal cord injury: the multicenter randomized Spinal Cord Injury Locomotor Trial.

BACKGROUND: The Spinal Cord Injury Locomotor Trial (SCILT) compared 12 weeks of step training with body weight support on a treadmill (BWSTT) that included overground practice to a defined but more conventional overground mobility intervention (CONT) in patients with incomplete traumatic SCI within 8 weeks of onset. No previous studies have reported walking-related outcomes during rehabilitation. METHODS: This single-blinded, randomized trial entered 107 American Spinal Injury Association (ASIA) C and D patients and 38 ASIA B patients with lesions between C5 and L3 who were unable to walk on admission for rehabilitation. The Functional Independence Measure (FIM-L) for walking, 15-m walking speed, and lower extremity motor score (LEMS) were collected every 2 weeks. RESULTS: No significant differences were found at entry and during the treatment phase (12-week mean FIM-L = 5, velocity = 0.8 m/s, LEMS = 35, distance walked in 6 min = 250 m). Combining the 2 arms, a FIM-L >or= 4 was achieved in < 10% of ASIA B patients, 92% of ASIA C patients, and all of ASIA D patients. Walking speed of >or= 0.6 m/s correlated with a LEMS near 40 or higher. CONCLUSIONS: Few ASIA B and most ASIA C and D patients achieved functional walking ability by the end of 12 weeks of BWSTT and CONT, consistent with the primary outcome data at 6 months. Walking-related measures assessed at 2-week intervals reveal that time after SCI is an important variable for entering patients into a trial with mobility outcomes. By about 6 weeks after entry, most patients who will recover have improved their FIM-L to >3 and are improving in walking speed. Future trials may reduce the number needed to treat by entering patients with FIM-L < 4 at > 8 weeks after onset if still graded ASIA B and at > 12 weeks if still ASIA C.

Initial structure and growth dynamics of YBa(2)Cu(3)O(7-delta) during pulsed laser deposition.

The initial heteroepitaxial growth of YBa{2}Cu{3}O{7-delta} films on SrTiO3(001) substrates during pulsed laser deposition shows a growth-mode transition and a change of growth unit. The growth starts with two blocks, each two-thirds the size of the complete unit cell. The first of these blocks grows in a step-flow fashion, whereas the second grows in the layer-by-layer mode. Subsequent deposition occurs layer-by-layer of complete unit cells. These results suggest that the surface diffusion in the heteroepitaxial case is strongly influenced by the competition with formation energies, which is important for the fabrication of heteroepitaxial devices on the unit cell scale.

Effect of harness application and postural changes on cardiovascular parameters of individuals with spinal cord injury.

STUDY DESIGN: Prospective assessment of cardiovascular parameters in individuals with spinal cord injury (SCI) in response to harness application and postural changes including orthostatic stress. OBJECTIVE: To evaluate arterial blood pressure and heart rate (HR) with and without harness application during sitting, supine, and standing positions in able-bodied and SCI individuals. METHODS: Measurements were obtained in all SCI research participants (n=11) before a locomotor training intervention and compared to data with able-bodied individuals (n=9). During standing, all research participants wore a harness and were suspended by an overhead, pneumatic body weight support system. RESULTS: Resting arterial blood pressure and HR in individuals with cervical SCI were significantly lower during sitting than in thoracic SCI and able-bodied individuals (P<0.05). Orthostatic stress significantly decreased arterial blood pressure only in individuals with cervical SCI (P<0.05). Harness application had no effect on cardiovascular parameters in able-bodied individuals, whereas diastolic blood pressure was significantly increased in those with SCI. Orthostatic changes in cervical SCI when sitting were ameliorated by harness application. However, while standing with harness, individuals with cervical SCI still developed orthostatic hypotension. CONCLUSIONS: Level of injury to the spinal cord influences baseline cardiovascular parameters. Application of harness in individuals with SCI could alter baseline cardiovascular parameters and the response to orthostatic stress. This should be carefully considered when assessing effects of therapeutic interventions using body weight support in individuals with SCI.

Weight-supported treadmill vs over-ground training for walking after acute incomplete SCI.

OBJECTIVE: To compare the efficacy of step training with body weight support on a treadmill (BWSTT) with over-ground practice to the efficacy of a defined over-ground mobility therapy (CONT) in patients with incomplete spinal cord injury (SCI) admitted for inpatient rehabilitation. METHODS: A total of 146 subjects from six regional centers within 8 weeks of SCI were entered in a single-blinded, multicenter, randomized clinical trial (MRCT). Subjects were graded on the American Spinal Injury Association Impairment Scale (ASIA) as B, C, or D with levels from C5 to L3 and had a Functional Independence Measure for locomotion (FIM-L) score < 4. They received 12 weeks of equal time of BWSTT or CONT. Primary outcomes were FIM-L for ASIA B and C subjects and walking speed for ASIA C and D subjects 6 months after SCI. RESULTS: No significant differences were found at entry between treatment groups or at 6 months for FIM-L (n = 108) or walking speed and distance (n = 72). In the upper motor neuron (UMN) subjects, 35% of ASIA B, 92% of ASIA C, and all ASIA D subjects walked independently. Velocities for UMN ASIA C and D subjects were not significantly different for BWSTT (1.1 +/- 0.6 m/s, n = 30) and CONT (1.1 +/- 0.7, n = 25) groups. CONCLUSIONS: The physical therapy strategies of body weight support on a treadmill and defined overground mobility therapy did not produce different outcomes. This finding was partly due to the unexpectedly high percentage of American Spinal Injury Association C subjects who achieved functional walking speeds, irrespective of treatment. The results provide new insight into disability after incomplete spinal cord injury and affirm the importance of the multicenter, randomized clinical trial to test rehabilitation strategies.

Admixtures to d-wave gap symmetry in untwinned YBa2Cu3O7 superconducting films measured by angle-resolved electron tunneling.

We report on an ab anisotropy of Jc parallel b/Jc parallel a approximately/= 1.8 IcRn parallelb/IcRn parallel a approximately/= 1.2 and in ramp-edge junctions between untwinned YBa2Cu3O7 and s-wave Nb. For these junctions, the angle theta with the YBa2Cu3O7 crystal b axis is varied as a single parameter. The RnA(theta) dependence presents twofold symmetry. The minima in IcRn at theta approximately/= 50 degrees suggest a real s-wave subdominant component and negligible d(xy)-wave or imaginary s-wave admixtures. The IcRn(theta) dependence is well fitted by 83% dx2-y2-, 15% isotropic s-, and 2% anisotropic s-wave order parameter symmetry, consistent with deltab/deltaa approximately/= 1.5.

Muscle activation during unilateral stepping occurs in the nonstepping limb of humans with clinically complete spinal cord injury.

STUDY DESIGN: Comparison of different kinematic and loading conditions on muscle activation in clinically complete spinal cord-injured subjects stepping unilaterally with manual assistance. OBJECTIVE: To determine if rhythmic lower limb loading or movement could produce rhythmic muscle activation in the nonstepping limb of subjects with clinically complete spinal cord injury (SCI). SETTING: Human Locomotion Research Center, Department of Neurology, University of California, Los Angeles, USA. METHODS: We recorded electromyography, joint kinematics, and vertical ground reaction forces as four subjects with clinically complete SCI stepped with manual assistance and partial bodyweight support. For all trials, one limb continuously stepped while the other limb underwent different conditions, including rhythmic lower limb loading in an extended position without limb movement, rhythmic lower limb movement similar to stepping without limb loading, and no lower limb loading or movement with the leg in an extended or flexed position. RESULTS: Three subjects displayed rhythmic muscle activity in the nonstepping limb for trials with rhythmic limb loading, but no limb movement. One subject displayed rhythmic muscle activity in the nonstepping limb for trials without ipsilateral limb loading or movement. The rhythmic muscle activity in the nonstepping limb was similar to the rhythmic muscle activity during bilateral stepping. CONCLUSIONS: The human spinal cord can use sensory information about ipsilateral limb loading to increase muscle activation even when there is no limb movement. The results also indicate that movement and loading in one limb can produce rhythmic muscle activity in the other limb even when it is stationary and unloaded. These findings emphasize the importance of optimizing load-related and contralateral sensory input during gait rehabilitation after SCI.

Robotic gait training: toward more natural movements and optimal training algorithms.

This paper overviews our recent efforts to develop robotic devices to help people relearn how to walk after spinal cord injury. Our efforts are focused on two goals. The first is to develop robotic devices that allow natural gait movements and good force control. We have developed a five degrees-of-freedom robot (PAM) that accommodates natural pelvic movement during walking. PAM uses pneumatic actuators and a nonlinear control algorithm to achieve good force control. We have also developed a novel leg robot, ARTHuR, which makes use of a linear motor to precisely apply forces to the leg during stepping. Our second goal is to develop optimal training algorithms for robotic gait training. Toward this goal, we have developed a small-scale robotic device that allows us to test locomotor training techniques in rodent models. We have also developed an instrumentation system that allows us to measure how experienced therapists manually assist limb movement. Finally, we are developing computational models of motor rehabilitation. These models suggest that assisting in stepping only as needed with a force-controlled robotic device may be an effective method for improving locomotor recovery.

Recruitment of spinal motor pools during voluntary movements versus stepping after human spinal cord injury.

We investigated the activation of lower limb motor pools by supraspinal and spinal networks after human spinal cord injury (SCI). We compared electromyographic (EMG) activity from six muscles during voluntarily attempted non-weight-bearing single-joint movements, multijoint movements approximating stepping in a supine position, and weight-bearing stepping on a treadmill with body weight support (BWST) in seven clinically incomplete and three clinically complete SCI subjects. Seven SCI subjects had previously completed Laufband therapy (a specific step training using variable levels of body weight support and manual assistance). Significant coactivation of agonists and antagonists and multijoint flexion or extension movements of the entire limb occurred during attempts at isolated knee or ankle single-joint movements in clinically incomplete SCI subjects. Further, some muscles that were not recruited during voluntary attempts at single-joint movements were activated during voluntary step-like multijoint movements (5/16 comparisons). This suggests that the residual voluntary motor control in incomplete SCI subjects evokes more generalized motor patterns (limb flexion or extension) rather than selective activation of individual muscles. Clinically incomplete and clinically complete SCI subjects could achieve greater activation of motor pools and more reciprocal patterns of activity between agonists and antagonists during weight bearing stepping than during non-weight-bearing voluntary movements. The EMG mean amplitudes were higher during stepping than during voluntary movements in 50/60 muscles studied (p < 0.05). These results suggest that stepping with knee and hip extension and flexion and alternating lower limb loading and unloading provides proprioceptive inputs to the spinal cord that increases motor recruitment and improves reciprocity between agonists and antagonists compared to voluntary efforts.

Neural plasticity after human spinal cord injury: application of locomotor training to the rehabilitation of walking.

Recovery of locomotion has been considered unattainable following a clinically complete or severe incomplete spinal cord injury even after conventional therapy. However, the locomotion of spinal animals can be improved by training that provides complex temporal patterns of sensory information related to stepping that is interpreted by the spinal cord. This review discusses the evidence that suggests human spinal networks can integrate and interpret complex sensory signals to produce functional efferent output and adapt to repetitive training. Locomotor training, a new rehabilitative approach, is based on principles that promote the movement of limbs and trunk to generate sensory information consistent with locomotion to improve the potential for the recovery of walking after neurologic injury.

Retraining the injured spinal cord.

The present review presents a series of concepts that may be useful in developing rehabilitative strategies to enhance recovery of posture and locomotion following spinal cord injury. First, the loss of supraspinal input results in a marked change in the functional efficacy of the remaining synapses and neurons of intraspinal and peripheral afferent (dorsal root ganglion) origin. Second, following a complete transection the lumbrosacral spinal cord can recover greater levels of motor performance if it has been exposed to the afferent and intraspinal activation patterns that are associated with standing and stepping. Third, the spinal cord can more readily reacquire the ability to stand and step following spinal cord transection with repetitive exposure to standing and stepping. Fourth, robotic assistive devices can be used to guide the kinematics of the limbs and thus expose the spinal cord to the new normal activity patterns associated with a particular motor task following spinal cord injury. In addition, such robotic assistive devices can provide immediate quantification of the limb kinematics. Fifth, the behavioural and physiological effects of spinal cord transection are reflected in adaptations in most, if not all, neurotransmitter systems in the lumbosacral spinal cord. Evidence is presented that both the GABAergic and glycinergic inhibitory systems are up-regulated following complete spinal cord transection and that step training results in some aspects of these transmitter systems being down-regulated towards control levels. These concepts and observations demonstrate that (a) the spinal cord can interpret complex afferent information and generate the appropriate motor task; and (b) motor ability can be defined to a large degree by training.

Locomotor training after human spinal cord injury: a series of case studies.

Many individuals with spinal cord injury (SCI) do not regain their ability to walk, even though it is a primary goal of rehabilitation. Mammals with thoracic spinal cord transection can relearn to step with their hind limbs on a treadmill when trained with sensory input associated with stepping. If humans have similar neural mechanisms for locomotion, then providing comparable training may promote locomotor recovery after SCI. We used locomotor training designed to provide sensory information associated with locomotion to improve stepping and walking in adults after SCI. Four adults with SCIs, with a mean postinjury time of 6 months, received locomotor training. Based on the American Spinal Injury Association (ASIA) Impairment Scale and neurological classification standards, subject 1 had a T5 injury classified as ASIA A, subject 2 had a T5 injury classified as ASIA C, subject 3 had a C6 injury classified as ASIA D, and subject 4 had a T9 injury classified as ASIA D. All subjects improved their stepping on a treadmill. One subject achieved overground walking, and 2 subjects improved their overground walking. Locomotor training using the response of the human spinal cord to sensory information related to locomotion may improve the potential recovery of walking after SCI.

How the science and engineering of spaceflight contribute to understanding the plasticity of spinal cord injury.

Space programs support experimental investigations related to the unique environment of space and to the technological developments from many disciplines of both science and engineering that contribute to space studies. Furthermore, interactions between scientists, engineers and administrators, that are necessary for the success of any science mission in space, promote interdiscipline communication, understanding and interests which extend well beyond a specific mission. NASA-catalyzed collaborations have benefited the spinal cord rehabilitation program at UCLA in fundamental science and in the application of expertise and technologies originally developed for the space program. Examples of these benefits include: (1) better understanding of the role of load in maintaining healthy muscle and motor function, resulting in a spinal cord injury (SCI) rehabilitation program based on muscle/limb loading; (2) investigation of a potentially novel growth factor affected by spaceflight which may help regulate muscle mass; (3) development of implantable sensors, electronics and software to monitor and analyze long-term muscle activity in unrestrained subjects; (4) development of hardware to assist therapies applied to SCI patients; and (5) development of computer models to simulate stepping which will be used to investigate the effects of neurological deficits (muscle weakness or inappropriate activation) and to evaluate therapies to correct these deficiencies.