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.Annually, approximately 10,000 Americans have a traumatic spinal cord injury (SCI). For many patients, the most visible lingering disability is the inability to walk or a slow spastic- NIH Public Access Author ManuscriptNeurology. Author manuscript; available in PMC 2014 July 17. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript paretic gait with high energy cost. 1 A gait training strategy, using body weight support on a treadmill (BWSTT), 2,3 has evolved from physiologic studies of the effects of the level and timing of limb loading during stepping and of stance and swing phase kinematics in spinal transected quadrupeds [4][5][6][7] and in patients with complete SCI. [8][9][10] The experimental intervention received clinical support from nonrandomized studies of patients with incomplete SCI early and late after injury. 2,3,[11][12][13] No randomized trials with blinded outcomes, however, had compared different physical therapy strategies aimed at the recovery of walking during initial inpatient and outpatient rehabilitation. Further, no prospective trials in SCI had collected measures related to functional walking, such as walking speed, distance, and the need for assistive devices. 14,15The Spinal Cord Injury Locomotor Trial (SCILT) was a single-bli...

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 ≥ 4 was achieved in < 10% of ASIA B patients, 92% of ASIA C patients, and all of ASIA D patients. Walking speed of ≥ 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.

The authors describe the rationale and methodology for the first prospective, multicenter, randomized clinical trial (RCT) of a task-oriented walking intervention for subjects during early rehabilitation for an acute traumatic spinal cord injury (SCI). The experimental strategy, body weight-supported treadmill training (BWSTT), allows physical therapists to systematically train patients to walk on a treadmill at increasing speeds typical of community ambulation with increasing weight bearing. The therapists provide verbal and tactile cues to facilitate the kinematic, kinetic, and temporal features of walking. Subjects were randomly assigned to a conventional therapy program for mobility versus the same intensity and duration of a combination of BWSTT and over-ground locomotor retraining. Subjects had an incomplete SCI (American Spinal Injury Association grades B, C, and D) from C-4 to T-10 (upper motoneuron group) or from T-11 to L-3 (lower motoneuron group). Within 8 weeks of a SCI, 146 subjects were entered for 12 weeks of intervention. The 2 single-blinded primary outcome measures are the level of independence for ambulation and, for those who are able to walk, the maximal speed for walking 50 feet, tested 6 and 12 months after randomization. The trial's methodology offers a model for the feasibility of translating neuroscientific experiments into a RCT to develop evidence-based rehabilitation practices. KeywordsMotor learning; Locomotor training; Neurologic rehabilitation; Spinal cord Ambulation is compromised in most of the more than 10,000 yearly survivors of a traumatic spinal cord injury (SCI) and for 250,000 people in the United States with chronic SCI. Table 1 2 ) and those graded ASIA B within 1 week to 1 month of the SCI recover walking in no more than 10% to 15% of cases. Most subjects who have had enough return of motor control to regain the ability to walk will do so at greater than normal energy cost. Outcome studies of ambulation vary with the method used to classify impairment, the time of assessment after SCI, and the measures employed. Previous observational studies of the recovery of walking after SCI, such as those from the American Model Systems program, 3 have not prospectively assessed relationships between functional recovery, rate of recovery, walking speed and endurance, and quality of life in patients who were admitted for inpatient rehabilitation.During inpatient rehabilitation soon after SCI, physical therapy ordinarily proceeds beyond supported standing only if the patient's legs are braced to lock them in extension or if the patient has the strength and balance necessary to maintain the legs in extension during weight bearing and to flex at the hips and knees when taking steps. If the arms are capable of partially supporting the person's weight during stepping in parallel bars or in a walker without inducing great energy cost, gait training proceeds.The Spinal Cord Injury Locomotor Trial (SCILT) is designed to compare conventional inpatient and outpatient physical therap...

The lack of effective therapies for spinal cord injury points to the need for identifying novel targets for therapeutic intervention. Here we report that a small molecule, LM11A-31, developed to block proNGF-p75 interaction and p75-mediated cell death crosses the blood–brain barrier efficiently when delivered orally. Administered starting 4 h postinjury, LM11A-31 promotes functional recovery without causing any toxicity or increased pain in a mouse model of spinal contusion injury. In both weight-bearing open-field tests and nonweight-bearing swim tests, LM11A-31 was effective in improving motor function and coordination. Such functional improvement correlated with a >50% increase in the number of surviving oligodendrocytes and myelinated axons. We also demonstrate that LM11A-31 indeed inhibits proNGF-p75 interaction in vivo, thereby curtailing the JNK3-mediated apoptotic cascade. These results thus highlight p75 as a novel therapeutic target for an orally delivered treatment for spinal cord injury.