David F. Apple

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.

Influence of complete spinal cord injury on skeletal muscle cross-sectional area within the first 6 months of injury

Abstract In this study we examined the influence of complete spinal cord injury (SCI) on affected skeletal muscle morphology within 6 months of SCI. Magnetic resonance (MR) images of the leg and thigh were taken as soon as patients were clinically stable, on average 6 weeks post injury, and 11 and 24 weeks after SCI to assess average muscle cross-sectional area (CSA). MR images were also taken from nine able-bodied controls at two time points separated from one another by 18 weeks. The controls showed no change in any variable over time. The patients showed differential atrophy (Pu2009=u20090.0001) of the ankle plantar or dorsi flexor muscles. The average CSA of m. gastrocnemius and m. soleus decreased by 24% and 12%, respectively (Pu2009=u20090.0001). The m. tibialis anterior CSA showed no change (Pu2009=u20090.3644). As a result of this muscle-specific atrophy, the ratio of average CSA of m. gastrocnemius to m. soleus, m. gastrocnemius to m. tibialis anterior and m. soleus to m. tibialis anterior declined (Pu2009=u20090.0001). The average CSA of m, quadriceps femoris, the hamstring muscle group and the adductor muscle group decreased by 16%, 14% and 16%, respectively (Pu2009≤u20090.0045). No differential atrophy was observed among these thigh muscle groups, thus the ratio of their CSAs did not change (Pu2009=u20090.6210). The average CSA of atrophied skeletal muscle in the patients was 45–80% of that of age- and weight-matched able-bodied controls 24 weeks after injury. In conclusion, the results of this study suggest that there is marked loss of contractile protein early after SCI which differs among affected skeletal muscles. While the mechanism(s) responsible for loss of muscle size are not clear, it is suggested that the development of muscular imbalance as well as diminution of muscle mass would compromise force potential early after SCI.

Medical complications during acute rehabilitation following spinal cord injury—current experience of the model systems☆☆☆

OBJECTIVESnTo examine the frequency of common secondary medical complications during acute rehabilitation in persons with new spinal cord injury (SCI).nnnDESIGNnSurvey and analysis of data in the National SCI Statistical Center (NSCISC) database.nnnSETTINGnEighteen Model System SCI Centers located in urban, public medical centers around the United States.nnnSUBJECTSnA total of 1,649 persons with new SCI entered into the NSCISC database between 1996 and mid-1998.nnnRESULTSnSince 1992, the number of days from injury to admission to rehabilitation has steadily decreased, resulting in the increased potential to develop common secondary medical complications during rehabilitation hospitalization. Pressure ulcers occur with high frequency and were found to have developed in 23.7% of patients during rehabilitation. In addition, autonomic dysreflexia and atelectasis/pneumonia also occur with relative frequency during rehabilitation. Conversely, deep vein thrombosis and pulmonary embolism have decreased, most likely because of greater awareness of their potential to develop, as well as improved methods of prophylaxis. Cardiopulmonary arrest and gastrointestinal hemorrhage occur with relatively small frequency. The frequency of renal complications is difficult to gauge because of the decreasing number of patients who have any renal testing performed during rehabilitation hospitalization.nnnCONCLUSIONnThe continued declining lengths of acute care hospitalization after SCI have resulted in the occurrence in the rehabilitation setting of medical complications that were previously seen in acute care. Greater awareness and attention to these conditions are necessary to reduce their occurrence, so that obstacles to recovery and functional improvement after SCI are minimized.

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 ≥ 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.

Intramuscular fat and glucose tolerance after spinal cord injury – a cross-sectional study

Study design: Survey.Objective: Determine intramuscular fat (IMF) in affected skeletal muscle after complete spinal cord injury using a novel analysis method and determine the correlation of IMF to plasma glucose or plasma insulin during an oral glucose tolerance test.Setting: General community of Athens, GA, USA.Methods: A total of 12 nonexercise-trained complete spinal cord injured (SCI) persons (10 males and two females 40±12 years old (mean±SD), range 26–71 years, and 8±5 years post SCI) and nine nonexercise-trained nondisabled (ND) controls 29±9 years old, range 23–51 years, matched for height, weight, and BMI, had T1 magnetic resonance images of their thighs taken and underwent an oral glucose tolerance test (OGTT) after giving consent.Results: Average skeletal muscle cross-sectional area (CSA) (mean±SD) was 58.6±21.6u2009cm2 in spinal cord subjects and 94.1±32.5u2009cm2 in ND subjects. Average IMF CSA was 14.5±6.0u2009cm2 in spinal cord subjects and 4.7±2.5u2009cm2 in nondisabled subjects, resulting in an almost four-fold difference in IMF percentage of 17.3±4.4% in spinal cord subjects and 4.6±2.6% in nondisabled subjects. The 60, 90 and 120u2009min plasma glucose or plasma insulin were higher in the SCI group. IMF (absolute and %) was related to the 90 or 120u2009min plasma glucose or plasma insulin (r 2=0.71–0.40).Conclusions: IMF is a good predictor of plasma glucose during an OGTT and may be a contributing factor to the onset of impaired glucose tolerance and type II diabetes, especially in SCI. In addition, reports of skeletal muscle CSA should be corrected for IMF.

Methods for a Randomized Trial of Weight-Supported Treadmill Training Versus Conventional Training for Walking During Inpatient Rehabilitation after Incomplete Traumatic Spinal Cord Injury

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 trials methodology offers a model for the feasibility of translating neuroscientific experiments into a RCT to develop evidence-based rehabilitation practices.

A simple means of increasing muscle size after spinal cord injury: a pilot study

Abstract This study tested that hypothesis that skeletal muscle within a year of spinal cord injury (SCI) would respond to intermittent high force loading by showing an increase in size. Three males about 46 weeks post clinically complete SCI underwent surface electrical stimulation of their left or right m. quadriceps femoris 2 days per week for 8 weeks to evoke 4 sets of ten isometric or dynamic actions each session. Conditioning increased average cross-sectional area of m. quadriceps femoris, assessed by magnetic resonance imaging, by 20u2009±u20091% (pu2009=u20090.0103). This reversed 48 weeks of atrophy such that m. quadriceps femoris 54 weeks after SCI was the same size as when the patients were first studied 6 weeks after injury. The results suggest that skeletal muscle is remarkably responsive to intermittent, high force loading after almost one year of little if any contractile activity.

Validity of the Walking Scale for Spinal Cord Injury and Other Domains of Function in a Multicenter Clinical Trial

Objective. To demonstrate criterion (concurrent and predictive) and construct validity of the Walking Index for Spinal Cord Injury (WISCI) scale and other walking measures in the Spinal Cord Injury Locomotor Trial (SCILT). Design. Prospective multicenter clinical trial of a walking intervention for patients with acute traumatic spinal cord injury (SCI). Participants/Methods. Body weight−supported treadmill training was compared to overground mobility training in 146 patients with incomplete SCI (C4 to L3) enrolled within 8 weeks of onset and treated for 12 weeks. Primary outcome measures were the Functional Independence Measure (FIM), 50-foot walking speed (50FW-S), and 6-minute walking distance (6MW-D), tested 3, 6, and 12 months after entry. Secondary measures were the Lower Extremity Motor Score (LEMS), Berg Balance Scale (BBS), WISCI, and FIM locomotor score (LFIM), assessed at 6 centers by blinded observers. Data for the 2 arms were combined since no significant differences in outcomes had been found. Results. Correlations with WISCI at 6 months were significant with BBS (r = .90), LEMS (r = .85), LFIM (r = .89), FIM (r = .77), 50FW-S (r = .85), and 6MW-D ( r = .79); similar correlations occurred at 3 and 12 months. Correlations of change scores from baseline WISCI were significant for change scores from baseline of LEMS/BBS/LFIM. Correlation of baseline LEMS and WISCI at 12 months were most significant (r = .73). The R 2 of baseline LEMS explained 57% of variability of WISCI levels at 3 months. Conclusion. Concurrent validity of the WISCI scale was supported by significant correlations with all measures at 3, 6, and 12 months. Correlation of change scores supports predictive validity. The LEMS at baseline was the best predictor of the WISCI score at 12 months and explained most of the variance, which supported both predictive and construct validity. The combination of the LEMS, BBS, WISCI, 50FW-S, and LFIM appears to encompass adequate descriptors for outcomes of walking trials for incomplete SCI.

Autologous incubated macrophage therapy in acute, complete spinal cord injury: results of the phase 2 randomized controlled multicenter trial.

Study design:Randomized controlled trial with single-blinded primary outcome assessment.Objectives:To determine the efficacy and safety of autologous incubated macrophage treatment for improving neurological outcome in patients with acute, complete spinal cord injury (SCI).Setting:Six SCI treatment centers in the United States and Israel.Methods:Participants with traumatic complete SCI between C5 motor and T11 neurological levels who could receive macrophage therapy within 14 days of injury were randomly assigned in a 2:1 ratio to the treatment (autologous incubated macrophages) or control (standard of care) groups. Treatment group participants underwent macrophage injection into the caudal boundary of the SCI. The primary outcome measure was American Spinal Injury Association (ASIA) Impairment Scale (AIS) A–B or better at ⩾6 months. Safety was assessed by analysis of adverse events (AEs).Results:Of 43 participants (26 treatment, 17 control) having sufficient data for efficacy analysis, AIS A to B or better conversion was experienced by 7 treatment and 10 control participants; AIS A to C conversion was experienced by 2 treatment and 2 control participants. The primary outcome analysis for subjects with at least 6 months follow-up showed a trend favoring the control group that did not achieve statistical significance (P=0.053). The mean number of AEs reported per participant was not significantly different between the groups (P=0.942).Conclusion:The analysis failed to show a significant difference in primary outcome between the two groups. The study results do not support treatment of acute complete SCI with autologous incubated macrophage therapy as specified in this protocol.

Influence of complete spinal cord injury on skeletal muscle mechanics within the first 6 months of injury

Abstract In this study we examined the influence of complete spinal cord injury (SCI) on the mechanical characteristics of skeletal muscle in vivo within 6 months of the injury. Surface electrical stimulation (ES) was applied to the left m. quadriceps femoris of patients at 6, 11 and 24 weeks after injury. Surface ES was also applied to seven able-bodied controls (AB) at two time points 18 weeks apart. ES consisted of 2 bouts of 20, 1-s isometric contractions with 2u2009s and 2 min of rest between contractions and bouts, respectively. The time from 20–80% of peak torque (rise time) and the half relaxation time (1/2 RT) were determined for the first and for the last few contractions. Force loss over repeat contractions was greater in SCI than AB (27% vs 95%; Pu2009=u20090.0001), and did not change over the 18-week period. Rise time did not change over repeat contractions, was not different between groups, and nor did it change over the 18-week period (range: 150–172u2009ms). 1/2 RT showed several group differences. Overall, 1/2 RT was longer at the beginning of ES in SCI than AB [mean (SE)u2009133u2009(15)u2009ms vs 90u2009(6)u2009ms, Pu2009=u20090.037]. Slowing of relaxation time with force loss over repeat contractions was found in SCI at 24 weeks after injury [167u2009(18)u2009ms, Pu2009=u20090.016], but not at 6 [128u2009(14)u2009ms] or 11 [145u2009(12)u2009ms] weeks after injury. AB, in contrast, showed prolonged relaxation times, with force loss at both time points [115u2009(10)u2009ms and 113u2009(11)u2009ms; Pu2009=u20090.0001]. The results indicate that SCI alters the relaxation but not contractile properties of mixed skeletal muscle within the first 24 weeks of injury. Altered calcium handling and contraction-induced fiber injury are suggested to explain the slower relaxation time per se, and the prolonged relaxation with force loss observed after SCI.