Phase II/III placebo-controlled randomized trial of safety and efficacy of growth hormone treatment in incomplete chronic traumatic spinal cord injury.

STUDY DESIGN: This is a double blind phase II/III placebo-controlled randomized trial of the safety and efficacy of GH treatment in incomplete chronic traumatic spinal cord injury. OBJECTIVE: The aim of this study was to investigate the possibility to use exogenous GH administration for motor recovery in chronic traumatic incomplete human SCI. The objectives were to establish safety and efficacy of a combined treatment of subcutaneous GH (or placebo) and rehabilitation in this population. SETTING: Hospital Nacional de Parapléjicos METHODS: The pharmacological treatment was a subcutaneous daily dose of growth hormone (GH, Genotonorm 0.4 mg, Pfizer Pharmaceuticals) or placebo for one year. The pharmacological treatment was performed, during the first six months under hospitalization and supervised rehabilitation. RESULTS: The main findings were that the combined treatment of GH plus rehabilitation treatment is feasible and safe, and that GH but not placebo increases the ISNCSCI motor score. On the other hand, the motor-score increment was marginal (after one-year combined treatment, the mean increment of the motor-score was around 2.5 points). Moreover, we found that intensive and long-lasting rehabilitation program per se increases the functional outcome of SCI individuals (measured using SCIM III and WISCI II). CONCLUSIONS: It is important to highlight that our aim was to propose GH as a possible treatment to improve motor functions in incomplete SCI individuals. At least with the doses we used, we think that the therapeutic effects of this approach are not clinically relevant in most subjects with SCI.

A comparison of robotic walking therapy and conventional walking therapy in individuals with upper versus lower motor neuron lesions: a randomized controlled trial.

OBJECTIVE: To compare a walking reeducation program with robotic locomotor training plus overground therapy (LKOGT) to conventional overground training (OGT) in individuals with incomplete upper motor neuron (UMN) or lower motor neuron (LMN) injuries having either traumatic or nontraumatic nonprogressive etiology. DESIGN: Randomized open controlled trial with blind evaluation by an independent observer. SETTING: An inpatient spinal cord injury rehabilitation center. PARTICIPANTS: A total of 88 adults within 6 months of spinal cord injury onset (group A, 44 with UMN injury, and group B, 44 with LMN injury) were graded on the American Spinal Injury Association Impairment Scale as C or D. Each of these groups was then randomly allocated to conditions 1 or 2. INTERVENTIONS: Condition 1: Subgroups A1 and B1 were treated with LKOGT for 60 minutes. Condition 2: Subgroups A2 and B2 received 60 minutes of conventional OGT 5 days per week for 8 weeks. Subjects with UMN and LMN were randomized into 2 training groups. MAIN OUTCOME MEASURES: Ten-meter walk test and 6-minute walk test (6MWT). Walking Index for Spinal Cord Injury II, lower extremity motor score (LEMS), and the FIM-Locomotor were secondary outcome measures. RESULTS: By using the LKOGT program compared with OGT, we found significant differences in the 6MWT for groups A1 and B1. LKOGT also provided higher scores than did OGT in secondary outcomes such as the LEMS and the FIM-Locomotor. CONCLUSIONS: Robotic-assisted step training yielded better results in the 6MWT and the LEMS in patients with UMN and LMN.

Effects of Growth Hormone Treatment and Rehabilitation in Incomplete Chronic Traumatic Spinal Cord Injury: Insight from Proteome Analysis.

Despite promising advances in the medical management of spinal cord injury (SCI), there is still no available effective therapy to repair the neurological damage in patients who experience this life-transforming condition. Recently, we performed a phase II/III placebo-controlled randomized trial of safety and efficacy of growth hormone (GH) treatment in incomplete chronic traumatic spinal cord injury. The main findings were that the combined treatment of GH plus rehabilitation treatment is feasible and safe, and that GH but not placebo slightly improves the SCI individual motor score. Moreover, we found that an intensive and long-lasting rehabilitation program per se increases the functional outcome of SCI individuals. To understand the possible mechanisms of the improvement due to GH treatment (motor score) and due to rehabilitation (functional outcome), we used a proteomic approach. Here, we used a multiple proteomic strategy to search for recovery biomarkers in blood plasma with the potential to predict response to somatropin treatment and to delayed intensive rehabilitation. Forty-six patients were recruited and followed for a minimum period of 1 year. Patients were classified into two groups based on their treatment: recombinant somatropin (0.4 mg) or placebo. Both groups received rehabilitation treatment. Our strategy allowed us to perform one of the deepest plasma proteomic analyses thus far, which revealed two proteomic signatures with predictive value: (i) response to recombinant somatropin treatment and (ii) response to rehabilitation. The proteins implicated in these signatures are related to homeostasis, inflammation, and coagulation functions. These findings open novel possibilities to assess and therapeutically manage patients with SCI, which could have a positive impact on their clinical response.

Prevalence of Fatigue and Associated Factors in a Spinal Cord Injury Population: Data from an Internet-Based and Face-to-Face Surveys.

Fatigue has a profound impact on patients with spinal cord injury (SCI), but only limited treatments are available. The aim of this study was to determine the prevalence of fatigue in SCI and its association with clinical and demographic factors. We used an internet-based survey and a face-to-face interview to estimate the prevalence of fatigue in a SCI population. Fatigue was measured using the Fatigue Severity Scale (FSS). Clinically significant fatigue was defined as FSS scores greater than or equal to four. A total of 253 participants with SCI were included in the study. Clinically significant fatigue was present in one third of our sample. There was no relationship between fatigue and injury level or completeness. We found significant correlations between depression, pain, and level of injury. The relation of fatigue with completeness of injury and spasticity is less clear. Moreover, the online survey and the standard face-to-face interview showed similar results concerning fatigue evaluation. Several factors may contribute to fatigue, however. Future studies should be conducted to clarify which are the most relevant ones and, if possible, to determine which factors are modifiable.

New Insights from Clinical Assessment of Upper Extremities in Cervical Traumatic Spinal Cord Injury.

Upper extremity function has a strong impact on the quality of life in cervical spinal cord-injured patients. Upper extremity function depends on many factors, such as muscle strength, level of lesion, and extension of the cord damage in its axial axis produced by the injury. These variables can be obtained by the International Standards for Neurological Classification of Spinal Cord Injury, which is the standard for the functional evaluation of traumatic spinal cord injury (SCI) patients. The aim of this study was to describe the relationship between upper limb muscle strength, level of injury, and axial damage with the functionality of upper limb measured using the Jebsen-Taylor Hand Function Test (JTHFT) and the 9 Hole Peg Test (9HPT) in cervical SCI. Twenty-nine patients were included in this study. Our results suggest that both the JTHFT and 9HPT can be similarly used to quantify functional impairment after cervical SCI. Moreover, our data suggest that the upper extremity motor score, JTHFT, and 9HPT strongly correlate with the American Spinal Injury Association (ASIA) impairment scale (graded from A to E), but not with the lesion level. Our findings can be of great importance for the clinician or researchers whose therapeutic interventions have as a main objective to improve upper limb functionality in patients with cervical SCI. We suggest that ASIA impairment scale, ASIA motor score, and functional tests (including JTHFT and/or 9HPT) could be used as outcome measures in cervical SCI clinical trials.

Lokomat robotic-assisted versus overground training within 3 to 6 months of incomplete spinal cord lesion: randomized controlled trial.

BACKGROUND: About 75% of persons with ASIA (American Spinal Injury Association) Impairment Scale C and D incomplete spinal cord injury (SCI) achieve walking ability. OBJECTIVE: To compare a walking reeducation program using Lokomat with conventional overground training among individuals with incomplete SCI of both traumatic and nontraumatic etiology. METHODS: A total of 80 participants from 3 to 6 months after onset admitted to 1 site for rehabilitation were included in a single-blind randomized clinical trial of 2 parallel groups, with blind evaluation by independent observers. Patients received 40 walking reeducation sessions of equal time using a Lokomat program with overground practice or overground mobility therapy alone. Primary measurements of outcome were walking speed and the Walking Index for Spinal Cord Injury (WISCI II). Secondary outcomes were the 6-minute walk test, locomotor section of the Functional Independence Measure, Lower Extremity Motor Score (LEMS), Ashworth Scale, and Visual Analog Scale for pain. RESULTS: No significant differences were found at entry between treatment groups. Walking speed for Lokomat (0.4m/s [0.6-0.2]) and overground therapy (0.3m/s [0.5-0.2]) groups did not differ. The WISCI II for the Lokomat group (16 [8.5-19]) was better than for overground therapy (9 [8-16]). The 6-minute walk test and LEMS displayed significant differences in favor of Lokomat therapy but were not corrected for multiple comparisons. CONCLUSIONS: Robotic-assisted training was equivalent to conventional walk training in patients with a variety of nonprogressive spinal cord pathologies for walking speed, but the need for orthotics and assistive devices was reduced, perhaps because of greater leg strength in the robotic group.