Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Martin-Rojas T

PROVIDER: S-EPMC7720149 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Martin-Rojas Tatiana T Sastre-Oliva Tamara T Esclarín-Ruz Ana A Gil-Dones Felix F Mourino-Alvarez Laura L Corbacho-Alonso Nerea N Moreno-Luna Rafael R Hernandez-Fernandez German G Lopez Juan Antonio JA Oliviero Antonio A Barderas María G MG

Journal of personalized medicine 20201021 4

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 feasi ...[more]

PMID: 33096745

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Project description:Deficient ankle control after incomplete spinal cord injury (iSCI) often accentuates walking impairments. Transcutaneous electrical spinal cord stimulation (tSCS) has been shown to augment locomotor activity after iSCI, presumably due to modulation of spinal excitability. However, the effects of possible excitability modulations induced by tSCS on ankle control have not yet been assessed. This study investigated the immediate (i.e., without training) effects during single-sessions of tonic tSCS on ankle control, spinal excitability, and locomotion in ten individuals with chronic, sensorimotor iSCI (American Spinal Injury Association Impairment Scale D). Participants performed rhythmic ankle movements (dorsi- and plantar flexion) at a given rate, and irregular ankle movements following a predetermined trajectory with and without tonic tSCS at 15 Hz, 30 Hz, and 50 Hz. In a subgroup of eight participants, the effects of tSCS on assisted over-ground walking were studied. Furthermore, the activity of a polysynaptic spinal reflex, associated with spinal locomotor networks, was investigated to study the effect of the stimulation on the dedicated spinal circuitry associated with locomotor function. Tonic tSCS at 30 Hz immediately improved maximum dorsiflexion by +4.6° ± 0.9° in the more affected lower limb during the rhythmic ankle movement task, resulting in an increase of +2.9° ± 0.9° in active range of motion. Coordination of ankle movements, assessed by the ability to perform rhythmic ankle movements at a given target rate and to perform irregular movements according to a trajectory, was unchanged during stimulation. tSCS at 30 Hz modulated spinal reflex activity, reflected by a significant suppression of pathological activity specific to SCI in the assessed polysynaptic spinal reflex. During walking, there was no statistical group effect of tSCS. In the subgroup of eight assessed participants, the three with the lowest as well as the one with the highest walking function scores showed positive stimulation effects, including increased maximum walking speed, or more continuous and faster stepping at a self-selected speed. Future studies need to investigate if multiple applications and individual optimization of the stimulation parameters can increase the effects of tSCS, and if the technique can improve the outcome of locomotor rehabilitation after iSCI.

Project description:Study Design: Scoping review Objective: To study the design, clinical setting and outcome measures used in spinal cord injury rehabilitation publications. Methods: A literature search on PubMed and Medline was conducted focusing on articles published between 1990-2016 and using "traumatic SCI", "functional outcomes", "rehabilitation", "work" and "return to work" as outcomes. Studies were categorized based on design (intervention, including RCTs vs. non-intervention studies), settings (inpatient vs. outpatient vs. transition), and outcome measures used (impairment vs. function vs. participation/integration vs. quality of life vs. symptoms). Work-related studies were categorized independently. Results: Five hundred forty-four articles met the inclusion criteria. Of these, 234 were interventional studies, including 23 RCTs. Studies were evenly divided among inpatient, outpatient and transition settings. Of the 234 interventional studies, 143 used functional evaluations. Sixty-one different functional instruments were used, with a predominant use of the Functional Independence Measure (61 times) and an additional use of SCI-specific measures, i.e. Spinal Cord Independence Measure and Craig Handicap Assessment and Reporting Technique (13 times each). Fifty-one studies measured mobility, while only three measured hand functions. The work-related sub-analysis revealed 32 intervention studies (no RCTs), of which 15 used functional evaluations and only three focused on tetraplegia. Conclusion: Our study revealed a paucity of intervention trials and RCTs, indicating a dearth of knowledge that would be needed to establish evidence-based practice guidelines. This is particularly true for tetraplegia. While standard measures of function were frequently used, providing valuable data, there is no consensus about what exact outcome measure to use. Using newer measurement techniques, for instance based on the application of item response theory, should be considered to enhance uniformity.

Dataset Information

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

Publications

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

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