Biomarkers in Traumatic Spinal Cord Injury—Technical and Clinical Considerations: A Systematic Review

Objective. To examine (1) if serological or cerebrospinal fluid (CSF) biomarkers can be used as diagnostic and/or prognostic tools in patients with spinal cord injury (SCI) and (2) if literature provides recommendations regarding timing and source of biomarker evaluation. Data Sources. A systematic literature search to identify studies reporting on diagnostic and prognostic blood and/or CSF biomarkers in SCI was conducted in PubMed/MEDLINE, CINAHL, Science Direct, The Cochrane Library, ISI Web of Science, and PEDro. Study Selection. Clinical trials, cohort, and pilot studies on patients with traumatic SCI investigating at least one blood or CSF biomarker were included. Following systematic screening, 19 articles were included in the final analysis. PRISMA guidelines were followed to conduct this review. Data Extraction. Independent extraction of articles was completed by 2 authors using predefined inclusion criteria and study quality indicators. Data Synthesis. Nineteen studies published between 2002 and April 2019 with 1596 patients were included in the systematic review. In 14 studies, blood biomarkers were measured, 4 studies investigated CSF biomarkers, and 1 study used both blood and CSF samples. Conclusions. Serum/CSF concentrations of several biomarkers (S100b, IL-6, GFAP, NSE, tau, TNF-α, IL-8, MCP-1, pNF-H, and IP-10) following SCI are highly time dependent and related to injury severity. Future studies need to validate these markers as true biomarkers and should control for secondary complications associated with SCI. A deeper understanding of secondary pathophysiological events after SCI and their effect on biomarker dynamics may improve their clinical significance as surrogate parameters in future clinical studies.

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Early CSF Biomarkers and Late Functional Outcomes in Spinal Cord Injury. A Pilot Study

International Journal of Molecular Sciences ◽

10.3390/ijms21239037 ◽

2020 ◽

Vol 21 (23) ◽

pp. 9037

Author(s):

Rita Capirossi ◽

Beatrice Piunti ◽

Mercedes Fernández ◽

Elisa Maietti ◽

Paola Rucci ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Injury Severity ◽

Rating Scale ◽

Treatment Effectiveness ◽

Neurological Diseases ◽

Csf Biomarkers ◽

Clinical Scores ◽

Cord Injury ◽

Scale Scores

Although, biomarkers are regarded as an important tool for monitoring injury severity and treatment efficacy, and for predicting clinical evolution in many neurological diseases and disorders including spinal cord injury, there is still a lack of reliable biomarkers for the assessment of clinical course and patient outcome. In this study, a biological dataset of 60 cytokines/chemokines, growth factorsm and intracellular and extracellular matrix proteins, analyzed in CSF within 24 h of injury, was used for correlation analysis with the clinical dataset of the same patients. A heat map was generated of positive and negative correlations between biomarkers and clinical rating scale scores at discharge, and between biomarkers and changes in clinical scores during the observation period. Using very stringent statistical criteria, we found 10 molecules which correlated with clinical scores at discharge, and five molecules, which correlated with changes in clinical scores. The proposed methodology may be useful for generating hypotheses regarding “predictive” and “treatment effectiveness” biomarkers, thereby suggesting potential candidates for disease-modifying therapies using a “bed-to-bench” approach.

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The Comparative Effects of Mesenchymal Stem Cell Transplantation Therapy for Spinal Cord Injury in Humans and Animal Models: A Systematic Review and Meta-Analysis

Biology ◽

10.3390/biology10030230 ◽

2021 ◽

Vol 10 (3) ◽

pp. 230

Author(s):

Louis D. V. Johnson ◽

Mark R. Pickard ◽

William E. B. Johnson

Keyword(s):

Systematic Review ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Stem Cell ◽

Animal Models ◽

Mesenchymal Stem Cell ◽

Meta Analysis ◽

Sensory Function ◽

Cochrane Library ◽

Cord Injury

Animal models have been used in preclinical research to examine potential new treatments for spinal cord injury (SCI), including mesenchymal stem cell (MSC) transplantation. MSC transplants have been studied in early human trials. Whether the animal models represent the human studies is unclear. This systematic review and meta-analysis has examined the effects of MSC transplants in human and animal studies. Following searches of PubMed, Clinical Trials and the Cochrane Library, published papers were screened, and data were extracted and analysed. MSC transplantation was associated with significantly improved motor and sensory function in humans, and significantly increased locomotor function in animals. However, there are discrepancies between the studies of human participants and animal models, including timing of MSC transplant post-injury and source of MSCs. Additionally, difficulty in the comparison of functional outcome measures across species limits the predictive nature of the animal research. These findings have been summarised, and recommendations for further research are discussed to better enable the translation of animal models to MSC-based human clinical therapy.

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The Impact of Mean Arterial Pressure on Functional Outcome Post Trauma-Related Acute Spinal Cord Injury: A Scoping Systematic Review of the Human Literature

Journal of Intensive Care Medicine ◽

10.1177/0885066616672643 ◽

2016 ◽

Vol 33 (1) ◽

pp. 3-15 ◽

Cited By ~ 6

Author(s):

Behzad Sabit ◽

Frederick Adam Zeiler ◽

Neil Berrington

Keyword(s):

Systematic Review ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Functional Outcome ◽

Acute Spinal Cord Injury ◽

Cochrane Library ◽

Cord Injury ◽

The Impact

Purpose: To perform a scoping systematic review on the literature surrounding mean arterial pressure (MAP) and functional outcomes post traumatic acute spinal cord injury (ASCI). Methods: We performed a systematic review of the literature via searching MEDLINE, BIOSIS, EMBASE, Global Health, SCOPUS, and Cochrane Library from inception to January 2015. We also performed a handsearch of various published meeting proceedings. Through a 2-step review process, employing 2 independent reviewers, we selected articles for the final review based on predefined inclusion/exclusion criteria. Results: Nine studies were included in the final review. Only 2 were prospective studies. All studies documented some degree of objective functional outcome in relation to MAP posttraumatic ASCI. Four studies documented a relation between higher MAP and improved functional outcome. Five studies failed to show any relationship between MAP and functional outcome. Conclusions: Although no definitive conclusions could be reached based on the data collected, this study does give valuable insight into future avenues of research on the topic of hemodynamic management in traumatic ASCI as well as provides guidelines for refinement of future study design.

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Upper Limb Robotic Rehabilitation for Patients With Cervical Spinal Cord Injury: A Comprehensive Review

10.20944/preprints202111.0065.v1 ◽

2021 ◽

Author(s):

Giovanni Morone ◽

Alessandro De Sire ◽

Alex Martino Cinnera ◽

Matteo Paci ◽

Luca Perrero ◽

...

Keyword(s):

Systematic Review ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Cervical Spinal Cord ◽

Cervical Spinal Cord Injury ◽

Cochrane Library ◽

Functional Impairments ◽

Robotic Assisted ◽

Study Results ◽

Cord Injury

The upper extremities limitation represents one of the essential functional impairments in patients with cervical spinal cord injury. Electromechanics assisted devices and robots are increasingly used in neurorehabilitation to help functional improvement in patients with neurological diseases. This review aimed to systematically report the evidence-based, state-of-art on clinical applications and robotic-assisted arm training (RAT) in motor and functional recovery in subjects affected by cervical spinal cord injury. The present study has been carried out within the framework of the Italian Consensus Conference on "Rehabilitation assisted by robotic and electromechanical devices for persons with disability of neurological origin" (CICERONE). PubMed/MEDLINE, Cochrane Library, and Physiotherapy Evidence Database (PEDro) databases were systematically searched from inception to September 2021. The 10-item PEDro scale assessed the study quality for the RCT and the AMSTAR-2 for the systematic review. Two different authors rated the studies included in this review. If consensus was not achieved after discussion, a third reviewer was interrogated. The 5-item Oxford CEBM scale was used to rate the level of evidence. A total of 11 studies were included. The selected studies were: two systematic reviews, two RCTs, one parallel-group controlled trial, one longitudinal intervention study and five case series. One RCT was scored as a high-quality study, while the systematic review was of low quality. RAT was reported as feasible and safe. Initial positive effects of RAT were found for arm function and quality of movement in addition to conventional therapy. The high clinical heterogeneity of treatment programs and the variety of robot devices could severely affect the generalizability of the study results; therefore, future studies are warranted to standardize the type of intervention and evaluate the role of robotic-assisted training in subjects affected by cervical spinal cord injury.

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Systematic review of the changes in the microbiome following spinal cord injury: animal and human evidence

Spinal Cord ◽

10.1038/s41393-021-00737-y ◽

2022 ◽

Author(s):

Ezra Valido ◽

Alessandro Bertolo ◽

Gion Philip Fränkl ◽

Oche Adam Itodo ◽

Tainá Pinheiro ◽

...

Keyword(s):

Systematic Review ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Urinary Tract ◽

Gut Microbiome ◽

Data Extraction ◽

Cochrane Central Register ◽

Animal Populations ◽

Significant Difference ◽

Cord Injury

Abstract Study design Systematic review. Objectives To investigate the changes in the microbiome among human and animal populations with spinal cord injury (SCI). Methods Four databases (EMBASE, Medline (Ovid), Web of Science, Cochrane Central Register of Trials (CENTRAL)) and Google Scholar were searched. No language restrictions were applied. Data extraction was done in parallel and independently by two reviewers. The search was last conducted on 07 April 2021. Results There were 6869 studies retrieved, 43 full-text studies reviewed, and 19 studies included. There were seven animal gut studies, six human gut studies, and six urinary tract studies identified. There were no publications found on other body sites. Among the included studies, we observed a consistent and significant difference in gut microbiome composition between populations with SCI and able-bodied populations. This is characterized by a decrease in beneficial butyrate-producing bacteria (Faecalbacterium, Megamonas, Roseburia) and an increase in inflammation-associated bacteria (Alistipes, Anaerotruncus, and Lachnoclostridium). On the other hand, the urine of individuals with SCI was polymicrobial and members of Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae) were frequently observed. Probiotics were shown to induce a significant but transient shift in the urinary tract microbiome. The studies had low to moderate risks of bias. Conclusions There are limited studies on the changes in microbiome among SCI populations. The gut microbiome was characterized by bacterial profiles associated with chronic inflammation and metabolic disorder while the studies of the urinary tract microbiome show the dominance of bacterial genera associated with urinary tract infection.

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Upper Limb Robotic Rehabilitation for Patients with Cervical Spinal Cord Injury: A Comprehensive Review

Brain Sciences ◽

10.3390/brainsci11121630 ◽

2021 ◽

Vol 11 (12) ◽

pp. 1630

Author(s):

Giovanni Morone ◽

Alessandro de Sire ◽

Alex Martino Cinnera ◽

Matteo Paci ◽

Luca Perrero ◽

...

Keyword(s):

Systematic Review ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Cervical Spinal Cord ◽

Cervical Spinal Cord Injury ◽

Cochrane Library ◽

Functional Impairments ◽

Robotic Assisted ◽

Study Results ◽

Cord Injury

The upper extremities limitation represents one of the essential functional impairments in patients with cervical spinal cord injury. Electromechanics assisted devices and robots are increasingly used in neurorehabilitation to help functional improvement in patients with neurological diseases. This review aimed to systematically report the evidence-based, state-of-art on clinical applications and robotic-assisted arm training (RAT) in motor and functional recovery in subjects affected by cervical spinal cord injury. The present study has been carried out within the framework of the Italian Consensus Conference on “Rehabilitation assisted by robotic and electromechanical devices for persons with disability of neurological origin” (CICERONE). PubMed/MEDLINE, Cochrane Library, and Physiotherapy Evidence Database (PEDro) databases were systematically searched from inception to September 2021. The 10-item PEDro scale assessed the study quality for the RCT and the AMSTAR-2 for the systematic review. Two different authors rated the studies included in this review. If consensus was not achieved after discussion, a third reviewer was interrogated. The five-item Oxford CEBM scale was used to rate the level of evidence. A total of 11 studies were included. The selected studies were: two systematic reviews, two RCTs, one parallel-group controlled trial, one longitudinal intervention study and five case series. One RCT was scored as a high-quality study, while the systematic review was of low quality. RAT was reported as feasible and safe. Initial positive effects of RAT were found for arm function and quality of movement in addition to conventional therapy. The high clinical heterogeneity of treatment programs and the variety of robot devices could severely affect the generalizability of the study results. Therefore, future studies are warranted to standardize the type of intervention and evaluate the role of robotic-assisted training in subjects affected by cervical spinal cord injury.

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Spinal Cord Injury: A Study Protocol for a Systematic Review and Meta-analysis of microRNA Alterations

10.21203/rs.3.rs-215119/v1 ◽

2021 ◽

Author(s):

Seth Stravers Tigchelaar ◽

Zihuai He ◽

Suzanne Tharin

Keyword(s):

Systematic Review ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Clinical Trials ◽

Injury Severity ◽

Meta Analysis ◽

Novel Therapies ◽

Neurologic Recovery ◽

Detection Technology ◽

Cord Injury

Abstract Spinal cord injury (SCI) is a condition often resulting in life-long disability, high rehabilitation costs, lost wages, and reduced quality of life. Clinical trials have been hampered in part by a lack of poor diagnostic and prognostic markers of injury severity and neurologic recovery. Furthermore, while many therapies have shown promise in preclinical animal models, there are currently no neurorestorative treatments for SCI. The development of objective biomarkers and novel therapies for SCI represent urgent unmet clinical needs. Biological markers of SCI that objectively stratify the severity of cord damage could greatly expand the depth and scope of clinical trials and represent targets for the development of novel therapies for acute SCI. MicroRNAs (miRNAs) represent promising candidates both as informative molecules of injury severity and recovery, and as therapeutic targets. miRNAs are small, stable, regulatory RNA molecules that are often tissue-specific and evolutionarily conserved across species. miRNAs could represent powerful predictors of pathology, particularly with respect to neurologic disorders. There is great heterogeneity in the current literature describing miRNA changes after SCI with respect to animal species, SCI model, miRNA detection technology, and normalization strategies. Here, we present a protocol to perform a systematic review and meta-analysis to investigate the conserved inter- and intra-species miRNA changes that occur post-SCI and provide a comprehensive resource for the SCI community.

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