Paediatric Spinal Cord Injury: A Review of Current Management.

Spinal cord injury (SCI) in the paediatric population is considered a separate entity from the same injury in adults due to the unique anatomical, physiological, and biomechanical properties of the pediatric spine. No comprehensive, standardized, international guidelines currently exist for physicians to follow regarding the management of paediatric spinal cord injuries. Therefore, a narrative literature review approach was employed to explore the management of paediatric spinal cord injuries. The review adhered to the methodological frameworks that entailed identifying a curated selection of pertinent articles on the topic, rather than an exhaustive comprehensive search that is utilised in systematic reviews, this was followed by a reflective interpretation of their content. Using the electronic databases, PubMed and Google Scholar, a search of peer-reviewed studies conducted only in the English language was included. Only studies in which the full article was available were included. Paediatric populations are defined as individuals aged between 0 and 18 years. In total, 26 studies were included in our review. We conclude that it is necessary to factor in specific paediatric considerations, such as disproportionate head size, increased ligament laxity, increased prevalence of upper cervical injury, and future development of scoliosis, in the prehospital, medical, and surgical management of paediatric spinal cord injuries. Clinicians should be made aware of these considerations, as they can improve the outcomes in the paediatric population who suffer from this devastating injury. There is a lack of high-quality studies and data concerning the paediatric population who have sustained SCIs. This literature review highlights the available data and calls for more studies to be conducted in this field.

Magnetic Stimulation of Gigantocellular Reticular Nucleus with Iron Oxide Nanoparticles Combined Treadmill Training Enhanced Locomotor Recovery by Reorganizing Cortico-Reticulo-Spinal Circuit.

Background: Gigantocellular reticular nucleus (GRNs) executes a vital role in locomotor recovery after spinal cord injury. However, due to its unique anatomical location deep within the brainstem, intervening in GRNs for spinal cord injury research is challenging. To address this problem, this study adopted an extracorporeal magnetic stimulation system to observe the effects of selective magnetic stimulation of GRNs with iron oxide nanoparticles combined treadmill training on locomotor recovery after spinal cord injury, and explored the possible mechanisms. Methods: Superparamagnetic iron oxide (SPIO) nanoparticles were stereotactically injected into bilateral GRNs of mice with moderate T10 spinal cord contusion. Eight-week selective magnetic stimulation produced by extracorporeal magnetic stimulation system (MSS) combined with treadmill training was adopted for the animals from one week after surgery. Locomotor function of mice was evaluated by the Basso Mouse Scale, Grid-walking test and Treadscan analysis. Brain MRI, anterograde virus tracer and immunofluorescence staining were applied to observe the tissue compatibility of SPIO in GRNs, trace GRNs' projections and evaluate neurotransmitters' expression in spinal cord respectively. Motor-evoked potentials and H reflex were collected for assessing the integrity of cortical spinal tract and the excitation of motor neurons in anterior horn. Results: (1) SPIO persisted in GRNs for a minimum of 24 weeks without inducing apoptosis of GRN cells, and degraded slowly over time. (2) MSS-enabled treadmill training dramatically improved locomotor performances of injured mice, and promoted cortico-reticulo-spinal circuit reorganization. (3) MSS-enabled treadmill training took superimposed roles through both activating GRNs to drive more projections of GRNs across lesion site and rebalancing neurotransmitters' expression in anterior horn of lumbar spinal cord. Conclusion: These results indicate that selective MSS intervention of GRNs potentially serves as an innovative strategy to promote more spared fibers of GRNs across lesion site and rebalance neurotransmitters' expression after spinal cord injury, paving the way for the structural remodeling of neural systems collaborating with exercise training, thus ultimately contributing to the reconstruction of cortico-reticulo-spinal circuit.

Value of the Brain and Spinal Injury Center Score in Assessment and Prognosis of Acute Traumatic Spinal Cord Injury.

The objective was to assess the severity of neurological injury in acute traumatic spinal cord injury (ATSCI) using the BASIC (Brain and Spinal Injury Center) score, to correlate with the American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade at admission and at 3 months postinjury in patients managed for ATSCI at National Hospital, Abuja, and thereby validate the novel BASIC score. This was a prospective longitudinal hospital-based study involving consecutive patients diagnosed with ATSCI and managed at the National Hospital, Abuja. Sixty-five participants met the inclusion criteria. Each patient was resuscitated along the Advanced Trauma Life Support protocol, followed by history, neurological examination according to the International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI), and AIS grades that were recorded. Magnetic resonance imaging scan of the injured spinal cord was done, and BASIC scores were assigned. Further management was as per the standard. Three months after injury, neurological examination was again carried out based on ISNCSCI and AIS grades assigned. Data were collected, analyzed, and correlated using Excel and SPSS version 23. Means, medians, correlation coefficients, and Fisher's exact t-tests were determined. p-Value <0.05 was considered statistically significant. Results show mean age was 39.1 ± 12.3 years. The majority (81.5%) were males, whereas 18.5% were females. The majority (67.7%) were skilled professionals, 13.8% were unskilled, and 18.5% were students. Most injuries (90.8%) were due to road traffic accidents, whereas 9.2% were due to falls. Majority (72.3%) of the patients had complete SCI (AIS grade A), whereas AIS grade E accounted for the least number (3.1%). Cervical spine injury affected 92.3% of patients, whereas 7.7% had thoracic spine injury. Most patients had BASIC 4 pattern on MRI (44.6%), whereas BASIC 1 pattern was the fewest (3.1%). Surgery was not done for 58.5% of patients, whereas 41.5% had surgical decompression and spine fusion. At 3 months postinjury, 15.4% of patients had AIS grade improvement, whereas 84.6% maintained their AIS grade. The largest AIS grade improvement was from grade B to C (6.2%), which was statistically significant (p = 0.04). BASIC score correlated moderately with admission AIS grade (p = 0.532). BASIC score also correlated moderately with AIS grade at 3 months postinjury (p = 0.546). BASIC score 4 was best at predicting poor outcome in ATSCI. In conclusion, BASIC score has a moderate correlation with AIS grade in ATSCI and can predict poor outcomes in ATSCI. BASIC score of 4 has the best discriminant value in prognosticating and represents severe SCI.

Effect-Size Discrepancies in Literature Versus Raw Datasets from Experimental Spinal Cord Injury Studies: A CLIMBER Meta-Analysis.

Translation of spinal cord injury (SCI) therapeutics from pre-clinical animal studies into human studies is challenged by effect size variability, irreproducibility, and misalignment of evidence used by pre-clinical versus clinical literature. Clinical literature values reproducibility, with the highest grade evidence (class 1) consisting of meta-analysis demonstrating large therapeutic efficacy replicating across multiple studies. Conversely, pre-clinical literature values novelty over replication and lacks rigorous meta-analyses to assess reproducibility of effect sizes across multiple articles. Here, we applied modified clinical meta-analysis methods to pre-clinical studies, comparing effect sizes extracted from published literature to raw data on individual animals from these same studies. Literature-extracted data (LED) from numerical and graphical outcomes reported in publications were compared with individual animal data (IAD) deposited in a federally supported repository of SCI data. The animal groups from the IAD were matched with the same cohorts in the LED for a direct comparison. We applied random-effects meta-analysis to evaluate predictors of neuroconversion in LED versus IAD. We included publications with common injury models (contusive injuries) and standardized end-points (open field assessments). The extraction of data from 25 published articles yielded n = 1841 subjects, whereas IAD from these same articles included n = 2441 subjects. We observed differences in the number of experimental groups and animals per group, insufficient reporting of dropout animals, and missing information on experimental details. Meta-analysis revealed differences in effect sizes across LED versus IAD stratifications, for instance, severe injuries had the largest effect size in LED (standardized mean difference [SMD = 4.92]), but mild injuries had the largest effect size in IAD (SMD = 6.06). Publications with smaller sample sizes yielded larger effect sizes, while studies with larger sample sizes had smaller effects. The results demonstrate the feasibility of combining IAD analysis with traditional LED meta-analysis to assess effect size reproducibility in SCI.

Olfactory Ensheathing Cell Ameliorate Neuroinflammation Following Spinal Cord Injury Through Upregulating REV-ERBα in Microglia.

Circadian dysregulation involved in the pathophysiology of spinal cord injury (SCI). Modulation of circadian rhythms hold promise for the SCI treatment. Here, we aim to investigated the mechanism of olfactory ensheathing cells (OEC) in alleviating neuroinflammation via modulating clock gene expression in microglia. In this study, SCI rats were randomly divided into OEC group and vehicle group. At 1 day after the surgery, OECs were intravenously transplanted into OEC group SCI rat, while the rats in vehicle group received culture medium. After 7 days post of OEC transplantation, tissues were collected from the brain (prefrontal cortex, hypothalamus, spinal cord) for PCR, western blotting and immunohistochemistry (IHC) assay at zeitgeber time (ZT) 6, ZT 12, ZT 18, and ZT 24. The roles of OEC in modulating REV-ERBα in microglia were studied by experimental inhibition of gene expression and the co-culture experiment. In the vehicle group, IHC showed a significant increase of Iba-1 expression in the cerebral white matter and spinal cord compared with control group (P < 0.0001 for all comparisons). The expression of Iba-1 was significantly decreased (P < 0.0001 for all comparisons). In the OEC group, the expression of PER 1, PER 2, CLOCK, and REV-ERBα was in a rhythmical manner in both spinal cord and brain regions. SCI disrupted their typical rhythms. And OECs transplantation could modulate those dysregulations by upregulating REV-ERBα. In vitro study showed that OECs couldn't reduce the activation of REV-ERBα inhibited microglia. The intravenous transplantation of OECs can mediate cerebral and spinal microglia activation through upregulation REV-ERBα after SCI.

Transcutaneous Electrical Spinal Cord Stimulation Increased Target-Specific Muscle Strength and Locomotion in Chronic Spinal Cord Injury.

BACKGROUND: The recovery of locomotion is greatly prioritized, and neuromodulation has been emerging as a promising approach in recent times. STUDY DESIGN: Single-subject research design. SETTINGS: A laboratory at The Hong Kong Polytechnic University. OBJECTIVES: To investigate the effects of augmenting activity-based therapy (ABT) to transcutaneous electrical spinal cord stimulation (TSCS) on enhancing specific lower limb muscle strength and improving locomotor ability in an individual with chronic incomplete spinal cord injury (iSCI). METHODS: An individual with iSCI underwent two phases of treatment, ABT alone followed by combined ABT+TSCS, each for a period of 10 weeks. The TSCS stimulated T10-T11 and T12-L1 segments with a frequency of 30 Hz at an intensity between 105 mA and 130 mA. Manual muscle testing, 6 min walk test (6MWT), and surface electromyography (EMG) responses of specific lower limb muscles were measured. Additionally, spasticity and sensorimotor examinations were conducted every two weeks, while pain tolerance was recorded after each treatment session. RESULTS: After the ABT+TSCS treatment, there was an increase in overall muscle strength grading (from 1.8 ± 0.3 to 2.2 ± 0.6 out of 5.0). The 6MWT showed a greater increase in walking distance (3.5 m to 10 m) after combined treatment than ABT alone. In addition, the EMG response of the anterior rectus femoris, biceps femoris, medial gastrocnemius, and tibialis anterior after ABT+TSCS increased more than after ABT alone. The spasticity grade was reduced (from 0.8 ± 0.7 to 0.5 ± 0.6) whereas the average lower limb motor score increased from 17 to 23 points. No adverse effects were reported. CONCLUSIONS: ABT+TSCS increased the target-specific lower limb muscle strength and walking ability more than ABT alone in an individual with chronic iSCI.

Selective Activation of the Spinal Cord with Epidural Electrical Stimulation.

Spinal cord epidural electrical stimulation (EES) has been successfully employed to treat chronic pain and to restore lost functions after spinal cord injury. Yet, the efficacy of this approach is largely challenged by the suboptimal spatial distribution of the electrode contacts across anatomical targets, limiting the spatial selectivity of stimulation. In this study, we exploited different ESS paradigms, designed as either Spatial-Selective Stimulation (SSES) or Orientation-Selective Epidural Stimulation (OSES), and compared them to Conventional Monopolar Epidural Stimulation (CMES). SSES, OSES, and CMES were delivered with a 3- or 4-contact electrode array. Amplitudes and latencies of the Spinally Evoked Motor Potentials (SEMPs) were evaluated with different EES modalities. The results demonstrate that the amplitudes of SEMPs in hindlimb muscles depend on the orientation of the electrical field and vary between stimulation modalities. These findings show that the electric field applied with SSES or OSES provides more selective control of amplitudes of the SEMPs as compared to CMES. We demonstrate that spinal cord epidural stimulation applied with SSES or OSES paradigms in the rodent model could be tailored to the functional spinal cord neuroanatomy and can be tuned to specific target fibers and their orientation, optimizing the effect of neuromodulation.

Evaluating Sex Steroid Hormone Neuroprotection in Spinal Cord Injury in Animal Models: Is It Promising in the Clinic?

The primary mechanism of traumatic spinal cord injury (SCI) comprises the initial mechanical trauma due to the transmission of energy to the spinal cord, subsequent deformity, and persistent compression. The secondary mechanism of injury, which involves structures that remained undamaged after the initial trauma, triggers alterations in microvascular perfusion, the liberation of free radicals and neurotransmitters, lipid peroxidation, alteration in ionic concentrations, and the consequent cell death by necrosis and apoptosis. Research in the treatment of SCI has sought to develop early therapeutic interventions that mitigate the effects of these pathophysiological mechanisms. Clinical and experimental evidence has demonstrated the therapeutic benefits of sex-steroid hormone administration after traumatic brain injury and SCI. The administration of estradiol, progesterone, and testosterone has been associated with neuroprotective effects, better neurological recovery, and decreased mortality after SCI. This review evaluated evidence supporting hormone-related neuroprotection over SCI and the possible underlying mechanisms in animal models. As neuroprotection has been associated with signaling pathways, the effects of these hormones are observed on astrocytes and microglia, modulating the inflammatory response, cerebral blood flow, and metabolism, mediating glutamate excitotoxicity, and their antioxidant effects. Based on the current evidence, it is essential to analyze the benefit of sex steroid hormone therapy in the clinical management of patients with SCI.

Folate-mediated transgenerational inheritance of sperm DNA methylation patterns correlate with spinal axon regeneration.

In mammals, the molecular mechanisms underlying transgenerational inheritance of phenotypic traits in serial generations of progeny after ancestral environmental exposures, without variation in DNA sequence, remain elusive. We've recently described transmission of a beneficial trait in rats and mice, in which F0 supplementation of methyl donors, including folic acid, generates enhanced axon regeneration after sharp spinal cord injury in untreated F1 to F3 progeny linked to differential DNA methylation levels in spinal cord tissue. To test whether the transgenerational effect of folic acid is transmitted via the germline, we performed whole-genome methylation sequencing on sperm DNA from F0 mice treated with either folic acid or vehicle control, and their F1, F2, and F3 untreated progeny. Transgenerational differentially methylated regions (DMRs) are observed in each consecutive generation and distinguish folic acid from untreated lineages, predominate outside of CpG islands and in regions of the genome that regulate gene expression, including promoters, and overlap at both the differentially methylated position (DMP) and gene levels. These findings indicate that molecular changes between generations are caused by ancestral folate supplementation. In addition, 29,719 DMPs exhibit serial increases or decreases in DNA methylation levels in successive generations of untreated offspring, correlating with a serial increase in the phenotype across generations, consistent with a 'wash-in' effect. Sibship-specific DMPs annotate to genes that participate in axon- and synapse-related pathways.

Human induced pluripotent stem cell/embryonic stem cell-derived pyramidal neuronal precursors show safety and efficacy in a rat spinal cord injury model.

Nerve regeneration and circuit reconstruction remain a challenge following spinal cord injury (SCI). Corticospinal pyramidal neurons possess strong axon projection ability. In this study, human induced pluripotent stem cells (iPSCs) were differentiated into pyramidal neuronal precursors (PNPs) by addition of small molecule dorsomorphin into the culture. iPSC-derived PNPs were transplanted acutely into a rat contusion SCI model on the same day of injury. Following engraftment, the SCI rats showed significantly improved motor functions compared with vehicle control group as revealed by behavioral tests. Eight weeks following engraftment, the PNPs matured into corticospinal pyramidal neurons and extended axons into distant host spinal cord tissues, mostly in a caudal direction. Host neurons rostral to the lesion site also grew axons into the graft. Possible synaptic connections as a bridging relay may have been formed between host and graft-derived neurons, as indicated by pre- and post-synaptic marker staining and the regulation of chemogenetic regulatory systems. PNP graft showed an anti-inflammatory effect at the injury site and could bias microglia/macrophages towards a M2 phenotype. In addition, PNP graft was safe and no tumor formation was detected after transplantation into immunodeficient mice and SCI rats. The potential to reconstruct a neuronal relay circuitry across the lesion site and to modulate the microenvironment in SCI makes PNPs a promising cellular candidate for treatment of SCI.

Systemic Inflammatory Changes in Spinal Cord Injured Patients after Adding Aquatic Therapy to Standard Physiotherapy Treatment.

Spinal cord injury (SCI) is a severe medical condition resulting in substantial physiological and functional consequences for the individual. People with SCI are characterised by a chronic, low-grade systemic inflammatory state, which contributes to further undesirable secondary injuries. This study aimed to evaluate the effect of adding aquatic therapy to the standard physiotherapy treatment, implemented in two different schedules, on systemic inflammation in SCI patients. Additionally, the relationship between cytokine blood levels and changes in functionality (measured with the 6MWT, 10MWT, WISCI, BBS, and TUG tests) throughout the study was assessed. A quantitative multiplexed antibody assay was performed to measure the expression level of 20 pro- and anti-inflammatory cytokines in blood samples from SCI patients at three time points: baseline, week 6, and immediately post-intervention (week 12). This study identified a complex signature of five cytokines (IL-12p70, IL-8, MCP-1, IL-1α, and IP10) associated with the time course of the two physiotherapy programs. Two other cytokines (IL-4 and TNF-α) were also associated with the functional recovery of patients. These could be important indicators for SCI prognosis and provide a basis for developing novel targeted therapies.

Effect of Detraining on Muscle Strength, Functional Capacity, Mental Health, and Body Composition in Individuals with Spinal Cord Injury.

Spinal cord injury (SCI) is a condition that significantly affects the quality of life (QoL) of individuals, causing motor, physiological, social, and psychological impairments. Physical exercise plays a crucial role in maintaining the health and functional capacity of these individuals, helping to minimize the negative impacts of SCI. The aim of this study was to evaluate the effect of detraining (DT) (reduction or cessation of physical exercise) during the pandemic on five individuals with thoracic SCI. We assessed muscle strength using strength tests, functional capacity using a functional agility test, mental health using anxiety and depression inventories, and body composition using dual-energy X-ray absorptiometry (DEXA). The results after 33 months of DT showed significant losses in functional agility and MS, as well as a worsening in symptoms of anxiety and depression. It was observed that total body mass and fat mass (FM) exhibited varied behaviors among the individuals. Similarly, the results for lean body mass were heterogeneous, with one participant showing significant deterioration. It is concluded that DT caused by the pandemic worsened the physical and mental condition of individuals with SCI, highlighting the importance of continuous exercise for this population and underscoring the need for individual assessments to fully understand the impacts of DT.

Advances and Challenges in Spinal Cord Injury Treatments.

Spinal cord injury (SCI) is a debilitating condition that is associated with long-term physical and functional disability. Our understanding of the pathogenesis of SCI has evolved significantly over the past three decades. In parallel, significant advances have been made in optimizing the management of patients with SCI. Early surgical decompression, adequate bony decompression and expansile duraplasty are surgical strategies that may improve neurological and functional outcomes in patients with SCI. Furthermore, advances in the non-surgical management of SCI have been made, including optimization of hemodynamic management in the critical care setting. Several promising therapies have also been investigated in pre-clinical studies, with some being translated into clinical trials. Given the recent interest in advancing precision medicine, several investigations have been performed to delineate the role of imaging, cerebral spinal fluid (CSF) and serum biomarkers in predicting outcomes and curating individualized treatment plans for SCI patients. Finally, technological advancements in biomechanics and bioengineering have also found a role in SCI management in the form of neuromodulation and brain-computer interfaces.

Impact of Frailty on Functional Improvement Following Traumatic Spinal Cord Injury: A Japanese Single-Center Experience.

Study Design: This is a retrospective case series study. Objective: The aim of this study was to investigate whether frailty contributes to functional recovery in individuals with spinal cord injury (SCI). Methods: A total of 121 patients with SCI (106 cervical SCI, 15 thoracic SCI) discharged from our center over the past three years were studied. Moreover, 11-factor modified frailty index (mFI) scores, the length of hospital stays, the rate of returning home, and improvement in Spinal Cord Independence Measure (SCIM) scores were assessed retrospectively. Results: The average age at the time of injury for all 121 cases was 59.6 years. Based on pre-injury assessments, 24 cases were categorized as the Frail group, and 97 cases were categorized as the Robust group. The Frail group had SCIM improvement rates of 16.7% and a home discharge rate of 45.8%. In contrast, the Robust group had SCIM improvement rates of 33.5% and a home discharge rate of 68.0%, with statistically significant differences between the two groups. A significant negative correlation was observed between mFI scores and SCIM improvement rates (R = -0.231, p = 0.014). Conclusions: This study suggests that individuals with pre-existing frailty before SCI experience poorer SCIM improvement rates and face challenges in returning home.

The Efficiency of Rehabilitation Therapy in Patients Diagnosed with Neurogenic Bladder: A Systematic Review.

Considerable research efforts have been directed towards investigating neurogenic bladder dysfunction over the preceding decade. This condition stands as the most prevalent and incapacitating pelvic floor disorder amidst patients afflicted with specific upper motor neuron syndromes, including multiple sclerosis, stroke, and spinal cord injury. The current study aims to bring up-to-date findings on rehabilitation methods for treating neurogenic bladder. The Web of Science database (MEDLINE, PsychINFO, EMBASE, CENTRAL, ISRCTN, and ICTRP) was screened for randomized controlled studies and clinical studies using combinations of keywords including "neurogenic bladder", "stroke", "multiple sclerosis", and "spinal cord injury". The PEDro scale was used to assess the quality of the articles included in this study. After a thorough examination, eleven articles met the criteria for inclusion in our research. The outcome measures showed a variety of forms of electrostimulation that can be combined with or without PFMT. These interventions significantly enhance health-related quality of life, as evidenced by various assessment methods. The physical approach constitutes an effective therapeutic method that can reduce the severity of urinary incontinence.

Stability of Conducting Polymer-Coated Carbon Microfibers for Long-Term Electrical Stimulation of Injured Neural Tissue.

Electroactive microfiber-based scaffolds aid neural tissue repair. Carbon microfibers (CMFs) coated with the conducting polymer poly(3,4-ethylenedioxythiophene) doped with poly[(4-styrenesulfonic acid)-co-(maleic acid)] (PEDOT:PSS-co-MA) provide efficient support and guidance to regrowing axons across spinal cord lesions in rodents and pigs. We investigated the electrical and structural performance of PEDOT:PSS-co-MA-coated carbon MFs (PCMFs) for long-term, biphasic electrical stimulation (ES). Chronopotentiometry and electrochemical impedance spectroscopy (EIS) allowed the characterization of charge transfer in PCMFs during ES in vitro, and morphological changes were assessed by scanning electron microscopy (SEM). PCMFs that were 4 mm long withstood two-million-biphasic pulses without reaching cytotoxic voltages, with a 6 mm length producing optimal results. Although EIS and SEM unveiled some polymer deterioration in the 6 mm PCMFs, no significant changes in voltage excursions appeared. For the preliminary testing of the electrical performance of PCMFs in vivo, we used 12 mm long, 20-microfiber assemblies interconnected by metallic microwires. PCMFs-assemblies were implanted in two spinal cord-injured pigs and submitted to ES for 10 days. A cobalt-alloy interconnected assembly showed safe voltages for about 1.5 million-pulses and was electrically functional at 1-month post-implantation, suggesting its suitability for sub-chronic ES, as likely required for spinal cord repair. However, improving polymer adhesion to the carbon substrate is still needed to use PCMFs for prolonged ES.

Noninvasive Electromagnetic Neuromodulation of the Central and Peripheral Nervous System for Upper-Limb Motor Strength and Functionality in Individuals with Cervical Spinal Cord Injury: A Systematic Review and Meta-Analysis.

(1) Background: Restoring arm and hand function is one of the priorities of people with cervical spinal cord injury (cSCI). Noninvasive electromagnetic neuromodulation is a current approach that aims to improve upper-limb function in individuals with SCI. The aim of this study is to review updated information on the different applications of noninvasive electromagnetic neuromodulation techniques that focus on restoring upper-limb functionality and motor function in people with cSCI. (2) Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were used to structure the search protocol. A systematic review of the literature was performed in three databases: the Cochrane Library, PubMed, and Physiotherapy Evidence Database (PEDro). (3) Results: Twenty-five studies were included: four were on transcranial magnetic stimulation (TMS), four on transcranial direct current stimulation (tDCS), two on transcutaneous spinal cord stimulation (tSCS), ten on functional electrical stimulation (FES), four on transcutaneous electrical nerve stimulation (TENS), and one on neuromuscular stimulation (NMS). The meta-analysis could not be completed due to a lack of common motor or functional evaluations. Finally, we realized a narrative review of the results, which reported that noninvasive electromagnetic neuromodulation combined with rehabilitation at the cerebral or spinal cord level significantly improved upper-limb functionality and motor function in cSCI subjects. Results were significant compared with the control group when tSCS, FES, TENS, and NMS was applied. (4) Conclusions: To perform a meta-analysis and contribute to more evidence, randomized controlled trials with standardized outcome measures for the upper extremities in cSCI are needed, even though significant improvement was reported in each non-invasive electromagnetic neuromodulation study.

Comparing reactive versus empiric cerebrospinal fluid drainage strategies for spinal perfusion pressure optimization in patients with acute traumatic spinal cord injuries.

BACKGROUND: Spinal cord hypoperfusion undermines clinical recovery in acute traumatic spinal cord injuries. New guidelines suggest cerebrospinal fluid (CSF) drainage is an important strategy for preventing spinal cord hypoperfusion in the acute post-injury phase. METHODS: This study included participants presenting to a single level 1 trauma center between 2018 and 2022 with cervical or thoracic traumatic spinal cord injury severity grade A-C, as evaluated by the American spinal injury association impairment scale (AIS). The primary objective of this study was to compare the efficacy of two CSF drainage protocols in preventing spinal cord hypoperfusion; 1) draining CSF only when spinal cord perfusion pressure (SCPP) drops below 65 mmHg (i.e. reactive) versus 2) empiric CSF drainage of 5-10 mL every hour. Intrathecal pressure, spinal cord perfusion pressure (SCPP), mean arterial pressure (MAP), and vasopressor utilization were compared using univariate T-test statistical analysis. RESULTS: While there was no difference in the incidence of sub-optimal SCPP (<65 mmHg; p = 0.1658), reactively drained participants were more likely to exhibit critical hypoperfusion (<50 mmHg; p = 0.0030) despite also having lower average intrathecal pressures (p < 0.001). There were no differences in average SCPP, mean arterial pressure (MAP), or vasopressor utilization between the two groups (p > 0.05). CONCLUSIONS: Empiric (vs reactive) CSF drainage resulted in fewer incidences of critical spinal cord hypoperfusion for patients with acute traumatic spinal cord injuries.

Irisflorentin improves functional recovery after spinal cord injury by protecting the blood-spinal cord barrier and promoting axonal growth.

Spinal cord injury (SCI) induces the disruption of the blood-spinal cord barrier (BSCB) and the failure of axonal growth. SCI activates a complex series of responses, including cell apoptosis and endoplasmic reticulum (ER) stress. Pericytes play a critical role in maintaining BSCB integrity and facilitating tissue growth and repair. However, the roles of pericytes in SCI and the potential mechanisms underlying the improvements in functional recovery in SCI remain unclear. Recent evidence indicates that irisflorentin exerts neuroprotective effects against Parkinson's disease; however, whether it has potential protective roles in SCI or not is still unknown. In this study, we found that the administration of irisflorentin significantly inhibited pericyte apoptosis, protected BSCB integrity, promoted axonal growth, and ultimately improved locomotion recovery in a rat model of SCI. In vitro, we found that the positive effects of irisflorentin on axonal growth were likely to be mediated by regulating the crosstalk between pericytes and neurons. Furthermore, irisflorentin effectively ameliorated ER stress caused by incubation with thapsigargin (TG) in pericytes. Meanwhile, the protective effect of irisflorentin on BSCB disruption is strongly related to the reduction of pericyte apoptosis via inhibition of ER stress. Collectively, our findings demonstrate that irisflorentin is beneficial for functional recovery after SCI and that pericytes are a valid target of interest for future SCI therapies.

Extent of Traumatic Spinal Cord Injury Is Lesion Level Dependent and Predictive of Recovery: A Multicenter Neuroimaging Study.

Assessing the extent of the intramedullary lesion after spinal cord injury (SCI) might help to improve prognostication. However, because the neurological level of injury impacts the recovery potential of SCI patients, the question arises whether lesion size parameters and predictive models based on those parameters are affected as well. In this retrospective observational study, the extent of the intramedullary lesion between individuals who sustained cervical and thoracolumbar SCI was compared, and its relation to clinical recovery was assessed. In total, 154 patients with subacute SCI (89 individuals with cervical lesions and 65 individuals with thoracolumbar lesions) underwent conventional clinical magnetic resonance imaging 1 month after injury and clinical examination at 1 and 12 months. The morphology of the focal lesion within the spinal cord was manually assessed on the midsagittal slice of T2-weighted magnetic resonance images and compared between cervical and thoracolumbar SCI patients, as well as between patients who improved at least one American Spinal Injury Association Impairment Scale (AIS) grade (converters) and patients without AIS grade improvement (nonconverters). The predictive value of lesion parameters including lesion length, lesion width, and preserved tissue bridges for predicting AIS grade conversion was assessed using regression models (conditional inference tree analysis). Lesion length was two times longer in thoracolumbar compared with cervical SCI patients (F = 39.48, p < 0.0001), whereas lesion width and tissue bridges width did not differ. When comparing AIS grade converters and nonconverters, converters showed a smaller lesion length (F = 5.46, p = 0.021), a smaller lesion width (F = 13.75, p = 0.0003), and greater tissue bridges (F = 12.87, p = 0.0005). Using regression models, tissue bridges allowed more refined subgrouping of patients in AIS groups B, C, and D according to individual recovery profiles between 1 month and 12 months after SCI, whereas lesion length added no additional information for further subgrouping. This study characterizes differences in the anteroposterior and craniocaudal lesion extents after SCI. The two times greater lesion length in thoracolumbar compared with cervical SCI might be related to differences in the anatomy, biomechanics, and perfusion between the cervical and thoracic spines. Preserved tissue bridges were less influenced by the lesion level while closely related to the clinical impairment. These results highlight the robustness and utility of tissue bridges as a neuroimaging biomarker for predicting the clinical outcome after SCI in heterogeneous patient populations and for patient stratification in clinical trials.