Acute Spinal Cord Injury Research Articles

Corticosteroid Effect in Acute Spinal Cord Injury in the Rural Area

Spinal cord injuries (SCI) are devastating traumatic events in the lives of patients, often resulting in severe and/or permanent neurologic disabilities. Nearly half a million people are living permanently disabled in the United States due to traumatic SCI and 12,000–15,000 patients per year incur new injuries. A 78-year-old male patient came to the emergency room with a history of falling from a height with a pelvic position below exposed to trees 30 hours before admission, found weakness in the lower limbs, unable to urinate since yesterday. On radiologic examination, a burst fracture was found in the collumna of the 1st lumbar vertebra. The patient could not be examined for MRI due to limitations and unavailability of equipment at the hospital. The patient was given high dose of Methylprednisolone treatment for 3 days and there was no motoric improvement in the patient. Acute spinal cord injury is a very dangerous disease because it can cause patients both psychological and non psychological disorders. In areas that are left behind and do not have very good facilities and medical personnel to carry out this treatment. There is no treatment option other than using corticosteroids. However, the effect of corticosteroids still needs to be further developed and researched.

Predictors of Early Mortality After Traumatic Spinal Cord Injury in South Africa

Study Design Retrospective cohort study. Objectives To identify predictors for early mortality following traumatic spinal cord injury (TSCI), as recognition of factors associated with early mortality is essential for public resource allocation and optimized acute care. Methods Retrospective Analysis of SCI patients admitted to the acute SCI ward from 2003 to 2022 was performed. Days elapsing from the date of injury to date of death established the survival time. Early mortality was defined as survival time ≤ 365 days. Multivariable logistic regression was used in modeling of early death following TSCI with age, gender, neurologic deficit, type of neurologic injury, ventilation status, and count of complications as covariates. Results Simple logistic regression indicated a significant association of early mortality with the number of complications ( P < .0001), neurological deficit ( P < .0001), complete neurological injury ( P < .0001), ventilation status ( P < .0001), and age group ( P < .0003). After adjusting for other covariates, complete neurological injury (OR: 1.75, P < .0001), ventilation (OR: 2.80, P < .0001), and Age group (over 60 OR: 17.71, P < .0001) were significantly associated with early mortality. The multivariable model showed a good overall fit (Hosmer-Lemeshow P = .315; AUC 0.85). Conclusions Predictors of early mortality after TSCI are high complete spinal cord injury, age, number of complications, and the need for ventilation. Identification of high-risk patients is crucial to rationalize and improve acute care to potentially reduce mortality rates.

Injectable alginate chitosan hydrogel as a promising bioengineered therapy for acute spinal cord injury

Dealing with spinal cord injuries presents problematic due to multiple secondary mechanisms. Beyond primary concerns like paralysis and disability, complications including urinary, gastrointestinal, cardiac, and respiratory disorders, along with substantial economic burdens may occur. Limited research focuses on modeling and treating contusion and compression injuries. Tissue engineering emerges as an innovative treatment, targeting lesion pathophysiology. This study was evaluated implanting injectable biomaterials into injury-induced cavity before glial scar formation, avoiding tissue incisions and minimizing further damage. The efficacy of injectable alginate/thiolated chitosan hydrogel was investigated for acute spinal cord injury induced by Vanický method in Wistar rats. Three days post-injury, hydrogel was administrated through microinjection after laminectomy. After 60 days, the hydrogel group demonstrated notable motor function enhancement compared to the control by the BBB locomotor test (P < 0.05). However, no statistically significant differences were observed in MRI assessment concerning lesion severity. Stereological and histopathological evaluations revealed a reduction in vacuole volume and the presence of axon profiles within the scaffold (P < 0.05), alongside reduced infiltration of inflammatory and Gitter cells in the hydrogel group, although the latter was not statistically significant compared to the control. Thiolated chitosan/ alginate hydrogel implantation may be regarded as a promising treatment to enhance motor function by restraining destructive processes post-acute spinal cord injury.

HUCMSC-derived exosomes mitigate blood-spinal cord barrier disruption by activating AMPK/mTOR-mediated autophagic flux after acute spinal cord injury

After spinal cord injury (SCI), the integrity of the blood-spinal cord barrier (BSCB) can be disrupted, leading to the secondary injuries such as inflammatory cell infiltration, neuronal death, and spinal cord hematoma. It is important to maintain the integrity of the BSCB to help restore function following SCI. While some studies have demonstrated the therapeutic effects of exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSC-exos), their role in preserving BSCB integrity remains unclear. In our study, we demonstrated the protective effects of hUCMSC-exos on the BSCB and its mechanism. The results of this study indicate that hUCMSC-exos promote motor function recovery, preserve spinal cord structure, and reduce neuronal loss by inhibiting BSCB leakage following SCI. Experimental investigations conducted in vivo and in vitro have demonstrated that hUCMSC-exos can mitigate the loss of adherens junctions (AJs) and tight junctions (TJs) and stimulate autophagy in spinal cord endothelial cells. The protective effects were also found to be significantly reversed following the inhibition of autophagy using 3-MA. In conclusion, our study demonstrates that hUCMSC-exos protect the integrity of BSCB by promoting the repair of spinal endothelial cells through activation of autophagy, thereby exerting a protective role in SCI.

Impact of commonly administered drugs on the progression of spinal cord injury: a systematic review

BackgroundComplications arising from acute traumatic spinal cord injury (SCI) are routinely managed by various pharmacological interventions. Despite decades of clinical application, the potential impact on neurological recovery has been largely overlooked. This study aims to highlight commonly administered drugs with potential disease-modifying effects.MethodsThis systematic literature review included studies referenced in PubMed, Scopus and Web of Science from inception to March 31st, 2021, which assess disease-modifying properties on neurological and/or functional recovery of drugs routinely administered following spinal cord injury. Drug effects were classified as positive, negative, mixed, no effect, or not (statistically) reported. Risk of bias was assessed separately for animal, randomized clinical trials, and observational human studies.ResultsWe analyzed 394 studies conducting 486 experiments that evaluated 144 unique or combinations of drugs. 195 of the 464 experiments conducted on animals (42%) and one study in humans demonstrate positive disease-modifying properties on neurological and/or functional outcomes. Methylprednisolone, melatonin, estradiol, and atorvastatin are the most common drugs associated with positive effects. Two studies on morphine and ethanol report negative effects on recovery.ConclusionDespite a large heterogeneity observed in study protocols, research from bed to bench and back to bedside provides an alternative approach to identify new candidate drugs in the context of SCI. Future research in human populations is warranted to determine if introducing drugs like melatonin, estradiol, or atorvastatin would contribute to enhancing neurological outcomes after acute SCI.

Magnetic resonance imaging tracing of superparamagnetic iron oxide nanoparticle-labeled mesenchymal stromal cells for repairing spinal cord injury.

Mesenchymal stromal cell transplantation Is an effective and promising approach for treating various systemic and diffuse diseases. However, the biological characteristics of transplanted mesenchymal stromal cells in humans remain unclear, including cell viability, distribution, migration, and fate. Conventional cell tracing methods cannot be used in the clinic. The use of superparamagnetic iron oxide nanoparticles as contrast agents allows for the observation of transplanted cells using magnetic resonance imaging. In 2016, the National Medical Products Administration of China approved a new superparamagnetic iron oxide nanoparticle, Ruicun, for use as a contrast agent in clinical trials.In the present study, an acute hemi-transection spinal cord injury model was established in beagle dogs. The injury was then treated by transplantation of Ruicun-labeled mesenchymal stromal cells. The results indicated that Ruicun-labeled mesenchymal stromal cells repaired damaged spinal cord fibers and partially restored neurological function in animals with acute spinal cord injury. T2*-weighted imaging revealed low signal areas on both sides of the injured spinal cord. The results of quantitative susceptibility mapping with ultrashort echo time sequences indicated that Ruicun-labeled mesenchymal stromal cells persisted stably within the injured spinal cord for over 4 weeks. These findings suggest that magnetic resonance imaging has the potential to effectively track the migration of Ruicun-labeled mesenchymal stromal cells and assess their ability to repair spinal cord injury.

Ketone Esters Partially and Selectively Rescue Mitochondrial Bioenergetics After Acute Cervical Spinal Cord Injury in Rats: A Time-Course

Spinal cord injury (SCI) pathology and pathophysiology can be attributed to both primary physical injury and secondary injury cascades. Secondary injury cascades involve dysregulated metabolism and energetic deficits directly linked to compromised mitochondrial bioenergetics. Rescuing mitochondrial function and reducing oxidative stress are associated with neuroprotection. In this regard, ketosis after traumatic brain injury (TBI), or after SCI, improves secondary neuropathology by decreasing oxidative stress, increasing antioxidants, reducing inflammation, and improving mitochondrial bioenergetics. Here, we follow up on our previous study and have used an exogenous ketone monoester, (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KE), as an alternative to a ketogenic diet, focusing on mitochondrial function between 1 and 14 days after injury. Starting 3 h following a cervical level 5 (C5) hemi-contusion injury, animals were fed either a standard control diet (SD) or a ketone ester diet (KED) combined with KE administered orally (OKE). We found that mitochondrial function was reduced after SCI at all times post-SCI, accompanied by reduced expression of most of the components of the electron transport chain (ETC). The KE rescued some of the bioenergetic parameters 1 day after SCI when D-β-Hydroxybutyrate (BHB) concentrations were ~2 mM. Still, most of the beneficial effects were observed 14 days after injury, with BHB concentrations reaching values of 4–6 mM. To our knowledge, this is the first report to show the beneficial effects of KE in rescuing mitochondrial function after SCI and demonstrates the suitability of KE in ameliorating the metabolic dysregulation that occurs after traumatic SCI without requiring a restrictive dietary regime.

Automatic Assist Level Adjustment Function of a Gait Exercise Rehabilitation Robot with Functional Electrical Stimulation for Spinal Cord Injury: Insights from Clinical Trials.

This study aimed to identify whether the combined use of functional electrical stimulation (FES) reduces the motor torque of a gait exercise rehabilitation robot in spinal cord injury (SCI) and to verify the effectiveness of the developed automatic assist level adjustment in people with paraplegia. Acute and chronic SCI patients (1 case each) performed 10 min of gait exercises with and without FES using a rehabilitation robot. Reinforcement learning was used to adjust the assist level automatically. The maximum torque values and assist levels for each of the ten walking cycles when walking became steady were averaged and compared with and without FES. The motor's output torque and the assist level were measured as outcomes. The assist level adjustment allowed both the motor torque and assist level to decrease gradually to a steady state. The motor torque and the assist levels were significantly lower with the FES than without the FES under steady conditions in both cases. No adverse events were reported. The combined use of FES attenuated the motor torque of a gait exercise rehabilitation robot for SCI. Automatic assistive level adjustment is also useful for spinal cord injuries.

Microenvironment‐Responsive Injectable Conductive Hydrogel for Spinal Cord Injury Repair

AbstractSpinal cord injury (SCI) represents a severe neurological condition often coupled with a drastic secondary inflammatory response, which further exacerbates the damage in most cases. Due to their unique electrical and mechanical compatibilities with the spinal cord, the utilization of conductive hydrogels through injection for SCI repair, particularly in scenarios involving non‐uniform and large gaps, has emerged as a promising approach. Herein, leveraging the acidic microenvironment characteristic of acute SCI sites, an injectable conductive hydrogel with pH‐responsive immunoregulation is engineered for SCI repair. Based on the dynamic Schiff base chemistry and covalent photo‐crosslinking, this composite hydrogel, composed of gelatin methacryloyl, oxidized dextran, and MoS2, exhibits adjustable mechanical and conductive properties, enabling a customized match with the natural spinal cord's attributes. Additionally, the incorporation of Wnt5a and its selective release in acidic conditions prompt the immediate suppression of inflammatory factors and enhances neural differentiation and regeneration. In the 2‐mm hemisection mouse SCI model, the optimized conductive hydrogel can effectively bridge the injury gap, establish nerve connections and signal, mitigate inflammatory response, and promoted recovery of mobility. This novel injectable conductive hydrogel system offers a promising advance in therapeutic materials for SCI repair.

Invasive devices to monitor the intraspinal perfusion pressure in the hemodynamic management of acute spinal cord injury: A systematic scoping review.

Various methods for measuring intrathecal pressure (ITP) after spinal cord injury (SCI) to guide hemodynamic management have been investigated. To synthesize the current literature, this current study conducted a scoping review of the use of intrathecal devices to monitor ITP during acute management of SCI with the aim of understanding the association between ITP monitoring with physiological and clinical outcomes. A systematic review of literature following the Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. All eligible studies were screened for inclusion and exclusion criteria. Data extracted included number of patients included, severity of injury, characteristics of the intervention-intrathecal device used to record the ITP, outcomes -hemodynamic parameters observed, changes in the American Spinal Injury Association (ASIA) Impairment Scale (AIS), total motor scores, association of ITP with other physiological variables. The search yielded a total of 1,698 articles, of which 30 observational studies and 2 randomized clinical trials were deemed eligible based on their use of an intrathecal invasive device to monitor spinal cord perfusion pressure (SCPP) in patients with SCI. Of these, 9 studies used a lumbar drain, 23 a Codman pressure probe and 1 study that used both. These studies underscore the crucial interplay between ITP, the SCPP and physiological variables, with neurological outcome. It is still unclear whether monitoring from a lumbar drain is accurate enough to highlight what is occurring at the site of SCI, which is the main advantage of Codman Probe, however, the latter requires specialized personnel that may not be available in most settings. Minor adverse effects were associated with lumbar drain catheters, while cerebrospinal fluid leak requiring repair (~ 7%) is the main concern with Codman Probes. Future investigation of SCPP protocols via lumbar drains and Codman probes ought to involve multi-centered randomized controlled trials and continued translational investigation with animal models.

Primary prevention of venous thromboembolic complications in spinal cord injury: modern concepts

Venous thromboembolism is a common complication following spinal cord injury that can significantly aggravate a pre-existing condition and lead to a death. Patients who suffer acute spinal cord injury have a higher prevalence of venous thromboembolism than patients who suffer other traumatic injuries with sparing of the spinal cord. It is important for physical medicine and rehabilitation specialists to have knowledge аbout primary prevention of venous thromboembolism in patients with acute, subacute and chronic spinal cord injury. This article provides a brief overview of typical venous thromboembolism frequency (leg deep vein thrombosis and pulmonary embolism), pathogenesis peculiarities, venous thromboembolism risk factors and diagnostic considerations. The main attention is given to the primary thromboprophylaxis (methods and duration) depending on the spinal cord injury period and the spinal cord injury level. Further studies are required to clarify the optimal prophylaxis methods and protocols to prevent venous thromboembolism following spinal cord injury.

Feasibility of implementing body composition assessment into clinical practice in patients with acute spinal cord injury

Feasibility of implementing body composition assessment into clinical practice in patients with acute spinal cord injury

Discriminating fingerprints of chronic neuropathic pain following spinal cord injury using artificial neural networks and mass spectrometry analysis of female mice serum

Spinal cord injury (SCI) often leads to central neuropathic pain, a condition associated with significant morbidity and is challenging in terms of the clinical management. Despite extensive efforts, identifying effective biomarkers for neuropathic pain remains elusive. Here we propose a novel approach combining matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with artificial neural networks (ANNs) to discriminate between mass spectral profiles associated with chronic neuropathic pain induced by SCI in female mice. Functional evaluations revealed persistent chronic neuropathic pain following mild SCI as well as minor locomotor disruptions, confirming the value of collecting serum samples. Mass spectra analysis revealed distinct profiles between chronic SCI and sham controls. On applying ANNs, 100% success was achieved in distinguishing between the two groups through the intensities of m/z peaks. Additionally, the ANNs also successfully discriminated between chronic and acute SCI phases. When reflexive pain response data was integrated with mass spectra, there was no improvement in the classification. These findings offer insights into neuropathic pain pathophysiology and underscore the potential of MALDI-TOF MS coupled with ANNs as a diagnostic tool for chronic neuropathic pain, potentially guiding attempts to discover biomarkers and develop treatments.

Epidemiology of traumatic spinal cord injury in Ireland, 2017-2022.

Retrospective population based study on traumatic spinal cord injury (SCI) in Ireland. To gather the most recent epidemiological data prior to the implementation of a new national trauma strategy. Also, to consider if the COVID-19 pandemic impacted on SCI epidemiology in Ireland. Republic of Ireland. All patients with TSCI discharged from the National Rehabilitation Hospital (NRH), the national acute SCI unit and two neurosciences centres were included. The International Spinal Cord Injury Core Data Set was collected on all patients at discharge from rehabilitation between 2017 and 2022. Overall crude incidence of TSCI was 14 per million per year, ranging between 11.3 and 18.4. 12.7% of patients did not survive to discharge from hospital. In those completing rehabilitation, the mean age of injury onset was 50.1 years (SD 19.9). Males accounted for 75.7%. The most common impairment was incomplete tetraplegia, 45.3% of all TSCI. Leading aetiology was falls, 53.9% of injuries. Patients with incomplete tetraplegia and those whose cause of injury were falls were older than those with all other impairments and injury aetiologies (p < 0.001). Overall incidence of TSCI is similar to our previous studies. Also similar is the predominant pattern of older people sustaining falls resulting in incomplete tetraplegia.

A Kinematic Deviation Index (KDI) for Evaluation of Forelimb Function in Rodents.

Rodent models are widely used to study neurological conditions and assess forelimb movement to measure function performance, deficit, recovery and treatment effectiveness. Traditional assessment methods based on endpoints such as whether the task is accomplished, while easy to implement, provide limited information on movement patterns important to assess different functional strategies. On the other side, detailed kinematic analysis provides granular information on the movement patterns but is difficult to compare across laboratories, and may not translate to clinical metrics of upper limb function. To address these limitations, we developed and validated a kinematic deviation index (KDI) for rodents that mimics current trends in clinical research. The KDI is a unitless summary score that quantifies the difference between an animal movement during a task and its optimal performance derived from spatiotemporal marker sequences without pre-specifying movements. We demonstrate the utility of KDI in assessing reaching and grasping in mice and validate its discrimination between trial endpoints in healthy animals. Furthermore, we show KDI sensitivity to interventions, including acute and chronic spinal cord injury and optogenetic disruption of sensorimotor circuits. The KDI provides a comprehensive measure of motor function that bridges the gap between detailed kinematic analysis and simple success/failure metrics, offering a valuable tool for assessing recovery and compensation in rodent models of neurological disorders.

Evaluation of the Chetomin effect on histopathological features in a murine acute spinal cord injury model

BackgroundSeveral research studies have been focused on improving the treatment and prognosis of acute spinal cord injury, as part of this initiative we investigated the use of Chetomin to reduce the inflammatory response in this pathology. MethodsAn experimental, prospective, cross-sectional study was performed using 42 Wistar rats where we analyzed the effect of Chetomin compared to methylprednisolone administered 1 and 8 h after the spinal cord injury in a murine model. ResultsChetomin administration 8h post-injury decreased IL-6 and VEGF expression; and, and its administration 1h post-injury decreased NF-kB expression. ConclusionsChetomin has anti-inflammatory effects in acute spinal cord injury, whether these effects are observable with other proinflammatory markers should be investigated.

Preventing OsteoPorosis in Spinal Cord Injury (POPSCI) Study—Early Zoledronic Acid Infusion in Patients with Acute Spinal Cord Injury

Accelerated sub-lesional bone loss is common in the first 2–3 years after traumatic spinal cord injury (TSCI), particularly in the distal femur and proximal tibia. Few studies have explored efficacy of antiresorptives for acute bone loss prevention post-TSCI, with limited data for knee bone mineral density (BMD) or beyond two years follow-up. An open-label non-randomized study was performed at Royal North Shore Hospital and Royal Rehab Centre, Sydney between 2018 and 2023. An ‘acute interventional cohort’ (n = 11) with TSCI (duration ≤ 12-weeks) received a single infusion of 4 mg zoledronic acid (ZOL) at baseline. A ‘chronic non-interventional cohort’ (n = 9) with TSCI (duration 1–5-years) did not receive ZOL. All participants underwent baseline and 6-monthly blood tests (including CTx and P1NP) and 12-monthly DXA BMD scans (including distal femur and proximal tibia). Participants were predominantly Caucasian and male (mean age 38.4 years). At baseline, the ‘acute’ cohort had higher serum CTx, P1NP and sclerostin concentrations, while the ‘chronic’ cohort had lower left hip and knee BMD. Majority with acute TSCI experienced an acute phase reaction after ZOL (9/11; 82%). In the acute cohort, left hip BMD fell by mean ~ 15% by 48 months. Left distal femoral and proximal tibial BMD declined by mean ~ 6–13% at 12 months and ~ 20–23% at 48 months, with a tendency towards greater BMD loss in motor-complete TSCI. A single early ZOL infusion in acute TSCI could not attenuate rapidly declining hip and knee BMD. Prospective controlled studies are required to establish the optimal strategy for preventing early bone loss after acute TSCI.

Clinical Assessment and Management of Acute Spinal Cord Injury.

The information contained in this article is suitable for clinicians practicing in the United States desiring a general overview of the assessment and management of spinal cord injury (SCI), focusing on initial care, assessment, acute management, complications, prognostication, and future research directions. SCI presents significant challenges, affecting patients physically, emotionally, and financially, with variable recovery outcomes ranging from full functionality to lifelong dependence on caregivers. Initial care aims to minimize secondary injury through thorough neurological evaluations and imaging studies to assess the severity of the injury. Acute management prioritizes stabilizing respiratory and cardiovascular functions and maintaining proper spinal cord perfusion. Patients with unstable or progressive neurological decline benefit from timely surgical intervention to optimize neurological recovery. Subacute management focuses on addressing common complications affecting the respiratory, gastrointestinal, and genitourinary systems, emphasizing a holistic, multidisciplinary approach. Prognostication is currently based on neurological assessments and imaging findings, but emerging biomarkers offer the potential to refine outcome predictions further. Additionally, novel therapeutic interventions, such as hypothermia therapy and neuroprotective medications are being explored to mitigate secondary damage and enhance recovery. This paper serves as a high-yield refresher for clinicians for the assessment and management of acute spinal cord injury during index admission.

Glucocorticoids in Acute Spinal Cord Injury: Why are they still used nowadays?

Glucocorticoids in Acute Spinal Cord Injury: Why are they still used nowadays?

Perfusion imaging metrics after acute traumatic spinal cord injury are associated with injury severity in rats and humans.

Traumatic spinal cord injury (tSCI) causes an immediate loss of neurological function, and the prediction of recovery is difficult in the acute phase. In this study, we used contrast-enhanced ultrasound imaging to quantify intraspinal vascular disruption acutely after tSCI. In a rodent thoracic tSCI model, contrast-enhanced ultrasound revealed a perfusion area deficit that was positively correlated with injury severity and negatively correlated with hindlimb locomotor function at 8 weeks after injury. The spinal perfusion index was calculated by normalizing the contrast inflow at the injury center to the contrast inflow in the injury periphery. The spinal perfusion index decreased with increasing injury severity and positively correlated with hindlimb locomotor function at 8 weeks after injury. The feasibility of intraoperative contrast-enhanced ultrasound imaging was further tested in a cohort of 27 patients with acute tSCI of varying severity and including both motor-complete and motor-incomplete tSCIs. Both the perfusion area deficit and spinal perfusion index were different between motor-complete and motor-incomplete patients. Moreover, the perfusion area deficit and spinal perfusion index correlated with the injury severity at intake and exhibited a correlation with extent of functional recovery at 6 months. Our data suggest that intraoperative contrast-enhanced, ultrasound-derived metrics are correlated with injury severity and chronic functional outcome after tSCI. Larger clinical studies are required to better assess the reliability of the proposed contrast-enhanced ultrasound biomarkers and their prognostic capacity.