Search Results (142)

Traumatic spinal cord injury (SCI) is a catastrophic condition associated with profound neurologic disability, psychosocial disruption, high long-term healthcare utilization, and reduced life expectancy. Globally, SCI remains a major cause of morbidity, most commonly resulting from traumatic mechanisms such as motor vehicle collisions and falls, with a bimodal age distribution affecting both younger adults and older individuals. This narrative review provides a comprehensive, clinically oriented overview of SCIs with emphasis on classification, initial evaluation, imaging, and contemporary management strategies. The review highlights the dual-phase pathophysiology of SCIs—primary mechanical insult followed by secondary injury cascades—underscoring the rationale for rapid stabilization and timely, injury-specific interventions. Initial care is framed around immobilization and trauma resuscitation principles, with cervical spine clearance guided by validated decision tools and early, appropriate imaging acquisition. We discuss adjunctive imaging considerations and address the ongoing debate regarding MRI use in obtunded patients with negative initial studies. Acute inpatient management priorities include prevention of secondary complications, hemodynamic optimization, respiratory support, and vigilant surveillance for autonomic dysfunction. Pharmacologic neuroprotection with high-dose methylprednisolone remains controversial; current guideline recommendations are reviewed. Finally, we outline operative decision-making and evidence supporting early decompression in selected patients, as well as common surgical approaches and their indications. This review consolidates foundational concepts and current standards to support practical, evidence-informed SCI evaluation and management. Full article

Background/Objectives: Traumatic spinal injury (TSI) is associated with substantial morbidity, but factors contributing to in-hospital complications remain insufficiently defined. This study evaluated factors associated with in-hospital complications after TSI. Methods: We conducted a retrospective cohort study at a tertiary center (January 2018–May 2025). Among 5380 trauma patients screened by computed tomography, 413 admitted patients with TSI were included. The primary outcome was any documented in-hospital complication. Factors were assessed using multivariable logistic regression and reported as adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Results: The median age was 28.0 years, 337 were male (81.6%), and four-wheel motorized vehicle accidents were the most common injury mechanism (57.1%). In-hospital complications occurred in 99 patients (24.0%). Pulmonary infection was most common (9.9%), followed by bloodstream infection (4.4%), urinary tract infection (3.9%), and surgical site infection (3.9%). Compared with patients without complications, those with complications had longer hospital stays, higher ICU admissions, longer ICU stays, and lower discharge home. In multivariate logistic regression, complications were associated with worse AIS grade (OR 1.690, 95% CI 1.241–2.302), inpatient physical therapy requirement (OR 4.385, 95% CI 2.494–7.711), greater number of associated non-spinal injuries (OR 1.729, 95% CI 1.463–2.042), and greater cervical vertebral injury burden (OR 1.479, 95% CI 1.061–2.062). Conclusions: Neurological severity, polytrauma burden, and cervical injury were independently associated with complications, supporting early risk stratification and multidisciplinary prevention in high-risk patients. Findings should be interpreted considering the retrospective single-center design, predominantly young male cohort, low spinal cord injury proportion, and limited post-discharge data. Full article

Spinal cord injury often causes persistent neurological dysfunction, whereas the developing central nervous system retains greater plasticity. This study investigated whether spontaneous hindlimb motor recovery occurs after complete spinal cord transection in neonatal mice and whether such recovery is accompanied by structural remodeling of the lumbar spinal cord distal to the lesion. C57BL/6J mice underwent complete T9 spinal cord transection at postnatal day 7, and recovery was assessed by Basso Mouse Scale scoring, CatWalk gait analysis, foot-fault testing, immunofluorescence, and electromyography. Compared with adult mice subjected to the same injury, neonatal mice showed progressive partial improvement in hindlimb motor function, including locomotor performance, gait coordination, and foot placement accuracy. Meanwhile, this recovery was accompanied by preservation of lumbar motor neurons and structural changes in the local neural network. Syn⁺ coverage around lumbar motor neurons was relatively preserved in neonatal injured mice compared with adult injured mice; excitatory synaptic input remained increased, and inhibitory input showed a dynamic pattern of early increase followed by later reduction. In addition, myelin-related alterations were less severe, and motor neuron innervation of peripheral muscles (EMG) were relatively preserved in neonatal mice. The results indicate that the restoration of hindlimb motor function after complete spinal cord transection in neonatal mice is associated with structural and functional remodeling of lumbar spinal motor circuits. This includes enhanced synaptic signals around motor neurons and reorganization of the neuromuscular junction. Full article

Closed-loop neuromodulation systems for spinal cord injury (SCI) comprise a sensor layer that detects motor state or intent, a controller that converts this information into stimulation commands, and a stimulation interface that modulates spinal, peripheral, or supraspinal circuits. Although neuromodulation has shown potential for improving stepping, standing, trunk control, and upper-limb function after SCI, the performance of closed-loop systems depends critically on their reliability, latency, and practicality. This structured narrative review focuses on the sensor inputs used in closed-loop neuromodulation for SCI, including kinematic sensors, electromyography, force and pressure sensors, vision-based sensing, and emerging neural interfaces. We summarize how these signals have been used to estimate gait phase, posture, motor intent, and task state, and how sensor-driven strategies have progressed from animal models to early clinical applications. Preclinical studies provide mechanistic insights into activity-dependent, phase-specific, and proprioceptive feedback-mediated control, whereas human studies suggest that sensor-guided stimulation may improve functional specificity; however, comparative evidence remains limited. Future translation will require robust multimodal sensing, standardized reporting of latency and calibration burden, and practical designs suitable for supervised clinical and, ultimately, home use. Full article

Stage-specific embryonic antigen-3-positive pluripotent-like/macrophage-like multilineage-differentiating stress-enduring (Muse) cells are a distinct subpopulation of mesenchymal stromal cells (MSCs), accounting for 1% to several percent of MSCs. Although stem cell therapy for spinal cord injury (SCI) typically targets the subacute phase to avoid the hostile acute environment, the therapeutic window for Muse cells remains unclear. C57BL/6J mice with severe T9 contusion SCI received a single tail vein injection of human bone marrow-derived (BM) Muse cells, BM-MSCs (both 5 × 10⁴ cells), or vehicle at 2, 8, 14, or 28 days post-injury (DPI) without immunosuppressants. Among the different administration time points, the 2-DPI Muse cell group exhibited significantly higher Basso Mouse Scale scores than the BM-MSC and vehicle groups from 14 days after injection, while no significant differences were observed at the other administration time points. The 2-DPI Muse cell group showed significantly greater homing to the injured spinal cord than the BM-MSC group, with persistent engraftment and neural-lineage marker expression at day 42. Ablation of engrafted Muse cells at day 42 partially reversed locomotor recovery, suggesting that engrafted Muse cells contributed to functional recovery. These findings suggest that intravenous Muse cell therapy exerts timing-dependent therapeutic effects after SCI, with greater efficacy during the early post-injury phase. Full article

Background/Objectives: Rehospitalization after traumatic spinal cord injury (SCI) is common, but binary or count summaries may obscure heterogeneity in timing, recurrence, frequency, and duration. We aimed to identify clinically interpretable rehospitalization burden profiles in the SCIMS 2021ARPublic dataset and examine descriptive associations with clinical correlates and participation outcomes. Methods: We analyzed Form I, Form II, and Record Status public-use files. Among 29,310 individuals with at least one non-lost follow-up interview, 28,745 with at least one non-missing rehospitalization indicator entered latent class analysis. Four prespecified indicators captured early, recurrent, frequent, and prolonged rehospitalization. Candidate two- through six-class models were compared using AIC, BIC, entropy, class size, posterior probabilities, and interpretability. Pairwise adjusted logistic models examined candidate clinical correlates in 10,407 participants with complete 2016+ follow-up data. Adjusted linear models examined CHART participation domains in 20,766–20,949 participants. Results: A four-profile solution was retained: low rehospitalization burden (59.8%), early/prolonged rehospitalization (18.9%), frequent/prolonged rehospitalization (7.7%), and high recurrent/frequent/prolonged burden (13.6%). UTI and pressure ulcer history showed the most consistent associations with burdened profiles. Severe pain and frequent sleep problems were associated with selected heavier-burden profiles, while depressive symptoms showed smaller and less precise associations. Sensitivity analyses supported structural stability while highlighting observation-time bias and classification uncertainty inherent to wave-based public-use data. Compared with the low-burden profile, burden profiles showed lower CHART scores, especially for mobility and occupation. Conclusions: Rehospitalization after traumatic SCI is heterogeneous. These utilization burden profiles summarize distinct observed patterns but require prospective validation before use in risk stratification or follow-up planning. Full article

Background/Objective: Rapid, validated dietary screening tools are lacking for individuals with spinal cord injury (SCI), where routine clinical check-ups do not allow sufficient time for extensive dietary assessments typically required to evaluate adherence to dietary recommendations. We developed a 15-item dietary screener (SCI NutriTool) and evaluated its accuracy in classifying non-adherence to a healthy food pyramid compared with a validated food frequency questionnaire (FFQ). Methods: The SCI NutriTool was developed through literature review and expert consensus. In a validation study, 51 adults with SCI (mean age 57.0 years; 76.5% men; 68.8% traumatic injury) completed the SCI NutriTool twice and a validated 97-item FFQ, which served as the reference method. Results: The SCI NutriTool demonstrated substantial variability in performance across food groups, reflecting its domain-specific screening properties. Sensitivity was high for fruits and vegetables (91.7%), protein-rich foods (90.5%), and sweetened/alcoholic beverages and snacks (82.4%), with relatively high positive predictive values (PPV: 73.7–90.5%), supporting the tool’s ability to identify individuals who are likely non-adherent and may benefit from further nutritional assessment or counselling. In contrast, for starchy foods and nuts, oils, and fatty spreads/sauces, sensitivity was low (20.0% and 50.0%), while specificity was modest. This indicates that the tool performs better in correctly identifying adherent individuals in these domains, which is reflected in higher negative predictive values (NPV: up to 94.1%). However, the low sensitivity suggests that individuals with non-adherence may be missed, limiting the tool’s usefulness as an early screening trigger for these food groups. Conclusions: The SCI NutriTool’s performance varies across food groups, demonstrating a stronger ability to identify non-adherence in protein-rich foods, fruit and vegetables, sweetened and alcoholic beverages, and snacks, but limited discriminatory capacity for others. In particular, it is not suitable for screening non-adherence to starchy foods and fats. Accordingly, it is best used as a triage tool to guide further dietary assessment and targeted nutritional interventions rather than as a standalone diagnostic instrument. Full article

Background: Spinal cord ischemia (SCI) is a severe complication of thoracoabdominal aortic aneurysm (TAAA) repair, associated with substantial morbidity and mortality. Despite advances in operative techniques, its pathophysiology remains incompletely understood, with no reliable biomarkers available for early detection or risk stratification. Methods: This narrative review synthesizes current evidence on the pathophysiology of SCI following aortic intervention, integrating insights from ischemic stroke and traumatic spinal cord injury to identify key mechanistic pathways and potential biomarker targets. Results: SCI results from multifactorial impairment of spinal cord perfusion pressure (SCPP) driven by extensive aortic coverage, disruption of segmental arterial inflow, hypotension, and impaired collateral circulation. While acute hypoperfusion initiates injury, secondary processes—including excitotoxicity, oxidative stress, and neuroinflammation—drive progression. Cytokine signaling and immune activation contribute to blood–spinal cord barrier disruption and vasogenic edema, with Aquaporin-4 playing a central role in delayed injury. Candidate biomarkers, including neuron-specific enolase, S100β, and glial fibrillary acidic protein, reflect neuronal damage but lack sufficient sensitivity and temporal resolution for clinical use. Emerging evidence supports a multimodal biomarker approach incorporating inflammatory, structural, and Aquaporin-4-dependent edema-related pathways. Conclusions: Spinal cord ischemia following thoracoabdominal aortic aneurysm repair is a dynamic and multifactorial process in which reduced spinal cord perfusion pressure represents a final common pathway linking diverse perioperative factors to ischemic injury. Secondary mechanisms, particularly neuroinflammation and Aquaporin-4-driven vasogenic edema, play a central role in injury propagation and represent promising targets for biomarker development. Future strategies should focus on longitudinal, multimodal biomarker approaches to improve early detection, risk stratification, and therapeutic intervention. Full article

Mesenchymal stromal cells (MSCs) are multipotent cells characterized by their regenerative capacity and strong immunomodulatory properties. In recent years, MSC-based therapy has attracted significant attention as a potential treatment for a wide range of immune-mediated and degenerative diseases. The therapeutic effects of MSCs are primarily mediated through paracrine signaling and secretion of cytokines that regulate immune responses and promote tissue repair. This review focuses on five key cytokines involved in MSC immunomodulation: interleukin-6 (IL-6), interleukin-10 (IL-10), transforming growth factor-beta (TGF-β), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β). These cytokines interact within a complex signaling network that allows MSCs to suppress excessive inflammation and restore immune balance. The role of MSC therapy is examined in several clinically relevant conditions, including systemic lupus erythematosus, systemic sclerosis, ischemic stroke, spinal cord injury, diabetes mellitus, and female infertility. Across these diseases, MSCs demonstrate the ability to inhibit pro-inflammatory immune cell activity, promote regulatory immune phenotypes, reduce oxidative stress, and stimulate regeneration through the secretion of growth factors and extracellular vesicles. Despite promising experimental and early clinical findings, several limitations remain, including variability in MSC sources, limited cell survival after transplantation, and the need for optimized dosing strategies. Overall, MSC therapy represents a multifunctional therapeutic approach combining immunomodulation, anti-inflammatory activity, and regenerative support. Further research is required to better understand cytokine interactions, improve standardization of MSC-based treatments, and enhance clinical efficacy across diverse pathological conditions. Full article

Peripheral nerve ischemia–reperfusion injury is considered to contribute to sensory disturbances that impair quality of life in patients with diabetic neuropathy and chemotherapy-induced neuropathy. However, the spinal mechanisms underlying these disturbances remain unclear, partly due to the lack of established animal models and evaluation systems. In the present study, we used a rat hindlimb ischemia–reperfusion model and in vivo extracellular recording to examine bidirectional changes in neuronal activity in the spinal dorsal horn. Ischemia was induced by tightly binding the rat ankle with a rubber band, followed by reperfusion. Behavioral analysis showed a significant increase in hindlimb licking behavior after reperfusion, indicating the development of sensory disturbance-like responses. Extracellular recordings from superficial dorsal horn neurons showed diverse patterns of spontaneous firing and responses to mechanical stimulation, with both hypersensitive and desensitized responses. Furthermore, mRNA expression levels of immediate early genes (Egr1, Egr3, and Fos) were upregulated in the spinal cord after reperfusion. These results suggest that this ischemia–reperfusion model reproduces complex neuronal responses relevant to peripheral neuropathy and provides a useful evaluation system for evaluating both increased and decreased neural activity. This approach may contribute to elucidating the mechanisms of sensory disturbances and to the development of new treatments for neuropathic conditions. Full article

Traumatic spinal cord injury (TSCI) frequently necessitates prolonged ventilatory support, raising the clinical dilemma of early versus late tracheostomy. Despite decades of debate, no randomized controlled trials (RCTs) have been conducted exclusively in TSCI populations, and evidence remains largely observational. This review synthesizes contemporary evidence on the timing and outcomes of tracheostomy in acute TSCI. Across multiple cohort studies and meta-analyses, early tracheostomy (≤7 days) is consistently associated with shorter mechanical ventilation duration, shorter ICU length of stay, reduced sedation exposure, and fewer immobility-related complications. Data suggested a lower incidence of ventilator-associated pneumonia, though mortality outcomes remain unchanged. Importantly, cervical-level injuries appear to derive the most significant benefit, while variability in defining “early” versus “late” complicates direct comparisons. Despite methodological limitations, including reliance on retrospective data, inconsistent definitions, and lack of long-term follow-up, cumulative evidence indicates that early tracheostomy improves short-term outcomes. The optimal timing of tracheostomy in TSCI remains uncertain. Current observational evidence suggests that early tracheostomy in cervical SCI is associated with a reduction in the duration of mechanical ventilation, ICU stay, and respiratory complications. These benefits might come from better access to the airways, less anatomical dead space, better clearance of secretions, less need for sedation, together with earlier mobilization and rehabilitation. Mortality outcomes remain inconclusive. In the absence of randomized trials and long-term data, individualized decisions based on injury level, clinical course, and institutional expertise are essential. Full article

Spinal cord injury (SCI) is an acute, devastating neurologic condition that results in permanent progressive motor deficits, sensory disturbances, and autonomic dysfunctions, which limit function, participation, and quality of life. Although substantial progress has been made during the last several decades for both early trauma care and rehabilitation protocols following SCI, long-term neurological recovery remains unpredictable and often incomplete. This manuscript summarizes mechanistic and clinical evidence regarding robotic-assisted rehabilitation (RAR) and spinal neuromodulation (SN), which have been published since 2010 until the present time in a structured narrative review of the literature on these two emerging areas for neurorehabilitation after SCI. RAR provides high-intensity, task-specific training that consistently results in improvements in functional outcomes such as balance, coordination, and independence; however, its impact is limited when it comes to walking speed or voluntary motor control. SN (particularly epidural stimulation) can activate the residual neural pathways to standing up and stepping even after a complete injury but effects are typically stimulus dependent, with heterogeneous clinical results that often lack strong long-term evidence due in part to variability in patient selection, stimulation parameters and rehabilitation protocols. However, there is emerging mechanistic data supporting combining modulation of excitability through SN approaches along with structured sensorimotor training as an approach for enhancing recovery. Collectively, these findings support a shift toward more physiology-driven neurorehabilitation strategies and the need for future research to improve clinical translation and outcome predictability by patient stratification using standardized intervention protocols that include longitudinal evaluation. Full article

Breathing-controlled electrical stimulation (BreEStim) is an innovative neuromodulation intervention that synchronizes deep voluntary breathing with peripheral electrical stimulation. Prior studies have shown its analgesic effects in healthy adults and spinal cord injury patients with neuropathic pain. The present study used EEG to examine BreEStim’s neural effects on sensory, affective, and cognitive components of pain. Fourteen healthy participants (7 M, 7 F) completed 30 min of BreEStim and conventional electrical stimulation (EStim) interventions in a randomized, crossover within-subject design. Electrical pain thresholds (EPT) and EEG were recorded pre- and post-intervention. Event-related potentials (ERPs) at pre-EPT-level stimuli before and immediately after each intervention were analyzed for early sensory (P30) and affective (P250) processing, while resting-state EEG assessed spectral power across delta, theta, alpha, and beta bands for cognitive processing. Both BreEStim and EStim increased EPT, indicating short-term habituation. There was no change in early ERP responses (P30) after each intervention, suggesting preserved sensory perception. BreEStim selectively reduced P250, reflective of the affective component of pain. BreEStim significantly increased delta and theta band power and reduced alpha band power on resting-state EEG analyses, whereas no significant changes after EStim were observed. Collectively, BreEStim preserves sensory encoding while selectively modulating affective and cognitive dimensions of pain, supporting its potential as a targeted, non-pharmacological neuromodulation strategy. Full article

Background/Objectives: Traumatic spine injury is a major cause of morbidity and mortality in low- and middle-income countries, yet detailed epidemiologic data from sub-Saharan Africa remain limited. We used a fracture registry to characterize injury patterns, care pathways, and short-term outcomes among patients presenting with traumatic spine injury at a tertiary referral center in Ethiopia. Methods: We performed a retrospective analysis of a prospectively maintained fracture registry at a tertiary referral hospital in Ethiopia from June 2023 to July 2025. Patients with traumatic spine injury were included. Variables included demographics, injury mechanism and context, injury region, AO morphology, neurologic status (ASIA), referral status, mode of transportation, time to presentation, treatment, and 30-day outcomes. Descriptive statistics were used to summarize the cohort. Bivariate associations were assessed using chi-square or Fisher’s exact tests, and crude odds ratios were calculated for prespecified 2 × 2 comparisons. Results: A total of 252 patients were included (mean age: 33.1 ± 13.6 years; 81.3% male). Falls (45.2%) and road traffic accidents (26.2%) were the most common mechanisms, and injuries most often occurred on farms (40.1%) and roads/streets (33.7%). The thoracolumbar (31.3%) and cervical (30.6%) regions were most frequently affected. Complete spinal cord injury (ASIA A) occurred in 36.5% of patients. Most patients were referred (88.5%), 62.7% presented >24 h after injury, and 65.5% were managed non-operatively. Referral status was strongly associated with delayed presentation (OR: 10.49, 95% CI: 3.84–28.64). Thirty-day mortality was 22.2%. Complete SCI (OR: 6.17, 95% CI: 3.23–11.90) and cervical/thoracic injuries (OR: 6.54, 95% CI: 3.12–13.70) were associated with higher mortality. Conclusions: Traumatic spine injury in this Ethiopian cohort disproportionately affected young adults and was marked by severe neurologic injury, delayed presentation, and high early mortality. Full article

Background/Objectives: Traumatic spinal cord injury (SCI) frequently results in permanent motor and sensory deficits. Tumor necrosis factor-α is rapidly upregulated after SCI and contributes to secondary injury cascades, including microglial activation, cytokine amplification, and blood–spinal cord barrier disruption. Etanercept, a TNF-α inhibitor, has been investigated in modulating post-SCI neuroinflammation. This systematic review synthesizes preclinical evidence evaluating the therapeutic role of etanercept in SCI. Methods: A systematic review was conducted in accordance with PRISMA 2020 guidelines. The review was not prospectively registered. PubMed, Scopus, and Web of Science were searched through 9 December 2025. Eligible studies included original investigations of etanercept administered for in vivo mammalian models of SCI. Non-English articles, preprints, conference abstracts, case reports, and reviews were excluded. Risk of bias was assessed independently by at least two reviewers using the SYRCLE tool. Due to heterogeneity in models and dosing strategies, meta-analysis was not performed. Results: Of 119 records identified, 36 duplicates were removed. After screening 83 titles and abstracts, 67 were excluded. One additional study was excluded after full-text retrieval. Thus, 15 articles were included. Primary outcomes varied between studies, including inflammation, histopathology, and functional recovery. Conclusions: Preclinical evidence suggests that etanercept may attenuate early neuroinflammation after SCI; however, methodological heterogeneity and limited data warrant further investigation. This work was supported by the College of Medicine at Central Michigan University, the John G. Kulhavi Professorship in Neuroscience, and the E. Malcolm Field and Gary Leo Dunbar Endowed Chair in Neuroscience at Central Michigan University. Full article