Duration of intensive care unit admission to maintain mean arterial pressure goals following acute traumatic spinal cord injury.

Liproxstatin-1 improves functional recovery after acute spinal cord injury by inhibiting ferroptosis-induced inflammation.

We applied an advanced diffusion model of Neurite Orientation Dispersion and Density Imaging (NODDI) to patients with acute traumatic cervical spinal cord injury and investigated the correlation of NODDI metrics with clinical symptoms and neurological prognosis. We enrolled 13 patients (mean age, 66.6 [48-80] years) who were admitted to our hospital with acute traumatic cervical spinal cord injury. Magnetic resonance imaging (MRI) diffusion-weighted images were acquired for 13 patients 6.4±1.7days post-injury and 10 healthy volunteers (mean age, 67.0 [53-79] years). Fractional anisotropy (FA), intracellular volume fraction (ICVF), isotropic volume fraction (ISO), and orientation dispersion index (ODI) were calculated at the level of the injury in patients and at C3/4, C4/5, and C5/6 in healthy volunteers. We assessed the American Spinal Injury Association International Standards Neurological Classification of Spinal Cord Injury (ASIA) motor score at injury onset and at 6months and 1year post-injury. Patients had significantly lower FA and higher ODI values than healthy volunteers. FA and ODI values were significantly correlated with the ASIA motor scores at onset and at 1year post-injury. ODI demonstrated the highest correlation with the ASIA motor score at 1year post-injury. Complete recovery of muscle weakness occurred in all six cases with ODI values <0.12, while muscle weakness persisted in six of seven cases with ODI values >0.12. ODI is a relevant predictor of motor function at 1year post-injury.

Acute neuroinflammation drives secondary degeneration after spinal cord injury (SCI), yet the precise immune cell states and upstream regulatory circuits that initiate this response remain unresolved. Defining these early-state determinants at multi-omics resolution is essential for identifying mechanistically grounded therapeutic targets. We implemented an integrated multi-omics framework combining high-temporal-resolution single-cell RNA sequencing, bulk transcriptomics, histological validation, and systems-level network modeling across uninjured and early post-injury time points. Cell-cell communication analysis delineated intercellular signaling architecture within the acute lesion niche. Transcriptional regulatory network inference with in silico perturbation identified candidate master regulators. Network-based compound prioritization and target engagement validation were followed by functional testing in activated macrophages and a mouse SCI model. We resolved a temporally restricted S100a4+ macrophage state that rapidly emerged after injury, peaked at 1day, and subsequently contracted. This state was defined by a coordinated transcriptional program integrating enhanced migratory capacity, amplified pro-inflammatory and pyroptotic signaling, and repression of homeostatic and reparative modules, constituting the dominant acute inflammatory signature at the tissue level. Systems-level analysis established a Cebpb-centered regulatory circuitry governing this state, thereby defining a C/EBPβ-S100a4+ macrophage axis as a principal driver of early neuroinflammation. Network topology positioned this axis as a densely connected and self-reinforcing hub within the injury microenvironment. Computational drug prioritization identified baicalein as a candidate regulator of C/EBPβ-dependent signaling. ChIP-qPCR and nuclear-cytoplasmic fractionation validated that baicalein effectively reduced the nuclear translocation of C/EBPβ and its binding to the S100a4 promoter. Experimental validation demonstrated that baicalein suppressed C/EBPβ expression, attenuated downstream inflammatory and pyroptotic pathways, and significantly improved functional recovery following SCI. This study delineates a C/EBPβ-S100a4+ macrophage axis that mechanistically structures the acute inflammatory landscape of SCI and represents a tractable therapeutic vulnerability. These findings advance a state-specific, network-informed framework for early immunomodulation in spinal cord injury.

NG101 is a recombinant antibody that neutralizes the nerve growth inhibitor Nogo-A, promoting neural repair and improving upper extremity motor function in spinal cord injury (SCI). This study evaluated spinal cord MRI biomarkers to detect treatment-related structural changes and enhance patient stratification using data from 106 participants with acute cervical SCI in the phase 2b NISCI trial. We assessed lesion volume, tissue bridges, and remote changes in cross-sectional cord area (CSA), and tract-specific myelin-sensitive magnetization transfer saturation (MTsat) over six months. Compared to placebo, NG101-treated participants exhibited faster lesion volume reduction and a slower decline of CSA and MTsat in the corticospinal tracts and dorsal columns. Crucially, multimodal stratification incorporating MRI and electrophysiological measures substantially enhanced the detection of clinical treatment effects. These findings suggest NG101 slows trauma-induced progressive macro- and microstructural degeneration or promotes fiber sprouting. Combining MRI with electrophysiology enables sensitive detection of treatment effects and efficient trial designs. ClinicalTrials.gov identifier: NCT03935321.

Background Hyponatremia is a prevalent electrolyte disorder in patients with acute spinal cord injury (SCI), which can significantly increase the risk of adverse complications and impair long-term prognosis. Despite its clinical significance, the existing evidence on the factors associated with hyponatremia in this patient population remains fragmented and inconsistent, leading to uncertainties in clinical prevention and management. Methods Systematic searches were conducted in PubMed, Embase, Web of Science, Cochrane Library, and Chinese databases including CNKI, Wan fang, and VIP, retrieving relevant studies from the inception of each database up to December 20, 2025. Included observational studies reporting factors associated with hyponatremia in patients with acute spinal cord injury. Two researchers independently performed literature screening, data extraction, and quality assessment. Results were synthesized using a random-effects model to calculate odds ratios (OR) with 95% confidence intervals (CI), with assessments of heterogeneity, publication bias, and sensitivity analyses. Results Twelve eligible studies involving 2,355 patients were included in the meta-analysis. The results indicate an association between upper cervical spine injury [OR = 6.05, 95%CI (2.79, 13.10)], complete SCI [OR = 5.35, 95%CI (3.15, 9.07)], hypoproteinemia [OR = 2.96, 95%CI (1.10, 7.92)], infection [OR = 2.20, 95%CI (1.67, 2.90)], and hyponatremia in patients with SCI. Conclusion This meta-analysis demonstrates that hyponatremia in patients with acute SCI is closely related to the level and severity of spinal cord injury, with upper cervical spine injury and complete SCI being potential major risk indicators. Additionally, hypoproteinemia and infection are important associated factors. These findings highlight the need for targeted monitoring and intervention of high-risk patients to reduce the incidence of hyponatremia and improve clinical outcomes.

Lipocalin-2 links spinal cord injury to neurogenic lung injury through MAPK/ERK-ferroptosis signaling: Preliminary evidence for a spinal cord-lung axis.

Acute traumatic spinal cord injury (TSCI) is a life-altering yet largely preventable neurological disorder with high morbidity and mortality. Clinical registries typically gather comprehensive trauma data from living patients but often exclude autopsy data from scene-of-injury fatalities, leaving the pathology of acute TSCI underexplored. To address this gap, we reviewed autopsy records from the New York City Office of the Chief Medical Examiner spanning a 15-year period (2003-2018) to characterize the demographic, forensic, and neuropathological features of lethal acute blunt TSCI. Cases were excluded if post-injury survival occurred beyond the acute phase, if there was pre-existing spinal disease or if there was a non-blunt trauma mechanism of injury. A total of 220 cases met inclusion criteria, with a mean age of 48.37 years (range 2-96). Most spinal injuries were accidental and resulted from motor vehicle collisions, falls from standing height, or descents from height. Ethanol was present in approximately one-third of cases. Atlanto-axial dislocation occurred in 14.5% of cases, predominantly among younger individuals who were involved in motor vehicle collisions. Lethal spinal injuries were most commonly single-level fractures. Neuropathological data were available for 184 cases, of which 147 (80%) had concomitant acute spinal cord injury, with cord transections, contusions, and parenchymal softening being the most frequent. Extra-axial hemorrhages involving the epidural and subdural spaces were the most common spinal hemorrhages related to blunt trauma.

Retrospective cohort study. To assess the impact of concomitant traumatic brain injury (TBI) on demographic data, injury characteristics, management choices, access to optimal care, and clinical, neurological and functional outcomes after acute traumatic spinal cord injury (tSCI). 18 acute care centers and 12 rehabilitation facilities across Canada. Data for the study was selected from the Rick Hansen Spinal Cord Injury Registry (RHSCIR) from 2004 to 2020 in Canada. The tSCI-alone group was compared with the tSCI+TBI group regarding injury epidemiology, management, and outcomes post-tSCI. There were 966 individuals with tSCI+TBI and 3520 individuals with tSCI alone. The latter included older and more predominantly White individuals who typically sustained a less severe tSCI, less often at cervical levels due to falls. While need for surgical spinal cord decompression and spine stabilization was more common in the tSCI-alone group (p = 0.0087), mechanical ventilation was more often required in the tSCI+TBI group (p < 0.0001). In-hospital mortality rate, length of stay in the acute care and rehabilitation centers were greater in the tSCI+TBI group (p < 0.0001). However, both groups had similar changes in the motor scores from admission to discharge from the hospital (p = 0.6096). While both groups had similar frequencies of pain (p = 0.9848), spasticity was more frequent in the tSCI+TBI group (p < 0.0001). Our results underscore significant differences between the tSCI+TBI group and the SCI-alone group regarding the injury epidemiology, management and outcomes. Those results suggest that concomitant TBI should be considered a major potential confounder in future SCI research studies.

Spinal cord injury (SCI) can result in severe neurological and socio-economic outcomes, particularly in young people. Monoclonal antibodies (mAbs), due to their target specificity and multimodal mechanism of action, represent a promising strategy to mitigate neuroinflammation, limit immune cell infiltration, and promote axonal regeneration after SCI. This study aims to analyze and visualize current research trends and evaluate the preclinical and clinical efficacy and safety of mAbs for SCI. Clarivate Analytics Web of Science was used to collect all studies on mAbs in treating SCI. Two independent reviewers screened studies for relevance. CiteSpace, VOSviewer, and Prism were used for analyzing and visualizing authors, countries, keywords, timelines, and co-citation of authors and references. Key study characteristics were further analyzed. One hundred eighteen studies were included, all studies in the field. The annual publication counts remained relatively stable, reflecting sustained research interest. The United States was the most productive and linked country. Schwab was the most prolific author, exhibiting the highest collaboration strength. Keyword analysis identified nerve regeneration, neuroplasticity, and anti-inflammatory as main hotspots. mAbs directed at 25 targets demonstrated safety and feasibility in treating acute SCI, and atinumab has progressed furthest toward clinical application. Our bibliometric analysis indicates sustained and global research activity on mAbs for SCI. mAbs have demonstrated preclinical promise, but there are challenges in optimizing local delivery and minimizing side effects. Substantial translational work is required before widespread clinical application.

Acute cervical spinal cord injury (CSCI) combined with traumatic brain injury (TBI) represents a severe form of polytrauma associated with high mortality and disability. The complex clinical presentation of acute CSCI with TBI poses numerous challenges throughout the diagnostic and therapeutic process. To standardize clinical diagnostic and therapeutic workflows, the Spine Committee, Sports Medicine Branch of the Chinese Medical Doctor Association, in collaboration with a multidisciplinary team of experts, has developed this consensus based on evidence-based medicine and the modified Delphi method. By standardizing diagnostic and treatment procedures, clarifying surgical timing and sequence, optimizing anesthesia and hemodynamic management, and strengthening prevention and treatment of complications, this consensus aims to improve patient survival, promote functional recovery, and reduce complications. The ultimate goals are to enhance overall quality of care and patients' quality of life, while providing theoretical and practical foundations for future research and innovation in this field.

Retrospective cohort study. Acute cervical spinal cord injury (CSCI) leads to severe and variable neurological outcomes. Early, accurate prognosis is crucial for clinical decisions and patient counseling. This study aimed to identify key prognostic factors and develop a reliable, imaging-based nomogram for predicting neurological recovery after surgical treatment. Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu, China. In a retrospective cohort of 103 surgically treated acute traumatic CSCI patients, neurological recovery was defined as ≥1 grade improvement on the ASIA Impairment Scale at 6 months. We analyzed clinical variables and MRI parameters: intramedullary edema length (IEL), intramedullary hemorrhage length (IHL), and maximum spinal cord compression (MSCC). Independent predictors were identified via multivariate logistic regression. A nomogram was built and internally validated using the C-index, calibration curves, ROC analysis, and DCA. Neurological recovery occurred in 73 patients (70.9%). Multivariate analysis identified IEL (OR = 0.904), IHL (OR = 0.808), and MSCC (OR = 0.812) as independent predictors (all p < 0.05). IEL showed a threshold effect at 48 mm, beyond which recovery probability declined markedly. The nomogram demonstrated excellent predictive performance, with C-indices of 0.969 (modeling) and 0.936 (validation). ROC and DCA confirmed its superior accuracy and clinical utility over single parameters. IEL, IHL, and MSCC are key imaging-based predictors of recovery after acute CSCI. The developed nomogram provides an accurate, practical tool for individualized prognosis, supporting precision clinical management. MRI-based parameters including intramedullary edema length (IEL), intramedullary hemorrhage length (IHL), and maximum spinal cord compression (MSCC) were integrated into a nomogram model to predict neurological recovery in patients with acute cervical spinal cord injury.

Dihydromyricetin exerts neuroprotective effects in acute spinal cord injury by inhibiting NLRP3/Caspase-1 inflammasome through gut microbiome modeling.

Systematic review. To synthesize human and animal evidence on the potential neuroprotective effects of sex hormones in women with spinal cord injury (SCI) and in female animal models, with the aim of comparing findings across experimental and clinical studies and identifying gaps in clinical research. EMBASE, Medline, Cochrane CENTRAL, and Web of Science were searched from inception to August 22, 2025, without language restrictions. Two reviewers independently performed study screening, data extraction, and risk of bias assessment. Of 2832 screened records, 26 studies were included (23 preclinical and 3 clinical). Human evidence was scarce and primarily addressed functional recovery after acute SCI, as well as cardiovascular risk factors and bone outcomes in small cohorts of pre- and postmenopausal women with chronic SCI. Preclinical studies consistently demonstrated broad neuroprotective effects of estradiol across multiple outcomes. Inhibition of estrogen synthesis with letrozole was associated with impaired motor recovery, while the presence of intact ovaries was linked to improved sensory outcomes, supporting a protective role of endogenous estrogens. Evidence for progesterone and dehydroepiandrosterone (DHEA) was mixed, although DHEA showed promising effects in two of three studies, including improved motor and sensory recovery and tissue preservation. This review highlights the therapeutic potential of sex hormones in SCI recovery while also revealing substantial gaps in human research. Future studies should investigate endogenous hormone profiles and hormone-based interventions during the acute and subacute phases of SCI to guide therapeutic development and bridge the gap between animal models and clinical practice.

Background: Cervical spine injuries resulting from minor trauma can lead to acute spinal cord injury (SCI) with significant neurological deficits, often without overt radiographic abnormalities. Identifying early predictors of SCI severity is critical for timely intervention and better outcomes. Aim: To investigate radiological parameters—such as TPR (Torg-Pavlov Ratio) and canal diameter (CD)—and their utility in predicting the risk and severity of acute cervical SCI following minor trauma. Material and Methods: A hospital-based observational study was conducted on 150 patients presenting with minor cervical trauma. Participants were divided into SCI (n=50) and control (n=100) groups. Demographic and anthropometric data were recorded. Radiological evaluations included conventional radiography, MRI, and measurements of TPR and CD. Statistical comparisons were made to assess the predictive value of each imaging modality and correlation between parameters. Results: The majority of SCI cases occurred in males and were primarily due to falls and traffic accidents. MRI-based TPR and CD via dynamic modalities demonstrated higher sensitivity (74% and 78%) and specificity (94% and 96%) than conventional radiographs. The strongest correlation was observed between TPR (MRI) and CD (DM) in SCI patients (r=0.71), indicating their diagnostic constructive collaboration. Conclusion: MRI and dynamic canal measurements are superior in predicting acute SCI following minor cervical trauma. Early MRI screening should be incorporated in diagnostic algorithms to enable accurate assessment and prevent secondary neurological deterioration.

Acute spinal cord injury (SCI) remains a life-threatening condition associated with substantial morbidity, mortality, and long-term disability. Despite the advances in trauma systems, surgical techniques, and critical care, the optimal management strategies for acute SCI continue to improve, and clinical practice remains heterogeneous across institutions. The pathophysiology of acute SCI involves an irreversible primary mechanical insult, followed by a dynamic secondary injury cascade characterized by ischemia, inflammation, excitotoxicity, and apoptotic cell death. Early neurological assessments using standardized clinical scales, along with advanced imaging, particularly magnetic resonance imaging, play a crucial role in injury characterization, prognostication, and treatment planning. The contemporary acute management of this condition focuses on the prevention of secondary injury through hemodynamic optimization, early stabilization, and timely surgical decompression. Growing evidence has supported early decompressive surgery, particularly within 24 hours after injury, to improve neurological outcomes. However, the optimal timing, surgical strategy, and patient selection process remain areas of ongoing debate. Pharmacologic neuroprotection, including high-dose methylprednisolone, has become increasingly controversial, while novel agents such as riluzole and minocycline have shown promising but inconclusive results in clinical trials. Beyond conventional management, novel therapeutic approaches-including cell-based therapies, biologics targeting neuroregeneration, neuromodulation, and advanced rehabilitation technologies-have been actively investigated. In parallel, advances in artificial intelligence and predictive modeling are beginning to influence early prognostication and individualized treatment strategies. This review aimed to synthesize current evidence regarding the assessment and management of acute SCI, highlight key controversies, and discuss novel therapies that may shape future clinical practice.

Timing of thromboprophylaxis in acute spinal cord injury patients: a TQIP study in 15,960 patients.

We characterized, in patients with severe acute traumatic spinal cord injuries, the relationships between intraoperative spinal cord blood flow (SCBF) and postoperative injury-site metabolism and physiology, preoperative magnetic resonance imaging (MRI) features, and neurological outcome. Twenty-six adults with severe, acute traumatic spinal cord injuries (American Spinal Injury Association Impairment Scale, grades A-C) had surgery within 72 h of injury. All had preoperative spine MRI and intraoperative laser speckle contrast imaging of SCBF. For four days after operation, we monitored fromthe injury site, intraspinal pressure (ISP), and spinal cord perfusion pressure (SCPP) as well as tissue metabolism with surface microdialysis. We observed three intraoperative SCBF patterns: necrosis-penumbra SCBF (SCBF-necr) in 34.6% of patients, patchy-perfusion SCBF (SCBF-patchy) in 38.5% of patients, and hyperperfusion SCBF (SCBF-hyper) in 26.9% of patients. On preoperative MRI, SCBF-necr was associated with higher Brain and Spinal Injury Center MRIscore versus SCBF-patchy or SCBF-hyper (median 4 vs. 2 or 2.5). SCBF-necr was associated with higher postoperative ISP, lower postoperative SCPP, and more deranged postoperative injury-site metabolism (lower glucose; higher lactate, glutamate, and glycerol) than SCBF-patchy or SCBF-hyper, with little difference between SCBF-patchy and SCBF-hyper. Machine learning analysis of physiological-metabolic data considered as seven-dimensional vectors (ISP, SCPP, glucose, pyruvate, lactate, glutamate, and glycerol) accurately distinguished between the three SCBF patterns with an area under the curve of 0.85-0.95. The seven-dimensional physiological-metabolic vectors were segregated as SCBF-necr, SCBF-patchy, and SCBF-hyper in Kohonen self-organizing maps. SCBF-patchy was associated with greater improvement in motor score than SCBF-necr or SCBF-hyper (35.3 vs. 5.2 or 2.2), independent of admission American Spinal Injury Association Impairment Scale grade. Our findings challenge the prevailing concept in the field, derived from animal experiments, that spinal cord injury causes necrosis at the injury site with surrounding penumbra. In humans, spinal cord injury causes three abnormal SCBF patterns detected intraoperatively, with distinct postoperative physiological-metabolic signatures, preoperative MRI characteristics, and neurological outcomes.

Delta ROX index as a dynamic predictor of respiratory exacerbation in acute cervical spinal cord injury: A retrospective study.

Health care advancements lead to increased survival after severe cervical spinal cord injury (cSCI). Already in the acute phase, the severity of the injury with its magnitude of expected medical complications and the devastating functional prognosis, can confront the patient and its medical team with pressing medical-ethical dilemmas regarding the (dis)continuation of treatment and/or end-of-life decisions. In this case series we discuss four patients with severe cSCI that were admitted to the Maastricht University Medical Center, the Netherlands, in 2024, and in whom questions regarding end-of-life decision arose within a couple of days. While the neurological presentations were very similar, the personal wishes, beliefs and psychosocial situations varied greatly. The process of shared decision making, with multiple meetings with the treatment team, the patients (when possible) and their significant others, lead to the formulation of personalized treatment plans regarding discontinuation of treatment and/or end-of-life decisions. This case series shows that end-of-life decisions in patients with cSCI are complex and multifactorial. A biopsychosocial approach is needed to tailor a personalized treatment plan that includes medical, prognostic, personal and external factors. An interdisciplinary team that actively involves the patient and its significant others, facilitates the process of shared decision making, which may also have a beneficial effect on the grieving process for the people left behind.