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Ultrasound technology can provide high-resolution imaging of blood flow following spinal cord injury (SCI). Blood flow imaging may improve critical care management of SCI, yet its duration is limited clinically by the amount of contrast agent injection required for high-resolution, continuous monitoring. In this study, we aim to establish non-contrast ultrasound as a clinically translatable imaging technique for spinal cord blood flow via comparison to contrast-based methods and by measuring the spatial distribution of blood flow after SCI. A rodent model of contusion SCI at the T12 spinal level was carried out using three different impact forces. We compared images of spinal cord blood flow taken using both non-contrast and contrast-enhanced ultrasound. Subsequently, we processed the images as a function of distance from injury, yielding the distribution of blood flow through space after SCI, and found the following. (1) Both non-contrast and contrast-enhanced imaging methods resulted in similar blood flow distributions (Spearman's ρ = 0.55, p < 0.0001). (2) We found an area of decreased flow at the injury epicenter, or umbra (p < 0.0001). Unexpectedly, we found increased flow at the periphery, or penumbra (rostral, p < 0.05; caudal, p < 0.01), following SCI. However, distal flow remained unchanged, in what is presumably unaffected tissue. (3) Finally, tracking blood flow in the injury zones over time revealed interesting dynamic changes. After an initial decrease, blood flow in the penumbra increased during the first 10 min after injury, while blood flow in the umbra and distal tissue remained constant over time. These results demonstrate the viability of non-contrast ultrasound as a clinical monitoring tool. Furthermore, our surprising observations of increased flow in the injury periphery pose interesting new questions about how the spinal cord vasculature reacts to SCI, with potentially increased significance of the penumbra. [ABSTRACT FROM AUTHOR]

Acute spinal cord injury (SCI) requires prompt diagnosis and intervention to minimize the risk of permanent neurologic deficit. Presently, SCI diagnosis and interventional planning rely on magnetic resonance imaging (MRI), which is not always available or feasible for severely injured patients. Detection of disease-specific biomarkers in biofluids via liquid biopsy may provide a more accessible and objective means of evaluating patients with suspected SCI. Cell-free DNA, which has been used for diagnosing and monitoring oncologic disease, may detect damage to spinal cord neurons via tissue-specific methylation patterns. Other types of biomarkers, including proteins and RNA species, have also been found to reflect neuronal injury and may be included as part of a multi-analyte assay to improve liquid biopsy performance. The feasibility of implementing liquid biopsy into current practices of SCI management is supported by the relative ease of blood sample collection as well as recent advancements in droplet digital polymerase chain reaction technology. In this review, we detail the current landscape of biofluid biomarkers for acute SCI and propose a framework for the incorporation of a putative blood test into the clinical management of SCI. [ABSTRACT FROM AUTHOR]

The secondary phase of spinal cord injury (SCI) is characterized by ischemic injury. Spinal cord perfusion pressure (SCPP), calculated as the difference between mean arterial pressure (MAP) and intrathecal pressure (ITP), has arisen as a therapeutic target for improving outcomes. Cerebrospinal fluid drainage (CSFD) may reduce ITP and thereby increase SCPP. Randomized controlled trial to evaluate the safety and feasibility of CSFD to improve SCPP and outcomes after acute SCI. Inclusion criteria included acute cervical SCI within 24 hours of presentation. All patients received lumbar drain placement and appropriate decompressive surgery. Patients randomized to the control group received MAP elevation only. Patients in the experimental group received MAP elevation and CSFD to achieve ITP <10 mmHg for 5 days. ITP and MAP were recorded hourly. Adverse events were documented and patients underwent functional assessments at enrollment, 72 hours, 90 days, and 180 days post-injury. Eleven patients were enrolled; 4 were randomized to receive CSFD. CSFD patients had a mean ITP of 5.3 ± 2.5 mmHg versus. 15 ± 3.0 mmHg in the control group. SCPP improved significantly, from 77 ± 4.5 mmHg in the control group to 101 ± 6.3 mmHg in the CSFD group (P < 0.01). Total motor scores improved by 15 ± 8.4 and 57 ± 24 points in the control and CSFD groups, respectively, over 180 days. No adverse events were attributable to CSFD. CSFD is a safe, effective mechanism for reducing ITP and improving SCPP in the acute period post-SCI. The favorable safety profile and preliminary efficacy should help drive recruitment in future studies. [ABSTRACT FROM AUTHOR]

Patients with acute cervical spinal cord injury present complex clinical challenges. These injuries may result in motor and sensory deficits and also in cardiovascular and respiratory perturbations. Increased attention to critical care support has led to improved survival and recovery in many patients. The methods and technology used to diagnose and classify these injuries as well as medical and surgical treatments have evolved significantly in recent decades. We review important aspects of the diagnosis and acute care of patients with traumatic cervical spinal cord injuries, emphasising the recent evidence. [ABSTRACT FROM AUTHOR]

Introduction: Spinal cord injury is a complex result of primary mechanical damage and the secondary vascular compromise and inflammatory reactions. Depending on timing, different treatment modalities may have various effects. Conclusions: We review the latest advances in terms of non-pharmacological experimental treatments. [ABSTRACT FROM AUTHOR]

Introduction: Occult spinal cord injury should be suspected based not only on the mechanism of trauma but also on the age of the patient. The pediatric spine has unique biomechanical and anatomical properties that must be considered carefully when evaluating spinal cord trauma. For instance, the hypermobility and elasticity of the spinal column in children often lead to self-reducing injuries that can mask spinal cord injury. Case illustration: We present the case of a 22-month-old male patient who was found to have ligamentous injury detected by magnetic resonance imaging (MRI) in the upper cervical spine but missed by MRI in the lower thoracic spine. Furthermore, there was no spinal cord injury in the upper cervical spine, but indeed a serious insult in the thoracic region. Since the advent of MRI, spinal cord injury without radiographic abnormality (SCIWORA) has become increasingly rare but not altogether extinct. Conclusions: We present a noteworthy example of the inadequacy of MRI in revealing SCIWORA, a term that is antiquated as we combine the latest imaging techniques with a better understanding of the biomechanics of trauma and spine injury. Based on the literature and our case illustration, we believe that the biomechanics of the pediatric spine must be considered when children who may have sustained a SCIWORA are examined. [ABSTRACT FROM AUTHOR]

Introduction: Spinal cord injury is a complex cascade of reactions secondary to the initial mechanical trauma that puts into action the innate properties of the injured cells, the circulatory, inflammatory, and chemical status around them, into a non-permissive and destructive environment for neuronal function and regeneration. Priming means putting a cell, in a state of 'arousal' towards better function. Priming can be mechanical as trauma is known to enhance activity in cells. Materials and methods: A comprehensive review of the literature was performed to better understand the possible chemical primers used for spinal cord injuries. Conclusions: Taken together, many studies have shown various promising results using the substances outlined herein for treating SCI. [ABSTRACT FROM AUTHOR]

Introduction: There are significant differences between the propensity of neural regeneration between the central and peripheral nervous systems. Materials and methods: Following a review of the literature, we describe the role of growth factors, guiding factors, and neurite outgrowth inhibitors in the physiology and development of the nervous system as well as the pathophysiology of the spinal cord. We also detail their therapeutic role as well as those of other chemical substances that have recently been found to modify regrowth following cord injury. Conclusions: Multiple factors appear to have promising futures for the possibility of improving spinal cord injury following injury. [ABSTRACT FROM AUTHOR]

Background: Experimental approaches to limit the spinal cord injury and to promote neurite outgrowth and improved function from a spinal cord injury have exploded in recent decades. Due to the cavitation resulting after a spinal cord injury, newer important treatment strategies have consisted of implanting scaffolds with or without cellular transplants. There are various scaffolds, as well as various different cellular transplants including stem cells at different levels of differentiation, Schwann cells and peripheral nerve implants, that have been reviewed. Also, attention has been given to different re-implantation techniques in avulsion injuries. Methods: Using standard search engines, this literature is reviewed. Conclusion: Cellular and paracellular transplantation for application to spinal cord injury offers promising results for those patients with spinal cord pathology. [ABSTRACT FROM AUTHOR]

Tethered cord syndrome (TCS) occurs as a constellation of neurologic signs and symptoms resulting from longitudinal traction on the spinal cord between fixed points. This condition involves a tug-of-war between ascent and inhibition of ascent of intrathecal nervous tissue within the vertebral canal during growth. Causes include thickened filum terminale, myelomeningocele, split cord malformation, and previous intradural surgery. Patients report low back, lower extremity, and perineal pain; lower extremity sensory and motor deficits; urinary and bowel incontinence; and sexual dysfunction. When not treated early or adequately, TCS can lead to neurologic devastation. [ABSTRACT FROM AUTHOR]

Blunt cerebrovascular injury (BCVI), defined as blunt traumatic injury to the carotid or vertebral arteries, is associated with significant risk of stroke and mortality. Cervical spine trauma is a recognized risk factor for BCVI. The objective of this study was to identify significant predictors of BCVI and its sequelae in patients with known cervical spine injury. Patients from 2007 to 2018 with blunt cervical spine injury diagnoses were identified in the National Trauma Data Bank. Multivariable logistic regression models were used to identify patient baseline and injury characteristics associated with BCVI, stroke, and mortality. We identified 229,254 patients with cervical spine injury due to blunt trauma. The overall rate of BCVI was 1.6%. Factors associated with BCVI in patients with cervical spine injury included lower Glasgow Coma Scale, motor vehicle crash, higher Injury Severity Score, concomitant traumatic brain or spinal cord injury, and current smoking status. BCVI was a strong predictor of stroke (odds ratio, 8.2; 95% confidence interval, 5.7–12.0) and was associated with mortality (odds ratio, 1.7; 95% confidence interval, 1.3–2.2). Stroke occurred in 3.3% of patients with BCVI versus 0.02% for patients without BCVI. While BCVI is rare following cervical spine injury due to blunt trauma, it is a significant predictor of stroke and mortality. The risk factors associated with BCVI, stroke, and mortality identified here should be used in the development of more effective predictive tools to improve care. [ABSTRACT FROM AUTHOR]

Prompt surgical decompression after traumatic spinal cord injury (TSCI) may be associated with improved sensorimotor outcomes. Delays in presentation may prevent timely decompression after TSCI. To systematically review existing studies investigating delays in presentation after TSCI in low- and middle-income countries (LMICs) and high-income countries (HICs). A systematic review was conducted and studies featuring quantitative or qualitative data on prehospital delays in TSCI presentation were included. Studies lacking quantitative or qualitative data on prehospital delays in TSCI presentation, case reports or series with <5 patients, review articles, or animal studies were excluded from our analysis. After exclusion criteria were applied, 24 studies were retained, most of which were retrospective. Eleven studies were from LMICs and 13 were from HICs. Patients with TSCI in LMICs were younger than those in HICs, and most patients were male in both groups. A greater proportion of patients with TSCI in studies from LMICs presented >24 hours after injury (HIC average proportion, 12.0%; LMIC average proportion, 49.9%; P = 0.01). Financial barriers, lack of patient awareness and education, and prehospital transportation barriers were more often cited as reasons for delays in LMICs than in HICs, with prehospital transportation barriers cited as a reason for delay by every LMIC study included in this review. Disparities in prehospital infrastructure between HICs and LMICs subject more patients in LMICs to increased delays in presentation to care. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a devastating condition that affects about 17,000 individuals every year in the United States, with approximately 294,000 people living with the ramifications of the initial injury. After the initial primary injury, SCI has a secondary phase during which the spinal cord sustains further injury due to ischemia, excitotoxicity, immune-mediated damage, mitochondrial dysfunction, apoptosis, and oxidative stress. The multifaceted injury progression process requires a sophisticated injury-monitoring technique for an accurate assessment of SCI patients. In this narrative review, we discuss SCI monitoring modalities, including pressure probes and catheters, micro dialysis, electrophysiologic measures, biomarkers, and imaging studies. The optimal next-generation injury monitoring setup should include multiple modalities and should integrate the data to produce a final simplified assessment of the injury and determine markers of intervention to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Abstract Severe spinal cord injury leads to hemorrhage, edema and elevated tissue pressures that propagate ischemia. Liquefactive necrosis of damaged tissue eventually results in chronic cavities due to a wound healing process lacking adhesive contractile cells. Biomaterials can potently influence wound healing responses. Internal decompression (ID) refers to pial opening, allowing spontaneous extrusion and irrigation of fluid necrotic debris relieving pressure and resulting in a space for biomaterial scaffold insertion. After thoracic contusions, rats were randomized to: contusion only, contusion + ID and contusion + ID + PLGA-PLL scaffold implantation, to test for neuroprotection and endogenous repair over 3 months. ID alone reduced inflammatory activity, cavity volume, and increased tissue sparing. Scaffold biodegradation produced delayed ingrowth of inflammatory and other cells resulting in endogenously derived laminin-rich tissue, marked reduction in cavitation and presence of tissue remodeling macrophages. Extensive recruitment of Schwann cells into adjacent spared white matter occurred, greatest in scaffold-implanted animals. Despite tissue preservation with myelin repair, no groups differed significantly in open field locomotion. However, across all rats, spared epicenter tissue and locomotor outcomes were correlated. Scaffold-implanted animals showed no obvious toxicity. To study the clinical feasibility, timing and indications for scaffold implantation, Göttingen minipigs underwent ID and were implanted with scaffolds 4, 6, and 24 h after T10 contusion. High intra-spinal tissue pressures fell to pre-injury levels after ID and scaffold implantation. Extrusion of necrotic debris left sufficient space for a sized scaffold. These results provided the preclinical rationale for a current clinical study of biomaterial scaffold implantation into the human injured spinal cord. Graphical abstract The Neuro-Spinal Scaffold promotes new tissue formation. Following contusion, hemorrhagic transformation of grey matter and extension of tissue loss due to secondary injury further destroys grey and white matter, culminating in the formation of a cavity spanned by thin trabeculae. This is a failure of wound healing. Our paradigm proposes that debridement of fluid necro-hemorrhagic debris creates a space into which a biocompatible PLGA-PLL scaffold may be inserted and is subsequently replaced by tissue, reducing or preventing cavitation. This new tissue supported in-migration of Schwann cells, fibroblasts, macrophages, NG2+ cells, axonal growth and myelination. Image 1 [ABSTRACT FROM AUTHOR]