A Review on the Etiology and Management of Pediatric Traumatic Spinal Cord Injuries.
ABSTRACT: Context:Pediatric traumatic spinal cord injury (SCI) is an uncommon presentation in the emergency department. Severe injuries are associated with devastating outcomes and complications, resulting in high costs to both the society and the economic system. Evidence acquisition:The data on pediatric traumatic spinal cord injuries has been narratively reviewed. Results:Pediatric SCI is a life-threatening emergency leading to serious outcomes and high mortality in children if not managed promptly. Pediatric SCI can impose many challenges to neurosurgeons and caregivers because of the lack of large studies with high evidence level and specific guidelines in terms of diagnosis, initial management and of in-hospital treatment options. Several novel potential treatment options for SCI have been developed and are currently under investigation. However, research studies into this field have been limited by the ethical and methodological challenges. Conclusion:Future research is needed to investigate the safety and efficacy of the recent uprising neurodegenerative techniques in SCI population. Owing to the current limitations, there is a need to develop novel trial methodologies that can overcome the current methodological and ethical limitations.
Project description:<h4>Background</h4>The study aimed to characterize trends in incidence, etiology, fracture types, surgical procedures, complications, and concurrent injuries associated with traumatic pediatric cervical fracture using a nationwide database.<h4>Methods</h4>The Kids' Inpatient Database (KID) was queried. Trauma cases from 2003 to 2012 were identified, and cervical fracture patients were isolated. Demographics, etiologies, fracture levels, procedures, complications, and concurrent injuries were assessed. The <i>t</i>-tests elucidated significance for continuous variables, and ?<sup>2</sup> for categoric values. Logistic regressions identified predictors of spinal cord injury (SCI), surgery, any complication, and mortality. Level of significance was <i>P</i> < .05.<h4>Results</h4>A total of 11?196 fracture patients were isolated (age, 16.63 years; male, 65.7%; white, 65.4%; adolescent, 55.4%). Incidence significantly increased since 2003 (2003 vs 2012, 2.39% vs 3.12%, respectively), as did Charlson Comorbidity Index (CCI; 2003 vs 2012, 0.2012 vs 0.4408, respectively). Most common etiology was motor vehicle accidents (50.5%). Infants and children frequently fractured at C2 (closed: 43.1%, 32.9%); adolescents and young adults frequently fractured at C7 (closed: 23.9%, 26.5%). Upper cervical SCI was less common (5.8%) than lower cervical SCI (10.9%). Lower cervical unspecified-SCI, anterior cord syndrome, and other specified SCIs significantly decreased since 2003. Complications were common (acute respiratory distress syndrome, 7.8%; anemia, 6.7%; shock, 3.0%; and mortality, 4.2%), with bowel complications, cauda equina, anemia, and shock rates significantly increasing since 2003. Concurrent injuries were common (15.2% ribs; 14.4% skull; 7.1% pelvis) and have significantly increased since 2003. Predictors of SCI included sports injury and CCI. Predictors of surgery included falls, sports injuries, CCI, length of stay, and SCI. CCI, SCIs, and concurrent injuries were predictors of any complication and mortality, all (<i>P</i> < .001).<h4>Conclusions</h4>Since 2003, incidence, complications, concurrent injuries, and fusions have increased. CCI, SCI, falls, and sports injuries were significant predictors of surgical intervention. Decreased mortality and SCI rates may indicate improving emergency medical services and management guidelines.<h4>Level of evidence</h4>III.<h4>Clinical relevance</h4>Clinicians should be aware of increased case complexity in the onset of added perioperative complications and concurrent injuries. Cervical fractures resultant of sports injuries should be scrutinized for concurrent SCIs.
Project description:Spinal cord injuries (SCI) can result in devastating paralysis, for which there is currently no robustly efficacious neuroprotective/neuroregenerative treatment. When the spinal cord is subjected to a traumatic injury, the local vasculature is disrupted and the blood-spinal cord barrier is compromised. Subsequent inflammation and ischemia may then contribute to further secondary damage, exacerbating neurological deficits. Therefore, understanding the vascular response to SCI and the molecular elements that regulate angiogenesis has considerable relevance from a therapeutic standpoint. In this paper, we review the nature of vascular damage after traumatic SCI and what is known about the role that angiogenic proteins-angiopoietin 1 (Ang1), angiopoietin 2 (Ang2) and angiogenin-may play in the subsequent response. To this, we add recent work that we have conducted in measuring these proteins in the cerebrospinal fluid (CSF) and serum after acute SCI in human patients. Intrathecal catheters were installed in 15 acute SCI patients within 48 h of injury. CSF and serum samples were collected over the following 3-5 days and analysed for Ang1, Ang2 and angiogenin protein levels using a standard ELISA technique. This represents the first description of the endogenous expression of these proteins in an acute human SCI setting.
Project description:BACKGROUND:A few reliable national data concerning the etiology of non-traumatic spinal cord injury (SCI) in sub-Sahara Africa exists, mainly because of the limitations of diagnostic imaging. These are both expensive and mostly unavailable in several resource-limited settings. Only a few studies have employed the magnetic resonance imaging (MRI) in documenting non-traumatic SCI and most of these studies are from South Africa. We sought to describe the clinical presentation, MRI radiological patterns, and one-year survival among subjects with non-traumatic SCI in Uganda. METHODS:We enrolled a prospective cohort of 103 participants with non-traumatic SCI at Mulago National Referral Hospital Kampala, Uganda in 2013-2015. Participants received standard of care management, with surgical intervention as needed, with one-year follow up. Data were analyzed using Descriptive statistics. RESULTS:In 103 participants with non-traumatic SCI, the median (IQR) age was 37 (18, 85) years and 25% of the participants were HIV-infected. Paraplegia/paraparesis was the most common clinical presentation in 70% (n?=?72). Severe disease was present in 82% (n?=?85) as per American Spinal Injury Association (ASIA) scale A-C. On MRI, 50% had extradural lesions. However, bone lesions accounted for only 75% of all the extradural lesions. More than 60% of the patients had lesions that could only be diagnosed on MRI. Deaths occurred in 42% (n?=?44) of participants, with the highest mortality among those with extradural lesions (60%). CONCLUSION:The mortality following non-traumatic spinal cord injuries in Uganda is high. We demonstrated an equal distribution between extradural and intradural lesions, which differs from the historical predominance of extradural lesions. Increased utilization of MRI particularly among young age groups is needed to make a diagnosis.
Project description:Traumatic injuries to the brain and spinal cord affect a large percentage of the world's population. However, there are currently no effective treatments for these central nervous system (CNS) injuries. In our study, we evaluated the neuroprotective role of functionalized multi-walled carbon nanotubes (MWCNTs) carrying brain derived neurotrophic factor (BNDF), nogo-66 receptor (NgR) and Ras homolog gene family member A (RhoA) in spinal cord injury (SCI). Our results showed that transfection into rat cortical neurons with BDNF-DNA significantly elevated the expression of BDNF both in vitro and in vivo. Meanwhile, transfection with NgR-siRNA and RhoA-siRNA resulted in an obvious down-regulation of NgR and RhoA in neuron cells and in injured spinal cords. In addition, the functionalized MWCNTs carrying BDNF-DNA, NgR-siRNA and RhoA-siRNA exhibited remarkable therapeutic effects on injured spinal cord. Taken together, our study demonstrates that functionalized MWCNTs have a potential therapeutic application on repair and regeneration of the CNS.
Project description:Excessive glutamate release following traumatic spinal cord injury (SCI) has been associated with exacerbating the extent of SCI. However, the mechanism behind sustained high levels of extracellular glutamate is unclear. Spinal cord segments mounted in a sucrose double gap recording chamber are an established model for traumatic spinal cord injury. We have developed a method to record, with micro-scale printed glutamate biosensors, glutamate release from ex vivo rat spinal cord segments following injury. This protocol would work equally well for similar glutamate biosensors.
Project description:Objective:Traumatic spinal cord injury (SCI) is considered one of the most devastating injuries leading to neuronal disruption. Olfactory ensheathing cells (OECs) and minocycline have been shown to promote locomotor function after spinal cord injury. In this study, we have tested the efficacy of combined treatment with minocycline and OECs after contusive spinal cord injury. Materials and Methods:In this experimental study, adult female Wistar rats were randomly divided into five groups. Rats received an intraperitoneal injection of minocycline immediately after SCI, and then 24 hours after the injury. Transplantations were performed 7 days after the injury. Functional recovery was evaluated using the Basso, Beattie and Bresnahan scale (BBB). After that, the animals were sacrificed, and T11 segment of the spinal cord was removed after 5 weeks, and then used for histopathological, immunohistochemical, and biochemical assessments. Western blot analysis was applied to determine the protein expression of tumor necrosis factor alpha (TNF-?), interleukin 1 beta (IL1?) and caspase3. Results:The results of this study showed that the combination of OECs graft and minocycline reduced the functional deficits and diminished cavitation and astrogliosis in spinal tissue. The analysis of protein expression by western blotting revealed that minocycline treatment along with OECs transplantation further decreased the level of IL-1?, TNF-?, caspase-3, and the oxidative stress as compared with when minocycline or OECs transplantation was used alone. Conclusion:The combinatory treatment with OECs graft and minocycline induced a more effective response to the repair of spinal cord injury, and it is considered a therapeutic potential for the treatment of SCI.
Project description:Spinal cord injuries (SCIs) are debilitating conditions for which no effective treatment currently exists. The damage of neural tissue causes disruption of neural tracts and neuron loss in the spinal cord. Stem cell replacement offers a solution for SCI treatment by providing a source of therapeutic cells for neural function restoration. Induced pluripotent stem cells (iPSCs) have been investigated as a potential type of stem cell for such therapies. Transplantation of iPSCs has been shown to be effective in restoring function after SCIs in animal models while they circumvent ethical and immunological concerns produced by other stem cell types. Another approach for the treatment of SCI involves the graft of a bioscaffold at the site of injury to create a microenvironment that enhances cellular viability and guides the growing axons. Studies suggest that a combination of these two treatment methods could have a synergistic effect on functional recovery post-neural injury. While much progress has been made, more research is needed before clinical trials are possible. This review highlights recent advancements using iPSCs and bioscaffolds for treatment of SCI.
Project description:Brain and spinal cord are implicated in incidences of two of the most severe injuries of central nervous system (CNS). Traumatic brain injury (TBI) is a devastating neurological deficit involving primary and secondary injury cascades. The primary and secondary mechanisms include complex consequences of activation of proinflammatory cytokines, cerebral edema, upregulation of NF-κ β, disruption of blood-brain barrier (BBB), and oxidative stress. Spinal cord injury (SCI) includes primary and secondary injury cascades. Primary injury leads to secondary injury in which generation of free radicals and oxidative or nitrative damage play an important pathophysiological role. The indoleamine melatonin is a hormone secreted or synthesized by pineal gland in the brain which helps to regulate sleep and wake cycle. Melatonin has been shown to be a versatile hormone having antioxidative, antiapoptotic, neuroprotective, and anti-inflammatory properties. It has a special characteristic of crossing BBB. Melatonin has neuroprotective role in the injured part of the CNS after TBI and SCI. A number of studies have successfully shown its therapeutic value as a neuroprotective agent in the treatment of neurodegenerative diseases. Here in this review we have compiled the literature supporting consequences of CNS injuries, TBI and SCI, and the protective role of melatonin in it.
Project description:Approximately half of traumatic spinal cord injury (SCI) cases affect cervical regions, resulting in chronic respiratory compromise. The majority of these injuries affect midcervical levels, the location of phrenic motor neurons (PMNs) that innervate the diaphragm. A valuable opportunity exists following SCI for preventing PMN loss that occurs during secondary degeneration. One of the primary causes of secondary injury is excitotoxicity due to dysregulation of extracellular glutamate homeostasis. Astrocytes express glutamate transporter 1 (GLT1), which is responsible for the majority of CNS glutamate clearance. Given our observations of GLT1 dysfunction post-SCI, we evaluated intraspinal transplantation of Glial-Restricted Precursors (GRPs)--a class of lineage-restricted astrocyte progenitors--into ventral horn following cervical hemicontusion as a novel strategy for reconstituting GLT1 function, preventing excitotoxicity and protecting PMNs in the acutely injured spinal cord. We find that unmodified transplants express low levels of GLT1 in the injured spinal cord. To enhance their therapeutic properties, we engineered GRPs with AAV8 to overexpress GLT1 only in astrocytes using the GFA2 promoter, resulting in significantly increased GLT1 protein expression and functional glutamate uptake following astrocyte differentiation in vitro and after transplantation into C4 hemicontusion. Compared to medium-only control and unmodified GRPs, GLT1-overexpressing transplants reduced lesion size, diaphragm denervation and diaphragm dysfunction. Our findings demonstrate transplantation-based replacement of astrocyte GLT1 is a promising approach for SCI.
Project description:Spinal cord injury (SCI) is currently incurable since treatments applied to clinic are limited to minimizing secondary complications and the mechanisms of injury-induced spinal cord damage are poorly understood. Zbtb38, also called CIBZ, is highly expressed in spinal cord and it functions as a negative regulator in SCI-induced apoptosis. We show here that Zbtb38 is downregulated under endoplasmic reticulum (ER) stress, which promotes ER stress-associated apoptosis in human bone marrow neuroblastoma cells. In the traumatic SCI mice, ER stress presented in injured spinal cord induced repression of Zbtb38 expression and triggered Zbtb38-mediated apoptosis. ChIP-QPCR analysis revealed that ATF4, an ER-stress inducible transcription factor, directly activated Zbtb38 transcription by binding to the Zbtb38 promoter. However, this binding was significantly reduced following SCI, leading to a sharp decrease in Zbtb38 expression. Restoring Zbtb38 function in injured spinal cord by injection of lentivirus containing Zbtb38 into SCI mice, significantly alleviated secondary damage of spinal cord with decreased ER stress-associated apoptosis and partially recovered spinal cord functions. These findings demonstrate that restoration of Zbtb38 expression can reduce secondary tissue damage after SCI, and suggest that a therapeutic strategy for targeting Zbtb38 may promote functional recovery of spinal cord for patients with SCI.