A 72-h sedated porcine model of traumatic spinal cord injury.

Introduction: There is an increasing focus on the prevention of secondary injuries following traumatic spinal cord injury (TSCI), especially through improvement of spinal cord perfusion and immunological modulation. Such therapeutic strategies require translational and controlled animal models of disease progression of the acute phases of human TSCI. Research question: Is it possible to establish a 72-h sedated porcine model of incomplete thoracic TSCI, enabling controlled use of continuous, invasive, and non-invasive modalities during the entire sub-acute phase of TSCI? Material and methods: A sham-controlled trial was conducted to establish the model, and 10 animals were assigned to either sham or TSCI. All animals underwent a laminectomy, and animals in the TSCI group were subjected to a weight-drop injury. Animals were then kept sedated for 72 h. The amount of injury was assessed by ex-vivo measures MRI-based fiber tractography, histology and immunohistochemistry. Results: In all animals, we were successful in maintaining sedation for 72 h without comprising vital physiological parameters. The MRI-based fiber tractography showed that all TSCI animals revealed a break in the integrity of spinal neurons, whereas histology demonstrated no transversal sections of the spine with complete injury. Notably, some animals displayed signs of secondary ischemic tissue in the cranial and caudal sections. Discussion and conclusions: This study succeeded in producing a porcine model of incomplete TSCI, which was physiologically stable up to 72 h. We believe that this TSCI model will constitute a potential translational model to study the pathophysiology secondary to TSCI in humans.

Field conditions is a risk factor for traumatic injury in youth football-A joint venture of medicine and hydrology.

INTRODUCTION: The risk of traumatic injury in football has been suggested to be affected by field conditions. This study, therefore, aimed to investigate whether near surface water content of the football field, influenced the risk of traumatic injuries during a youth football tournament. METHODS: At Dana Cup, an annual international youth football tournament in Denmark, all injuries were registered and classified at the on-site emergency department over 7 years. The incidence rate of traumatic injury was computed. Meteorological data and soil characteristics were used to simulate near surface water content of the playing fields. The incidence rate ratio (IRR) between water content and injury incidence rate was analyzed using a multivariate Poisson regression, controlling for tournament stage and demographical parameters. RESULTS: About 2704 injuries were recorded corresponding to a risk time of 284 905 player hours. An inverse relation between water contents and the incidence rate of traumatic injury was found (IRR = 0.24 95% CI 0.1-0.7, p = 0.01). The incidence rate of traumatic injury increased with advancing tournament stage, that is, for the finals (IRR = 4.30 95% CI 2.8-6.6, p < 0.001). Also we found an interaction between dry fields and the final stage of tournament, further exacerbating this effect. CONCLUSIONS: Our data suggest that the incidence rate of traumatic injury is increased with drier field conditions and advanced tournament stages.

Incidence and risk factors for incidental durotomy in spine surgery for lumbar stenosis and herniated disc.

PURPOSE: Incidental durotomy (ID) is one of the most common complications in degenerative surgery. Due to the negative consequences of ID, knowledge about incidence and risk factors is warranted. METHODS: A total of 1,139 surgical procedures for lumbar spinal stenosis (LS) and lumbar herniated disc (LDH) were included from the spine surgery database: DaneSpine. Uni- and multivariate analyses were performed for the assessment of possible risk factors. RESULTS: ID occurred in 10.4% of the surgical procedures. A multivariate regression analysis revealed an increased relative risk of ID by 2% per year of age, 58% by revision surgery, and 55% by decompression on multiple levels. CONCLUSION: In our single-centre cohort study, one in ten patients experiences an ID. Increasing age, revision surgery and decompression of multiple levels are risk factors of ID in degenerative surgery of the lumbar spine.

Diffusional kurtosis imaging as a possible prognostic marker of cervical incomplete spinal cord injury outcome: a prospective pilot study.

BACKGROUND: Spinal cord injury (SCI) is associated with substantial chronic morbidity and mortality. Routine imaging techniques such as T1- and T2-weighted magnetic resonance imaging (MRI) are not effective in predicting neurological deficiency grade or outcome. Diffusional kurtosis imaging (DKI) is an MR imaging technique that provides microstructural information about biological tissue. There are no longitudinal prospective studies assessing DKI metrics in acute traumatic SCI. Therefore, the purpose of this study was to establish a DKI protocol for acute SCI and correlate the DKI metrics to the functional neurological outcome of the patients. METHODS: Eight consecutive SCI patients referred to our institution with cervical SCI were included in the study. An acute diagnostic MRI scan was supplemented with a novel fast, mean kurtosis DKI protocol, which describes the average deviation from Gaussian diffusional along nine different directions. Mean kurtosis values were measured at the injury site and normalized to the mean kurtosis values of a non-injured site. At discharge form specialized rehabilitation, patients were evaluated using the Spinal Cord Independence Measure-III (SCIM-III). The DKI metrics and SCIM-III were analysed using Spearman's rank correlation. RESULTS: This pilot study found a significant correlation between decreasing mean kurtosis values at the injury site of the spinal cord and higher grade of disability measured by the SCIM-III (p = 0.002). CONCLUSION: This pilot study found that DKI may be a valuable tool as a prognostic marker in the acute phase of SCI.

A review of spinal cord perfusion pressure guided interventions in traumatic spinal cord injury.

PURPOSE: To evaluate the causality between interventions on spinal cord perfusion pressure and neurological outcome in traumatic spinal cord injury. METHODS: A systematic review was conducted in concordance with PRISMA guidelines. The literature was found in the EMBASE, PUBMED, SCOPUS, and WEB OF SCIENCE. Eligible studies included those that reported measurements and interventions on the spinal cord perfusion pressure in either animals or patients suffering from spinal cord injury. Only studies that reported a clinical or relevant clinical outcome measure (i.e., neurophysiology) were included. RESULTS: The search yielded 795 unique records, and six studies were included after careful review. These studies suggested a positive correlation between spinal cord perfusion pressure and neurological outcome, but conclusions on causality could not be made. CONCLUSION: In spite of growing indications that neurological outcomes are related to the spinal cord perfusion pressure in traumatic spinal cord injuries, a solid conclusion cannot be made due to the limited literature available. Additional well-designed studies are needed to address this issue.

Characteristics in a traumatic spinal cord injury population.

INTRODUCTION: The aim of this study was to describe core characteristics in a Danish population of rehabilitated traumatic spinal cord injury (SCI) patients. METHODS: Retrospectively, data were extracted from a database on all traumatic patients with SCI admitted to the Spinal Cord Injury Centre of Western Denmark having sustained an injury to the spinal cord between 1 January 1997 and 1 January 2017. Age is presented as medians and interquartile ranges (IQR). RESULTS: A total of 584 (women = 122; men = 462) traumatic patients with SCI with a median age of 42.9 years (26.4-58.3 years) were identified of whom 390 underwent surgery (SG) and 55 were treated conservatively forming a conservative group (CG). The acute treatment regime was unknown in 139 patients with SCI. Patients in the CG were significantly older (median 63.6 years (IQR: 39.1-71.5) than patients in the SG (median 52.8 years (IQR: 37.2-67.2), p = 0.02). The relative risk (RR) of fractures was higher in the SG (RR = 2.74 (1.91-3.95), p less than 0.0001). The initial American Spinal Injury Association Impairment Scale (AIS) grades (A, B, C and D) differed significantly (Kruskal-Wallis test, p less than 0.02) with a higher frequency of AIS Din the CG. Fewer persons with a cervical than with a non-cervical level of injury underwent spinal surgery (RR = 0.65 (0.54-0.77), p less than 0.0004). CONCLUSIONS: In a Danish population of patients with traumatic SCI, we observed a preponderance for surgical treatment among a) younger patients, b) patients with vertebral fractures, and c) more severe SCI cases. FUNDING: This study received no external funding. TRIAL REGISTRATION: The study was conducted in accordance with the Helsinki II Declaration. Data were obtained with permission from the Danish Data Protection Agency (record number 2012-41-0572).

Initial blood pressure is important for long-term outcome after traumatic spinal cord injury.

OBJECTIVE: Patients with traumatic spinal cord injury (TSCI) are at risk of developing neurogenic shock that causes hypotension and thereby secondary injury to the spinal cord due to ischemia. Hemodynamic treatment of patients with acute TSCI remains inadequately elucidated. Guidelines for management are divergent and based on limited evidence. To this end, the authors evaluated whether mean arterial blood pressure (MABP) during the prehospital and initial hospital phases of TSCI treatment is correlated with long-term neurological outcome. METHODS: The authors performed a retrospective cohort study based on a chart review of MABP data collected during the prehospital transport, in the operating room (OR), and in the neurointensive care unit (NICU) during the first 7 days after trauma. Data from the NICU were divided into two periods: days 1-2 and days 3-7. Data were analyzed using Spearman's rank correlation to evaluate for any correlation between MABP and changes in the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) score 1 year postinjury. In the analysis, the MABP target value was 80 mm Hg. Hypotension was treated with metaoxedrin or norepinephrine. Statistically significant differences were evaluated using Spearman's rank correlation coefficient. RESULTS: The chart review yielded 129 patients treated for TSCI. The inclusion period was 2010-2017. For the prehospital transport measurements of MABP, the Spearman's rank correlation coefficient was a rho of 0.5662 (p < 0.001), for OR measurements it was a rho of 0.6818 (p < 0.001), and for the NICU measurements it was a rho of 0.4611 (p < 0.001); for NICU unit days 1-2 and days 3-7, the Spearman's rank correlation coefficient was a rho of 0.2209 (p = 0.0681). CONCLUSIONS: Continuous MABP levels exceeding 80 mm Hg have a significant impact on neurological outcome-from earliest possible stabilization in the prehospital care, through hospital admission, the surgical phase, and into the first 2 days in the NICU.

A clinically relevant blunt spinal cord injury model in the regeneration competent axolotl (Ambystoma mexicanum) tail.

A randomized controlled and blinded animal trial was conducted in the axolotl (Ambystoma mexicanum), which has the ability to regenerate from transectional spinal cord injury (SCI). The objective of the present study was to investigate the axolotl's ability to regenerate from a blunt spinal cord trauma in a clinical setting. Axolotls were block-randomized to the intervention (n=6) or sham group (n=6). A laminectomy of two vertebrae at the level caudal to the hind limbs was performed. To induce a blunt SCI, a 25 g rod was released on the exposed spinal cord. Multiple modalities were applied at baseline (pre-surgery), and subsequently every third week for a total of 9 weeks. Gradient echo magnetic resonance imaging (MRI) was applied to assess anatomical regeneration. To support this non-invasive modality, regeneration was assessed by histology, and functional regeneration was investigated using swimming tests and functional neurological examinations. MRI suggested regeneration within 6 to 9 weeks. Histological analysis at 9 weeks confirmed regeneration; however, this regeneration was not complete. By the experimental end, all animals exhibited restored full neurological function. The present study demonstrated that the axolotl is capable of regenerating a contusion SCI; however, the duration of complete regeneration required further investigation.

High-Intensity Resistance Training Does Not Produce Immediate Ultrasonographic Changes in Muscle Tendons.

BACKGROUND: Chronic overload injuries to tendons can be visualized using ultrasonography, with characteristics such as tendon thickening and darkening. PURPOSE: To investigate whether these characteristics are evident in the patellar and Achilles tendons immediately after 1 session of high-intensity resistance training. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 18 volunteers were randomized to an experimental group (n = 10) and a sham group (n = 8). The experimental group performed 5 circuits at maximum effort consisting of 5 weighted front squats, 10 box jumps (60/50 cm), and 15 double-under jump-rope jumps. The sham group performed a similar circuit consisting of 5 weighted shoulder presses, 10 push-ups, and 15 weighted biceps curls. Ultrasonograms were obtained before and after exercise, for a total of 30 minutes at intervals of 2.5 minutes for the first 10 minutes and 5 minutes for the remaining time. Tendon thickness and tendon matrix signals were measured. Statistics were performed using repeated-measures mixed analysis of variance (ANOVA). RESULTS: Tendon thickness did not increase significantly over 30 minutes after both circuits. The mean grayscale value for the patellar and Achilles tendons increased for both the experimental and the sham groups. ANOVA showed that the experimental group was not a significant explanatory variable; however, the increased work of both groups was. A post hoc analysis found that the maximum increase in the tendon signal was a grayscale value of 10.8 for the patellar tendon (99.4% CI, 3.7-17.9; P = .002). CONCLUSION: This trial failed to reproduce an earlier study in which tendon thickness increased after high-intensity training. The tendons produced a hyperechoic signal after high-intensity resistance training, regardless of loading to the tendon. Chronic overload characteristics on ultrasonography were not evident immediately after acute loading of tendons. CLINICAL RELEVANCE: There is a need for prognostic and diagnostic markers of tendinopathy especially because of the protracted course of subclinical development of an injury. This study assessed whether clinical findings for a chronic overload injury can be detected during acute overloading.

2D and 3D Echocardiography in the Axolotl (Ambystoma Mexicanum).

Cardiac malfunction as a result of ischemic heart disease is a major challenge, and regenerative therapies to the heart are in high demand. A few model species such as zebrafish and salamanders that are capable of intrinsic heart regeneration hold promise for future regenerative therapies for human patients. To evaluate the outcome of cardioregenerative experiments it is imperative that heart function can be monitored. The axolotl salamander (A. mexicanum) represents a well-established model species in regenerative biology attaining sizes that allows for evaluation of cardiac function. The purpose of this protocol is to establish methods to reproducibly measure cardiac function in the axolotl using echocardiography. The application of different anesthetics (benzocaine, MS-222, and propofol) is demonstrated, and the acquisition of two-dimensional (2D) echocardiographic data in both anesthetized and unanesthetized axolotls is described. 2D echocardiography of the three-dimensional (3D) heart can suffer from imprecision and subjectivity of measurements, and to alleviate this phenomenon a solid method, namely intra/inter-operator/observer analysis, to measure and minimize this bias is demonstrated. Finally, a method to acquire 3D echocardiographic data of the beating axolotl heart at a very high spatiotemporal resolution and with pronounced blood-to-tissue contrast is described. Overall, this protocol should provide the necessary methods to evaluate cardiac function and model anatomy, and flow dynamics in the axolotl using ultrasound imaging with applications in both regenerative biology and general physiological experiments.

Propofol (2,6-diisopropylphenol) is an applicable immersion anesthetic in the axolotl with potential uses in hemodynamic and neurophysiological experiments.

The Mexican axolotl (Ambystoma mexicanum) is an important model species in regenerative biology. Traditionally, axolotls are anesthetized using benzocaine or MS-222, both of which act to inhibit voltage gated sodium channels thereby preventing action potential propagation. In some neurophysiological experiments this is not desirable; therefore we tested propofol as an alternative anesthetic in the axolotl. We evaluated benzocaine, MS-222, and propofol's cardiovascular effects, effects on action potential propagation in the spinal cord, and gross limb regenerative effects. We found that propofol is applicable as a general anesthetic in the axolotl allowing for neurophysiological experiments and yielding a stable anesthesia with significantly less cardiovascular effect than both benzocaine and MS-222. Additionally, propofol did not affect gross limb regeneration. In conclusion we suggest the consideration of propofol as an alternative immersion anesthetic to benzocaine and MS-222.