ATF3 is a neuron-specific biomarker for spinal cord injury and ischaemic stroke.

BACKGROUND: Although many molecules have been investigated as biomarkers for spinal cord injury (SCI) or ischemic stroke, none of them are specifically induced in central nervous system (CNS) neurons following injuries with low baseline expression. However, neuronal injury constitutes a major pathology associated with SCI or stroke and strongly correlates with neurological outcomes. Biomarkers characterized by low baseline expression and specific induction in neurons post-injury are likely to better correlate with injury severity and recovery, demonstrating higher sensitivity and specificity for CNS injuries compared to non-neuronal markers or pan-neuronal markers with constitutive expressions. METHODS: In animal studies, young adult wildtype and global Atf3 knockout mice underwent unilateral cervical 5 (C5) SCI or permanent distal middle cerebral artery occlusion (pMCAO). Gene expression was assessed using RNA-sequencing and qRT-PCR, while protein expression was detected through immunostaining. Serum ATF3 levels in animal models and clinical human samples were measured using commercially available enzyme-linked immune-sorbent assay (ELISA) kits. RESULTS: Activating transcription factor 3 (ATF3), a molecular marker for injured dorsal root ganglion sensory neurons in the peripheral nervous system, was not expressed in spinal cord or cortex of naïve mice but was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Additionally, ATF3 protein levels in mouse blood significantly increased 1 day after SCI or ischemic stroke. Importantly, ATF3 protein levels in human serum were elevated in clinical patients within 24 hours after SCI or ischemic stroke. Moreover, Atf3 knockout mice, compared to the wildtype mice, exhibited worse neurological outcomes and larger damage regions after SCI or ischemic stroke, indicating that ATF3 has a neuroprotective function. CONCLUSIONS: ATF3 is an easily measurable, neuron-specific biomarker for clinical SCI and ischemic stroke, with neuroprotective properties. HIGHLIGHTS: ATF3 was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Serum ATF3 protein levels are elevated in clinical patients within 24 hours after SCI or ischemic stroke. ATF3 exhibits neuroprotective properties, as evidenced by the worse neurological outcomes and larger damage regions observed in Atf3 knockout mice compared to wildtype mice following SCI or ischemic stroke.

Correction: Expert-augmented automated machine learning optimizes hemodynamic predictors of spinal cord injury outcome.

[This corrects the article DOI: 10.1371/journal.pone.0265254.].

Safety and comparative efficacy of initiating low-molecular-weight heparin within 24 hours of injury or surgery for venous thromboembolism prophylaxis in patients with spinal cord injury: a prospective TRACK-SCI registry study.

OBJECTIVE: Venous thromboembolism (VTE) following traumatic spinal cord injury (SCI) is a significant clinical concern. This study sought to determine the incidence of VTE and hemorrhagic complications among patients with SCI who received low-molecular-weight heparin (LMWH) within 24 hours of injury or surgery and identify variables that predict VTE using the prospective Transforming Research and Clinical Knowledge in SCI (TRACK-SCI) database. METHODS: The TRACK-SCI database was queried for individuals with traumatic SCI from 2015 to 2022. Primary outcomes of interest included rates of VTE (including deep vein thrombosis [DVT] and pulmonary embolism [PE]) and in-hospital hemorrhagic complications that occurred after LWMH administration. Secondary outcomes included intensive care unit and hospital length of stay, discharge location type, and in-hospital mortality. RESULTS: The study cohort consisted of 162 patients with SCI. Fifteen of the 162 patients withdrew from the study, leading to loss of data for certain variables for these patients. One hundred thirty patients (87.8%) underwent decompression and/or fusion surgery for SCI. DVT occurred in 11 (7.4%) of 148 patients, PE in 9 (6.1%) of 148, and any VTE in 18 (12.2%) of 148 patients. The analysis showed that admission lower-extremity motor score (p = 0.0408), injury at the thoracic level (p = 0.0086), admission American Spinal Injury Association grade (p = 0.0070), and younger age (p = 0.0372) were significantly associated with VTE. There were 3 instances of postoperative spine surgery-related bleeding (2.4%) in the 127 patients who had spine surgery with bleeding complication data available, with one requiring return to surgery (0.8%). Thirteen (8.8%) of 147 patients had a bleeding complication not related to spine surgery. There were 2 gastrointestinal bleeds associated with nasogastric tube placement, 3 cases of postoperative non-spine-related surgery bleeding, and 8 cases of other bleeding complications (5.4%) not related to any surgery. CONCLUSIONS: Initiation of LMWH within 24 hours was associated with a low rate of spine surgery-related bleeding. Bleeding complications unrelated to SCI surgery still occur with LMWH administration. Because neurosurgical intervention is typically the limiting factor in initializing chemical DVT prophylaxis, many of these bleeding complications would have likely occurred regardless of the protocol.

Hypotension requiring vasopressor treatment and increased cardiac complications in elderly spinal cord injury patients: a prospective TRACK-SCI registry study.

OBJECTIVE: Increasing life expectancy has led to an older population. In this study, the authors analyzed complications and outcomes in elderly patients following spinal cord injury (SCI) using the established multi-institutional prospective study Transforming Research and Clinical Knowledge in SCI (TRACK-SCI) database collected in the Department of Neurosurgical Surgery at the University of California, San Francisco. METHODS: TRACK-SCI was queried for elderly individuals (≥ 65 years of age) with traumatic SCI from 2015 to 2019. Primary outcomes of interest included total hospital length of stay, perioperative complications, postoperative complications, and in-hospital mortality. Secondary outcomes included disposition location, and neurological improvement based on the American Spinal Injury Association Impairment Scale (AIS) grade at discharge. Descriptive analysis, Fisher's exact test, univariate analysis, and multivariable regression analysis were performed. RESULTS: The study cohort consisted of 40 elderly patients. The in-hospital mortality rate was 10%. Every patient in this cohort experienced at least 1 complication, with a mean of 6.6 separate complications (median 6, mode 4). The most common complication categories were cardiovascular, with a mean of 1.6 complications (median 1, mode 1), and pulmonary, with a mean of 1.3 (median 1, mode 0) complications, with 35 patients (87.5%) having at least 1 cardiovascular complication and 25 (62.5%) having at least 1 pulmonary complication. Overall, 32 patients (80%) required vasopressor treatment for mean arterial pressure (MAP) maintenance goals. The use of norepinephrine correlated with increased cardiovascular complications. Only 3 patients (7.5%) of the total cohort had an improved AIS grade compared with their acute level at admission. CONCLUSIONS: Given the increased frequency of cardiovascular complications associated with vasopressor use in elderly SCI patients, caution is warranted when targeting MAP goals in these patients. A downward adjustment of blood pressure maintenance goals and prophylactic cardiology consultation to select the most appropriate vasopressor agent may be advisable for SCI patients ≥ 65 years of age.

Decision tree-based machine learning analysis of intraoperative vasopressor use to optimize neurological improvement in acute spinal cord injury.

OBJECTIVE: Previous work has shown that maintaining mean arterial pressures (MAPs) between 76 and 104 mm Hg intraoperatively is associated with improved neurological function at discharge in patients with acute spinal cord injury (SCI). However, whether temporary fluctuations in MAPs outside of this range can be tolerated without impairment of recovery is unknown. This retrospective study builds on previous work by implementing machine learning to derive clinically actionable thresholds for intraoperative MAP management guided by neurological outcomes. METHODS: Seventy-four surgically treated patients were retrospectively analyzed as part of a longitudinal study assessing outcomes following SCI. Each patient underwent intraoperative hemodynamic monitoring with recordings at 5-minute intervals for a cumulative 28,594 minutes, resulting in 5718 unique data points for each parameter. The type of vasopressor used, dose, drug-related complications, average intraoperative MAP, and time spent in an extreme MAP range (< 76 mm Hg or > 104 mm Hg) were collected. Outcomes were evaluated by measuring the change in American Spinal Injury Association Impairment Scale (AIS) grade over the course of acute hospitalization. Features most predictive of an improvement in AIS grade were determined statistically by generating random forests with 10,000 iterations. Recursive partitioning was used to establish clinically intuitive thresholds for the top features. RESULTS: At discharge, a significant improvement in AIS grade was noted by an average of 0.71 levels (p = 0.002). The hemodynamic parameters most important in predicting improvement were the amount of time intraoperative MAPs were in extreme ranges and the average intraoperative MAP. Patients with average intraoperative MAPs between 80 and 96 mm Hg throughout surgery had improved AIS grades at discharge. All patients with average intraoperative MAP > 96.3 mm Hg had no improvement. A threshold of 93 minutes spent in an extreme MAP range was identified after which the chance of neurological improvement significantly declined. Finally, the use of dopamine as compared to norepinephrine was associated with higher rates of significant cardiovascular complications (50% vs 25%, p < 0.001). CONCLUSIONS: An average intraoperative MAP value between 80 and 96 mm Hg was associated with improved outcome, corroborating previous results and supporting the clinical verifiability of the model. Additionally, an accumulated time of 93 minutes or longer outside of the MAP range of 76-104 mm Hg is associated with worse neurological function at discharge among patients undergoing emergency surgical intervention for acute SCI.

Expert-augmented automated machine learning optimizes hemodynamic predictors of spinal cord injury outcome.

Artificial intelligence and machine learning (AI/ML) is becoming increasingly more accessible to biomedical researchers with significant potential to transform biomedicine through optimization of highly-accurate predictive models and enabling better understanding of disease biology. Automated machine learning (AutoML) in particular is positioned to democratize artificial intelligence (AI) by reducing the amount of human input and ML expertise needed. However, successful translation of AI/ML in biomedicine requires moving beyond optimizing only for prediction accuracy and towards establishing reproducible clinical and biological inferences. This is especially challenging for clinical studies on rare disorders where the smaller patient cohorts and corresponding sample size is an obstacle for reproducible modeling results. Here, we present a model-agnostic framework to reinforce AutoML using strategies and tools of explainable and reproducible AI, including novel metrics to assess model reproducibility. The framework enables clinicians to interpret AutoML-generated models for clinical and biological verifiability and consequently integrate domain expertise during model development. We applied the framework towards spinal cord injury prognostication to optimize the intraoperative hemodynamic range during injury-related surgery and additionally identified a strong detrimental relationship between intraoperative hypertension and patient outcome. Furthermore, our analysis captured how evolving clinical practices such as faster time-to-surgery and blood pressure management affect clinical model development. Altogether, we illustrate how expert-augmented AutoML improves inferential reproducibility for biomedical discovery and can ultimately build trust in AI processes towards effective clinical integration.

Topological network analysis of patient similarity for precision management of acute blood pressure in spinal cord injury.

Background: Predicting neurological recovery after spinal cord injury (SCI) is challenging. Using topological data analysis, we have previously shown that mean arterial pressure (MAP) during SCI surgery predicts long-term functional recovery in rodent models, motivating the present multicenter study in patients. Methods: Intra-operative monitoring records and neurological outcome data were extracted (n = 118 patients). We built a similarity network of patients from a low-dimensional space embedded using a non-linear algorithm, Isomap, and ensured topological extraction using persistent homology metrics. Confirmatory analysis was conducted through regression methods. Results: Network analysis suggested that time outside of an optimum MAP range (hypotension or hypertension) during surgery was associated with lower likelihood of neurological recovery at hospital discharge. Logistic and LASSO (least absolute shrinkage and selection operator) regression confirmed these findings, revealing an optimal MAP range of 76-[104-117] mmHg associated with neurological recovery. Conclusions: We show that deviation from this optimal MAP range during SCI surgery predicts lower probability of neurological recovery and suggest new targets for therapeutic intervention. Funding: NIH/NINDS: R01NS088475 (ARF); R01NS122888 (ARF); UH3NS106899 (ARF); Department of Veterans Affairs: 1I01RX002245 (ARF), I01RX002787 (ARF); Wings for Life Foundation (ATE, ARF); Craig H. Neilsen Foundation (ARF); and DOD: SC150198 (MSB); SC190233 (MSB).

Spinal cord injury is a devastating condition that involves damage to the nerve fibers connecting the brain with the spinal cord, often leading to permanent changes in strength, sensation and body functions, and in severe cases paralysis. Scientists around the world work hard to find ways to treat or even repair spinal cord injuries but few patients with complete immediate paralysis recover fully. Immediate paralysis is caused by direct damage to neurons and their extension in the spinal cord. Previous research has shown that blood pressure regulation may be key in saving these damaged neurons, as spinal cord injuries can break the communication between nerves that is involved in controlling blood pressure. This can lead to a vicious cycle of dysregulation of blood pressure and limit the supply of blood and oxygen to the damaged spinal cord tissue, exacerbating the death of spinal neurons. Management of blood pressure is therefore a key target for spinal cord injury care, but so far, the precise thresholds to enable neurons to recover are poorly understood. To find out more, Torres-Espin, Haefeli et al. used machine learning software to analyze previously recorded blood pressure and heart rate data obtained from 118 patients that underwent spinal cord surgery after acute spinal cord injury. The analyses revealed that patients who suffered from either low or high blood pressure during surgery had poorer prospects of recovery. Statistical models confirming these findings showed that the optimal blood pressure range to ensure recovery lies between 76 to 104-117 mmHg. Any deviation from this narrow window would dramatically worsen the ability to recover. These findings suggests that dysregulated blood pressure during surgery affects to odds of recovery in patients with a spinal cord injury. Torres-Espin, Haefeli et al. provide specific information that could improve current clinical practice in trauma centers. In the future, such machine learning tools and models could help develop real-time models that could predict the likelihood of a patient's recovery following spinal cord injury and related neurological conditions.

Diagnostic blood RNA profiles for human acute spinal cord injury.

Diagnosis of spinal cord injury (SCI) severity at the ultra-acute stage is of great importance for emergency clinical care of patients as well as for potential enrollment into clinical trials. The lack of a diagnostic biomarker for SCI has played a major role in the poor results of clinical trials. We analyzed global gene expression in peripheral white blood cells during the acute injury phase and identified 197 genes whose expression changed after SCI compared with healthy and trauma controls and in direct relation to SCI severity. Unsupervised coexpression network analysis identified several gene modules that predicted injury severity (AIS grades) with an overall accuracy of 72.7% and included signatures of immune cell subtypes. Specifically, for complete SCIs (AIS A), ROC analysis showed impressive specificity and sensitivity (AUC: 0.865). Similar precision was also shown for AIS D SCIs (AUC: 0.938). Our findings indicate that global transcriptomic changes in peripheral blood cells have diagnostic and potentially prognostic value for SCI severity.

Injury volume extracted from MRI predicts neurologic outcome in acute spinal cord injury: A prospective TRACK-SCI pilot study.

Conventional MRI measures of traumatic spinal cord injury severity largely rely on 2-dimensional injury characteristics such as intramedullary lesion length and cord compression. Recent advances in spinal cord (SC) analysis have led to the development of a robust anatomic atlas incorporated into an open-source platform called the Spinal Cord Toolbox (SCT) that allows for quantitative volumetric injury analysis. In the current study, we evaluate the prognostic value of volumetric measures of spinal cord injury on MRI following registration of T2-weighted (T2w) images and segmented lesions from acute SCI patients with a standardized atlas. This IRB-approved prospective cohort study involved the image analysis of 60 blunt cervical SCI patients enrolled in the TRACK-SCI clinical research protocol. Axial T2w MRI data obtained within 24 h of injury were processed using the SCT. Briefly, SC MRIs were automatically segmented using the sct_deepseg_sc tool in the SCT and segmentations were manually corrected by a neuro-radiologist. Lesion volume data were used as predictor variables for correlation with lower extremity motor scores at discharge. Volumetric MRI measures of T2w signal abnormality comprising the SCI lesion accurately predict lower extremity motor scores at time of patient discharge. Similarly, MRI measures of injury volume significantly correlated with motor scores to a greater degree than conventional 2-D metrics of lesion size. The volume of total injury and of injured spinal cord motor regions on T2w MRI is significantly and independently associated with neurologic outcome at discharge after injury.

Transforming Research and Clinical Knowledge in Spinal Cord Injury (TRACK-SCI): an overview of initial enrollment and demographics.

OBJECTIVE: Traumatic spinal cord injury (SCI) is a dreaded condition that can lead to paralysis and severe disability. With few treatment options available for patients who have suffered from SCI, it is important to develop prospective databases to standardize data collection in order to develop new therapeutic approaches and guidelines. Here, the authors present an overview of their multicenter, prospective, observational patient registry, Transforming Research and Clinical Knowledge in SCI (TRACK-SCI). METHODS: Data were collected using the National Institute of Neurological Disorders and Stroke (NINDS) common data elements (CDEs). Highly granular clinical information, in addition to standardized imaging, biospecimen, and follow-up data, were included in the registry. Surgical approaches were determined by the surgeon treating each patient; however, they were carefully documented and compared within and across study sites. Follow-up visits were scheduled for 6 and 12 months after injury. RESULTS: One hundred sixty patients were enrolled in the TRACK-SCI study. In this overview, basic clinical, imaging, neurological severity, and follow-up data on these patients are presented. Overall, 78.8% of the patients were determined to be surgical candidates and underwent spinal decompression and/or stabilization. Follow-up rates to date at 6 and 12 months are 45% and 36.3%, respectively. Overall resources required for clinical research coordination are also discussed. CONCLUSIONS: The authors established the feasibility of SCI CDE implementation in a multicenter, prospective observational study. Through the application of standardized SCI CDEs and expansion of future multicenter collaborations, they hope to advance SCI research and improve treatment.

XGBoost, a Machine Learning Method, Predicts Neurological Recovery in Patients with Cervical Spinal Cord Injury.

The accurate prediction of neurological outcomes in patients with cervical spinal cord injury (SCI) is difficult because of heterogeneity in patient characteristics, treatment strategies, and radiographic findings. Although machine learning algorithms may increase the accuracy of outcome predictions in various fields, limited information is available on their efficacy in the management of SCI. We analyzed data from 165 patients with cervical SCI, and extracted important factors for predicting prognoses. Extreme gradient boosting (XGBoost) as a machine learning model was applied to assess the reliability of a machine learning algorithm to predict neurological outcomes compared with that of conventional methodology, such as a logistic regression or decision tree. We used regularly obtainable data as predictors, such as demographics, magnetic resonance variables, and treatment strategies. Predictive tools, including XGBoost, a logistic regression, and a decision tree, were applied to predict neurological improvements in the functional motor status (ASIA [American Spinal Injury Association] Impairment Scale [AIS] D and E) 6 months after injury. We evaluated predictive performance, including accuracy and the area under the receiver operating characteristic curve (AUC). Regarding predictions of neurological improvements in patients with cervical SCI, XGBoost had the highest accuracy (81.1%), followed by the logistic regression (80.6%) and the decision tree (78.8%). Regarding AUC, the logistic regression showed 0.877, followed by XGBoost (0.867) and the decision tree (0.753). XGBoost reliably predicted neurological alterations in patients with cervical SCI. The utilization of predictive machine learning algorithms may enhance personalized management choices through pre-treatment categorization of patients.

Clinical Implementation of Novel Spinal Cord Perfusion Pressure Protocol in Acute Traumatic Spinal Cord Injury at U.S. Level I Trauma Center: TRACK-SCI Study.

OBJECTIVE: We sought to report the safety of implementation of a novel standard of care protocol using spinal cord perfusion pressure (SCPP) maintenance for managing traumatic spinal cord injury (SCI) in lieu of mean arterial pressure goals at a U.S. Level I trauma center. METHODS: Starting in December 2017, blunt SCI patients presenting <24 hours after injury with admission American Spinal Injury Association Impairment Scale (AIS) A-C (or AIS D at neurosurgeon discretion) received lumbar subarachnoid drain (LSAD) placement for SCPP monitoring in the intensive care unit and were included in the TRACK-SCI (Transforming Research and Clinical Knowledge in Spinal Cord Injury) data registry. This SCPP protocol comprises standard care at our institution. SCPPs were monitored for 5 days (goal ≥65 mm Hg) achieved through intravenous fluids and vasopressor support. AISs were assessed at admission and day 7. RESULTS: Fifteen patients enrolled to date were aged 60.5 ± 17 years. Injury levels were 93.3% (cervical) and 6.7% (thoracic). Admission AIS was 20.0%/20.0%/26.7%/33.3% for A/B/C/D. All patients maintained mean SCPP ≥65 mm Hg during monitoring. Fourteen of 15 cases required surgical decompression and stabilization with time to surgery 8.8 ± 7.1 hours (71.4% <12 hours). At day 7, 33.3% overall and 50% of initial AIS A-C had an improved AIS. Length of stay was 14.7 ± 8.3 days. None had LSAD-related complications. There were 7 respiratory complications. One patient expired after transfer to comfort care. CONCLUSIONS: In our initial experience of 15 patients with acute SCI, standardized SCPP goal-directed care based on LSAD monitoring for 5 days was feasible. There were no SCPP-related complications. This is the first report of SCPP implementation as clinical standard of care in acute SCI.

Value of aggressive surgical and intensive care unit in elderly patients with traumatic spinal cord injury.

OBJECTIVEThe elderly are a growing subpopulation within traumatic spinal cord injury (SCI) patients. Studies have reported high morbidity and mortality rates in elderly patients who undergo surgery for SCI. In this study, the authors compare the perioperative outcomes of surgically managed elderly SCI patients with those of a younger cohort and those reported in the literature.METHODSData on a consecutive series of adult traumatic SCI patients surgically managed at a single institution in the period from 2007 to 2017 were retrospectively reviewed. The cohort was divided into two groups based on age: younger than 70 years and 70 years or older. Assessed outcomes included complications, in-hospital mortality, intensive care unit (ICU) stay, hospital length of stay (LOS), disposition, and neurological status.RESULTSA total of 106 patients were included in the study: 83 young and 23 elderly. The two groups were similar in terms of imaging features (cord hemorrhage and fracture), operative technique, and American Spinal Injury Association Impairment Scale (AIS) grade. The elderly had a significantly higher proportion of cervical SCIs (95.7% vs 71.1%, p = 0.047). There were no significant differences between the young and the elderly in terms of the ICU stay (13.1 vs 13.3 days, respectively, p = 0.948) and hospital LOS (23.3 vs 21.7 days, p = 0.793). Elderly patients experienced significantly higher complication (73.9% vs 43.4%, p = 0.010) and mortality (13.0% vs 1.2%, p = 0.008) rates; in other words, the elderly patients had 1.7 times and 10.8 times the rate of complications and mortality, respectively, than the younger patients. No elderly patients were discharged home (0.0% vs 18.1%, p = 0.029). Discharge AIS grade and AIS grade change were similar between the groups.CONCLUSIONSElderly patients had higher complication and mortality rates than those in younger patients and were less likely to be discharged home. However, it does seem that mortality rates have improved compared to those in prior historical reports.

Yield of Emergent CT in Patients With Epilepsy Presenting With a Seizure.

BACKGROUND: Studies of emergent neuroimaging in the management of patients presenting with a breakthrough seizure are lacking. We sought to determine how often emergent computed tomography (CT) scans are obtained in patients with known epilepsy presenting with a seizure and how often acute abnormalities are found. METHODS: This multicenter retrospective cohort study was performed in the emergency department at 2 academic medical centers. The primary outcomes were percentage of visits where a CT scan was obtained, whether CT findings represented acute abnormalities, and whether these findings changed acute management. RESULTS: Of the 396 visits included, CT scans were obtained in 39%, and 8% of these scans demonstrated acute abnormalities. Patients who were older, had status epilepticus, a brain tumor, head trauma, or an abnormal examination were all significantly more likely to undergo acute neuroimaging (P < .05). In the multivariable model, only history of brain tumor (odds ratio [OR] 5.88, 95% confidence interval [CI], 1.33-26.1) and head trauma as a result of seizure (OR 3.92, 95% CI, 1.01-15.2) reached statistical significance in predicting an acutely abnormal scan. The likelihood of an acute imaging abnormality in visits for patients without a history of brain tumor or head trauma as a result of the seizure was 2.7% (2 visits). Both of these patients had abnormal neurological examinations. CONCLUSION: Obtaining an emergent CT scan for patients with epilepsy presenting with a seizure may be avoidable in most cases, but might be indicated for patients with a history of brain tumor or head trauma as a result of seizure.

Ultra-Early (<12 Hours) Surgery Correlates With Higher Rate of American Spinal Injury Association Impairment Scale Conversion After Cervical Spinal Cord Injury.

BACKGROUND: Cervical spinal cord injury (SCI) is a devastating condition with very few treatment options. It remains unclear if early surgery correlated with conversion of American Spinal Injury Association Impairment Scale (AIS) grade A injuries to higher grades. OBJECTIVE: To determine the optimal time to surgery after cervical SCI through retrospective analysis. METHODS: We collected data from 48 patients with cervical SCI. Based on the time from Emergency Department (ED) presentation to surgical decompression, we grouped patients into ultra-early (decompression within 12 h of presentation), early (within 12-24 h), and late groups (>24 h). We compared the improvement in AIS grade from admission to discharge, controlling for confounding factors such as AIS grade on admission, injury severity, and age. The mean time from injury to ED for this group of patients was 17 min. RESULTS: Patients who received surgery within 12 h after presentation had a relative improvement in AIS grade from admission to discharge: the ultra-early group improved on average 1.3. AIS grades compared to 0.5 in the early group (P = .02). In addition, 88.8% of patients with an AIS grade A converted to a higher grade (AIS B or better) in the ultra-early group, compared to 38.4% in the early and late groups (P = .054). CONCLUSION: These data suggest that surgical decompression after SCI that takes place within 12 h may lead to a relative improved neurological recovery compared to surgery that takes place after 12 h.

Low Yield of Paired Head and Cervical Spine Computed Tomography in Blunt Trauma Evaluation.

BACKGROUND: With increased computed tomography (CT) utilization, clinicians may simultaneously order head and neck CT scans, even when injury is suspected only in one region. OBJECTIVE: We sought to determine: 1) the frequency of simultaneous ordering of a head CT scan when a neck CT scan is ordered; 2) the yields of simultaneously ordered head and neck CT scans for clinically significant injury (CSI); and 3) whether injury in one region is associated with a higher rate of injury in the other. METHODS: This was a retrospective study of all adult patients who received neck CT scans (and simultaneously ordered head CT scans) as part of their blunt trauma evaluation at an urban level 1 trauma center in 2013. An expert panel determined CSI of head and neck injuries. We defined yield as number of patients with injury/number of patients who had a CT scan. RESULTS: Of 3223 patients who met inclusion criteria, 2888 (89.6%) had simultaneously ordered head and neck CT scans. CT yield for CSI in both the head and neck was 0.5% (95% confidence interval [CI] 0.3-0.8%), and the yield for any injury in both the head and neck was 1.4% (95% CI 1.0-1.8%). The yield for CSI in one region was higher when CSI was seen in the other region. CONCLUSIONS: The yield of CT for CSI in both the head and neck concomitantly is very low. When injury is seen in one region, there is higher likelihood of injury in the other. These findings argue against paired ordering of head and neck CT scans and suggest that CT scans should be ordered individually or when injury is detected in one region.

Motor Evoked Potentials Correlate With Magnetic Resonance Imaging and Early Recovery After Acute Spinal Cord Injury.

BACKGROUND: While the utilization of neurophysiologic intraoperative monitoring with motor evoked potentials (MEPs) has become widespread in surgery for traumatic spine fractures and spinal cord injury (SCI), clinical validation of its diagnostic and therapeutic benefit has been limited. OBJECTIVE: To describe the use of intraoperative MEP at a large level I trauma center and assess the prognostic capability of this technology. METHODS: The SCI REDCap database at our institution, a level I trauma center, was queried for acute cervical SCI patients who underwent surgery with intraoperative monitoring between 2005 and 2011, yielding 32 patients. Of these, 23 patients had severe SCI (association impairment scale [AIS] A, B, C). We assessed preoperative and postoperative SCI severity (AIS grade), surgical data, use of steroids, and early magnetic resonance imaging (MRI) findings (preoperatively in 27 patients), including axial T2 MRI grade (Brain and Spinal Injury Center score). RESULTS: The presence of MEPs significantly predicted AIS at discharge (P< .001). In the group of severe SCI (ie, AIS A, B, C) patients with elicitable MEPs, AIS improved by an average of 1.5 grades (median = 1), as compared to the patients without elicitable MEP who improved on average 0.5 grades (median = 0, P< .05). In addition, axial MRI grade significantly correlated with MEP status. Patients without MEPs had a significantly higher axial MRI grade in comparison to the patients with MEPs (P< .001). CONCLUSION: In patients with severe SCI, MEPs predicted neurological improvement and correlated with axial MRI grade. These significant findings warrant future prospective studies of MEPs as a prognostic tool in SCI.

Safety and effectiveness of early chemical deep venous thrombosis prophylaxis after spinal cord injury: pilot prospective data.

OBJECTIVE Spinal cord injuries (SCIs) occur in approximately 17,000 people in the US each year. The average length of hospital stay is 11 days, and deep venous thrombosis (DVT) rates as high as 65% are reported in these patients. There is no consensus on the appropriate timing of chemical DVT prophylaxis for this critically injured patient cohort. The object of this study was to determine if low-molecular-weight heparin (LMWH) was safe and effective if given within 24 hours of SCI. METHODS The Transforming Research and Clinical Knowledge in SCIs study is a prospective observational study conducted by the UCSF Brain and Spinal Injury Center. Protocol at this center includes administration of LMWH within 24 hours of SCI. Data were retrospectively reviewed to determine DVT rate, pulmonary embolism (PE) rate, and hemorrhagic complications. RESULTS Forty-nine patients were enrolled in the study. There were 3 DVTs (6.1%), 2 PEs (4.1%), and no hemorrhagic complications. Regression modeling did not find an association between DVT and/or PE and age, American Spinal Injury Association grade, sex, race, or having undergone a neurosurgical procedure. CONCLUSIONS A standardized protocol in which LMWH is given to patients with SCI within 24 hours of injury is effective in keeping venous thromboembolism at the lower end of the reported range, and is safe, with a zero rate of adverse bleeding events.

Protease-Activated Receptor-1 Supports Locomotor Recovery by Biased Agonist Activated Protein C after Contusive Spinal Cord Injury.

Thrombin-induced secondary injury is mediated through its receptor, protease activated receptor-1 (PAR-1), by "biased agonism." Activated protein C (APC) acts through the same PAR-1 receptor but functions as an anti-coagulant and anti-inflammatory protein, which counteracts many of the effects of thrombin. Although the working mechanism of PAR-1 is becoming clear, the functional role of PAR-1 and its correlation with APC in the injured spinal cord remains to be elucidated. Here we investigated if PAR-1 and APC are determinants of long-term functional recovery after a spinal cord contusive injury using PAR-1 null and wild-type mice. We found that neutrophil infiltration and disruption of the blood-spinal cord barrier were significantly reduced in spinal cord injured PAR-1 null mice relative to the wild-type group. Both locomotor recovery and ability to descend an inclined grid were significantly improved in the PAR-1 null group 42 days after injury and this improvement was associated with greater long-term sparing of white matter and a reduction in glial scarring. Wild-type mice treated with APC acutely after injury showed a similar level of improved locomotor recovery to that of PAR-1 null mice. However, improvement of APC-treated PAR-1 null mice was indistinguishable from that of vehicle-treated PAR-1 null mice, suggesting that APC acts through PAR-1. Collectively, our findings define a detrimental role of thrombin-activated PAR-1 in wound healing and further validate APC, also acting through the PAR-1 by biased agonism, as a promising therapeutic target for spinal cord injury.