A minimum data set-Core outcome set, core data elements, and core measurement set-For degenerative cervical myelopathy research (AO Spine RECODE DCM): A consensus study.

BACKGROUND: Degenerative cervical myelopathy (DCM) is a progressive chronic spinal cord injury estimated to affect 1 in 50 adults. Without standardised guidance, clinical research studies have selected outcomes at their discretion, often underrepresenting the disease and limiting comparability between studies. Utilising a standard minimum data set formed via multi-stakeholder consensus can address these issues. This combines processes to define a core outcome set (COS)-a list of key outcomes-and core data elements (CDEs), a list of key sampling characteristics required to interpret the outcomes. Further "how" these outcomes should be measured and/or reported is then defined in a core measurement set (CMS). This can include a recommendation of a standardised time point at which outcome data should be reported. This study defines a COS, CDE, and CMS for DCM research. METHODS AND FINDINGS: A minimum data set was developed using a series of modified Delphi processes. Phase 1 involved the setup of an international DCM stakeholder group. Phase 2 involved the development of a longlist of outcomes, data elements, and formation into domains. Phase 3 prioritised the outcomes and CDEs using a two-stage Delphi process. Phase 4 determined the final DCM minimal data set using a consensus meeting. Using the COS, Phase 5 finalised definitions of the measurement construct for each outcome. In Phase 6, a systematic review of the literature was performed, to scope and define the psychometric properties of measurement tools. Phase 7 used a modified Delphi process to inform the short-listing of candidate measurement tools. The final measurement set was then formed through a consensus meeting (Phase 8). To support implementation, the data set was then integrated into template clinical research forms (CRFs) for use in future clinical trials (Phase 9). In total, 28 outcomes and 6 domains (Pain, Neurological Function, Life Impact, Radiology, Economic Impact, and Adverse Events) were entered into the final COS. Thirty two outcomes and 4 domains (Individual, Disease, Investigation, and Intervention) were entered into the final CDE. Finally, 4 outcome instruments (mJOA, NDI, SF-36v2, and SAVES2) were identified for the CMS, with a recommendation for trials evaluating outcomes after surgery, to include baseline measurement and at 6 months from surgery. CONCLUSIONS: The AO Spine RECODE-DCM has produced a minimum data set for use in DCM clinical trials today. These are available at https://myelopathy.org/minimum-dataset/. While it is anticipated the CDE and COS have strong and durable relevance, it is acknowledged that new measurement tools, alongside an increasing transition to study patients not undergoing surgery, may necessitate updates and adaptation, particularly with respect to the CMS.

Cervical spinal cord angiography and vessel-selective perfusion imaging in the rat.

Arterial spin labeling (ASL) has been widely used to evaluate arterial blood and perfusion dynamics, particularly in the brain, but its application to the spinal cord has been limited. The purpose of this study was to optimize vessel-selective pseudocontinuous arterial spin labeling (pCASL) for angiographic and perfusion imaging of the rat cervical spinal cord. A pCASL preparation module was combined with a train of gradient echoes for dynamic angiography. The effects of the echo train flip angle, label duration, and a Cartesian or radial readout were compared to examine their effects on visualizing the segmental arteries and anterior spinal artery (ASA) that supply the spinal cord. Lastly, vessel-selective encoding with either vessel-encoded pCASL (VE-pCASL) or super-selective pCASL (SS-pCASL) were compared. Vascular territory maps were obtained with VE-pCASL perfusion imaging of the spinal cord, and the interanimal variability was evaluated. The results demonstrated that longer label durations (200 ms) resulted in greater signal-to-noise ratio in the vertebral arteries, improved the conspicuity of the ASA, and produced better quality maps of blood arrival times. Cartesian and radial readouts demonstrated similar image quality. Both VE-pCASL and SS-pCASL adequately labeled the right or left vertebral arteries, which revealed the interanimal variability in the segmental artery with variations in their location, number, and laterality. VE-pCASL also demonstrated unique interanimal variations in spinal cord perfusion with a right-sided dominance across the six animals. Vessel-selective pCASL successfully achieved visualization of the arterial inflow dynamics and corresponding perfusion territories of the spinal cord. These methodological developments provide unique insights into the interanimal variations in the arterial anatomy and dynamics of spinal cord perfusion.

Comparison and optimization of pCASL and VSASL for rat thoracolumbar spinal cord MRI at 9.4 T.

PURPOSE: To evaluate pseudo-continuous arterial spin labeling (pCASL) and velocity-selective arterial spin labeling (VSASL) for quantification of spinal cord blood flow (SCBF) in the rat thoracolumbar spinal cord. METHODS: Labeling efficiency (LE) was compared between pCASL and three VSASL variants in simulations and both phantom and in vivo experiments at 9.4 T. For pCASL, the effects of label plane position and shimming were systematically evaluated. For VSASL, the effects of composite pulses and phase cycling were evaluated to reduce artifacts. Additionally, vessel suppression, respiratory, and cardiac gating were evaluated to reduce motion artifacts. pCASL and VSASL maps of spinal cord blood flow were acquired with the optimized protocols. RESULTS: LE of the descending aorta was larger in pCASL compared to VSASL variants. In pCASL, LE off-isocenter was improved by local shimming positioned at the label plane and the anatomical level of labeling for the thoracic cord was only viable at the level of the T10 vertebra. Cardiac gating was essential to reduce motion artifacts. Both pCASL and VSASL successfully demonstrated comparable SCBF values in the thoracolumbar cord. CONCLUSION: pCASL demonstrated high and consistent LE in the thoracic aorta, and VSASL was also feasible, but with reduced efficiency. A combination of cardiac gating and recording of actual post-label delays was important for accurate SCBF quantification. These results highlight the challenges and solutions to achieve sufficient ASL labeling and contrast at high field in organs prone to motion.

Lived experience-centred word clouds may improve research uncertainty gathering in priority setting partnerships.

INTRODUCTION: AO Spine RECODE-DCM was a multi-stakeholder priority setting partnership (PSP) to define the top ten research priorities for degenerative cervical myelopathy (DCM). Priorities were generated and iteratively refined using a series of surveys administered to surgeons, other healthcare professionals (oHCP) and people with DCM (PwDCM). The aim of this work was to utilise word clouds to enable the perspectives of people with the condition to be heard earlier in the PSP process than is traditionally the case. The objective was to evaluate the added value of word clouds in the process of defining research uncertainties in National Institute for Health Research (NIHR) James Lind Alliance (JLA) Priority Setting Partnerships. METHODS: Patient-generated word clouds were created for the four survey subsections of the AO Spine RECODE-DCM PSP: diagnosis, treatment, long-term management and other issues. These were then evaluated as a nested methodological study. Word-clouds were created and iteratively refined by an online support group of people with DCM, before being curated by the RECODE-DCM management committee and expert healthcare professional representatives. The final word clouds were embedded within the surveys administered at random to 50% of participants. DCM research uncertainties suggested by participants were compared pre- and post-word cloud presentation. RESULTS: A total of 215 (50.9%) participants were randomised to the word cloud stream, including 118 (55%) spinal surgeons, 52 (24%) PwDCM and 45 (21%) oHCP. Participants submitted 434 additional uncertainties after word cloud review: word count was lower and more uniform across each survey subsections compared to pre-word cloud uncertainties. Twenty-three (32%) of the final 74 PSP summary questions did not have a post-word cloud contribution and no summary question was formed exclusively on post-word cloud uncertainties. There were differences in mapping of pre- and post-word cloud uncertainties to summary questions, with greater mapping of post-word cloud uncertainties to the number 1 research question priority: raising awareness. Five of the final summary questions were more likely to map to the research uncertainties suggested by participants after having reviewed the word clouds. CONCLUSIONS: Word clouds may increase the perspective of underrepresented stakeholders in the research question gathering stage of priority setting partnerships. This may help steer the process towards research questions that are of highest priority for people with the condition.

Diffusion-prepared fast spin echo for artifact-free spinal cord imaging.

PURPOSE: Diffusion MRI provides unique contrast important for the detection and examination of pathophysiology after acute neurologic insults, including spinal cord injury. Diffusion weighted imaging of the rodent spinal cord has typically been evaluated with axial EPI readout. However, Diffusion weighted imaging is prone to motion artifacts, whereas EPI is prone to susceptibility artifacts. In the context of acute spinal cord injury, diffusion filtering has previously been shown to improve detection of injury by minimizing the confounding effects of edema. We propose a diffusion-preparation module combined with a rapid acquisition with relaxation enhancement readout to minimize artifacts for sagittal imaging. METHODS: Sprague-Dawley rats with cervical contusion spinal cord injury were scanned at 9.4 Tesla. The sequence optimization included the evaluation of motion-compensated encoding diffusion gradients, gating strategy, and different spinal cord-specific diffusion-weighting schemes. RESULTS: A diffusion-prepared rapid acquisition with relaxation enhancement achieved high-quality images free from susceptibility artifacts with both second-order motion-compensated encoding and gating necessary for reduction of motion artifacts. Axial diffusivity obtained from the filtered diffusion-encoding scheme had greater lesion-to-healthy tissue contrast (52%) compared to the similar metric from DTI (25%). CONCLUSION: This work demonstrated the feasibility of high-quality diffusion sagittal imaging in the rodent cervical cord with diffusion-prepared relaxation enhancement. The sequence and results are expected to improve injury detection and evaluation in acute spinal cord injury.

Acute Adverse Events After Spinal Cord Injury and Their Relationship to Long-term Neurologic and Functional Outcomes: Analysis From the North American Clinical Trials Network for Spinal Cord Injury.

OBJECTIVES: There are few contemporary, prospective multicenter series on the spectrum of acute adverse events and their relationship to long-term outcomes after traumatic spinal cord injury. The goal of this study is to assess the prevalence of adverse events after traumatic spinal cord injury and to evaluate the effects on long-term clinical outcome. DESIGN: Multicenter prospective registry. SETTING: Consortium of 11 university-affiliated medical centers in the North American Clinical Trials Network. PATIENTS: Eight-hundred one spinal cord injury patients enrolled by participating centers. INTERVENTIONS: Appropriate spinal cord injury treatment at individual centers. MEASUREMENTS AND MAIN RESULTS: A total of 2,303 adverse events were recorded for 502 patients (63%). Penalized maximum logistic regression models were fitted to estimate the likelihood of neurologic recovery (ASIA Impairment Scale improvement ≥ 1 grade point) and functional outcomes in subjects who developed adverse events at 6 months postinjury. After accounting for potential confounders, the group that developed adverse events showed less neurologic recovery (odds ratio, 0.55; 95% CI, 0.32-0.96) and was more likely to require assisted breathing (odds ratio, 6.55; 95% CI, 1.17-36.67); dependent ambulation (odds ratio, 7.38; 95% CI, 4.35-13.06) and have impaired bladder (odds ratio, 9.63; 95% CI, 5.19-17.87) or bowel function (odds ratio, 7.86; 95% CI, 4.31-14.32) measured using the Spinal Cord Independence Measure subscores. CONCLUSIONS: Results from this contemporary series demonstrate that acute adverse events are common and are associated with worsened long-term outcomes after traumatic spinal cord injury.

Filter-probe diffusion imaging improves spinal cord injury outcome prediction.

OBJECTIVE: Diffusion-weighted imaging (DWI) is a powerful tool for investigating spinal cord injury (SCI), but has limited specificity for axonal damage, which is the most predictive feature of long-term functional outcome. In this study, a technique designed to detect acute axonal injury, filter-probe double diffusion encoding (FP-DDE), is compared with standard DWI for predicting long-term functional and cellular outcomes. METHODS: This study extends FP-DDE to predict long-term functional and histological outcomes in a rat SCI model of varying severities (n = 58). Using a 9.4T magnetic resonance imaging (MRI) system, a whole-cord FP-DDE spectroscopic voxel was acquired in 3 minutes at the lesion site and compared to DWI at 48 hours postinjury. Relationships with chronic (30-day) locomotor and histological outcomes were evaluated with linear regression. RESULTS: The FP-DDE measure of parallel diffusivity (ADC|| ) was significantly related to chronic hind limb locomotor functional outcome (R2 = 0.63, p < 0.0001), and combining this measurement with acute functional scores demonstrated prognostic benefit versus functional testing alone (p = 0.0007). Acute ADC|| measurements were also more closely related to the number of injured axons measured 30 days after the injury than standard DWI. Furthermore, acute FP-DDE images showed a clear and easily interpretable pattern of injury that closely corresponded with chronic MRI and histology observations. INTERPRETATION: Collectively, these results demonstrate FP-DDE benefits from greater specificity for acute axonal damage in predicting functional and histological outcomes with rapid acquisition and fully automated analysis, improving over standard DWI. FP-DDE is a promising technique compatible with clinical settings, with potential research and clinical applications for evaluation of spinal cord pathology. Ann Neurol 2018;83:37-50.

The challenge of recruitment for neurotherapeutic clinical trials in spinal cord injury.

STUDY DESIGN: Narrative review by individuals experienced in the recruitment of participants to neurotherapeutic clinical trials in spinal cord injury (SCI). OBJECTIVES: To identify key problems of recruitment and explore potential approaches to overcoming them. METHODS: Published quantitative experience with recruitment of large-scale, experimental neurotherapeutic clinical studies targeting central nervous system and using primary outcome assessments validated for SCI over the last 3 decades was summarized. Based on this experience, potential approaches to improving recruitment were elicited from the authors. RESULTS: The rate of recruitment has varied between studies, depending on protocol design and other factors, but particularly inclusion/exclusion criteria. The recruitment rate also ranged over an order of magnitude between individual centers in a given study. In older multicenter studies, average recruitment rate was approximately one person per study center per month. More recent trials experienced lower rates of recruitment and potential reasons for this trend were examined. The current roles and potential of various stakeholder organizations in addressing problems of recruitment were explored. In addition, recent developments in methodology may help reduce the number of subjects required for well-powered studies. CONCLUSIONS: Several approaches are emerging to improve clinical trial design, efficacy outcome measures, and quantifiable surrogate markers, all of which should reduce the number of participants required for adequate statistical power. There is a growing sense of cooperation between various stakeholders but more should be done to bring together consumer and provider groups to improve recruitment and the effectiveness and relevance of neurotherapeutic clinical trials.

Correlation of magnetic resonance diffusion tensor imaging parameters with American Spinal Injury Association score for prognostication and long-term outcomes.

OBJECTIVEConventional MRI is routinely used to demonstrate the anatomical site of spinal cord injury (SCI). However, quantitative and qualitative imaging parameters have limited use in predicting neurological outcomes. Currently, there are no reliable neuroimaging biomarkers to predict short- and long-term outcome after SCI.METHODSA prospective cohort of 23 patients with SCI (19 with cervical SCI [CSCI] and 4 with thoracic SCI [TSCI]) treated between 2007 and 2014 was included in the study. The American Spinal Injury Association (ASIA) score was determined at the time of arrival and at 1-year follow-up. Only 15 patients (12 with CSCI and 3 with TSCI) had 1-year follow-up. Whole-cord fractional anisotropy (FA) was determined at C1-2, following which C1-2 was divided into upper, middle, and lower segments and the corresponding FA value at each of these segments was calculated. Correlation analysis was performed between FA and ASIA score at time of arrival and 1-year follow-up.RESULTSCorrelation analysis showed a positive but nonsignificant correlation (p = 0.095) between FA and ASIA score for all patients (CSCI and TCSI) at the time of arrival. Additional regression analysis consisting of only patients with CSCI showed a significant correlation (p = 0.008) between FA and ASIA score at time of arrival as well as at 1-year follow-up (p = 0.025). Furthermore, in case of patients with CSCI, a significant correlation between FA value at each of the segments (upper, middle, and lower) of C1-2 and ASIA score at time of arrival was found (p = 0.017, p = 0.015, and p = 0.002, respectively).CONCLUSIONSIn patients with CSCI, the measurement of diffusion anisotropy of the high cervical cord (C1-2) correlates significantly with injury severity and long-term follow-up. However, this correlation is not seen in patients with TSCI. Therefore, FA can be used as an imaging biomarker for evaluating neural injury and monitoring recovery in patients with CSCI.

Rapid in vivo detection of rat spinal cord injury with double-diffusion-encoded magnetic resonance spectroscopy.

PURPOSE: Diffusion-weighted imaging is a common experimental tool for evaluating spinal cord injury (SCI), yet it suffers from complications that decrease its clinical effectiveness. The most commonly used technique, diffusion tensor imaging (DTI), is often confounded by effects of edema accompanying acute SCI, limiting its sensitivity to the important functional status marker of axonal integrity. The purpose of this study is to introduce a novel diffusion-acquisition method with the goal of overcoming these limitations. METHODS: A double diffusion encoding (DDE) pulse sequence was implemented with a diffusion-weighted filter orthogonal to the spinal cord for suppressing nonneural signals prior to diffusion weighting parallel to the cord. A point-resolved spectroscopy readout (DDE-PRESS) was used for improved sensitivity and compared with DTI in a rat model of SCI with varying injury severities. RESULTS: The DDE-PRESS parameter, restricted fraction, showed a strong relationship with injury severity (P < 0.001, R2 = 0.67). Although the whole-cord averaged DTI parameter values exhibited only minor injury relationships, a weighted region of interest (ROI) based DTI analysis improved sensitivity to injury (P < 0.001, R2 = 0.66). CONCLUSIONS: In a rat model of SCI, DDE-PRESS demonstrated high sensitivity to injury with substantial decreases in acquisition time and data processing. This method shows promise for application in rapid evaluation of SCI severity. Magn Reson Med 77:1639-1649, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Severity of spinal cord injury influences diffusion tensor imaging of the brain.

BACKGROUND: The purpose of this study was to determine whether DTI changes in the brain induced by a thoracic spinal cord injury are sensitive to varying severity of spinal contusion in rats. METHODS: A control, mild, moderate, or severe contusion injury was administered over the eighth thoracic vertebral level in 32 Sprague-Dawley rats. At 11 weeks postinjury, ex vivo DTI of the brain was performed on a 9.4T Bruker scanner using a pulsed gradient spin-echo sequence. RESULTS: Mean water diffusion in the internal capsule regions of the brain and pyramid locations of the brainstem were correlated with motor function (r(2) = 0.55). Additionally, there were significant differences between injury severity groups for mean diffusivity and fractional anisotropy at regions associated with the corticospinal tract (P = 0.05). CONCLUSION: These results indicate that DTI is sensitive to changes in brain tissue as a consequence of thoracic SCI.

Detection of acute nervous system injury with advanced diffusion-weighted MRI: a simulation and sensitivity analysis.

Diffusion-weighted imaging (DWI) is a powerful tool to investigate the microscopic structure of the central nervous system (CNS). Diffusion tensor imaging (DTI), a common model of the DWI signal, has a demonstrated sensitivity to detect microscopic changes as a result of injury or disease. However, DTI and other similar models have inherent limitations that reduce their specificity for certain pathological features, particularly in tissues with complex fiber arrangements. Methods such as double pulsed field gradient (dPFG) and q-vector magic angle spinning (qMAS) have been proposed to specifically probe the underlying microscopic anisotropy without interference from the macroscopic tissue organization. This is particularly important for the study of acute injury, where abrupt changes in the microscopic morphology of axons and dendrites manifest as focal enlargements known as beading. The purpose of this work was to assess the relative sensitivity of DWI measures to beading in the context of macroscopic fiber organization and edema. Computational simulations of DWI experiments in normal and beaded axons demonstrated that, although DWI models can be highly specific for the simulated pathologies of beading and volume fraction changes in coherent fiber pathways, their sensitivity to a single idealized pathology is considerably reduced in crossing and dispersed fibers. However, dPFG and qMAS have a high sensitivity for beading, even in complex fiber tracts. Moreover, in tissues with coherent arrangements, such as the spinal cord or nerve fibers in which tract orientation is known a priori, a specific dPFG sequence variant decreases the effects of edema and improves specificity for beading. Collectively, the simulation results demonstrate that advanced DWI methods, particularly those which sample diffusion along multiple directions within a single acquisition, have improved sensitivity to acute axonal injury over conventional DTI metrics and hold promise for more informative clinical diagnostic use in CNS injury evaluation.

An Update of a Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on the Role and Timing of Decompressive Surgery.

STUDY DESIGN: Clinical practice guideline development. OBJECTIVES: Acute spinal cord injury (SCI) can result in devastating motor, sensory, and autonomic impairment; loss of independence; and reduced quality of life. Preclinical evidence suggests that early decompression of the spinal cord may help to limit secondary injury, reduce damage to the neural tissue, and improve functional outcomes. Emerging evidence indicates that "early" surgical decompression completed within 24 hours of injury also improves neurological recovery in patients with acute SCI. The objective of this clinical practice guideline (CPG) is to update the 2017 recommendations on the timing of surgical decompression and to evaluate the evidence with respect to ultra-early surgery (in particular, but not limited to, <12 hours after acute SCI). METHODS: A multidisciplinary, international, guideline development group (GDG) was formed that consisted of spine surgeons, neurologists, critical care specialists, emergency medicine doctors, physical medicine and rehabilitation professionals, as well as individuals living with SCI. A systematic review was conducted based on accepted methodological standards to evaluate the impact of early (within 24 hours of acute SCI) or ultra-early (in particular, but not limited to, within 12 hours of acute SCI) surgery on neurological recovery, functional outcomes, administrative outcomes, safety, and cost-effectiveness. The GRADE approach was used to rate the overall strength of evidence across studies for each primary outcome. Using the "evidence-to-recommendation" framework, recommendations were then developed that considered the balance of benefits and harms, financial impact, patient values, acceptability, and feasibility. The guideline was internally appraised using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool. RESULTS: The GDG recommended that early surgery (≤24 hours after injury) be offered as the preferred option for adult patients with acute SCI regardless of level. This recommendation was based on moderate evidence suggesting that patients were 2 times more likely to recover by ≥ 2 ASIA Impairment Score (AIS) grades at 6 months (RR: 2.76, 95% CI 1.60 to 4.98) and 12 months (RR: 1.95, 95% CI 1.26 to 3.18) if they were decompressed within 24 hours compared to after 24 hours. Furthermore, patients undergoing early surgery improved by an additional 4.50 (95% 1.70 to 7.29) points on the ASIA Motor Score compared to patients undergoing surgery after 24 hours post-injury. The GDG also agreed that a recommendation for ultra-early surgery could not be made on the basis of the current evidence because of the small sample sizes, variable definitions of what constituted ultra-early in the literature, and the inconsistency of the evidence. CONCLUSIONS: It is recommended that patients with an acute SCI, regardless of level, undergo surgery within 24 hours after injury when medically feasible. Future research is required to determine the differential effectiveness of early surgery in different subpopulations and the impact of ultra-early surgery on neurological recovery. Moreover, further work is required to define what constitutes effective spinal cord decompression and to individualize care. It is also recognized that a concerted international effort will be required to translate these recommendations into policy.

Characterization and limitations of diffusion tensor imaging metrics in the cervical spinal cord in neurologically intact subjects.

PURPOSE: To characterize diffusion tensor imaging (DTI) metrics across all levels of the cervical spinal cord (CSC) and to study the impact of age and signal quality on these metrics. MATERIALS AND METHODS: DTI metrics were calculated for gray matter (GM) and white matter (WM) funiculi throughout the CSC (C1-T1) in 25 healthy subjects (22-85 years old). Signal-to-noise ratios (SNRs) and mean DTI metrics were measured for the upper (C1-3), middle (C4-6) and lower (C7-T1) cervical segments. Age-related changes in DTI metrics were analyzed for the individual segment groups. RESULTS: Fractional anisotropy (FA), mean diffusivity (MD) and transverse apparent diffusion coefficient (tADC) showed significant differences between GM and WM funiculi. Significant age-related changes were observed in FA in upper and middle CSC segments but not in the lower CSC. The median SNR was significantly lower in the middle and lower segment groups as compared to the upper levels, contributing to poor spatial resolution in these regions. CONCLUSION: This study provides DTI data for GM and WM funiculi throughout the CSC. While DTI metrics may be used to define cord pathology, variations in metrics due to age and signal quality need to be accounted for before making definitive conclusions.

Differential Trajectory of Diffusion and Perfusion Magnetic Resonance Imaging of Rat Spinal Cord Injury.

Traumatic spinal cord injury causes rapid neuronal and vascular injury, and predictive biomarkers are needed to facilitate acute patient management. This study examined the progression of magnetic resonance imaging (MRI) biomarkers after spinal cord injury and their ability to predict long-term neurological outcomes in a rodent model, with an emphasis on diffusion-weighted imaging (DWI) markers of axonal injury and perfusion-weighted imaging of spinal cord blood flow (SCBF). Adult Sprague-Dawley rats received a cervical contusion injury of varying severity (injured = 30, sham = 9). MRI at 4 h, 48-h, and 12-weeks post-injury included T1, T2, perfusion, and DWI. Locomotor outcome was assessed up to 12 weeks post-injury. At 4 h, the deficit in SCBF was larger than the DWI lesion, and although SCBF partially recovered by 48 h, the DWI lesion expanded. At 4 h, the volume of the SCBF deficit (R2 = 0.56, padj < 0.01) was significantly correlated with 12-week locomotor outcome, whereas DWI (R2 = 0.30, padj < 0.01) was less predictive of outcome. At 48 h, SCBF (R2 = 0.41, padj < 0.01) became less associated with outcome, and DWI (R2 = 0.38, padj < 0.01) lesion volume became more closely related to outcome. Spinal cord perfusion has unique spatiotemporal dynamics compared with diffusion measures of axonal damage and highlights the importance of acute perfusion abnormalities. Perfusion and diffusion offer complementary and clinically relevant insight into physiological and structural abnormalities following spinal cord injury beyond those afforded by T1 or T2 contrasts.

Evolving Profile of Acute Spinal Cord Injury Demographics, Outcomes, and Surgical Treatment in North America: Analysis of a Prospective Multi-Center Dataset of 989 Patients.

Changes in demography and injury patterns have altered the profile and outcome of acute spinal cord injury (SCI) over time. This study sought to describe recent trends in epidemiology and early clinical outcomes using the multi-center North American Clinical Trial Network (NACTN) for Spinal Cord Injury Registry. All participants with blunt acute traumatic SCI (n = 782) were grouped into three five-year time intervals from 2005 to 2019 (2005-2009, 2010-2014, and 2015-2019). Baseline demographics, clinical scores, medical co-morbidities, as well as early clinical outcomes were extracted. Categorical and continuous variables were analyzed to determine between-group differences. Subgroup analysis was performed for participants <50 and ≥50 years of age. Over the duration of the study period, there was an increase in age at presentation (p = 0.0077) as well as a greater incidence of falls as the mechanism of injury. Participants who were ≥50 years of age were more likely to sustain incomplete SCI (<0.0003) and central cord syndrome (< 0.0001). In the most recent period (2015-2019), a greater proportion of NACTN participants underwent surgery within 24 h of injury (63% vs. 41% vs. 41%, p = 0.0001). There was a statistically significant increase in cardiac complications (p < 0.0001) and decrease in pulmonary complications (p < 0.0001) during the study period. Data from the NACTN registry shows that the age of participants with acute SCI is increasing, falls have become the major mechanism of injury, and central cord injury is becoming increasingly prevalent. While early surgical intervention for acute SCI is more common in recent years, cardiac complications are more prevalent while pulmonary complications are less prevalent.

Variability in Early Surgery for Acute Cervical Spinal Cord Injury Patients: An Opportunity for Enhanced Care Delivery.

Data supporting the benefits of early surgical intervention in acute spinal cord injury (SCI) is growing. For early surgery to be accomplished, understanding the causes of variabilities that effect the timing of surgery is needed to achieve this goal. The purpose of this analysis is to determine factors that affect the timing of surgery for acute cervical SCI within the North American Clinical Trials Network (NACTN) for SCI registry. Patients in the NACTN SCI registry from 2005 to 2019 with a cervical SCI, excluding acute traumatic central cord syndrome, were analyzed for time elapsed from injury to arrival to the hospital, and time to surgery. Two categories were defined: 1) Early Arrival with Early Surgery (EAES) commenced within 24 h of injury, and 2) Early Arrival but Delayed Surgery (EADS), with surgery occurring between 24 to 72 h post-injury. Patients' demographic features, initial clinical evaluation, medical comorbidities, neurological status, surgical intervention, complications, and outcome data were correlated with respect to the two arrival groups. Of the 222 acute cervical SCI patients undergoing surgery, 163 (73.4%) were EAES, and 59 (26.6%) were EADS. There was no statistical difference in arrival time between the EAES and EADS groups. There was a statistical difference in the median arrival time to surgery between the EAES group (9 h) compared with the EADS group (31 h; p < 0.05). There was no statistical difference in race, sex, age, mechanism of injury, Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II scores, or medical comorbidities between the two groups, but the EAES group did present with a significantly lower systolic blood pressure (p < 0.05). EADS patients were more likely to present as an American Spinal Injury Association Impairment Scale (AIS) D than EAES (p < 0.05). Early surgery was statistically more likely to occur if the injury occurred over the weekend (p < 0.05). There were variations in the rates of early surgery between the eight NACTN sites within the study, ranging from 57 to 100%. Of the 114 patients with 6-month outcome data, there was no significant change between the two groups regarding AIS grade change and motor/pin prick/light touch score recovery. A trend towards improved motor scores with early surgery was not statistically significant (p = 0.21). Although there is data that surgery within 24 h of injury improves outcomes and can be performed safely, there remain variations in care outside of clinical trials. In the present study of cervical SCI, NACTN achieved its goal of early surgery in 73.4% of patients from 2005-2019 who arrived within 24 h of their injury. Variability in achieving this goal was related to severity of neurological injury, the day of the week, and the treating NACTN center. Evaluating variations within our network improves understanding of potential systemic limitations and our decision-making process to accomplish the goal of early surgery.

Trends in the Use of Corticosteroids in the Management of Acute Spinal Cord Injury in North American Clinical Trials Network Sites.

Immunomodulatory therapeutics represent a potential neuroprotective strategy for the management of acute spinal cord injury (SCI). One of the most intensely debated neuroprotective drugs has been methylprednisolone sodium succinate (MPSS), which was investigated initially for its role in mitigating lipid peroxidation. More recently, the anti-inflammatory/immunomodulatory properties of MPSS have been increasingly appreciated. Over the past two decades, several systematic reviews and clinical practice guidelines related to MPSS use in SCI have been published. The goal of this study was to investigate the temporal changes in the use of steroids at North American Clinical Trials Network (NACTN) centers and to correlate these changes with the evolution in published literature and guidelines. Data on patients enrolled from 2008-2018 in the prospective, multi-center NACTN registry, and in whom information related to the use of steroids was available, were analyzed. Patients were stratified based on whether they received steroids or not. The primary outcome was the change in the rate of steroid use per year between 2008 and 2018. Secondary outcomes included cardiac, gastrointestinal and genitourinary (GIGU), pulmonary, and dermatological complications. We identified 608 patients, of whom 171 (28.1%) were given steroids. In 2008 and 2009, the prevailing paradigm across NACTN centers was in favor of steroid administration and as such 70% (n = 56) of patients received steroids in 2008 and 71.9% (n = 46) in 2009. An abrupt practice reversal was observed in 2010, whereby only 19.7% of patients (n = 14) received steroids, a trend that continued over subsequent years. Increasing literature in the 2000s arguing against the use of steroids culminated in the 2013 CNS/AANS practice guidelines for the management of acute SCI. These guidelines recommended against the use of MPSS for the treatment of those with acute SCI. Over the following years (2013-2018), steroids continued to be an uncommonly used therapeutic option in NACTN centers (range 3.9-16.9%). Patients receiving steroids had significantly higher rates of pulmonary complications (87%, n = 147) compared with those not receiving steroids (73%, n = 265; p = 0.0003). Compared with patients receiving steroids, however, those who did not receive steroids had significantly higher rates of cardiac (40%, [n = 146] versus 23%, [n = 39]; p = 0.0001) and gastrointestinal/genitourinary complications (55%, [n = 189], versus 31%, [n = 52]; p < 0.0001). The 2013 AANS/CNS guidelines and preceding literature appeared to have an impact on dramatically lowering the rates of corticosteroid use for acute SCI in NACTN sites after 2009. Of note, this analysis may not reflect the impact of the 2017 AO Spine Clinical Practice guidelines, which suggested the use of methylprednisolone as a valid practice option for acute SCI, especially for cervical injuries. Enhanced patient involvement in the clinical decision-making process and opportunities to personalize SCI management exist in reference to the use of MPSS in acute SCI.

Mortality in ASIA Impairment Scale grade A to D Patients With Odontoid Fracture and Magnetic Resonance Imaging Evidence of Spinal Cord Injury.

Odontoid fractures are common, often presenting in the elderly after a fall and infrequently associated with traumatic spinal cord injury (tSCI). The goal of this study was to analyze predictors of mortality and neurological outcome when odontoid fractures were associated with signal change on magnetic resonance imaging (MRI) at admission. Over an 18-year period (2001-2019), 33 patients with odontoid fractures and documented tSCI on MRI were identified. Mean age was 65.3 years (standard deviation [SD] = 17.2), and 21 patients were male. The mechanism of injury was falls in 25 patients, motor vehicle accidents in 5, and other causes in 3. Mean Injury Severity Score (ISS) was 40.5 (SD = 30.2), Glasgow Coma Scale (GCS) score was 13 (SD = 3.4), and American Spinal Injury Association (ASIA) motor score (AMS) was 51.6 (SD = 42.7). ASIA Impairment Scale (AIS) grade was A, B, C, and D in 9, 2, 3, and 19 patients, respectively. Mean intramedullary lesion length was 32.3 mm (SD = 18.6). The odontoid peg was displaced ventral or dorsal in 15 patients. Twenty patients had surgical intervention: anterior odontoid screw fixation in 7 and posterior spinal fusion in 13. Eleven (33.3%) patients died in this series: withdrawal of medical care in 5; anoxic brain injury in 4; and failure of critical care management in 2. Univariate logistic regression indicated that GCS score (p < 0.014), AMS (p < 0.002), AIS grade (p < 0.002), and ISS (p < 0.009) were risk factors for mortality. Multi-variate regression analysis indicated that only AMS (p < 0.002) had a significant relationship with mortality when odontoid fracture was associated with tSCI (odds ratio, 0.963; 95% confidence interval, 0.941-0.986).