Initial feasibility evaluation of the RISES system: An innovative and activity-based closed-loop framework for spinal cord injury rehabilitation and recovery.

Background: Electrical stimulation of the spinal cord may improve rewiring of the affected pathways. Immediate modulation of stimulation parameters, and its effects of it on kinematics and electromyographic variables is unclear. Methods: This study piloted the safety and feasibility of the Reynolds Innovative Spinal Electrical Stimulation (RISES) technology with a focus on its novel closed-loop setting. This personalized, task-specific non-invasive stimulation system enables real-time stimulation parameter modulation and supports multi-data acquisition and storage. Four SCI participants underwent a clinical trial coupled with activity-based training. Primary safety outcome measures included adverse events (AEs) and skin integrity; secondary measures were vital signs, pain, and fatigue assessed at the pre, mid, and post-stimulation sessions. The trial included open-loop and closed-loop blocks of transcutaneous spinal cord stimulation (tSCS). Results: Results showed no serious adverse events, with skin integrity unaffected. Vital signs and pain showed no significant differences across session timepoints. Fatigue levels differed significantly with post-session > mid-session > pre-session. Comparisons between open-loop and closed-loop blocks showed no significant differences in setup time, vital signs, pain, or fatigue. Average stimulation duration per task was significantly longer for open-loop (467.6 sec) than Closed-loop (410.8 sec). Conclusions: RISES, demonstrated safety and feasibility. Further work will focus on clinical efficacy.

Acute Implantation of a Bioresorbable Polymer Scaffold in Patients With Complete Thoracic Spinal Cord Injury: A Randomized Controlled Trial (INSPIRE 2.0).

BACKGROUND AND OBJECTIVES: Traumatic spinal cord injury (SCI) remains a devastating condition with no proven effective treatment options available. In a prior single-arm study of patients with thoracic complete SCI (INSPIRE; ClinicalTrials.gov, NCT02138110), acute implantation of an investigational bioresorbable polymer scaffold (Neuro-Spinal Scaffold [NSS]) appeared to be safe through 24 months postimplantation and was associated with an American Spinal Injury Association Impairment Scale (AIS) conversion rate that exceeded historical controls. Here, we evaluated whether NSS implantation demonstrates probable benefit for safety and neurological recovery in patients with thoracic complete SCI vs standard-of-care spine surgery. METHODS: INSPIRE 2.0 was a randomized, controlled, parallel, multicenter study conducted at Level I trauma centers in the United States (ClinicalTrials.gov, NCT03762655; funded by InVivo Therapeutics Corporation). Patients with AIS grade A, thoracic (T2-T12), nonpenetrating SCI requiring spine surgery ≤7 days postinjury were randomized (1:1, computer-generated allocation) to undergo NSS implantation or spine surgery alone (control group). Patients and follow-up International Standards for Neurological Classification of SCI assessors were blinded. A predefined study success criterion required the proportion of patients with improvement of ≥1 AIS grade at 6 months postsurgery (primary endpoint) to be ≥20% higher in the NSS group than in the control group. RESULTS: Target enrollment was reached (N = 20) with 10 patients randomized and analyzed in each group. At 6 months postsurgery, an improvement in the AIS grade was reported in 2 NSS patients (20%; both to AIS C) and 3 control group patients (30%; to AIS B [n = 2] or AIS C [n = 1]). No serious or unanticipated adverse device effects were reported. The study was closed to further follow-up because of not meeting its primary endpoint. CONCLUSION: In this small group of patients with thoracic complete (AIS A) SCI, implantation of an intraparenchymal bioresorbable scaffold did not produce probable clinical benefit. However, this study provides evidence that surgical intervention in an injured spinal cord parenchyma may be performed safely.

Controversies in the Management of Type II Odontoid Fractures.

The management of type II odontoid fractures in the elderly is controversial, as these patients often have numerous medical comorbidities that increase the risks of surgery, but they may also fail to achieve fracture healing with nonsurgical management. Recent changes in technology and surgeon attitudes may influence the preferred approach to both surgical and nonsurgical treatments for many clinicians. While bony fracture healing remains the goal of management, a stable fibrous union is increasingly considered a satisfactory outcome. The optimal surgical approach remains debated, with some authors raising concerns about the risk of swallowing dysfunction being particularly problematic with odontoid screw placement in the elderly. The use of BMP-2 applied either anteriorly into the fracture site or posteriorly in the interlaminar space and placement of temporary posterior fixation to be removed upon demonstration of anterior bony healing are novel surgical techniques that are presently the subject of investigation. A clearer understanding of the currently available treatment options and the associated controversies may improve clinician decision-making and potentially better patient outcomes in the management of type II odontoid fractures for the growing geriatric population.

Traumatic Central Cord Syndrome.

Central cord syndrome (CCS) is the most common form of incomplete spinal cord injury, with an increasing incidence with the aging population. This is a clinical diagnosis defined by weakness greater in the upper than lower extremities and often prominent sensory complaints in the hands. CCS is typically seen in individuals with underlying cervical canal stenosis from spondylosis who experience sudden forceful movement of the neck, especially hyperextension, resulting in contusion of the spinal cord. The prognosis in CCS is relatively favorable with improvement in neurological deficits, except for fine motor control of the hands. Neuropathic pain may persist even in those with excellent motor recovery. Nonoperative management may be appropriate in selected patients, but surgery is usually necessary in those with poor neurological recovery or further deterioration. The optimal timing of surgical intervention has not been defined, but recent evidence suggests that early surgery (≤24 h) may lead to greater neurological recovery, shorter hospital stay, and fewer inpatient complications. Management in any given patient must be considered in the context of the anatomy and location of spinal cord compression, the presence of fractures or ligamentous instability, the temporal course of signs and symptoms, as well as the patient's overall health.

Periaqueductal gray connectivity in spinal cord injury-induced neuropathic pain.

BACKGROUND AND PURPOSE: Neuropathic pain (NP) is a debilitating condition following spinal cord injury (SCI). The role of periaqueductal gray (PAG) in NP development following SCI remains underexplored. Using resting-state functional MRI (rsfMRI), our study aimed to demonstrate the alterations in functional connectivity (FC) of PAG in NP following SCI. METHODS: Ten SCI patients (SCI + NP, n = 7, and SCI - NP, n = 3), alongside 10 healthy controls (HCs), were enrolled. rsfMRI was conducted followed by seed-to-voxel analysis using PAG as the seed region and then group-based analysis comprising three groups (SCI + NP, SCI - NP, and HC). Age and gender were considered as confounding variables. RESULTS: Compared to HCs, SCI + NP demonstrated decreased FC between PAG and right insula, right frontal orbital cortex, right pallidum, dorsal raphe nucleus (DRN), red nuclei (RN), substantia nigra (SN), and ventral posterolateral (VPL) thalamic nuclei. Compared to SCI - NP, SCI + NP demonstrated increased FC between PAG and posterior cingulate cortex (PCC), hippocampus, cerebellar vermis lobules IV and V, and thalamic structures (posterior and lateral pulvinar, the mediodorsal nuclei, and the ventral lateral nuclei). Additionally, decreased FC between the PAG and VPL, geniculate bodies, intralaminar nuclei of thalamus, DRN, RN, SN, and prefrontal cortex was observed in this comparison. CONCLUSIONS: Altered FC between PAG and right anterior insula, VPL, DRN, RN, SN, cerebellar vermis lobules IV and V, frontal cortex, and PCC was associated with NP sequelae of SCI. Additionally, SCI was independently associated with decreased FC between PAG and right posterior insula, cerebellar lobules IV and V, and cerebellar vermis lobules III, IV, and V.

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.

Immediate vs delayed venous thromboembolism prophylaxis following spine surgery: increased rate of unplanned reoperation for postoperative hematoma with immediate prophylaxis.

BACKGROUND CONTEXT: There is significant variability in postoperative chemoprophylaxis protocols amongst spine providers due to perceived risks and benefits, but limited data on the topic. At our institution, both orthopaedic spine and neurosurgery departments utilize unfractionated subcutaneous heparin in identical dosages and frequency, with the only difference being time to initiation postoperatively. PURPOSE: To evaluate the rate of symptomatic venous thromboembolism (VTEs) and unplanned reoperation for hematoma based on timing of chemoprophylaxis initiation. STUDY DESIGN/SETTING: Single institution retrospective cohort study. PATIENT SAMPLE: Patients undergoing elective spine surgery, excluding patients undergoing surgery in the setting of trauma, malignancy, or infection. OUTCOME MEASURES: Outcome measures included the diagnosis of a venous thromboembolism within 90 days of surgery and unplanned reoperation for a hematoma. METHODS: Patients undergoing elective spine surgery from 2017 to 2021 were grouped based on chemoprophylaxis protocol. In the "immediate" group, patients received subcutaneous heparin 5000 units every 8 hours starting immediately after surgery, and in the "delayed" group, patients received chemoprophylaxis starting postoperative day (POD)-2 for any decompressions and/or fusions involving a spinal cord level (ie, L2 and above) and POD-1 for those involving only levels below the spinal cord (ie, L3 to pelvis). A cox proportional hazards model was created to assess independent predictors of venous thromboembolic events, while a logistic regression was utilized for unplanned reoperations for hematoma. RESULTS: Of 8,704 patients, a total of 98 (1.13%) VTE events occurred, of which 43 (0.49%) were pulmonary embolism. Fifty-four patients (0.62%) had unplanned reoperations for postoperative hematomas. On cox proportional hazards model analysis, immediate chemoprophylaxis was not protective of a venous thromboembolism (Hazard Ratio: 1.18, p=.436), but, it was a significant independent predictor for unplanned reoperation for hematoma on multivariable logistic regression modeling (Odds Ratio: 3.29, p<.001). CONCLUSIONS: Both chemoprophylaxis protocols in our study resulted in low rates of VTE and postoperative hematoma. However, our findings suggest that the delayed chemoprophylaxis protocol may mitigate postoperative hematoma formation without increasing the risk for a thrombotic event.

Riluzole for Degenerative Cervical Myelopathy: A Secondary Analysis of the CSM-PROTECT Trial.

Importance: The modified Japanese Orthopaedic Association (mJOA) scale is the most common scale used to represent outcomes of degenerative cervical myelopathy (DCM); however, it lacks consideration for neck pain scores and neglects the multidimensional aspect of recovery after surgery. Objective: To use a global statistical approach that incorporates assessments of multiple outcomes to reassess the efficacy of riluzole in patients undergoing spinal surgery for DCM. Design, Setting, and Participants: This was a secondary analysis of prespecified secondary end points within the Efficacy of Riluzole in Surgical Treatment for Cervical Spondylotic Myelopathy (CSM-PROTECT) trial, a multicenter, double-blind, phase 3 randomized clinical trial conducted from January 2012 to May 2017. Adult surgical patients with DCM with moderate to severe myelopathy (mJOA scale score of 8-14) were randomized to receive either riluzole or placebo. The present study was conducted from July to December 2023. Intervention: Riluzole (50 mg twice daily) or placebo for a total of 6 weeks, including 2 weeks prior to surgery and 4 weeks following surgery. Main Outcomes and Measures: The primary outcome measure was a difference in clinical improvement from baseline to 1-year follow-up, assessed using a global statistical test (GST). The 36-Item Short Form Health Survey Physical Component Score (SF-36 PCS), arm and neck pain numeric rating scale (NRS) scores, American Spinal Injury Association (ASIA) motor score, and Nurick grade were combined into a single summary statistic known as the global treatment effect (GTE). Results: Overall, 290 patients (riluzole group, 141; placebo group, 149; mean [SD] age, 59 [10.1] years; 161 [56%] male) were included. Riluzole showed a significantly higher probability of global improvement compared with placebo at 1-year follow-up (GTE, 0.08; 95% CI, 0.00-0.16; P = .02). A similar favorable global response was seen at 35 days and 6 months (GTE for both, 0.07; 95% CI, -0.01 to 0.15; P = .04), although the results were not statistically significant. Riluzole-treated patients had at least a 54% likelihood of achieving better outcomes at 1 year compared with the placebo group. The ASIA motor score and neck and arm pain NRS combination at 1 year provided the best-fit parsimonious model for detecting a benefit of riluzole (GTE, 0.11; 95% CI, 0.02-0.16; P = .007). Conclusions and Relevance: In this secondary analysis of the CSM-PROTECT trial using a global outcome technique, riluzole was associated with improved clinical outcomes in patients with DCM. The GST offered probability-based results capable of representing diverse outcome scales and should be considered in future studies assessing spine surgery outcomes.

Comparison of Traumatic Spinal Fracture Patterns Between Motorcyclists and Occupants of Other Nonheavy Motor Vehicles: A Report from the National Spinal Cord and Column Injury Registry of Iran.

OBJECTIVE: To compare traumatic spinal injury patterns between motorcyclists and occupants of other nonheavy motor vehicles using data from the National Spinal Cord and Column Injury Registry of Iran. METHODS: All drivers/riders and passengers of motorcycles, cars, pick-up trucks, and vans registered between January 2017 to July 2023, met the inclusion criteria for the present study. The logistic regression models were used to compare the patterns of vertebral fracture between the 2 groups. RESULTS: One thousand seven hundred twenty-six spinal fracture patients were identified, 385 (22.3%) motorcyclists and 1341 (77.7%) car occupants with mean ages 33.2 ± 14.3 and 36.1 ± 13.6 years, respectively (P < 0.001). Only 45 (11.7%) motorcyclists used helmets, whereas 856 (63.8%) car occupants used seat belts (P < 0.001). The average numbers of fractured vertebrae were 3.9 ± 1.4 and 3.7 ± 1.1 among car occupants and motorcyclists, respectively (P = 0.004). The proportions of motorcyclists and car occupants with injuries in each spinal region are as follows: lumbar (50.5% of motorcyclists vs. 40.4% of car occupants; P = 0.003), thoracic (39.2% vs. 30.9%; P = 0.01), cervical (24.3% vs. 37.0%; P < 0.001), and sacral (1.3% vs. 7.5%; P < 0.001). The AO Spine type C injuries were present in 6.1% of motorcyclists and 10.1% of car occupants (P = 0.03). CONCLUSIONS: Motorcyclists were younger, less educated, had a higher proportion of males, and less commonly used safety devices than car occupants. The most commonly fractured spine region among both groups was the lumbar region. The cervical and sacral vertebrae fractures were significantly more common in car occupants, whereas the thoracic and lumbar vertebrae fractures were significantly more common in motorcyclists.

Postoperative C5 Palsy after Anterior or Posterior Decompression for Degenerative Cervical Myelopathy: A Subgroup Analysis of the Multicenter, Prospective, Randomized, Phase III, CSM-Protect Clinical Trial.

STUDY DESIGN: Retrospective cohort study of prospectively accrued data. OBJECTIVE: To evaluate a large, prospective, multicentre dataset of surgically treated degenerative cervical myelopathy (DCM) cases on the contemporary risk of C5 palsy with surgical approach. SUMMARY OF BACKGROUND DATA: The influence of surgical technique on postoperative C5 palsy after decompression for DCM is intensely debated. Comprehensive, covariate-adjusted analyses are needed using contemporary data. METHODS: Patients with moderate to severe DCM were prospectively enrolled in the multicenter, randomized, Phase III CSM-Protect clinical trial and underwent either anterior or posterior decompression between Jan 31, 2012 and May 16, 2017. The primary outcome was the incidence of postoperative C5 palsy, defined as the onset of muscle weakness by at least one grade in manual muscle test at the C5 myotome with slight or absent sensory disruption after cervical surgery. Two comparative cohorts were made based on the anterior or posterior surgical approach. Multivariate hierarchical mixed-effects logistic regression was used to estimate odds ratios (OR) with 95% confidence intervals (CI) for C5 palsy. RESULTS: A total of 283 patients were included, and 53.4% underwent posterior decompression. The total incidence of postoperative C5 palsy was 7.4% and was significantly higher in patients who underwent posterior decompression compared with anterior decompression (11.26% vs. 3.03%, P =0.008). After multivariable regression, the posterior approach was independently associated with greater than four times the likelihood of postoperative C5 palsy ( P =0.017). Rates of C5 palsy recovery were comparable between the two surgical approaches. CONCLUSION: The odds of postoperative C5 palsy are significantly higher after posterior decompression compared to anterior decompression for DCM. This may influence surgical decision-making when there is equipoise in deciding between anterior and posterior treatment options for DCM. LEVEL OF EVIDENCE: Therapeutic Level-II.

A Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on Hemodynamic Management.

STUDY DESIGN: Clinical practice guideline development following the GRADE process. OBJECTIVES: Hemodynamic management is one of the only available treatment options that likely improves neurologic outcomes in patients with acute traumatic spinal cord injury (SCI). Augmenting mean arterial pressure (MAP) aims to improve blood perfusion and oxygen delivery to the injured spinal cord in order to minimize secondary ischemic damage to neural tissue. The objective of this guideline was to update the 2013 AANS/CNS recommendations on the hemodynamic management of patients with acute traumatic SCI, acknowledging that much has been published in this area since its publication. Specifically, we sought to make recommendations on 1. The range of mean arterial pressure (MAP) to be maintained by identifying an upper and lower MAP limit; 2. The duration of such MAP augmentation; and 3. The choice of vasopressor. Additionally, we sought to make a recommendation on spinal cord perfusion pressure (SCPP) targets. METHODS: A multidisciplinary guideline development group (GDG) was formed that included health care professionals from a wide range of clinical specialities, patient advocates, and individuals living with SCI. The GDG reviewed the 2013 AANS/CNS guidelines and voted on whether each recommendation should be endorsed or updated. A systematic review of the literature, following PRISMA standards and registered in PROSPERO, was conducted to inform the guideline development process and address the following key questions: (i) what are the effects of goal-directed interventions to optimize spinal cord perfusion on extent of neurological recovery and rates of adverse events at any time point of follow-up? and (ii) what are the effects of particular monitoring techniques, perfusion ranges, pharmacological agents, and durations of treatment on extent of neurological recovery and rates of adverse events at any time point of follow-up? The GDG combined the information from this systematic review with their clinical expertise in order to develop recommendations on a MAP target range (specifically an upper and lower limit to target), the optimal duration for MAP augmentation, and the use of vasopressors or inotropes. Using methods outlined by the GRADE working group, recommendations were formulated that considered the balance of benefits and harms, financial impact, acceptability, feasibility and patient preferences. RESULTS: The GDG suggested that MAP should be augmented to at least 75-80 mmHg as the "lower limit," but not actively augmented beyond an "upper limit" of 90-95 mmHg in order to optimize spinal cord perfusion in acute traumatic SCI. The quality of the evidence around the "target MAP" was very low, and thus the strength of this recommendation is weak. For duration of hemodynamic management, the GDG "suggested" that MAP be augmented for a duration of 3-7 days. Again, the quality of the evidence around the duration of MAP support was very low, and thus the strength of this recommendation is also weak. The GDG felt that a recommendation on the choice of vasopressor or the use of SCPP targets was not warranted, given the dearth of available evidence. CONCLUSION: We provide new recommendations for blood pressure management after acute SCI that acknowledge the limitations of the current evidence on the relationship between MAP and neurologic recovery. It was felt that the low quality of existing evidence and uncertainty around the relationship between MAP and neurologic recovery justified a greater range of MAP to target, and for a broader range of days post-injury than recommended in previous guidelines. While important knowledge gaps still remain regarding hemodynamic management, these recommendations represent current perspectives on the role of MAP augmentation for acute SCI.

Influence of Body Mass Index on Surgical and Patient Outcomes for Cervical Spine Surgery.

STUDY DESIGN: Secondary analysis of prospectively collected registry. OBJECTIVE: We aim to investigate the effects of body mass index (BMI) on postsurgical cervical spine surgery outcomes and identify a potential substratification of obesity with worse outcomes. SUMMARY OF BACKGROUND DATA: The impact of BMI on cervical spine surgery is unknown, with controversial outcomes for patients high and low BMI. METHODS: The cervical spine Quality Outcomes Database was queried for a total of 10,381 patients who underwent single-stage cervical spine surgery. Patients were substratified into 6 groups based on BMI. Surgical outcomes, complications, hospitalization outcomes, and patient-reported outcomes for each cohort, including modified Japanese Orthopedic Association Score, Numeric Rating Scale arm pain, Numeric Rating Scale neck pain, Neck Disability Index, and EuroQol Health Survey, were assessed. Univariate analysis was performed for 3- and 12-month follow-up after surgical intervention. RESULTS: Obese patients (class I, II, and III) requiring spine surgery were statistically younger than nonobese patients and had higher rates of diabetes compared with normal BMI patients. The surgical length was found to be longer for overweight and all classes of obese patients ( P < 0.01). Class III obese patients had higher odds of postoperative complications. Patients with class II and III obesity had lower odds of achieving optimal modified Japanese Orthopedic Association Score at 3 months [OR = 0.8 (0.67-0.94), P < 0.01, OR = 0.68 (0.56-0.82), P < 0.001, respectively] and 12 months [OR = 0.82 (0.68-0.98), P = 0.03, OR = 0.79 (0.64-0.98), P = 0.03, respectively]. CONCLUSIONS: This study investigates the relationship between substratified BMI and postoperative outcomes of cervical spine surgery. Class II and III obese patients have substantially greater risk factors and poor outcomes postoperatively. In addition, low BMI also presents unique challenges for patients. Further research is needed for comprehensive analysis on outcomes of cervical spine surgery after correcting BMI.

The Impact of Interhospital Transfer on the Extent of Neurological Recovery in Acute Traumatic Spinal Cord Injury: Analysis of a Prospective Multicenter Data Set in 970 Cases.

BACKGROUND AND OBJECTIVES: Interhospital transfer from community hospitals to centers specialized in managing traumatically injured individuals can strain patients, healthcare systems, and delay appropriate care. The purpose was to compare long-term neurological outcomes in transferred or directly admitted patients with traumatic spinal cord injury (SCI). METHODS: An ambispective cohort study was conducted using prospectively collected data (between 2005 and 2018) from 11 specialized level 1 trauma centers across the United States and Canada. All patients who underwent surgical management for SCI were included and placed into 2 comparison cohorts: (1) direct admission and (2) transfer from intermediate hospital. Outcomes were change in American Spinal Injury Association Impairment Scale grade and its components: upper-extremity motor, lower-extremity motor, pinprick, and light touch scores from baseline (assessed ≤72 hours after injury) to follow-up (12-52 weeks). Nearest-neighbor 1:1 propensity score matching between the transferred and directly admitted cohorts was performed. Paired analysis using McNemar's test and paired Student's t -test was used to determine the extent of the difference in neurological outcomes. RESULTS: Nine hundred seventy patients (55.5% male, 55.2 ± 18.9 years) with traumatic SCI were directly admitted to a specialized trauma center (N = 474, 48.9%) or transferred from an intermediate hospital (N = 496, 51.1%). After propensity score matching, 283 pairs were matched. Compared with a matched cohort of transferred patients, American Spinal Injury Association Impairment Scale grade improved more in directly admitted patients (56.2% vs 46.3%, P = .024), as did upper-extremity motor score (13.7 ± 12.8 vs 10.4 ± 11.5, P = .018) and light touch score (22.0 ± 29.7 vs 16.9 ± 26.6, P = .034). CONCLUSION: Patients with SCI directly admitted to specialized trauma centers have greater neurological recovery compared with patients transferred from an intermediate hospital. Feasibility of direct admission to a center specialized in the management of acute SCI through implementation of a standardized code program must be further investigated. LEVEL OF EVIDENCE: Therapeutic level II.

Metal artifact reduction around cervical spine implant using diffusion tensor imaging at 3T: A phantom study.

PURPOSE: Diffusion MRI continues to play a key role in non-invasively assessing spinal cord integrity and pre-operative injury evaluation. However, post-operative Diffusion Tensor Imaging (DTI) acquisition of patients with metal implants results in severe geometric distortion. We propose and demonstrate a method to alleviate the technical challenges facing the acquisition of DTI on post-operative cases and longitudinal evaluation of therapeutics. MATERIAL AND METHODS: The described technique is based on the combination of the reduced Field-Of-View (rFOV) strategy and the phase segmented EPI, termed rFOV-PS-EPI. A custom-built phantom based on a cervical spine model with metal implants was used to collect DTI data at 3 Tesla scanner using: rFOV-PS-EPI, reduced Field-Of-View single-shot EPI (rFOV-SS-EPI), and conventional full FOV techniques including SS-EPI, PS-EPI, and readout-segmented EPI (RS-EPI). Geometric distortion, SNR, and signal void were assessed to evaluate images and compare the sequences. A two-sample t-test was performed with p-value of 0.05 or less to indicate statistical significance. RESULTS: The reduced FOV techniques showed better capability to reduce distortions compared to the Full FOV techniques. The rFOV-PS-EPI method provided DTI images of the phantom at the level of the hardware whereas the conventional rFOV-SS-EPI is useful only when the metal is approximately 20 mm away. In addition, compared to the rFOV-SS-EPI technique, the suggested approach produced smaller signal voids area as well as significantly reduced geometric distortion in Circularity (p < 0.005) and Eccentricity (p < 0.005) measurements. No statistically significant differences were found for these geometric distortion measurements between the rFOV-PS-EPI DTI sequence and conventional structural T2 images (p > 0.05). CONCLUSION: The combination of rFOV and a phase-segmented acquisition approach is effective for reducing metal-induced distortions in DTI scan on spinal cord with metal hardware at 3 T.

An Introduction to the North American Clinical Trials Network for Spinal Cord Injury Special Edition: Reflections on Accomplishments and a Look to the Future.

The North American Clinical Trials Network (NACTN) has been established as a network of translational clinical research centers focused on traumatic spinal cord injury (SCI) with the goals of facilitating clinical translational research, promotion of enhanced clinical care protocols including the principle of early surgery for SCI, and improving outcomes for individuals with acute SCI. Since its foundation in 2004 by Dr. Robert Grossman, NACTN has evolved into a powerful multi-stakeholder consortium of eight neurosurgical department faculties at university-affiliated institutions in the United States and Canada, a data management center, and a pharmacological center. To date, high-quality data from more than 1000 patients have been prospectively collected, providing us with a strong body of evidence surrounding SCI epidemiology, the natural history, and complications of acute and subacute SCI management. Key accomplishments of NACTN are summarized in this Focus issue. They include the launch, in collaboration with AO Spine, of the international, multi-center, placebo-controlled, Phase III Riluzole in Acute Spinal Cord Injury Study (RISCIS) that recruited 192 patients. While the primary analyses did not achieve the predetermined endpoint of efficacy for Riluzole, likely related to insufficient power, pre-planned secondary analyses demonstrated that all subgroups of cervical SCI subjects (AIS grades A, B and C) treated with Riluzole showed significant gains in functional recovery. The Focus Issue also includes a detailed analysis of the pharmacokinetics and pharmacodynamics of riluzole in the setting of acute SCI (RISCIS-PK study). Additional achievements include key contributions to the evidence supporting the role of early surgery in acute SCI, and a better understanding of the impact of complications on the outcomes of SCI. Future directions of NACTN will build on past accomplishments and focus on enhanced collaborations with other SCI networks, advanced analytics to examine large datasets, and a greater focus on chronic SCI.

Secondary analysis of a James Lind Alliance priority setting partnership to facilitate knowledge translation in degenerative cervical myelopathy (DCM): insights from AO Spine RECODE-DCM.

OBJECTIVES: To explore whether a James Lind Alliance Priority Setting Partnership could provide insights on knowledge translation within the field of degenerative cervical myelopathy (DCM). DESIGN: Secondary analysis of a James Lind Alliance Priority Setting Partnership process for DCM. PARTICIPANTS AND SETTING: DCM stake holders, including spinal surgeons, people with myelopathy and other healthcare professionals, were surveyed internationally. Research suggestions submitted by stakeholders but considered answered were identified. Sampling characteristics of respondents were compared with the overall cohort to identify subgroups underserved by current knowledge translation. RESULTS: The survey was completed by 423 individuals from 68 different countries. A total of 22% of participants submitted research suggestions that were considered 'answered'. There was a significant difference between responses from different stakeholder groups (p<0.005). Spinal surgeons were the group which was most likely to submit an 'answered' research question. Respondents from South America were also most likely to submit 'answered' questions, when compared with other regions. However, there was no significant difference between responses from different stakeholder regions (p=0.4). CONCLUSIONS: Knowledge translation challenges exist within DCM. This practical approach to measuring knowledge translation may offer a more responsive assessment to guide interventions, complementing existing metrics.

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).

Safety and Efficacy of Riluzole in Acute Spinal Cord Injury Study (RISCIS): A Multi-Center, Randomized, Placebo-Controlled, Double-Blinded Trial.

Riluzole is a sodium-glutamate antagonist that attenuates neurodegeneration in amyotrophic lateral sclerosis (ALS). It has shown favorable results in promoting recovery in pre-clinical models of traumatic spinal cord injury (tSCI) and in early phase clinical trials. This study aimed to evaluate the efficacy and safety of riluzole in acute cervical tSCI. An international, multi-center, prospective, randomized, double-blinded, placebo-controlled, adaptive, Phase III trial (NCT01597518) was undertaken. Patients with American Spinal Injury Association Impairment Scale (AIS) A-C, cervical (C4-C8) tSCI, and <12 h from injury were randomized to receive either riluzole, at an oral dose of 100 mg twice per day (BID) for the first 24 h followed by 50 mg BID for the following 13 days, or placebo. The primary efficacy end-point was change in Upper Extremity Motor (UEM) scores at 180 days. The primary efficacy analyses were conducted on an intention to treat (ITT) and completed cases (CC) basis. The study was powered at a planned enrolment of 351 patients. The trial began in October 2013 and was halted by the sponsor on May 2020 (and terminated in April 2021) in the face of the global COVID-19 pandemic. One hundred ninety-three patients (54.9% of the pre-planned enrolment) were randomized with a follow-up rate of 82.7% at 180 days. At 180 days, in the CC population the riluzole-treated patients compared with placebo had a mean gain of 1.76 UEM scores (95% confidence interval: -2.54-6.06) and 2.86 total motor scores (CI: -6.79-12.52). No drug-related serious adverse events were associated with the use of riluzole. Additional pre-planned sensitivity analyses revealed that in the AIS C population, riluzole was associated with significant improvement in total motor scores (estimate: standard error [SE] 8.0; CI 1.5-14.4) and upper extremity motor scores (SE 13.8; CI 3.1-24.5) at 6 months. AIS B patients had higher reported independence, measured by the Spinal Cord Independence Measure score (45.3 vs. 27.3; d: 18.0 CI: -1.7-38.0) and change in mental health scores, measured by the Short Form 36 mental health domain (2.01 vs. -11.58; d: 13.2 CI: 1.2-24.8) at 180 days. AIS A patients who received riluzole had a higher average gain in neurological levels at 6 months compared with placebo (mean 0.50 levels gained vs. 0.12 in placebo; d: 0.38, CI: -0.2-0.9). The primary analysis did not achieve the predetermined end-point of efficacy for riluzole, likely related to insufficient power. However, on pre-planned secondary analyses, all subgroups of cervical SCI subjects (AIS grades A, B and C) treated with riluzole showed significant gains in functional recovery. The results of this trial may warrant further investigation to extend these findings. Moreover, guideline development groups may wish to assess the possible clinical relevance of the secondary outcome analyses, in light of the fact that SCI is an uncommon orphan disorder without an accepted neuroprotective treatment.