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Background: Intra-abdominal vascular injuries are rare during posterior lumbar spinal surgery, but they can result in major morbidity or mortality when they do occur. We are aware of no prior studies that have used prone patient positioning during magnetic resonance imaging for the purpose of characterizing the retroperitoneal iliac vasculature with respect to the intervertebral disc. The purpose of this study was to define the vascular anatomy adjacent to the lower lumbar spine with use of supine and prone magnetic resonance imaging.Methods: A prospective observational study included thirty patients without spinal abnormality who underwent supine and prone magnetic resonance imaging without abdominal compression. The spinal levels of the aortic bifurcation and confluence of the common iliac veins were identified. The proximity of the anterior iliac vessels to the anterior and posterior aspects of the anulus fibrosus in sagittal and coronal planes was measured by two observers, and interobserver reliability was calculated.Results: The aortic bifurcation and confluence of the common iliac veins were most commonly at the level of the L4 vertebral body and migrated cranially with prone positioning. The common iliac vessels were closer to the anterior aspect of the intervertebral disc and to the midline at L4-L5 as compared with L5-S1, consistent with the bifurcation at the L4 vertebral body. Prone positioning resulted in greater distances between the disc and iliac vessels at L4-L5 and L5-S1 by an average of 3 mm. The position of the anterior aspect of the anulus with respect to each iliac vessel demonstrated substantial variation between subjects. The intraclass correlation coefficient for measurement of vessel position exceeded 0.9, demonstrating excellent interobserver reliability.Conclusions: This study confirmed the L4 level of the aortic bifurcation and iliac vein coalescence but also demonstrated substantial mobility of the great vessels with positioning. Supine magnetic resonance imaging will underestimate the proximity of the vessels to the intervertebral disc. Large interindividual variation in the location of vasculature was noted, emphasizing the importance of careful study of the location of the retroperitoneal vessels on a case-by-case basis. [ABSTRACT FROM AUTHOR]

STUDY DESIGN: Systematic review of published incidence of radiographic adjacent segment degeneration (ASDeg) and symptomatic adjacent segment disease (ASDis) after arthrodesis or total disc replacement. OBJECTIVE: Assess impact of surgery method and other factors on the incidence of ASDeg and ASDis. SUMMARY OF BACKGROUND DATA: Twenty-seven articles, none of which were class I or II, met the inclusion criteria. Twenty involved arthrodesis (1732 patients) and 7 involved arthroplasty (758 patients). Nineteen detailed ASDeg and 16 detailed ASDis. METHODS: Data were established for number of patients, gender, average patient age, incidence of ASDeg and ASDis, average time to follow-up, and level and type of surgery. Multivariate logistic regression was used to identify which parameters had a significant effect on the incidence of ASDeg and ASDis. RESULTS: Three hundred fourteen of 926 patients in the arthrodesis group (34%) and 31 out of 313 patients in the total disc replacement group (9%) developed ASDeg. (P < 0.0001) Multivariate logistic regression indicated that higher odds of ASDeg were associated with: older patients (P < 0.001); arthodesis (P = 0.0008); and longer follow-up (P = 0.0025). For ASDis, 173/1216 (14%) arthrodesis patients developed ASDis compared to 7/595 (1%) of arthroplasty patients (P < 0.0001). Using multivariate logistic regression, higher odds of ASDis were seen in studies with fusion (P < 0.0001), higher percentages of male patients (P = 0.0019), and shorter follow-up (P < 0.05). CONCLUSION: Analysis of the literature suggests a correlation between fusion and the development of ASDeg compared to arthroplasty, but this association is dampened by the influence of patient age. There is a stronger correlation between fusion and ASDis compared to arthroplasty. The data supports only a class C recommendation (lowest tier) for the use of arthroplasty to reduce ASDis and disc degeneration compared to arthrodesis. [ABSTRACT FROM AUTHOR]

Although several studies have examined the effects of cimetidine on pituitary-thyroid function, few have investigated ranitidine in this respect. We found no changes in thyroid-stimulating-hormone (TSH) or prolactin responses to TSH-releasing-hormone (TRH) in 10 patients with peptic ulcer disease given oral ranitidine. Serum total and free thyroxine (TT4 and FT4) concentrations declined slightly, whereas total and free triiodothyronine (TT3 and FT3) increased slightly following ranitidine. None of these changes achieved statistical significance. Both the ratio of TT4/TT3 and FT4/FT3, however, declined (P less than 0.05) following ranitidine. Thus ranitidine may have a minor influence on peripheral deiodination of thyroxine but has little effect on hormone production from the thyroid gland. The diagnostic value of biochemical tests of thyroid function is not seriously compromised in patients receiving ranitidine. [ABSTRACT FROM AUTHOR]

Study Design: Clinically based systematic review. Objective: To define optimal clinical care for patients after sport-related neuropraxic injuries using a systematic review supported with expert opinion. Summary Of Background Data: Athletes who participate in contact sports may experience cervical cord neuropraxia, with bilateral motor or sensory symptoms such as burning, numbness, or loss of sensation referable to the cervical spinal cord. The symptoms last from minutes to hours, but recovery is usually believed to be complete. The underlying condition is cervical spinal stenosis that predisposes the athlete to a transient compression or concussive injury to the spinal cord. Methods: Focused questions on the treatment of cervical spine sport-related injuries resulting in transient neuropraxia were refined by a panel of spine traumatology surgeons consisting of fellowship-trained neurologic and orthopedic surgeons. Medical subject heading keywords were searched through MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews to identify pertinent English-language abstracts and articles whose focus was human subjects. The quality of literature was rated as high, moderate, low, or very low. The proposed questions were answered using the Grading of Recommendations Assessment, Development and Evaluation evidence-based review system. These treatment recommendations were rated as either strong or weak based on the quality of evidence and clinical expertise. Results: The literature searches revealed low and very low quality evidence with no prospective or randomized studies. One hundred fifty-three pertinent articles were identified; these were supplemented with additional articles to form an evidentiary table with 17 original articles containing unique patient data. Conclusion: Literature regarding the optimal treatment of patients with transient neuropraxia is of low quality. On the basis of expert opinion, there was a recommendation that a return to full participation in high-energy contact sports could be based on radiographic findings: patients with transient neuropraxia without stenosis could return as a strong recommendation, whereas stenotic patients could not return as a weak recommendation. Furthermore, a strong recommendation was made to permit players to return to full participation after decompression with a single-level anterior cervical fusion. [ABSTRACT FROM AUTHOR]

STUDY DESIGN: Clinically based systematic review. OBJECTIVE: To define optimal clinical care for primary spinal aggressive 'benign' osseous neoplasms using a systematic review with expert opinion. METHODS: Predefined focused questions on treatment of osteoblastomas, aneurysmal bone cysts and giant cell tumors were refined by a panel of spine oncology surgeons, medical and radiation oncologist. Keywords were searched through Medline and pertinent abstracts and articles obtained. The quality of literature was rated as high, moderate, low or very low. Based on literature review and expert opinion recommendations were composed through the GRADE system and rated as either strong or weak. RESULTS: The literature searches revealed very low quality evidence with no prospective or randomized studies. There are a limited number of patients with aggressive primary osseous tumors. The osteoblastoma initial search identified 211 articles of which 17 were pertinent to the spinal questions. The aneurysmal bone cysts initial search revealed 482 articles initially of which 6 were pertinent; and the search on giant cell tumors identified 178 articles of which only 8 were focused on the predefined treatment questions. CONCLUSION: Spinal aggressive benign osseous neoplasms have varying histology. Despite these differences surgical treatment should be directed at gross resection of the tumor, understanding that this may be limited by anatomic confines and the potential for morbidity. [ABSTRACT FROM AUTHOR]

We describe a case of epidural thoracic abscess presenting similar to epidural lymphoma on imaging and review the imaging findings and clinical characteristics of both to help differentiate the two. Typical magnetic resonance imaging characteristics for epidural abscess are a heterogeneously enhancing epidural collection, which is isointense/hypointense on T1 images and hyperintense on T2 images with granulation tissue typically having a rim of enhancement with gadolinium. In contrast, typical imaging characteristics for an epidural lymphoma include an isointense/hypointense appearance on T1-weighted magnetic resonance imaging (MRI) and a hyperintense or even hypointense appearance on T2 images. Lymphomas tend to enhance uniformly and diffusely with contrast. The patient's MRI revealed a compressive thoracic epidural mass at T8-T10. The mass was hypointense on T1- and T2-weighted images and enhanced intensely and uniformly on T1 images after gadolinium injection. Additionally, abnormal hyperintense signal within the left T9-T10 facet joint was identified on T2 images. The imaging findings were felt to be most consistent with lymphoma, but the possibility of epidural abscess, and less likely, epidural hematoma were also considered. Although the patient's abscess presented similar to lymphoma on MRI, possibly the most revealing clue on imaging that infection was the likely diagnosis was hyperintense signal within the left facet joint seen on T2-weighted images. This is important as primary radiation treatment based on imaging characteristics alone, without a tissue diagnosis, is often suggested in cases of lymphoma. This mode of treatment would be contraindicated in the setting of infection. A diagnosis that is not conclusive by needle biopsy or imagine may require an open procedure for definitive diagnosis. [ABSTRACT FROM AUTHOR]

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., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2024 The Author(s). Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)

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., Competing Interests: Declaration of competing interest One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.)

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., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Davies et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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.

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: Modified DELPHI Consensus Process., Objective: To agree a single unifying term and definition. Globally, cervical myelopathy caused by degenerative changes to the spine is known by over 11 different names. This inconsistency contributes to many clinical and research challenges, including a lack of awareness., Method: AO Spine RECODE-DCM (Research objectives and Common Data Elements Degenerative Cervical Myelopathy). To determine the index term, a longlist of candidate terms and their rationale, was created using a literature review and interviews. This was shared with the community, to select their preferred terms (248 members (58%) including 149 (60%) surgeons, 45 (18%) other healthcare professionals and 54 (22%) People with DCM or their supporters) and finalized using a consensus meeting. To determine a definition, a medical definition framework was created using inductive thematic analysis of selected International Classification of Disease definitions. Separately, stakeholders submitted their suggested definition which also underwent inductive thematic analysis (317 members (76%), 190 (59%) surgeons, 62 (20%) other healthcare professionals and 72 (23%) persons living with DCM or their supporters). Using this definition framework, a working definition was created based on submitted content, and finalized using consensus meetings., Results: Degenerative Cervical Myelopathy was selected as the unifying term, defined in short, as a progressive spinal cord injury caused by narrowing of the cervical spinal canal., Conclusion: A consistent term and definition can support education and research initiatives. This was selected using a structured and iterative methodology, which may serve as an exemplar for others in the future., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Study Design: Cross-sectional, international survey., Objectives: To examine current international practices as well as knowledge, adoption, and barriers to guideline implementation for acute spinal cord injury (SCI) management., Methods: A survey was distributed to members of AO Spine. The questionnaire was structured to obtain demographic data and preferred acute SCI practices surrounding steroid use, hemodynamic management, and timing of surgical decompression., Results: 593 members completed the survey including orthopaedic surgeons (54.3%), neurosurgeons (35.6%), and traumatologists (8.4%). Most (61.2%) respondents were from low and middle-income countries (LMICs). 53.6% of physicians used steroids for the treatment of acute SCIs. Respondents from LMICs were more likely to administer steroids than HICs (178 vs. 78; P < .001). 331 respondents (81.5%) answered that patients would receive mean arterial pressure (MAP) targeted treatment. In LMICs, SCI patients were less likely to be provided with MAP-targeted treatment (76.9%) as compared to HICs (89%; P < .05). The majority of respondents (87.8%) reported that patients would benefit from early decompression. Despite overwhelming evidence and surgeons' responses that would offer early surgery, 62.4% of respondents stated they encounter logistical barriers in their institutions. This was particularly evident in LMICs, where 57.9% of respondents indicated that early intervention was unlikely to be accomplished, while only 21.1% of respondents from HICs stated the same ( P < .001)., Conclusion: This survey highlights challenges in the implementation of standardized global practices in the management of acute SCI. Future research efforts will need to refine SCI guidelines and address barriers to guideline implementation., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., Competing Interests: Declaration of Competing Interest We have no conflict of interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Abstract Individuals with SCI are severely affected by immune system changes, resulting in increased risk of infections and persistent systemic inflammation. While recent data support that immunological changes after SCI differ in the acute and chronic phases of living with SCI, only limited immunological phenotyping in humans is available. To characterize dynamic molecular and cellular immune phenotypes over the first year, we assess RNA (bulk-RNA sequencing), protein, and flow cytometry (FACS) profiles of blood samples from 12 individuals with SCI at 0-3 days and at 3, 6, and 12 months post injury (MPI) compared to 23 uninjured individuals (controls). We identified 967 differentially expressed (DE) genes in individuals with SCI (FDR <0.001) compared to controls. Within the first 6 MPI we detected a reduced expression of NK cell genes, consistent with reduced frequencies of CD56 bright , CD56 dim NK cells present at 12 MPI. Over 6MPI, we observed increased and prolonged expression of genes associated with inflammation (e.g. HMGB1, Toll-like receptor signaling) and expanded frequencies of monocytes acutely. Canonical T-cell related DE genes (e.g. FOXP3, TCF7, CD4) were upregulated during the first 6 MPI and increased frequencies of activated T cells at 3-12 MPI. Neurological injury severity was reflected in distinct whole blood gene expression profiles at any time after SCI, verifying a persistent 'neurogenic' imprint. Overall, 2876 DE genes emerge when comparing motor complete to motor incomplete SCI (ANOVA, FDR <0.05), including those related to neutrophils, inflammation, and infection. In summary, we identify a dynamic immunological phenotype in humans, including molecular and cellular changes which may provide potential targets to reduce inflammation, improve immunity, or serve as candidate biomarkers of injury severity.

Competing Interests: J.M.R.: Alphatec Spine: Paid consultant; Paid presenter or speaker. Biomet: IP royalties. Cervical Spine Research Society: Board or committee member. Medtronic: Paid presenter or speaker. Stryker: IP royalties; Paid presenter or speaker. Wolters Kluwer Health—Lippincott Williams & Wilkins: Publishing royalties, financial or material support. Zimmer: Paid presenter or speaker. K.D.R.: Amedica: Stock or stock options. AOSpine: Board or committee member. AxioMed: Stock or stock options. Benvenue: Stock or stock options. Biomet: IP royalties; Paid presenter or speaker. Clinics in orthopedics: Editorial or governing board. European Spine Journal : Editorial or governing board. Expanding Orthopedics, PSD: Stock or stock options. Global Spine Journal : Editorial or governing board. HAPPE Spine: Unpaid consultant. Medtronic: Paid presenter or speaker. Neurosurgery : Editorial or governing board. North American Spine Society: Board or committee member. Nuvasive: Paid consultant; Paid presenter or speaker. Paradigm Spine: Stock or stock options. Spinal Kinetics: Stock or stock options. Spine : Editorial or governing board. Spine Surgery Today : Editorial or governing board. Spineology: Stock or stock options. Vertiflex: Stock or stock options. A.R.V.: Health Care Entity Relationships and Investments: Medtronics, Receipt of Royalty Payments; Stryker Spine, Receipt of Royalty Payments; Globus, Receipt of Royalty Payments, Stock / Stock Option Ownership Interests; Stout Medical, Stock / Stock Option Ownership Interests; Progressive Spinal Technologies, Stock / Stock Option Ownership Interests; Advanced Spinal Intellectual Properties, Stock / Stock Option Ownership Interests; Flagship Surgical, Stock / Stock Option Ownership Interests; Cytonics, Stock / Stock Option Ownership Interests; Electrocore, Stock / Stock Option Ownership Interests; AVKN Patient Driven Care, Stock / Stock Option Ownership Interests; FlowPharma, Stock / Stock Option Ownership Interests; Rothman Institute and Related Properties, Stock / Stock Option Ownership Interests; AO Spine, Member in good standing// Independent Contractor; Innovative Surgical Design, Stock / Stock Option Ownership Interests; Orthobullets, Stock / Stock Option Ownership Interests; Thieme, Receipt of Royalty Payments; Jaypee, Receipt of Royalty Payments; Elseviere, Receipt of Royalty Payments; Taylor Francis/Hodder and Stoughton, Receipt of Royalty Payments; Expert testimony, Member in good standing// Independent Contractor; Avaz Surgical, Stock/Stock Option Ownership Interests; Dimension Orthotics, LLC, Stock/Stock Option Ownership Interests; SpineWave, Receipt of Royalty Payments; Atlas Spine, Receipt of Royalty Payments, Stock/Stock Option Ownership Interests; Nuvasive, Stock/Stock Option Ownership Interests; Parvizi Surgical Innovation, Stock/Stock Option Ownership Interests; Jushi, Stock/Stock Option Ownership Interests; Deep Health, Stock/Stock Option Ownership Interests; ViewFi Health, Stock/Stock Option Ownership Interests; Sentryx, Service on Scientific Advisory Board/Board of Directors/Service on Committees,Stock/Stock Option Ownership Interests; National Spine Health Foundation (NSHF), Service on Scientific Advisory Board/Board of Directors/Service on Committees; Accellus, Service on Scientific Advisory Board/Board of Directors/Service on Committees, Stock/Stock Option Ownership Interests; Spinal Elements, Consulting/Independent Contractor, Receipt of Royalty Payments; Alphatec (Atec), Receipt of Royalty Payments; Harvard Medtech, Stock/Stock Option Ownership Interests.. T.J.A.: Augmedics: Stock or stock options. Back Story, LLC: Board or committee member. Biomet: IP royalties. Care Equity: Stock or stock options. CytoDyn Inc.: Stock or stock options. DePuy, A Johnson & Johnson Company: IP royalties. Hospital for Special Surgery: Board or committee member. HS2, LLC: Stock or stock options. In ViVo Therapeutics: Stock or stock options. Innovative Surgical Designs, Inc.: Stock or stock options. Journal of Bone and Joint Surgery — American : Editorial or governing board. JP Medical Publishers: Publishing royalties, financial or material support. Morphogenesis: Stock or stock options. Nuvasive: Paid consultant. Orthopedics Today : Board or committee member; Editorial or governing board. Paradigm Spine: Stock or stock options. Parvizi Surgical Innovations: Stock or stock options. Physician Recommended Nutriceuticals: Stock or stock options. Precision Orthopedics: Stock or stock options. Pulse Equity: Stock or stock options. Saunders/Mosby-Elsevier: Publishing royalties, financial or material support. Spine : Editorial or governing board. Spine Deformity Journal : Editorial or governing board. Spine Universe: Board or committee member. Spinicity: Stock or stock options. Springer: Publishing royalties, financial or material support. Strathspey Crown: Stock or stock options. Surg.IO LLC: Stock or stock options. Thieme: Publishing royalties, financial or material support. James S. Harrop, MD, MSHQS: DePuy: Honoraria. Stryker: Honoraria. NuVasive: Honoraria. The remaining authors no conflict of interest.

The North American Clinical Trials Network (NACTN) for Spinal Cord Injury (SCI) is a consortium of neurosurgery departments at university affiliated hospitals with medical, nursing, and rehabilitation personnel who are skilled in the assessment, evaluation, and management of SCI. NACTN was established with the goal of consistently advancing the quality of life of people with SCI through clinical trials of new therapies that provide robust evidence of safety and effectiveness. A prospective multi-center Registry was created to collect the natural course of the acute traumatic SCI patient from time of injury to 12 months follow-up. NACTN's network of hospitals enrolls a significant number of patients, defines and adheres to standard protocols, and provides the infrastructure and highly skilled personnel to conduct trials of therapy for SCI. Registry data have been used by academic institutions and by the biotechnology and pharmaceutical sectors to create comparison datasets for Phase I clinical trials of new therapies.

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.

This is a historical account of the origin and accomplishments of the North American Clinical Trials Network (NACTN) for traumatic spinal cord injury (SCI), which was established in 2004 by Christopher Reeve and Robert Grossman. Christopher Reeve was an actor who became quadriplegic and started the Christopher & Dana Reeve Foundation (CDRF), and Robert Grossman was a neurosurgeon experienced in neurotrauma and a university professor in Houston. NACTN has member investigators at university and military centers in North America and has contributed greatly to the improvement of care, primarily acute care, of patients sustaining traumatic SCI. Its accomplishments are a clinical registry database of >1000 acute SCI patients documenting the care pathways, including complications. NACTN has assessed the effectiveness of treatment, including pharmacotherapy and the role and timing of surgery, and has also identified barriers to early surgery. The principal focus has been on improving neurological recovery. NACTN has trained many SCI practitioners and has collaborated with other SCI networks and organizations internationally to promote the care of SCI patients.

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.

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.

To date, no drug therapy has shown significant efficacy in improving functional outcomes in patients with acute spinal cord injury (SCI). Riluzole is an approved benzothiazole sodium channel blocker to attenuate neurodegeneration in amyotrophic lateral sclerosis (ALS) and is of interest for neuroprotection in SCI. In a Phase I clinical trial (ClinicalTrials.gov Identifier: NCT00876889), riluzole was well tolerated with a 2-week treatment at the dose level approved for ALS and exhibited potential efficacy in patients with SCI. The acute and progressive nature of traumatic SCI and the complexity of secondary injury processes alter the pharmacokinetics (PK) of therapeutics. In the PK sub-study of the multi-center, randomized, placebo-controlled, double-blinded Riluzole in Spinal Cord Injury Study (RISCIS) Phase II/III trial (ClinicalTrials.gov Identifier: NCT01597518), a total of 32 SCI patients were enrolled, and most of our patients were middle-age Caucasian males with head and neck injuries. We studied the PK and pharmacodynamics (PD) of riluzole on motor recovery, measured by International Standards for Neurological Classification of SCI (ISNCSCI) Motor Score at injury and at 3-month and 6-month follow-ups, along with levels of the axonal injury biomarker phosphorylated neurofilament heavy chain (pNF-H), during the 2-week treatment. PK modeling, PK/PD correlations were developed to identify the potential effective exposure of riluzole for intended PD outcomes. The longitudinal impacts of SCI on the PK of riluzole are characterized. A time-varying population PK model of riluzole is established, incorporating time-varying clearance and volume of distribution from combined data of Phase I and Phase II/III trials. With the developed model, a rational, optimal dosing scheme can be designed with time-dependent modification to preserve the required therapeutic exposure of riluzole. The PD of riluzole and the relationship between PK and neurological outcomes of the treatment were established. The time course of efficacy in total motor score improvement (ΔTMS) and pNF-H were monitored. A three-dimensional (3D) PK/PD correlation was established for ΔTMS at 6 months with overall riluzole exposure area under the curve for Day 0-Day14 (AUC D0-D14 ) and baseline TMS for individual patients. Patients with baseline TMS between 1 and 36 benefited from the optimal exposure range of 16-48 mg*h/mL. The PD models of pNF-H revealed the riluzole efficacy, as treated subjects exhibited a diminished increase in progression of pNF-H, indicative of reduced axonal breakdown. The independent parameter of area between effective curves (ABEC) between the time profiles of pNF-H in placebo and treatment groups was statistically identified as a significant predictor for the treatment effect on the biomarker. A mechanistic clinical outcomes (CO)/PD (pNF-H) model was established, and the proposed structure demonstrated the feasibility of PK/PD/CO correlation model. No appreciable hepatic toxicity was observed with the current riluzole treatment regimen. The development of effective treatment for SCI is challenging. However, the future model-informed and PK-guided drug development and regimen modification can be rationally executed with the optimal dosing regimen design based on the developed 3D PK/PD model. The PK/PD/CO model can serve as a rational guide for future drug development, PKPD model refinement, and extension to other studies in SCI settings.

Only 100 years ago, traumatic spinal cord injury (SCI) was commonly lethal. Today, most people who sustain SCI survive with continual efforts to improve their quality of life and neurological outcomes. SCI epidemiology is changing as preventative interventions reduce injuries in younger individuals, and there is an increased incidence of incomplete injuries in aging populations. Early treatment has become more intensive with decompressive surgery and proactive interventions to improve spinal cord perfusion. Accurate data, including specialized outcome measures, are crucial to understanding the impact of epidemiological and treatment trends. Dedicated SCI clinical research and data networks and registries have been established in the United States, Canada, Europe, and several other countries. We review four registry networks: the North American Clinical Trials Network (NACTN) SCI Registry, the National Spinal Cord Injury Model Systems (SCIMS) Database, the Rick Hansen SCI Registry (RHSCIR), and the European Multi-Center Study about Spinal Cord Injury (EMSCI). We compare the registries' focuses, data platforms, advanced analytics use, and impacts. We also describe how registries' data can be combined with electronic health records (EHRs) or shared using federated analysis to protect registrants' identities. These registries have identified changes in epidemiology, recovery patterns, complication incidence, and the impact of practice changes such as early decompression. They've also revealed latent disease-modifying factors, helped develop clinical trial stratification models, and served as matched control groups in clinical trials. Advancing SCI clinical science for personalized medicine requires advanced analytical techniques, including machine learning, counterfactual analysis, and the creation of digital twins. Registries and other data sources help drive innovation in SCI clinical science.

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.

The bulbocavernosus reflex (BCR) has been used during the initial evaluation of a spinal cord injury patient as a metric to determine prognosis and whether the patient is in "spinal shock." This reflex has been less utilized over the last decade, and therefore a review was performed to assess the value of BCR in patient prognosis. The North American Clinical Trials Network (NACTN) for Spinal Cord Injury (SCI) is a consortium of tertiary medical centers that includes a prospective SCI registry. The NACTN registry data was analyzed to evaluate the prognostic implication of the BCR during the initial evaluation of a spinal cord injury patient. SCI patients were divided into those with an intact or absent BCR during their initial evaluation. Associations of participants' descriptors and neurological status on follow-up were performed, followed by associations with the presence of a BCR. A total of 769 registry patients with recorded BCRs were included in the study. The median age was 49 years (32-61 years), and the majority were male ( n  = 566, 77%) and white ( n  = 519, 73%). Among included patients, high blood pressure was the most common comorbidity ( n  = 230, 31%). Cervical spinal cord injury was the most common ( n  = 470, 76%) with fall ( n  = 320, 43%) being the most frequent mechanism of injury. BCR was present in 311 patients (40.4%), while 458 (59.6%) had a negative BCR within 7 days of injury or before surgery. At 6 months post-injury, 230 patients (29.9%) followed up, of which 145 had a positive BCR, while 85 had a negative BCR. The presence/absence of BCR was significantly different in patients with cervical ( p  = 0.0015) or thoracic SCI ( p  = 0.0089), or conus medullaris syndrome ( p  = 0.0035), and in those who were American Spinal Injury Association Impairment Scale grade A ( p  = 0.0313). No significant relationship was observed between BCR results and demographics, AIS grade conversion, motor score changes ( p  = 0.1669), and changes in pin prick ( p  = 0.3795) and light touch scores ( p  = 0.8178). In addition, cohorts were not different in surgery decision ( p  = 0.7762) and injury to surgery time ( p  = 0.0681). In our review of the NACTN spinal cord registry, the BCR did not provide prognostic utility in the acute evaluation of spinal cord injury patients. Therefore, it should not be used as a reliable marker for predicting neurological outcomes post-injury.

Abstract The North America Clinical Trials Network (NACTN) for Spinal Cord Injury (SCI) is a consortium of tertiary medical centers that has maintained a prospective SCI registry since 2004, and it has espoused that early surgical intervention is associated with improved outcome. It has previously been shown that initial presentation to a lower acuity center and necessity of transfer to a higher acuity center reduce rates of early surgery. The NACTN database was evaluated to examine the association between interhospital transfer (IHT), early surgery, and outcome, taking into account distance traveled and site of origin for the patient. Data from a 15-year period of the NACTN SCI Registry were analyzed (years 2005-2019). Patients were stratified into transfers directly from the scene to a Level 1 trauma center (NACTN site) versus IHT from a Level 2 or 3 trauma facility. The main outcome was surgery within 24 hours of injury (yes/no), whereas secondary outcomes were length of stay, death, discharge disposition, and 6-month American Spinal Injury Association Impairment Scale (AIS) grade conversion. For the IHT patients, distance traveled for transfer was calculated by measuring the shortest distance between origin and NACTN hospital. Analysis was performed with Brown-Mood test and chi-square tests. Of 724 patients with transfer data, 295 (40%) underwent IHT and 429 (60%) were admitted directly from the scene of injury. Patients who underwent IHT were more likely to have a less severe SCI (AIS D; p  = 0.002), have a central cord injury ( p  = 0.004), and have a fall as their mechanism of injury ( p  < 0.0001) than those directly admitted to an NACTN center. Of the 634 patients who had surgery, direct admission to an NACTN site was more likely to result in surgery within 24 hours compared with IHT patients (52% vs. 38%) ( p  < 0.0003). Median IHT distance was 28 miles (interquartile range [IQR] = 13-62 miles). There was no significant difference in death, length of stay, discharge to a rehab facility versus home, or 6-month AIS grade conversion rates between the two groups. Patients who underwent IHT to an NACTN site were less likely to have surgery within 24 hours of injury, compared with those directly admitted to the Level 1 trauma facility. Although there was no difference in mortality rates, length of stay, or 6-month AIS conversion between groups, patients with IHT were more likely be older with a less severe level of injury (AIS D). This study suggests there are barriers to timely recognition of SCI in the field, appropriate admission to a higher level of care after recognition, and challenges related to the management of individuals with less severe SCI.

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.