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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. [ABSTRACT FROM AUTHOR]

Background: Degenerative cervical myelopathy represents the most common form of non-traumatic spinal cord injury. This trial investigated whether riluzole enhances outcomes in patients undergoing decompression surgery for degenerative cervical myelopathy.Methods: This multicentre, double-blind, placebo-controlled, randomised, phase 3 trial was done at 16 university-affiliated centres in Canada and the USA. Patients with moderate-to-severe degenerative cervical myelopathy aged 18-80 years, who had a modified Japanese Orthopaedic Association (mJOA) score of 8-14, were eligible. Patients were randomly assigned (1:1) to receive either oral riluzole (50 mg twice a day for 14 days before surgery and then for 28 days after surgery) or placebo. Randomisation was done using permuted blocks stratified by study site. Patients, physicians, and outcome assessors remained masked to treatment group allocation. The primary endpoint was change in mJOA score from baseline to 6 months in the intention-to-treat (ITT) population, defined as all individuals who underwent randomisation and surgical decompression. Adverse events were analysed in the modified intention-to-treat (mITT) population, defined as all patients who underwent randomisation, including those who did not ultimately undergo surgical decompression. This study is registered with ClinicalTrials.gov, NCT01257828.Findings: From Jan 31, 2012, to May 16, 2017, 408 patients were screened. Of those screened, 300 were eligible (mITT population); 290 patients underwent decompression surgery (ITT population) and received either riluzole (n=141) or placebo (n=149). There was no difference between the riluzole and placebo groups in the primary endpoint of change in mJOA score at 6-month follow-up: 2·45 points (95% CI 2·08 to 2·82 points) versus 2·83 points (2·47 to 3·19), difference -0·38 points (-0·90 to 0·13; p=0·14). The most common adverse events were neck or arm or shoulder pain, arm paraesthesia, dysphagia, and worsening of myelopathy. There were 43 serious adverse events in 33 (22%) of 147 patients in the riluzole group and 34 serious adverse events in 29 (19%) of 153 patients in the placebo group. The most frequent severe adverse events were osteoarthrosis of non-spinal joints, worsening of myelopathy, and wound complications.Interpretation: In this trial, adjuvant treatment for 6 weeks perioperatively with riluzole did not improve functional recovery beyond decompressive surgery in patients with moderate-to-severe degenerative cervical myelopathy. Whether riluzole has other benefits in this patient population merits further study.Funding: AOSpine North America. [ABSTRACT FROM AUTHOR]

Study Design: Reliability analysis based on expert panel case series review and grading per the Enneking and Weinstein-Boriani-Biagini classification systems., Objective: To assess the reliability of the Enneking and Weinstein-Boriani-Biagini classification systems., Summary of Background Data: The Enneking and Weinstein-Boriani-Biagini (WBB) classifications were developed to stage and facilitate treatment planning in patients with primary spine tumors. To date, their interobserver and intraobserver reliability has not been assessed-a fundamental step in facilitating broader clinical and research use., Methods: Clinical information, imaging studies, and biopsy results were compiled from 15 selected patients with primary spinal tumors. Eighteen spine surgeons independently estimated and scored the cases for Enneking grade, tumor and metastasis categories, Enneking stage, Enneking-recommended surgical margin, WBB zones and layers, and WBB-recommended surgical procedures, with a second assessment performed after random resorting of cases. Interobserver and intraobserver reliability of each category were assessed by percent agreement or proportional overlap. The Fleiss, Cohen, and Mezzich kappa statistics (kappa) were then applied, determined by the type of variable analyzed., Results: The kappa statistics for interobserver reliability were 0.82, 0.22, 0.00, 0.57, 0.47, 0.31, 0.58, and 0.54 for the fields of Enneking grade, tumor and metastasis categories, Enneking stage, Enneking-recommended surgical margin, WBB zones and layers, and WBB-recommended surgical procedures, respectively. The kappa statistics for intraobserver reliability were 0.97, 0.53, 0.47, 0.82, 0.67, 0.63, 0.79, and 0.79 for the same respective fields. According to Landis and Koch, the ranges of kappa values of 0.00 to 0.20, 0.21 to 0.40, 0.41 to 0.60, 0.61 to 0.80, and >0.80 imply slight, fair, moderate, substantial, and near-perfect agreement, respectively., Conclusion: Results indicate moderate interobserver reliability and substantial and near-perfect intraobserver reliability for both the Enneking and WBB classification in terms of staging and guidance for treatment, despite a less than moderate interobserver reliability in interpreting the Enneking local tumor extension and WBB sector. Before incorporating the classifications in the clinical practice and research studies, further work is required to investigate the validity of the classifications.

Study Design: Questionnaires administered to practicing orthopedic and neurosurgical spine surgeons from various regions of the United States and abroad., Objectives: To determine similarities and differences in the treatment of spinal trauma., Summary of Background Data: Spinal trauma is generally referred to subspecialists of orthopedic or neurosurgical training. Prior studies have suggested that there is significant variability in the management of such injuries., Methods: Questionnaires based on eight clinical scenarios of commonly encountered cervical, thoracic, and lumbar injuries were administered to 35 experienced spinal surgeons. Surgeons completed profile information and answered approximately one dozen questions for each case. Data were analyzed with SPSS software to determine the levels of agreement and characteristics of respondents that might account for a lack of agreement on particular aspects of management., Results: Of the 35 surgeons completing the questionnaire, 63% were orthopedists, 37% were neurosurgeons, and 80% had been in practice for more than 5 years. Considerable agreement was found in the majority of clinical decisions, including whether or not to operate and the timing of surgery. Of the differences noted, neurosurgeons were more likely to obtain a MRI, and orthopedists were more likely to use autograft as a sole graft material. Physicians from abroad were, in general, more likely to operate and to use an anterior approach during surgery than physicians from the northeastern United States., Conclusions: More commonalities were identified in the management of spinal trauma than previously reported. When found, variability in opinion was related to professional and regional differences.