Harrop, James Shields

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. 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

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.

Purpose: Anterior cervical discectomy and fusion has a low but well-established profile of adverse events. The goal of this study was to gauge surgeon opinion regarding the frequency and acceptability of these events. Methods: A 2-page survey was distributed to attendees at the 2015 Cervical Spine Research Society (CSRS) meeting. Respondents were asked to categorize 18 anterior cervical discectomy and fusion–related adverse events as either: “common and acceptable,” “uncommon and acceptable,” “uncommon and sometimes acceptable,” or “uncommon and unacceptable.” Results were compiled to generate the relative frequency of these responses for each complication. Responses for each complication event were also compared between respondents based on practice location (US vs. non-US), primary specialty (orthopedics vs. neurosurgery) and years in practice. Results: Of 150 surveys distributed, 115 responses were received (76.7% response rate), with the majority of respondents found to be US-based (71.3%) orthopedic surgeons (82.6%). Wrong level surgery, esophageal injury, retained drain, and spinal cord injury were considered by most to be unacceptable and uncommon complications. Dysphagia and adjacent segment disease occurred most often, but were deemed acceptable complications. Although surgeon experience and primary specialty had little impact on responses, practice location was found to significantly influence responses for 12 of 18 complications, with non-US surgeons found to categorize events more toward the uncommon and unacceptable end of the spectrum as compared with US surgeons. Conclusions: These results serve to aid communication and transparency within the field of spine surgery, and will help to inform future quality improvement and best practice initiatives.

Abstract BACKGROUND: The learning and development of technical skills are paramount for neurosurgical trainees. External influences and a need for maximizing efficiency and proficiency have encouraged advancements in simulator-based learning models. OBJECTIVE: To confirm the importance of establishing an educational curriculum for teaching minimally invasive techniques of pedicle screw placement using a computer-enhanced physical model of percutaneous pedicle screw placement with simultaneous didactic and technical components. METHODS: A 2-hour educational curriculum was created to educate neurosurgical residents on anatomy, pathophysiology, and technical aspects associated with image-guided pedicle screw placement. Predidactic and postdidactic practical and written scores were analyzed and compared. Scores were calculated for each participant on the basis of the optimal pedicle screw starting point and trajectory for both fluoroscopy and computed tomographic navigation. RESULTS: Eight trainees participated in this module. Average mean scores on the written didactic test improved from 78% to 100%. The technical component scores for fluoroscopic guidance improved from 58.8 to 52.9. Technical score for computed tomography—navigated guidance also improved from 28.3 to 26.6. CONCLUSION: Didactic and technical quantitative scores with a simulator-based educational curriculum improved objectively measured resident performance. A minimally invasive spine simulation model and curriculum may serve a valuable function in the education of neurosurgical residents and outcomes for patients.

Abstract BACKGROUND: The potential for simulation-based learning in neurosurgical training has led the Congress of Neurosurgical Surgeons to develop a series of simulation modules. The Northwestern Objective Microanastomosis Assessment Tool (NOMAT) was created as the corresponding assessment tool for the Congress of Neurosurgical Surgeons Microanastomosis Module. The face and construct validity of the NOMAT have been previously established. OBJECTIVE: To further validate the NOMAT by determining its interrater reliability (IRR) between raters of varying levels of microsurgical expertise. METHODS: The NOMAT was used to assess residents’ performance in a microanastomosis simulation module in 2 settings: Northwestern University and the Society of Neurological Surgeons 2014 Boot Camp at the University of Indiana. At Northwestern University, participants were scored by 2 experienced microsurgeons. At the University of Indiana, participants were scored by 2 postdoctoral fellows and an experienced microsurgeon. The IRR of NOMAT was estimated by computing the intraclass correlation coefficient using SPSS v22.0 (IBM, Armonk, New York). RESULTS: A total of 75 residents were assessed. At Northwestern University, 21 residents each performed microanastomosis on 2 model vessels of different sizes, one 3 mm and one 1 mm. At the University of Indiana, 54 residents performed a single microanastomosis procedure on 3-mm vessels. The intraclass correlation coefficient of the total NOMAT scores was 0.88 at Northwestern University and 0.78 at the University of Indiana. CONCLUSION: This study indicates high IRR for the NOMAT. These results suggest that the use of raters with varying levels of expertise does not compromise the precision or validity of the scale. This allows for a wider adoption of the scale and, hence, a greater potential educational impact.

OBJECT In this clinically based systematic review of cervical facet fractures, the authors’ aim was to determine the optimal clinical care for patients with isolated fractures of the cervical facets through a systematic review. METHODS A systematic review of nonoperative and operative treatment methods of cervical facet fractures was performed. Reduction and stabilization treatments were compared, and analysis of postoperative outcomes was performed. MEDLINE and Scopus databases were used. This work was supported through support received from the Association for Collaborative Spine Research and AOSpine North America. RESULTS Eleven studies with 368 patients met the inclusion criteria. Forty-six patients had bilateral isolated cervical facet fractures and 322 had unilateral isolated cervical facet fractures. Closed reduction was successful in 56.4% (39 patients) and 63.8% (94 patients) of patients using a halo vest and Gardner-Wells tongs, respectively. Comparatively, open reduction was successful in 94.9% of patients (successful reduction of open to closed reduction OR 12.8 [95% CI 6.1–26.9], p < 0.0001); 183 patients underwent internal fixation, with an 87.2% success rate in maintaining anatomical alignment. When comparing the success of patients who underwent anterior versus posterior procedures, anterior approaches showed a 90.5% rate of maintenance of reduction, compared with a 75.6% rate for the posterior approach (anterior vs posterior OR 3.1 [95% CI 1.0–9.4], p = 0.05). CONCLUSIONS In comparison with nonoperative treatments, operative treatments provided a more successful outcome in terms of failure of treatment to maintain reduction for patients with cervical facet fractures. Operative treatment appears to provide superior results to the nonoperative treatments assessed.

Study Design: Evidence-based systematic review. Objectives: To define the optimal treatment of fractures involving the C2 body, including those with concomitant injuries, based upon a systematic review of the literature. Summary of Background Data: Axis body fractures have customarily been treated nonoperatively, but there are some injuries that may require operative intervention. High-quality literature is sparse and there are few class I or class II studies to guide treatment decisions. Materials and Methods: A literature search was conducted using PubMed (MEDLINE), Cochrane Central Register of Controlled Trials, and Scopus (EMBASE, MEDLINE, COMPENDEX). The quality of literature was rated according to a grading tool developed by the Center for Evidence-based Medicine. Operative and nonoperative treatment of axis body fractures were compared using fracture bony union as the primary outcome measure. As risk factors for nonunion were not consistently reported, cases were analyzed individually. Results: The literature search identified 62 studies, of which 10 were case reports which were excluded from the analysis. A total of 920 patients from 52 studies were included. The overall bony union rate for all axis body fractures was 91%. Although the majority of fractures were treated nonoperatively, there has been an increasing trend toward operative intervention for Benzel type III (transverse) axis body fractures. Nearly 76% of axis body fractures were classified as type III fractures, of which 88% united successfully. Nearly all Benzel type I and type II axis body fractures were successfully treated nonoperatively. The risk factors for nonunion included: a higher degree of subluxation, fracture displacement, comminution, concurrent injuries, delay in treatment, and older age. Conclusions: High rates for fracture union are reported in the literature for axis body fractures with nonoperative treatment. High-quality prospective studies are required to develop consensus as to which C2 body fractures require operative fixation.