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

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

The Spinal Instability Neoplastic Score : Impact On Oncologic Decision-Making

STUDY DESIGN.: Systematic literature review OBJECTIVE.: To address the following questions in a systematic literature review: 1. How is spinal neoplastic instability defined or classified in the literature before and after the introduction of the Spinal Instability Neoplastic Score (SINS)? 2. How has SINS affected daily clinical practice? 3. Can SINS be used as a prognostic tool? SUMMARY OF BACKGROUND DATA.: Spinal neoplastic-related instability was defined in 2010 and simultaneously SINS was introduced as a novel tool with criteria agreed upon by expert consensus to assess the degree of spinal stability. METHODS.: Pubmed, Embase, and clinical trial databases were searched with the key words “spinal neoplasm”, “spinal instability”, “spinal instability neoplastic score”, and synonyms. Studies describing spinal neoplastic-related instability were eligible for inclusion. Primary outcomes included studies describing and/or defining neoplastic-related instability, SINS, and studies using SINS as a prognostic factor. RESULTS.: The search identified 1414 articles, of which 51 met the inclusion criteria. No precise definition or validated assessment tool was used specific to spinal neoplastic-related instability prior to the introduction of SINS. Since the publication of SINS in 2010, the vast majority of the literature regarding spinal instability has used SINS to assess or describe instability. Twelve studies specifically investigated the prognostic value of SINS in patients who underwent radiotherapy or surgery. CONCLUSION.: No consensus could be determined regarding the definition, assessment, or reporting of neoplastic-related instability before introduction of SINS. Defining spinal neoplastic-related instability and the introduction of SINS have led to improved uniform reporting within the spinal neoplastic literature. Currently, the prognostic value of SINS is controversial.Level of Evidence: N/

The Spinal Instability Neoplastic Score : Impact On Oncologic Decision-Making

STUDY DESIGN.: Systematic literature review OBJECTIVE.: To address the following questions in a systematic literature review: 1. How is spinal neoplastic instability defined or classified in the literature before and after the introduction of the Spinal Instability Neoplastic Score (SINS)? 2. How has SINS affected daily clinical practice? 3. Can SINS be used as a prognostic tool? SUMMARY OF BACKGROUND DATA.: Spinal neoplastic-related instability was defined in 2010 and simultaneously SINS was introduced as a novel tool with criteria agreed upon by expert consensus to assess the degree of spinal stability. METHODS.: Pubmed, Embase, and clinical trial databases were searched with the key words “spinal neoplasm”, “spinal instability”, “spinal instability neoplastic score”, and synonyms. Studies describing spinal neoplastic-related instability were eligible for inclusion. Primary outcomes included studies describing and/or defining neoplastic-related instability, SINS, and studies using SINS as a prognostic factor. RESULTS.: The search identified 1414 articles, of which 51 met the inclusion criteria. No precise definition or validated assessment tool was used specific to spinal neoplastic-related instability prior to the introduction of SINS. Since the publication of SINS in 2010, the vast majority of the literature regarding spinal instability has used SINS to assess or describe instability. Twelve studies specifically investigated the prognostic value of SINS in patients who underwent radiotherapy or surgery. CONCLUSION.: No consensus could be determined regarding the definition, assessment, or reporting of neoplastic-related instability before introduction of SINS. Defining spinal neoplastic-related instability and the introduction of SINS have led to improved uniform reporting within the spinal neoplastic literature. Currently, the prognostic value of SINS is controversial.Level of Evidence: N/

Development of a Patient-Oriented Intervention to Support Patient-Provider Conversations about Unnecessary Lower Back Pain Imaging

Background: despite the efforts of multiple stakeholders to promote appropriate care throughout the healthcare system, studies show that two out of three lower back pain (LBP) patients expect to receive imaging. We used the Choosing Wisely Canada patient-oriented framework, prioritizing patient engagement, to develop an intervention that addresses lower back pain imaging overuse. Methods: to develop this intervention, we collaborated with a multidisciplinary advisory team, including two patient partners with lower back pain, researchers, clinicians, healthcare administrators, and the Choosing Wisely Canada lead for Saskatchewan. For this qualitative study, data were collected through two advisory team meetings, two individual interviews with lower back pain patient partners, and three focus groups with lower back pain patient participants. A lower back pain prescription pad was developed as an outcome of these consultations. Results: participants reported a lack of interactive and informative communication was a significant barrier to receiving appropriate care. The most cited content information for inclusion in this intervention was treatments known to work, including physical activity, useful equipment, and reliable sources of educational material. Participants also suggested it was important that benefits and risks of imaging were explained on the pad. Three key themes derived from the data were also used to guide development of the intervention: (a) the role of imaging in LBP diagnosis; (b) the impact of the patient-physician relationship on LBP diagnosis and treatment; and (c) the lack of patient awareness of Choosing Wisely Canada and their recommendations. Conclusions: the lower back pain patient-developed prescription pad may help patients and clinicians engage in informed conversations and shared decision making that could support reduce unnecessary lower back pain imaging

A Randomized Controlled Trial of Local Delivery of a Rho Inhibitor (VX-210) in Patients with Acute Traumatic Cervical Spinal Cord Injury

Acute traumatic spinal cord injury (SCI) can result in severe, lifelong neurological deficits. After SCI, Rho activation contributes to collapse of axonal growth cones, failure of axonal regeneration, and neuronal loss. This randomized, double-blind, placebo-controlled phase 2b/3 study evaluated the efficacy and safety of Rho inhibitor VX-210 (9 mg) in patients after acute traumatic cervical SCI. The study enrolled patients 14-75 years of age with acute traumatic cervical SCIs, C4-C7 (motor level) on each side, and American Spinal Injury Association Impairment Scale (AIS) Grade A or B who had spinal decompression/stabilization surgery commencing within 72 h after injury. Patients were randomized 1:1 with stratification by age (<30 vs. ≥30 years) and AIS grade (A vs. B with sacral pinprick preservation vs. B without sacral pinprick preservation). A single dose of VX-210 or placebo in fibrin sealant was administered topically onto the dura over the site of injury during decompression/stabilization surgery. Patients were evaluated for medical, neurological, and functional changes, and serum was collected for pharmacokinetics and immunological analyses. Patients were followed up for up to 12 months after treatment. A planned interim efficacy-based futility analysis was conducted after ∼33% of patients were enrolled. The pre-defined futility stopping rule was met, and the study was therefore ended prematurely. In the final analysis, the primary efficacy end-point was not met, with no statistically significant difference in change from baseline in upper-extremity motor score at 6 months after treatment between the VX-210 (9-mg) and placebo groups. This work opens the door to further improvements in the design and conduct of clinical trials in acute SCI

Supplemental Material, RCC_Supp_tables - The Challenges of Renal Cell Carcinoma Metastatic to the Spine: A Systematic Review of Survival and Treatment

<p> Supplemental Material, RCC_Supp_tables for The Challenges of Renal Cell Carcinoma Metastatic to the Spine: A Systematic Review of Survival and Treatment by C. Rory Goodwin, A. Karim Ahmed, Christine Boone, Nancy Abu-Bonsrah, Risheng Xu, Niccole Germscheid, Daryl R. Fourney, Michelle Clarke, Ilya Laufer, Charles G. Fisher, Chetan Bettegowda, and Daniel M. Sciubba in Global Spine Journal </p