Regional and age-related diversity of human mature oligodendrocytes.

Morphological and emerging molecular studies have provided evidence for heterogeneity within the oligodendrocyte population. To address the regional and age-related heterogeneity of human mature oligodendrocytes (MOLs) we applied single-cell RNA sequencing to cells isolated from cortical/subcortical, subventricular zone brain tissue samples, and thoracolumbar spinal cord samples. Unsupervised clustering of cells identified transcriptionally distinct MOL subpopulations across regions. Spinal cord MOLs, but not microglia, exhibited cell-type-specific upregulation of immune-related markers compared to the other adult regions. SVZ MOLs showed an upregulation of select number of development-linked transcription factors compared to other regions; however, pseudotime trajectory analyses did not identify a global developmental difference. Age-related analysis of cortical/subcortical samples indicated that pediatric MOLs, especially from under age 5, retain higher expression of genes linked to development and to immune activity with pseudotime analysis favoring a distinct developmental stage. Our regional and age-related studies indicate heterogeneity of MOL populations in the human CNS that may reflect developmental and environmental influences.

Advanced practice physiotherapy for adults with spinal pain: a systematic review with meta-analysis.

OBJECTIVE: To appraise the available evidence on advanced practice physiotherapy (APP) models of care (MoC) in specialized secondary care such as orthopaedic, rheumatology or neurosurgery outpatients' clinics for adults with spinal pain. METHODS: Systematic review with meta-analysis. Electronic searches were conducted up to July 2020 in Medline, Embase, Cochrane CENTRAL and CINAHL. Studies on APP MoC in specialized secondary care for adults with spinal pain were included. RESULTS: Eighteen studies (n = 9405), including two randomized controlled trials and sixteen observational studies were included. One study was considered at high quality, fourteen studies were considered of moderate quality and three were considered of low quality. Pooled results for change in disability for patients with spinal pain reported no significant difference between APP and usual medical care (UMC). Mean wait time for initial consultation was lower with APP (1-9.4 weeks) than with UMC MoC (23-65 weeks). Following the implementation of APP MoC, wait time for a consultation with a medical specialist was reduced (6-16 weeks). Physiotherapists in APP MoC managed independently 89.2% of the patients referred (n = 8393). Stakeholders and patients reported high satisfaction with APP care. CONCLUSIONS: APP MoC and UMC likely result in comparable pain, disability and quality of life improvement for adults with spinal pain. However, APP MoC have the potential to improve health care access by reducing wait time for consultation in specialized care and maintaining a high level of satisfaction among stakeholders and patients.

Economic evaluation of advanced practice physiotherapy models of care: a systematic review with meta-analyses.

BACKGROUND: The objective of this systematic review is to appraise evidence on the economic evaluations of advanced practice physiotherapy (APP) care compared to usual medical care. METHODS: Systematic searches were conducted up to September 2021 in selected electronic bibliographical databases. Economic evaluation studies on an APP model of care were included. Economic data such as health care costs, patient costs, productivity losses were extracted. Methodological quality of included studies was assessed with the Effective Public Health Practice Project tool and the Critical Appraisal Skills Programme checklist. Meta-analyses were performed and mean differences (MD) in costs per patient were calculated using random-effect inverse variance models. Certainty of the evidence was assessed with the GRADE Approach. RESULTS: Twelve studies (n = 14,649 participants) including four randomized controlled trials, seven analytical cohort studies and one economic modeling study were included. The clinical settings of APP models of care included primary, emergency and specialized secondary care such as orthopaedics, paediatrics and gynaecology. The majority of the included participants were adults with musculoskeletal disorders (n = 12,915). Based on low quality evidence, health system costs including salaries, diagnostic tests, medications, and follow-up visits were significantly lower with APP care than with usual medical care, at 2 to 12-month follow-up (MD: - 145.02 €/patient; 95%CI: - 251.89 to - 38.14; n = 7648). Based on low quality evidence, patient costs including travel and paid medication prescriptions, or treatments were significantly higher with APP care compared to usual medical care, at 2 to 6-month follow-up (MD: 22.18 €/patient; 95%CI: 0.40 to 43.96; n = 1485). Based on very low quality evidence, no significant differences in productivity losses per patient were reported between both types of care (MD: 450 €/patient; 95%CI: - 80 to 970; n = 819). CONCLUSIONS: This is the first systematic review and meta-analysis on the economic evaluation of APP models of care. Low quality evidence suggests that APP care might result in lower health care costs, but higher patient costs compared to usual medical care. Costs differences may vary depending on various factors such as the cost methodology used and on the clinical setting. More evidence is needed to evaluate cost benefits of APP models of care.

Clinical and pathological outcomes after resection of intramedullary spinal cord tumors: a single-institution case series.

OBJECTIVE The objective of this study was to identify clinically relevant predictors of progression-free survival and functional outcomes in patients who underwent surgery for intramedullary spinal cord tumors (ISCTs). METHODS An institutional spinal tumor registry and billing records were reviewed to identify adult patients who underwent resection of ISCTs between 1993 and 2014. Extensive data were collected from patient charts and operative notes, including demographic information, extent of resection, tumor pathology, and functional and oncological outcomes. Survival analysis was used to determine important predictors of progression-free survival. Logistic regression analysis was used to evaluate the association between an "optimal" functional outcome on the Frankel or McCormick scale at 1-year follow-up and various clinical and surgical characteristics. RESULTS The consecutive case series consisted of 63 patients (50.79% female) who underwent resection of ISCTs. The mean age of patients was 41.92 ± 14.36 years (range 17.60-75.40 years). Complete microsurgical resection, defined as no evidence of tumor on initial postoperative imaging, was achieved in 34 cases (54.84%) of the 62 patients for whom this information was available. On univariate analysis, the most significant predictor of progression-free survival was tumor histology (p = 0.0027). Patients with Grade I/II astrocytomas were more likely to have tumor progression than patients with WHO Grade II ependymomas (HR 8.03, 95% CI 2.07-31.11, p = 0.0026) and myxopapillary ependymomas (HR 8.01, 95% CI 1.44-44.34, p = 0.017). Furthermore, patients who underwent radical or subtotal resection were more likely to have tumor progression than those who underwent complete resection (HR 3.46, 95% CI 1.23-9.73, p = 0.018). Multivariate analysis revealed that tumor pathology was the only significant predictor of tumor progression. On univariate analysis, the most significant predictors of an "optimal" outcome on the Frankel scale were age (OR 0.94, 95% CI 0.89-0.98, p = 0.0062), preoperative Frankel grade (OR 4.84, 95% CI 1.33-17.63, p = 0.017), McCormick score (OR 0.22, 95% CI 0.084-0.57, p = 0.0018), and region of spinal cord (cervical vs conus: OR 0.067, 95% CI 0.012-0.38, p = 0.0023; and thoracic vs conus: OR 0.015: 95% CI 0.001-0.20, p = 0.0013). Age, tumor pathology, and region were also important predictors of 1-year McCormick scores. CONCLUSIONS Extent of tumor resection and histopathology are significant predictors of progression-free survival following resection of ISCTs. Important predictors of functional outcomes include tumor histology, region of spinal cord in which the tumor is present, age, and preoperative functional status.

Advanced practice physiotherapy surgical triage and management of adults with spinal disorders referred to specialized spine medical care: a retrospective observational study.

INTRODUCTION: In this novel advanced practice physiotherapy (APP) model of care, advanced practice physiotherapists (APPTs) assess, triage, and manage adults with spinal disorders to alleviate the growing demands in specialized spine medical care. OBJECTIVES: To describe this APP model of care, to assess change in disability 3 months after rehabilitation care and to assess surgical triage and diagnostic concordance between APPTs and spine surgeons. METHODS: In this retrospective observational study, consecutive patients who completed the 3-month follow-up data were analyzed. Sociodemographic, clinical characteristics, and self-reported disabilities including the Oswestry Disability Index (ODI) and Neck Disability Index (NDI) at baseline and 3 months were extracted. Paired t-tests were used to assess changes in disability. Surgical triage and diagnostic concordance between APPTs and surgeons were measured with raw agreement, Cohen's Kappa, and PABAK. RESULTS: In this model, trained APPTs triaged surgical candidates and provided rehabilitation care including education and exercises to patients with spinal disorders. The APPTs referred only 18/46 participants to spine surgeons. Surgical triage and diagnostic concordance were high with raw agreement of 94% and 89%. At the 3-month follow-up, significant improvements in disability were observed among nonsurgical candidates with back (mean difference (MD): -13.0/100 [95%CI: -19.8 to -6.3], n = 23) or neck disorders (MD: -16.0/100 [95%CI: -29.6 to -2.4], n = 5), but not among surgical candidates referred by APPTs to spine surgeons. CONCLUSION: In this limited sample, adults with spinal disorders that were initially referred to a spine surgeon by family physicians were effectively assessed, triaged, and managed by an APPT.

Effect of Feedback Modality on Simulated Surgical Skills Learning Using Automated Educational Systems- A Four-Arm Randomized Control Trial.

OBJECTIVE: To explore optimal feedback methodologies to enhance trainee skill acquisition in simulated surgical bimanual skills learning during brain tumor resections. HYPOTHESES: (1) Providing feedback results in better learning outcomes in teaching surgical technical skill when compared to practice alone with no tailored performance feedback. (2) Providing more visual and visuospatial feedback results in better learning outcomes when compared to providing numerical feedback. DESIGN: A prospective 4-parallel-arm randomized controlled trial. SETTING: Neurosurgical Simulation and Artificial Intelligence Learning Centre, McGill University, Canada. PARTICIPANTS: Medical students (n = 120) from 4 Quebec medical schools. RESULTS: Participants completed a virtually simulated tumor resection task 5 times while receiving 1 of 4 feedback based on their group allocation: (1) practice-alone without feedback, (2) numerical feedback, (3) visual feedback, and (4) visuospatial feedback. Outcome measures were participants' scores on 14-performance metrics and the number of expert benchmarks achieved during each task. There were no significant differences in the first task which determined baseline performance. A statistically significant interaction between feedback allocation and task repetition was found on the number of benchmarks achieved, F (10.558, 408.257)=3.220, p < 0.001. Participants in all feedback groups significantly improved their performance compared to baseline. The visual feedback group achieved significantly higher number of benchmarks than the practice-alone group by the third repetition of the task, p = 0.005, 95%CI [0.42 3.25]. Visual feedback and visuospatial feedback improved performance significantly by the second repetition of the task, p = 0.016, 95%CI [0.19 2.71] and p = 0.003, 95%CI [0.4 2.57], respectively. CONCLUSION: Simulations with autonomous visual computer assistance may be effective pedagogical tools in teaching bimanual operative skills via visual and visuospatial feedback information delivery.

Real-Time multifaceted artificial intelligence vs In-Person instruction in teaching surgical technical skills: a randomized controlled trial.

Trainees develop surgical technical skills by learning from experts who provide context for successful task completion, identify potential risks, and guide correct instrument handling. This expert-guided training faces significant limitations in objectively assessing skills in real-time and tracking learning. It is unknown whether AI systems can effectively replicate nuanced real-time feedback, risk identification, and guidance in mastering surgical technical skills that expert instructors offer. This randomized controlled trial compared real-time AI feedback to in-person expert instruction. Ninety-seven medical trainees completed a 90-min simulation training with five practice tumor resections followed by a realistic brain tumor resection. They were randomly assigned into 1-real-time AI feedback, 2-in-person expert instruction, and 3-no real-time feedback. Performance was assessed using a composite-score and Objective Structured Assessment of Technical Skills rating, rated by blinded experts. Training with real-time AI feedback (n = 33) resulted in significantly better performance outcomes compared to no real-time feedback (n = 32) and in-person instruction (n = 32), .266, [95% CI .107 .425], p < .001; .332, [95% CI .173 .491], p = .005, respectively. Learning from AI resulted in similar OSATS ratings (4.30 vs 4.11, p = 1) compared to in-person training with expert instruction. Intelligent systems may refine the way operating skills are taught, providing tailored, quantifiable feedback and actionable instructions in real-time.

Pharmacological Treatment of Degenerative Cervical Myelopathy: A Critical Review of Current Evidence.

Degenerative cervical myelopathy (DCM) is the leading cause of spinal cord dysfunction in adults, representing substantial morbidity and significant financial and resource burdens. Typically, patients with progressive DCM will eventually receive surgical treatment. Nonetheless, despite advancements in pharmacotherapeutics, evidence for pharmacological therapy remains limited. Health professionals from various fields would find interest in pharmacological agents that could benefit patients with mild DCM or enhance surgical outcomes. This review aims to consolidate all clinical and experimental evidence on the pharmacological treatment of DCM. We conducted a comprehensive narrative review that presents all pharmacological agents that have been investigated for DCM treatment in both humans and animal models. Riluzole exhibits effectiveness solely in rat models, but not in treating mild DCM in humans. Cerebrolysin emerges as a potential neuroprotective agent for myelopathy in animals but had contradictory results in clinical trials. Limaprost alfadex demonstrates motor function improvement in animal models and exhibits promising outcomes in a small clinical trial. Glucocorticoids not only fail to provide clinical benefits but may also lead to adverse events. Cilostazol, anti-Fas ligand antibody, and Jingshu Keli display promise in animal studies, while erythropoietin, granulocyte colony-stimulating factor and limaprost alfadex exhibit potential in both animal and human research. Existing evidence mainly rests on weak clinical data and animal experimentation. Current pharmacological efforts target ion channels, stem cell differentiation, inflammatory, vascular, and apoptotic pathways. The inherent nature and pathogenesis of DCM offer substantial prospects for developing neurodegenerative or neuroprotective therapies capable of altering disease progression, potentially delaying surgical intervention, and optimizing outcomes for those undergoing surgical decompression.

Anxiety and Depression in Pediatric-Onset Traumatic Spinal Cord Injury: A Systematic Review.

BACKGROUND: Traumatic spinal cord injury (TSCI) is a debilitating neurological condition with significant long-term consequences on the mental health and well-being of affected individuals. We aimed to investigate anxiety and depression in individuals with pediatric-onset TSCI. METHODS: PubMed, Scopus, and Web of Science databases were searched from inception to December 20th, 2022 following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, and studies were included according to the eligibility criteria. RESULTS: A total of 1013 articles were screened, and 18 studies with 4234 individuals were included in the final review. Of these, 1613 individuals (38.1%) had paraplegia, whereas 1658 (39.2%) had tetraplegia. A total of 1831 participants (43.2%) had complete TSCI, whereas 1024 (24.2%) had incomplete TSCI. The most common etiology of TSCI with 1545 people (36.5%) was motor vehicle accidents. The youngest mean age at the time of injury was 5.92 ± 4.92 years, whereas the oldest was 14.6 ± 2.8 years. Patient Health Questionnaire-9 was the most common psychological assessment used in 9 studies (50.0%). Various risk factors, including pain in 4 studies (22.2%), reduced sleep quality, reduced functional independence, illicit drug use, incomplete injury, hospitalization, reduced quality of life, and duration of injury in 2 (11.1%) studies, each, were associated with elevated anxiety and depression. CONCLUSIONS: Different biopsychosocial risk factors contribute to elevated rates of anxiety and depression among individuals with pediatric-onset TSCI. Individuals at risk of developing anxiety and depression should be identified, and targeted support should be provided. Future large-scale studies with long-term follow-up are required to validate and extend these findings.

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

STUDY DESIGN: Retrospective cohort study of prospectively accrued data. OBJECTIVE: To evaluate a large, prospective, multicentre dataset of surgically-treated 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 degenerative cervical myelopathy (DCM) is intensely debated. Comprehensive analyses are needed using contemporary data and accounting for covariates. METHODS: Patients with moderate to severe DCM were prospectively enrolled in the multicenter, randomized CSM-Protect clinical trial and underwent either anterior or posterior decompression between Jan 31, 2012, to May 16, 2017. The primary outcome was the incidence of postoperative C5 palsy, defined as 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 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 that underwent posterior decompression compared to anterior decompression (11.26% vs. 3.03%, P=0.008). After multivariable regression, 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 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.

Pathophysiology and surgical decision-making in central cord syndrome and degenerative cervical myelopathy: correcting the somatotopic fallacy.

Our understanding of Central Cord Syndrome (CCS), a form of incomplete spinal cord injury characterized by disproportionate upper extremity weakness, is evolving. Recent advances challenge the traditional somatotopic model of corticospinal tract organization within the spinal cord, suggesting that CCS is likely a diffuse injury rather than focal lesion. Diagnostic criteria for CCS lack consensus, and varied definitions impact patient identification and treatment. Evidence has mounted for early surgery for CCS, although significant variability persists in surgical timing preferences among practitioners. A demographic shift toward an aging population has increased the overlap between CCS and Degenerative Cervical Myelopathy (DCM). Understanding this intersection is crucial for comprehensive patient care. Assessment tools, including quantitative measures and objective evaluations, aid in distinguishing CCS from DCM. The treatment landscape for CCS in the context of pre-existing DCM is complex, requiring careful consideration of pre-existing neurologic injury, patient factors, and injury factors. This review synthesizes emerging evidence, outlines current guidelines in diagnosis and management, and emphasizes the need for ongoing research to refine our understanding and treatment strategies for this evolving patient population.

Patient, clinical, surgical, and institutional factors associated with length of stay in scheduled degenerative thoracolumbar spine surgery: National Multicenter Cohort Analysis from the Canadian Spine Outcomes and Research Network.

OBJECTIVE: Length of stay (LOS) is a contributor to costs and resource utilization. The primary goal of this study was to identify patient, clinical, surgical, and institutional variables that influence LOS after elective surgery for thoracolumbar degenerative pathology. The secondary objective was to examine variability in LOS and institutional strategies used to decrease LOS. METHODS: This is a retrospective study of prospectively collected data from a multicentric cohort enrolled in the Canadian Spine Outcomes and Research Network (CSORN) between January 2015 and October 2020 who underwent elective thoracolumbar surgery (discectomy [1 or 2 levels], laminectomy [1 or 2 levels], and posterior instrumented fusion [up to 5 levels]). Prolonged LOS was defined as LOS greater than the median. Logistic regression models were used to determine factors associated with prolonged LOS for each procedure. A survey was sent to the principal investigators of the participating healthcare institutions to understand institutional practices that are used to decrease LOS. RESULTS: A total of 3700 patients were included (967 discectomies, 1094 laminectomies, and 1639 fusions). The median LOSs for discectomy, laminectomy, and fusion were 0.0 (IQR 1.0), 1.0 (IQR 2.0), and 4.0 (IQR 2.0) days, respectively. On multivariable analysis, predictors of prolonged LOS for discectomy were having more leg pain, higher Oswestry Disability Index (ODI) scores, symptom duration more than 2 years, having undergone an open procedure, occurrence of an adverse event (AE), and treatment at an institution without protocols to reduce LOS (p < 0.05). Predictors of prolonged LOS for laminectomy were increased age, living alone, higher ODI scores, higher BMI, open procedures, longer operative time, AEs, and treatment at an institution without protocols to reduce LOS (p < 0.05). For posterior instrumented fusion, predictors of prolonged LOS were older age, living alone, more comorbidities, higher ODI scores, longer operative time, AEs, and treatment at an institution without protocols to reduce LOS (p < 0.05). The laminectomy group had the largest variability in LOS (SD 4.4 days, range 0-133 days). Three hundred fifty-four patients (22%) had an LOS above the 75th percentile. Ten institutions (53%) had either Enhanced Recovery After Surgery or standardized protocols in place. CONCLUSIONS: Among the factors identified in this study, worse baseline ODI scores, experiencing AEs, and treatment at an institution without protocols aimed at reducing LOS were predictive of prolonged LOS in all surgical groups. The laminectomy group had the largest variability in LOS.

Ultrasound-based navigated pedicle screw insertion without intraoperative radiation: feasibility study on porcine cadavers.

BACKGROUND: Navigation systems for spinal fusion surgery rely on intraoperative computed tomography (CT) or fluoroscopy imaging. Both expose patient, surgeons and operating room staff to significant amounts of radiation. Alternative methods involving intraoperative ultrasound (iUS) imaging have recently shown promise for image-to-patient registration. Yet, the feasibility and safety of iUS navigation in spinal fusion have not been demonstrated. PURPOSE: To evaluate the accuracy of pedicle screw insertion in lumbar and thoracolumbar spinal fusion using a fully automated iUS navigation system. STUDY DESIGN: Prospective porcine cadaver study. METHODS: Five porcine cadavers were used to instrument the lumbar and thoracolumbar spine using posterior open surgery. During the procedure, iUS images were acquired and used to establish automatic registration between the anatomy and preoperative CT images. Navigation was performed with the preoperative CT using tracked instruments. The accuracy of the system was measured as the distance of manually collected points to the preoperative CT vertebral surface and compared against fiducial-based registration. A postoperative CT was acquired, and screw placements were manually verified. We report breach rates, as well as axial and sagittal screw deviations. RESULTS: A total of 56 screws were inserted (5.50 mm diameter n=50, and 6.50 mm diameter n=6). Fifty-two screws were inserted safely without breach. Four screws (7.14%) presented a medial breach with an average deviation of 1.35±0.37 mm (all <2 mm). Two breaches were caused by 6.50 mm diameter screws, and two by 5.50 mm screws. For vertebrae instrumented with 5.50 mm screws, the average axial diameter of the pedicle was 9.29 mm leaving a 1.89 mm margin in the left and right pedicle. For vertebrae instrumented with 6.50 mm screws, the average axial diameter of the pedicle was 8.99 mm leaving a 1.24 mm error margin in the left and right pedicle. The average distance to the vertebral surface was 0.96 mm using iUS registration and 0.97 mm using fiducial-based registration. CONCLUSIONS: We successfully implanted all pedicle screws in the thoracolumbar spine using the ultrasound-based navigation system. All breaches recorded were minor (<2 mm) and the breach rate (7.14%) was comparable to existing literature. More investigation is needed to evaluate consistency, reproducibility, and performance in surgical context. CLINICAL SIGNIFICANCE: Intraoperative US-based navigation is feasible and practical for pedicle screw insertion in a porcine model. It might be used as a low-cost and radiation-free alternative to intraoperative CT and fluoroscopy in the future.

Continuous monitoring of surgical bimanual expertise using deep neural networks in virtual reality simulation.

In procedural-based medicine, the technical ability can be a critical determinant of patient outcomes. Psychomotor performance occurs in real-time, hence a continuous assessment is necessary to provide action-oriented feedback and error avoidance guidance. We outline a deep learning application, the Intelligent Continuous Expertise Monitoring System (ICEMS), to assess surgical bimanual performance at 0.2-s intervals. A long-short term memory network was built using neurosurgeon and student performance in 156 virtually simulated tumor resection tasks. Algorithm predictive ability was tested separately on 144 procedures by scoring the performance of neurosurgical trainees who are at different training stages. The ICEMS successfully differentiated between neurosurgeons, senior trainees, junior trainees, and students. Trainee average performance score correlated with the year of training in neurosurgery. Furthermore, coaching and risk assessment for critical metrics were demonstrated. This work presents a comprehensive technical skill monitoring system with predictive validation throughout surgical residency training, with the ability to detect errors.

Single-cell RNA sequencing reveals time- and sex-specific responses of mouse spinal cord microglia to peripheral nerve injury and links ApoE to chronic pain.

Activation of microglia in the spinal cord following peripheral nerve injury is critical for the development of long-lasting pain hypersensitivity. However, it remains unclear whether distinct microglia subpopulations or states contribute to different stages of pain development and maintenance. Using single-cell RNA-sequencing, we show that peripheral nerve injury induces the generation of a male-specific inflammatory microglia subtype, and demonstrate increased proliferation of microglia in male as compared to female mice. We also show time- and sex-specific transcriptional changes in different microglial subpopulations following peripheral nerve injury. Apolipoprotein E (Apoe) is the top upregulated gene in spinal cord microglia at chronic time points after peripheral nerve injury in mice. Furthermore, polymorphisms in the APOE gene in humans are associated with chronic pain. Single-cell RNA sequencing analysis of human spinal cord microglia reveals a subpopulation with a disease-related transcriptional signature. Our data provide a detailed analysis of transcriptional states of mouse and human spinal cord microglia, and identify a link between ApoE and chronic pain in humans.

Evaluation of an Ultrasound-Based Navigation System for Spine Neurosurgery: A Porcine Cadaver Study.

BACKGROUND: With the growing incidence of patients receiving surgical treatment for spinal metastatic tumours, there is a need for developing cost-efficient and radiation-free alternatives for spinal interventions. In this paper, we evaluate the capabilities and limitations of an image-guided neurosurgery (IGNS) system that uses intraoperative ultrasound (iUS) imaging for guidance. METHODS: Using a lumbosacral section of a porcine cadaver, we explored the impact of CT image resolution, ultrasound depth and ultrasound frequency on system accuracy, robustness and effectiveness. Preoperative CT images with an isotropic resolution of , and were acquired. During surgery, vertebrae L1 to L6 were exposed. For each vertebra, five iUS scans were acquired using two depth parameters (5 cm and 7 cm) and two frequencies (6 MHz and 12 MHz). A total of 120 acquisition trials were evaluated. Ultrasound-based registration performance is compared to the standard alignment procedure using intraoperative CT. We report target registration error (TRE) and computation time. In addition, the scans' trajectories were analyzed to identify vertebral regions that provide the most relevant features for the alignment. RESULTS: For all acquisitions, the median TRE ranged from 1.42 mm to 1.58 mm and the overall computation time was 9.04 s ± 1.58 s. Fourteen out of 120 iUS acquisitions (11.66%) yielded a level-to-level mismatch (and these are included in the accuracy measurements reported). No significant effect on accuracy was found with CT resolution (F (2,10) = 1.70, p = 0.232), depth (F (1,5) = 0.22, p= 0.659) nor frequency (F (1,5) = 1.02, p = 0.359). While misalignment increases linearly with the distance from the imaged vertebra, accuracy was satisfactory for directly adjacent levels. A significant relationship was found between iUS scan coverage of laminae and articular processes, and accuracy. CONCLUSION: Intraoperative ultrasound can be used for spine surgery neuronavigation. We demonstrated that the IGNS system yield acceptable accuracy and high efficiency compared to the standard CT-based navigation procedure. The flexibility of the iUS acquisitions can have repercussions on the system performance, which are not fully identified. Further investigation is needed to understand the relationship between iUS acquisition and alignment performance.

Single session compared with multiple sessions of education and exercise for older adults with spinal pain in an advanced practice physiotherapy model of care: protocol for a randomised controlled trial.

OBJECTIVES: To assess the effectiveness and cost-effectiveness of a single session compared with multiple sessions of education and exercise for older adults with spinal pain treated conservatively in an advanced practice physiotherapy model of care. METHODS AND ANALYSIS: In this pragmatic randomised controlled trial, 152 older adults (≥65 years old) with neck or back pain initially referred for a consultation in neurosurgery, but treated conservatively, will be recruited through the advanced practice physiotherapy neurosurgery CareAxis programme in the Montreal region (Quebec, Canada). In the CareAxis programme, older patients with spinal pain are triaged by an advance practice physiotherapist and are offered conservative care and only potential surgical candidates are referred to a neurosurgeon. Participants will be randomised into one of two arms: 1-a single session or 2-multiple sessions (6 sessions over 12 weeks) of education and exercise with the advance practice physiotherapist (1:1 ratio). The primary outcome measure will be the Brief Pain Inventory (pain severity and interference subscales). Secondary measures will include self-reported disability (the Neck Disability Index or Oswestry Disability Index), the Pain Catastrophizing Scale, satisfaction with care questionnaires (9-item Visit-specific Satisfaction Questionnaire and MedRisk), and the EQ-5D-5L. Participants' healthcare resources use and related costs will be measured. Outcomes will be collected at baseline and at 6, 12 and 26 weeks after enrolment. Intention-to-treat analyses will be performed, and repeated mixed-model analysis of variance will assess differences between treatment arms. Cost-utility analyses will be conducted from the perspective of the healthcare system. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Comité d'éthique de la recherche du CIUSS de l'Est-de-l'Île-de-Montréal (FWA00001935 and IRB00002087). Results of this study will be presented to different stakeholders, published in peer-reviewed journals and presented at international conferences. PROTOCOL VERSION: V.4 August 2021. TRIAL REGISTRATION NUMBER: NCT04868591; Pre-results.

Safety and efficacy of riluzole in patients undergoing decompressive surgery for degenerative cervical myelopathy (CSM-Protect): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial.

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.