BACKGROUND: Cervical posterior instrumentation and fusion is often performed to avoid post-laminectomy kyphosis. However, larger comparative analyses of cervical laminectomy with or without fusion are sparse. METHODS: A retrospective, two-center, comparative cohort study included patients after stand-alone dorsal laminectomy with (n = 91) or without (n = 46) additional fusion for degenerative cervical myelopathy with a median follow-up of 59 (interquartile range (IQR) 52) months. The primary outcome was the C2-7 Cobb angle and secondary outcomes were Neck Disability Index (NDI), modified Japanese Orthopaedic Association (mJOA) scale, revision rates, T1 slope and C2-7 sagittal vertical axis (C2-7 SVA) at final follow-up. Logistic regression analysis adjusted for potential confounders (i.e. age, operated levels, and follow-up). RESULTS: Preoperative C2-7 Cobb angle and T1 slope were higher in the laminectomy group, while the C2-7 SVA was similar. The decrease in C2-7 Cobb angle from pre- to postoperatively was more pronounced in the laminectomy group (- 6° (IQR 20) versus -1° (IQR 7), p = 0.002). When adjusting for confounders, the decrease in C2-7 Cobb angle remained higher in the laminectomy group (coefficient - 12 (95% confidence interval (CI) -18 to -5), p = 0.001). However, there were no adjusted differences for postoperative NDI (- 11 (- 23 to 2), p = 0.10), mJOA, revision rates, T1 slope and C2-7 SVA. CONCLUSION: Posterior cervical laminectomy without fusion is associated with mild loss of cervical lordosis of around 6° in the mid-term after approximately five years, however without any clinical relevance regarding NDI or mJOA in well-selected patients (particularly in shorter segment laminectomies of < 3 levels).
BACKGROUND AND OBJECTIVES: The palliative impact of spine surgery for metastatic disease is evolving with improvements in surgical technique and multidisciplinary cancer care. The goal of this study was to prospectively evaluate long-term clinical outcomes including health-related quality-of-life (HRQOL) measures, using spine cancer-specific patient-reported-outcome (PRO) measures, in patients with symptomatic spinal metastases who underwent surgical management. METHODS: The Epidemiology, Process, and Outcomes of Spine Oncology (EPOSO, ClinicalTrials.gov identifier: NCT01825161) trial is a prospective-observational cohort study that included 10 specialist centers in North America and Europe. Patients aged 18 to 75 years who underwent surgery for spinal metastases were included. Prospective assessments included both spine tumor-specific and generic PRO tools which were collected for a minimum of 2 years post-treatment or until death. RESULTS: Two hundred and eighty patients (51.8% female, mean age 57.9 years) were included. At presentation, the mean Charlson Comorbidity Index was 6.0, 35.7% had neurological deficits as defined by the American Spinal Cord Injury Association scores, 47.2% had high-grade epidural spinal cord compression (2-3), and 89.6% had impending or frank instability as measured by a Spinal Instability Neoplastic Score of ≥7. The most common primary tumor sites were breast (20.2%), lung (18.8%), kidney (16.2%), and prostate (6.5%). The median overall survival postsurgery was 501 days, and the 2-year progression-free-survival rate was 38.4%. Compared with baseline, significant and durable improvements in HRQOL were observed at the 6-week, 12-week, 26-week, 1-year, and 2-year follow-up assessments from a battery of PRO questionnaires including the spine cancer-specific, validated, Spine Oncology Study Group Outcomes Questionnaire v2.0, the Short Form 36 version 2, EuroQol-5 Dimension (3L), and pain numerical rating scale score. CONCLUSION: Multi-institutional, prospective-outcomes data confirm that surgical decompression and/or stabilization provides meaningful and durable improvements in multiple HRQOL domains, including spine-specific outcomes based on the Spine Oncology Study Group Outcomes Questionnaire v2.0, for patients with metastatic spine disease.
BACKGROUND CONTEXT: Postoperative infection after spinal deformity correction in pediatric patients is associated with significant costs. Identifying risk factors associated with postoperative infection would help surgeons identify high-risk patients that may require interventions to minimize infection risk. PURPOSE: To investigate risk factors associated with 30-day postoperative infection in pediatric patients who have received posterior arthrodesis for spinal deformity correction. STUDY DESIGN/SETTING: Retrospective review of prospectively collected data. PATIENT SAMPLE: The National Surgical Quality Improvement Program Pediatric database for years 2016-2021 was used for this study. Patients were included if they received posterior arthrodesis for scoliosis or kyphosis correction (CPT 22,800, 22,802, 22,804). Anterior only approaches were excluded. OUTCOME MEASURES: TThe outcome of interest was 30-day postoperative infection. METHODS: Patient demographics and outcomes were analyzed using descriptive statistics. Multivariable logistic regression analysis using likelihood ratio backward selection method was used to identify significant risk factors for 30-day infection to create the Pediatric Scoliosis Infection Risk Score (PSIR Score). ROC curve analysis, predicted probabilities, and Hosmer Lemeshow goodness-of-fit test were done to assess the scoring system on a validation cohort. RESULTS: A total of 31,742 patients were included in the study. The mean age was 13.8 years and 68.7% were female. The 30-day infection rate was 2.2%. Reoperation rate in patients who had a post-operative infection was 59.4%. Patients who had post-operative infection had a higher likelihood of non-home discharge (X2 = 124.8, p < 0.001). In our multivariable regression analysis, high BMI (OR = 1.01, p < 0.001), presence of open wound (OR = 3.18, p < 0.001), presence of ostomy (OR = 1.51, p < 0.001), neuromuscular etiology (OR = 1.56, p = 0.009), previous operation (OR = 1.74, p < 0.001), increasing ASA class (OR = 1.43, p < 0.001), increasing operation time in hours (OR = 1.11, p < 0.001), and use of only minimally invasive techniques (OR = 4.26, p < 0.001) were associated with increased risk of 30-day post-operative infection. Idiopathic etiology (OR = 0.53, p < 0.001) and intraoperative topical antibiotic use (B = 0.71, p = 0.003) were associated with reduced risk of 30-day postoperative infection. The area under the curve was 0.780 and 0.740 for the derivation cohort and validation cohort, respectively. CONCLUSIONS: To our knowledge, this is the largest study of risk factors for infection in pediatric spinal deformity surgery. We found 5 patient factors (BMI, ASA, osteotomy, etiology, and previous surgery, and 3 surgeon-controlled factors (surgical time, antibiotics, MIS) associated with risk. The Pediatric Scoliosis Infection Risk Score (PSIR) Score can be applied for risk stratification and to investigate implementation of novel protocols to reduce infection rates in high-risk patients.
Introduction: It was not even a century ago when a spinal cord injury (SCI) would inevitably result in a fatal outcome, particularly for those with complete SCI. Throughout history, there have been extensive endeavours to change the prospects for SCI patients by performing surgery, even though many believed that there was no way to alter the catastrophic course of SCI. To this day, the debate regarding the efficacy of surgery in improving the neurological outcome for SCI patients persists, along with discussions about the timing of surgical intervention. Research question: How have the historical surgical results shaped our perspective on the surgical treatment of SCI? Material and methods: Narrative literature review. Results: Throughout history there have been multiple surgical attempts to alter the course of SCI, with conflicting results. While studies suggest a potential link between timing of surgery and neurological recovery, the exact impact of immediate surgery on individual cases remains ambiguous. It is becoming more evident that, alongside surgical intervention, factors specific to both the patient and their surgical treatment will significantly influence neurological recovery. Conclusion: Although a growing number of studies indicates a potential correlation of surgical timing and neurological outcome, the precise influence of urgent surgery on an individual basis remains uncertain. It is increasingly apparent that, despite surgery, patient- and treatment-specific factors will also play a role in determining the neurological outcome. Notably, these very factors have influenced the results in previous studies and our views concerning surgical timing.
Traumatic spinal cord injuries (SCIs) continue to be a major healthcare concern, with a rising prevalence worldwide. In response to this growing medical challenge, considerable scientific attention has been devoted to developing neuroprotective and neuroregenerative strategies aimed at improving the prognosis and quality of life for individuals with SCIs. This comprehensive review aims to provide an up-to-date and thorough overview of the latest neuroregenerative and neuroprotective therapies currently under investigation. These strategies encompass a multifaceted approach that include neuropharmacological interventions, cell-based therapies, and other promising strategies such as biomaterial scaffolds and neuro-modulation therapies. In addition, the review discusses the importance of acute clinical management, including the role of hemodynamic management as well as timing and technical aspects of surgery as key factors mitigating the secondary injury following SCI. In conclusion, this review underscores the ongoing scientific efforts to enhance patient outcomes and quality of life, focusing on upcoming strategies for the management of traumatic SCI. Each section provides a working knowledge of the fundamental preclinical and patient trials relevant to clinicians while underscoring the pathophysiologic rationale for the therapies.
BACKGROUND AND PURPOSE: Simultaneous assessment of neurodegeneration in both the cervical cord and brain across multiple centres can enhance the effectiveness of clinical trials. Thus, this study aims to simultaneously assess microstructural changes in the cervical cord and brain above the stenosis in degenerative cervical myelopathy (DCM) using quantitative magnetic resonance imaging (MRI) in a multicentre study. METHODS: We applied voxelwise analysis with a probabilistic brain/spinal cord template embedded in statistical parametric mappin (SPM-BSC) to process multi parametric mapping (MPM) including effective transverse relaxation rate (R2*), longitudinal relaxation rate (R1), and magnetization transfer (MT), which are indirectly sensitive to iron and myelin content. Regression analysis was conducted to establish associations between neurodegeneration and clinical impairment. Thirty-eight DCM patients (mean age ± SD = 58.45 ± 11.47 years) and 38 healthy controls (mean age ± SD = 41.18 ± 12.75 years) were recruited at University Hospital Balgrist, Switzerland and Toronto Western Hospital, Canada. RESULTS: Remote atrophy was observed in the cervical cord (p = 0.002) and in the left thalamus (0.026) of the DCM group. R1 was decreased in the periaqueductal grey matter (p = 0.014), thalamus (p = 0.001), corpus callosum (p = 0.0001), and cranial corticospinal tract (p = 0.03). R2* was increased in the primary somatosensory cortices (p = 0.008). Sensory impairments were associated with increased iron-sensitive R2* in the thalamus and periaqueductal grey matter in DCM. CONCLUSIONS: Simultaneous assessment of the spinal cord and brain revealed DCM-induced demyelination, iron deposition, and atrophy. The extent of remote neurodegeneration was associated with sensory impairment, highlighting the intricate and expansive nature of microstructural neurodegeneration in DCM, reaching beyond the stenosis level.
Cervical Cord , Magnetic Resonance Imaging , Humans , Male , Female , Middle Aged , Aged , Adult , Cervical Cord/diagnostic imaging , Cervical Cord/pathology , Brain/diagnostic imaging , Brain/pathology , Spinal Cord Diseases/diagnostic imaging , Spinal Cord Diseases/pathology , Neurodegenerative Diseases/diagnostic imaging , Neurodegenerative Diseases/pathology
STUDY DESIGN: Protocol for the development of clinical practice guidelines following the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) standards. OBJECTIVES: Acute SCI or intraoperative SCI (ISCI) can have devastating physical and psychological consequences for patients and their families. The treatment of SCI has dramatically evolved over the last century as a result of preclinical and clinical research that has addressed important knowledge gaps, including injury mechanisms, disease pathophysiology, medical management, and the role of surgery. In an acute setting, clinicians are faced with critical decisions on how to optimize neurological recovery in patients with SCI that include the role and timing of surgical decompression and the best strategies for hemodynamic management. The lack of consensus surrounding these treatments has prevented standardization of care across centers and has created uncertainty with respect to how to best manage patients with SCI. ISCI is a feared complication that can occur in the best of hands. Unfortunately, there are no systematic reviews or clinical practice guidelines to assist spine surgeons in the assessment and management of ISCI in adult patients undergoing spinal surgery. Given these limitations, it is the objective of this initiative to develop evidence-based recommendations that will inform the management of both SCI and ISCI. This protocol describes the rationale for developing clinical practice guidelines on (i) the timing of surgical decompression in acute SCI; (ii) the hemodynamic management of acute SCI; and (iii) the prevention, identification, and management of ISCI in patients undergoing surgery for spine-related pathology. METHODS: Systematic reviews were conducted according to PRISMA standards in order to summarize the current body of evidence and inform the guideline development process. The guideline development process followed the approach proposed by the GRADE working group. Separate multidisciplinary, international groups were created to perform the systematic reviews and formulate the guidelines. All potential conflicts of interest were vetted in advance. The sponsors exerted no influence over the editorial process or the development of the guidelines. RESULTS: This process resulted in both systematic reviews and clinical practice guidelines/care pathways related to the role and timing of surgery in acute SCI; the optimal hemodynamic management of acute SCI; and the prevention, diagnosis and management of ISCI. CONCLUSIONS: The ultimate goal of this clinical practice guideline initiative was to develop evidence-based recommendations for important areas of controversy in SCI and ISCI in hopes of improving neurological outcomes, reducing morbidity, and standardizing care across settings. Throughout this process, critical knowledge gaps and future directions were also defined.
STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: In an effort to prevent intraoperative neurological injury during spine surgery, the use of intraoperative neurophysiological monitoring (IONM) has increased significantly in recent years. Using IONM, spinal cord function can be evaluated intraoperatively by recording signals from specific nerve roots, motor tracts, and sensory tracts. We performed a systematic review and meta-analysis of diagnostic test accuracy (DTA) studies to evaluate the efficacy of IONM among patients undergoing spine surgery for any indication. METHODS: The current systematic review and meta-analysis was performed using the Preferred Reporting Items for a Systematic Review and Meta-analysis statement for Diagnostic Test Accuracy Studies (PRISMA-DTA) and was registered on PROSPERO. A comprehensive search was performed using MEDLINE, EMBASE and SCOPUS for all studies assessing the diagnostic accuracy of neuromonitoring, including somatosensory evoked potential (SSEP), motor evoked potential (MEP) and electromyography (EMG), either on their own or in combination (multimodal). Studies were included if they reported raw numbers for True Positives (TP), False Negatives (FN), False Positives (FP) and True Negative (TN) either in a 2 × 2 contingency table or in text, and if they used postoperative neurologic exam as a reference standard. Pooled sensitivity and specificity were calculated to evaluate the overall efficacy of each modality type using a bivariate model adapted by Reitsma et al, for all spine surgeries and for individual disease groups and regions of spine. The risk of bias (ROB) of included studies was assessed using the quality assessment tool for diagnostic accuracy studies (QUADAS-2). RESULTS: A total of 163 studies were included; 52 of these studies with 16,310 patients reported data for SSEP, 68 studies with 71,144 patients reported data for MEP, 16 studies with 7888 patients reported data for EMG and 69 studies with 17,968 patients reported data for multimodal monitoring. The overall sensitivity, specificity, DOR and AUC for SSEP were 71.4% (95% CI 54.8-83.7), 97.1% (95% CI 95.3-98.3), 41.9 (95% CI 24.1-73.1) and .899, respectively; for MEP, these were 90.2% (95% CI 86.2-93.1), 96% (95% CI 94.3-97.2), 103.25 (95% CI 69.98-152.34) and .927; for EMG, these were 48.3% (95% CI 31.4-65.6), 92.9% (95% CI 84.4-96.9), 11.2 (95% CI 4.84-25.97) and .773; for multimodal, these were found to be 83.5% (95% CI 81-85.7), 93.8% (95% CI 90.6-95.9), 60 (95% CI 35.6-101.3) and .895, respectively. Using the QUADAS-2 ROB analysis, of the 52 studies reporting on SSEP, 13 (25%) were high-risk, 10 (19.2%) had some concerns and 29 (55.8%) were low-risk; for MEP, 8 (11.7%) were high-risk, 21 had some concerns and 39 (57.3%) were low-risk; for EMG, 4 (25%) were high-risk, 3 (18.75%) had some concerns and 9 (56.25%) were low-risk; for multimodal, 14 (20.3%) were high-risk, 13 (18.8%) had some concerns and 42 (60.7%) were low-risk. CONCLUSIONS: These results indicate that all neuromonitoring modalities have diagnostic utility in successfully detecting impending or incident intraoperative neurologic injuries among patients undergoing spine surgery for any condition, although it is clear that the accuracy of each modality differs.PROSPERO Registration Number: CRD42023384158.
OBJECTIVE: Chiari malformations (CMs) are a group of congenital or acquired disorders characterized by hindbrain overcrowding into an underdeveloped posterior cranial fossa. CM is considered largely sporadic-however, there exists growing evidence of transmissible genetic underpinnings. The purpose of this systematic review of all familial studies of CM was to investigate the existence of an inherited component and provide recommendations to manage and monitor at-risk family members. METHODS: This paper includes the following: 1) a unique case report of dizygotic twins who presented at the Toronto Western Hospital Spinal Cord Clinic with symptomatic CM type 1 (CM-1) and syringomyelia; and 2) a systematic review of familial CM. The EMBASE and MEDLINE databases were searched on June 27, 2023, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only articles in the English language concerning the diagnosis of CM in > 1 human family member presented as a case study, case series, or literature review were included. RESULTS: Among the 29 articles included in the final analysis, a total of 34 families with CM were analyzed. An average of 3 cases of CM were found per family among all generations. Eighty-one cases (88%) reported CM-1, whereas the other 11 (12%) cases reported either CM-0, CM-1.5, or tonsillar ectopia. A syrinx was present in 37 (54%) cases, with 14 (38%) of these patients also reporting a skeletal abnormality, the most common comorbidity. Most family members diagnosed with CM were siblings (18; 35%), followed by monozygotic twins/triplets (12; 23%). CONCLUSIONS: Patients most often presented with headaches, sensory disturbances, or generalized symptoms. Overall, there exists mounting evidence for a hereditary component of CM. It is unlikely to be explained by a classic mendelian inheritance pattern, but is rather a polygenic architecture influenced by variable penetrance, cosegregation, and entirely nongenetic factors. For first-degree relatives of those affected by CM, the authors' findings may influence clinicians to conduct closer clinical and radiographic monitoring, promote patient education, and consider earlier genetic testing.
Vaccines are highly effective at preventing severe coronavirus disease (COVID-19). With mRNA vaccines, further research is needed to understand the association between immunogenicity and reactogenicity, which is defined as the physical manifestation of an inflammatory response to a vaccination. This study analyzed the immune response and reactogenicity in humans, post immunization, to the former SARS-CoV-2 mRNA investigational vaccine CVnCoV (CV-NCOV-001 and CV-NCOV-002 clinical trials). Immunogenicity was investigated using whole-blood RNA sequencing, serum cytokine levels, and SARS-CoV-2-specific antibodies. The T cell responses in peripheral blood were assessed using intracellular cytokine staining (ICS) and high-dimensional profiling in conjunction with SARS-CoV-2 antigen-specificity testing via mass cytometry. Reactogenicity was graded after participants' first and second doses of CVnCoV using vaccine-related solicited adverse events (AEs). Finally, a Spearman correlation was performed between reactogenicity, humoral immunity, and serum cytokine levels to assess the relationship between reactogenicity and immunogenicity post CVnCoV vaccination. Our findings showed that the gene sets related to innate and inflammatory immune responses were upregulated one day post CVnCoV vaccination, while the gene sets related to adaptive immunity were upregulated predominantly one week after the second dose. The serum levels of IFNα, IFNγ, IP-10, CXCL11, IL-10, and MCP-1 increased transiently, peaking one day post vaccination. CD4+ T cells were induced in all vaccinated participants and low frequencies of CD8+ T cells were detected by ex vivo ICS. Using mass cytometry, SARS-CoV-2 spike-specific CD8+ T cells were induced and were characterized as having an activated effector memory phenotype. Overall, the results demonstrated a positive correlation between vaccine-induced systemic cytokines, reactogenicity, and adaptive immunity, highlighting the importance of the balance between the induction of innate immunity to achieve vaccine efficacy and ensuring low reactogenicity.
Background: Spinal metastases are a significant complication of advanced cancer. In this study, we assess temporal trends in the incidence and timing of spinal metastases and examine underlying patient demographics and primary cancer associations. Methods: In this population-based retrospective cohort study, health data from 2007 to 2019 in Ontario, Canada were analyzed (nâ =â 37, 375 patients identified with spine metastases). Primary outcomes were annual incidence of spinal metastasis, and time to metastasis after primary diagnosis. Results: The age-standardized incidence of spinal metastases increased from 229 to 302 cases per million over the 13-year study period. The average annual percent change (AAPC) in incidence was 2.2% (95% CI: 1.4% to 3.0%) with patients aged ≥85 years demonstrating the largest increase (AAPC 5.2%; 95% CI: 2.3% to 8.3%). Lung cancer had the greatest annual incidence, while prostate cancer had the greatest increase in annual incidence (AAPC 6.5; 95% CI: 4.1% to 9.0%). Lung cancer patients were found to have the highest risk of spine metastasis with 10.3% (95% CI: 10.1% to 10.5%) of patients being diagnosed at 10 years. Gastrointestinal cancer patients were found to have the lowest risk of spine metastasis with 1.0% (95% CI: 0.9% to 1.0%) of patients being diagnosed at 10 years. Conclusions: The incidence of spinal metastases has increased in recent years, particularly among older patients. The incidence and timing vary substantially among different primary cancer types. These findings contribute to the understanding of disease trends and emphasize a growing population of patients who require subspecialty care.
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.
Human neural progenitor cells (hNPCs) hold promise for treating spinal cord injury. Studies to date have focused on improving their regenerative potential and therapeutic effect. Equally important is ensuring successful delivery and engraftment of hNPCs at the injury site. Unfortunately, no current imaging solution for cell tracking is compatible with long-term monitoring in vivo. The objective of this study was to apply a novel bright-ferritin magnetic resonance imaging (MRI) mechanism to track hNPC transplants longitudinally and on demand in the rat spinal cord. We genetically modified hNPCs to stably overexpress human ferritin. Ferritin-overexpressing (FT) hNPCs labeled with 0.2 mM manganese provided significant T1-induced bright contrast on in vitro MRI, with no adverse effect on cell viability, morphology, proliferation, and differentiation. In vivo, 2 M cells were injected into the cervical spinal cord of Rowett nude rats. MRI employed T1-weighted acquisitions and T1 mapping on a 3 T scanner. Conventional short-term cell tracking was performed using exogenous Mn labeling prior to cell transplantation, which displayed transient bright contrast on MRI 1 day after cell transplantation and disappeared after 1 week. In contrast, long-term cell tracking using bright-ferritin allowed on-demand signal recall upon Mn supplementation and precise visualization of the surviving hNPC graft. In fact, this new cell tracking technology identified 7 weeks post-transplantation as the timepoint by which substantial hNPC integration occurred. Spatial distribution of hNPCs on MRI matched that on histology. In summary, bright-ferritin provides the first demonstration of long-term, on-demand, high-resolution, and specific tracking of hNPCs in the rat spinal cord.
Cell Tracking , Ferritins , Magnetic Resonance Imaging , Neural Stem Cells , Rats, Nude , Spinal Cord , Animals , Magnetic Resonance Imaging/methods , Neural Stem Cells/cytology , Neural Stem Cells/transplantation , Neural Stem Cells/metabolism , Cell Tracking/methods , Humans , Rats , Ferritins/metabolism , Spinal Cord/metabolism , Spinal Cord/diagnostic imaging , Stem Cell Transplantation/methods , Cell Differentiation , Spinal Cord Injuries/therapy
STUDY DESIGN: This study is a scoping review. OBJECTIVE: There is a broad variability in the definition of degenerative cervical myelopathy (DCM) and no standardized set of diagnostic criteria to date. METHODS: We interrogated the Myelopathy.org database, a hand-indexed database of primary clinical studies conducted exclusively on DCM in humans between 2005-2021. The DCM inclusion criteria used in these studies were inputted into 3 topic modeling algorithms: Hierarchical Dirichlet Process (HDP), Latent Dirichlet Allocation (LDA), and BERtopic. The emerging topics were subjected to manual labeling and interpretation. RESULTS: Of 1676 reports, 120 papers (7.16%) had well-defined inclusion criteria and were subjected to topic modeling. Four topics emerged from the HDP model: disturbance from extremity weakness and motor signs; fine-motor and sensory disturbance of upper extremity; a combination of imaging and clinical findings is required for the diagnosis; and "reinforcing" (or modifying) factors that can aid in the diagnosis in borderline cases. The LDA model showed the following topics: disturbance to the patient is required for the diagnosis; reinforcing factors can aid in the diagnosis in borderline cases; clinical findings from the extremities; and a combination of imaging and clinical findings is required for the diagnosis. BERTopic identified the following topics: imaging abnormality, typical clinical features, range of objective criteria, and presence of clinical findings. CONCLUSIONS: This review provides quantifiable data that only a minority of past studies in DCM provided meaningful inclusion criteria. The items and patterns found here are very useful for the development of diagnostic criteria for DCM.
STUDY DESIGN: Clinical practice guideline development. OBJECTIVES: Acute spinal cord injury (SCI) can result in devastating motor, sensory, and autonomic impairment; loss of independence; and reduced quality of life. Preclinical evidence suggests that early decompression of the spinal cord may help to limit secondary injury, reduce damage to the neural tissue, and improve functional outcomes. Emerging evidence indicates that "early" surgical decompression completed within 24 hours of injury also improves neurological recovery in patients with acute SCI. The objective of this clinical practice guideline (CPG) is to update the 2017 recommendations on the timing of surgical decompression and to evaluate the evidence with respect to ultra-early surgery (in particular, but not limited to, <12 hours after acute SCI). METHODS: A multidisciplinary, international, guideline development group (GDG) was formed that consisted of spine surgeons, neurologists, critical care specialists, emergency medicine doctors, physical medicine and rehabilitation professionals, as well as individuals living with SCI. A systematic review was conducted based on accepted methodological standards to evaluate the impact of early (within 24 hours of acute SCI) or ultra-early (in particular, but not limited to, within 12 hours of acute SCI) surgery on neurological recovery, functional outcomes, administrative outcomes, safety, and cost-effectiveness. The GRADE approach was used to rate the overall strength of evidence across studies for each primary outcome. Using the "evidence-to-recommendation" framework, recommendations were then developed that considered the balance of benefits and harms, financial impact, patient values, acceptability, and feasibility. The guideline was internally appraised using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool. RESULTS: The GDG recommended that early surgery (≤24 hours after injury) be offered as the preferred option for adult patients with acute SCI regardless of level. This recommendation was based on moderate evidence suggesting that patients were 2 times more likely to recover by ≥ 2 ASIA Impairment Score (AIS) grades at 6 months (RR: 2.76, 95% CI 1.60 to 4.98) and 12 months (RR: 1.95, 95% CI 1.26 to 3.18) if they were decompressed within 24 hours compared to after 24 hours. Furthermore, patients undergoing early surgery improved by an additional 4.50 (95% 1.70 to 7.29) points on the ASIA Motor Score compared to patients undergoing surgery after 24 hours post-injury. The GDG also agreed that a recommendation for ultra-early surgery could not be made on the basis of the current evidence because of the small sample sizes, variable definitions of what constituted ultra-early in the literature, and the inconsistency of the evidence. CONCLUSIONS: It is recommended that patients with an acute SCI, regardless of level, undergo surgery within 24 hours after injury when medically feasible. Future research is required to determine the differential effectiveness of early surgery in different subpopulations and the impact of ultra-early surgery on neurological recovery. Moreover, further work is required to define what constitutes effective spinal cord decompression and to individualize care. It is also recognized that a concerted international effort will be required to translate these recommendations into policy.
STUDY DESIGN: Mixed-methods approach. OBJECTIVES: Intra-operative spinal cord injury (ISCI) is a devastating complication of spinal surgery. Presently, a uniform definition for ISCI does not exist. Consequently, the reported frequency of ISCI and important risk factors vary in the existing literature. To address these gaps in knowledge, a mixed-methods knowledge synthesis was undertaken. METHODS: A scoping review was conducted to review the definitions used for ISCI and to ascertain the frequency of ISCI. The definition of ISCI underwent formal review, revision and voting by the Guidelines Development Group (GDG). A systematic review of the literature was conducted to determine the risk factors for ISCI. Based on this systematic review and GDG input, a table was created to summarize the factors deemed to increase the risk for ISCI. All reviews were done according to PRISMA standards and were registered on PROSPERO. RESULTS: The frequency of ISCI ranged from 0 to 61%. Older age, male sex, cardiovascular disease including hypertension, severe myelopathy, blood loss, requirement for osteotomy, coronal deformity angular ratio, and curve magnitude were associated with an increased risk of ISCI. Better pre-operative neurological status and use of intra-operative neuromonitoring (IONM) were associated with a decreased risk of ISCI. The risk factors for ISCI included a rigid thoracic curve with high deformity angular ratio, revision congenital deformity with significant cord compression and myelopathy, extrinsic intradural or extradural lesions with cord compression and myelopathy, intramedullary spinal cord tumor, unstable spine fractures (bilateral facet dislocation and disc herniation), extension distraction injury with ankylosing spondylitis, ossification of posterior longitudinal ligament (OPLL) with severe cord compression, and moderate to severe myelopathy. CONCLUSIONS: ISCI has been defined as "a new or worsening neurological deficit attributable to spinal cord dysfunction during spine surgery that is diagnosed intra-operatively via neurophysiologic monitoring or by an intraoperative wake-up test, or immediately post-operatively based on clinical assessment". This paper defines clinical and imaging factors which increase the risk for ISCI and that could assist clinicians in decision making.
STUDY DESIGN: Development of a clinical practice guideline following the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) process. OBJECTIVE: The objectives of this study were to develop guidelines that outline the utility of intraoperative neuromonitoring (IONM) to detect intraoperative spinal cord injury (ISCI) among patients undergoing spine surgery, to define a subset of patients undergoing spine surgery at higher risk for ISCI and to develop protocols to prevent, diagnose, and manage ISCI. METHODS: All systematic reviews were performed according to PRISMA standards and registered on PROSPERO. A multidisciplinary, international Guidelines Development Group (GDG) reviewed and discussed the evidence using GRADE protocols. Consensus was defined by 80% agreement among GDG members. A systematic review and diagnostic test accuracy (DTA) meta-analysis was performed to synthesize pooled evidence on the diagnostic accuracy of IONM to detect ISCI among patients undergoing spinal surgery. The IONM modalities evaluated included somatosensory evoked potentials (SSEPs), motor evoked potentials (MEPs), electromyography (EMG), and multimodal neuromonitoring. Utilizing this knowledge and their clinical experience, the multidisciplinary GDG created recommendations for the use of IONM to identify ISCI in patients undergoing spine surgery. The evidence related to existing care pathways to manage ISCI was summarized and based on this a novel AO Spine-PRAXIS care pathway was created. RESULTS: Our recommendations are as follows: (1) We recommend that intraoperative neurophysiological monitoring be employed for high risk patients undergoing spine surgery, and (2) We suggest that patients at "high risk" for ISCI during spine surgery be proactively identified, that after identification of such patients, multi-disciplinary team discussions be undertaken to manage patients, and that an intraoperative protocol including the use of IONM be implemented. A care pathway for the prevention, diagnosis, and management of ISCI has been developed by the GDG. CONCLUSION: We anticipate that these guidelines will promote the use of IONM to detect and manage ISCI, and promote the use of preoperative and intraoperative checklists by surgeons and other team members for high risk patients undergoing spine surgery. We welcome teams to implement and evaluate the care pathway created by our GDG.
STUDY DESIGN: Systematic review update. OBJECTIVES: Interventions that aim to optimize spinal cord perfusion are thought to play an important role in minimizing secondary ischemic damage and improving outcomes in patients with acute traumatic spinal cord injuries (SCIs). However, exactly how to optimize spinal cord perfusion and enhance neurologic recovery remains controversial. We performed an update of a recent systematic review (Evaniew et al, J. Neurotrauma 2020) to evaluate the effects of Mean Arterial Pressure (MAP) support or Spinal Cord Perfusion Pressure (SCPP) support on neurological recovery and rates of adverse events among patients with acute traumatic SCI. METHODS: We searched PubMed/MEDLINE, EMBASE and ClinicalTrials.gov for new published reports. Two reviewers independently screened articles, extracted data, and evaluated risk of bias. We implemented the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach to rate confidence in the quality of the evidence. RESULTS: From 569 potentially relevant new citations since 2019, we identified 9 new studies for inclusion, which were combined with 19 studies from a prior review to give a total of 28 studies. According to low or very low quality evidence, the effect of MAP support on neurological recovery is uncertain, and increased SCPP may be associated with improved neurological recovery. Both approaches may involve risks for specific adverse events, but the importance of these adverse events to patients remains unclear. Very low quality evidence failed to yield reliable guidance about particular monitoring techniques, perfusion ranges, pharmacological agents, or durations of treatment. CONCLUSIONS: This update provides an evidence base to support the development of a new clinical practice guideline for the hemodynamic management of patients with acute traumatic SCI. While avoidance of hypotension and maintenance of spinal cord perfusion are important principles in the management of an acute SCI, the literature does not provide high quality evidence in support of a particular protocol. Further prospective, controlled research studies with objective validated outcome assessments are required to examine interventions to optimize spinal cord perfusion in this setting.
STUDY DESIGN: This study is a mixed methods approach. OBJECTIVES: Intraoperative spinal cord injury (ISCI) is a challenging complication in spine surgery. Intra-operative neuromonitoring (IONM) has been developed to detect changes in neural function. We report on the first multidisciplinary, international effort through AO Spine and the Praxis Spinal Cord Institute to develop a comprehensive guideline and care pathway for the prevention, diagnosis, and management of ISCI. METHODS: Three literature reviews were registered on PROSPERO (CRD 42022298841) and performed according to PRISMA guidelines: (1) Definitions, frequency, and risk factors for ISCI, (2) Meta-analysis of the accuracy of IONM for diagnosis of ISCI, (3) Reported management approaches for ISCI and related events. The results were presented in a consensus session to decide the definition of IONM and recommendation of its use in high-risk cases. Based on a literature review of management strategies for ISCI, an intra-operative checklist and overall care pathway was developed by the study team. RESULTS: An operational definition and high-risk patient categories for ISCI were established. The reported incidence of deficits was documented to be higher in intramedullary tumour spine surgery. Multimodality IONM has a high sensitivity and specificity. A guideline recommendation of IONM to be employed for high-risk spine cases was made. The different sections of the intraoperative checklist include surgery, anaesthetic and neurophysiology. The care pathway includes steps (1) initial clinical assessment, (2) pre-operative planning, (3) surgical/anaesthetic planning, (4) intra-operative management, and (5) post-operative management. CONCLUSIONS: This is the first evidence based comprehensive guideline and care pathway for ISCI using the GRADE methodology. This will facilitate a reduction in the incidence of ISCI and improved outcomes from this complication. We welcome the wide implementation and validation of these guidelines and care pathways in prospective, multicentre studies.
