Genome-wide gene expression profiling of stress response in a spinal cord clip compression injury model.

BackgroundThe aneurysm clip impact-compression model of spinal cord injury (SCI) is a standard injury model in animals that closely mimics the primary mechanism of most human injuries: acute impact and persisting compression. Its histo-pathological and behavioural outcomes are extensively similar to human SCI. To understand the distinct molecular events underlying this injury model we analyzed global mRNA abundance changes during the acute, subacute and chronic stages of a moderate to severe injury to the rat spinal cord.ResultsTime-series expression analyses resulted in clustering of the majority of deregulated transcripts into eight statistically significant expression profiles. Systematic application of Gene Ontology (GO) enrichment pathway analysis allowed inference of biological processes participating in SCI pathology. Temporal analysis identified events specific to and common between acute, subacute and chronic time-points. Processes common to all phases of injury include blood coagulation, cellular extravasation, leukocyte cell-cell adhesion, the integrin-mediated signaling pathway, cytokine production and secretion, neutrophil chemotaxis, phagocytosis, response to hypoxia and reactive oxygen species, angiogenesis, apoptosis, inflammatory processes and ossification. Importantly, various elements of adaptive and induced innate immune responses span, not only the acute and subacute phases, but also persist throughout the chronic phase of SCI. Induced innate responses, such as Toll-like receptor signaling, are more active during the acute phase but persist throughout the chronic phase. However, adaptive immune response processes such as B and T cell activation, proliferation, and migration, T cell differentiation, B and T cell receptor-mediated signaling, and B cell- and immunoglobulin-mediated immune response become more significant during the chronic phase.ConclusionsThis analysis showed that, surprisingly, the diverse series of molecular events that occur in the acute and subacute stages persist into the chronic stage of SCI. The strong agreement between our results and previous findings suggest that our analytical approach will be useful in revealing other biological processes and genes contributing to SCI pathology

A clinical practice guideline for the management of degenerative cervical myelopathy: introduction, rationale, and scope

Degenerative cervical myelopathy (DCM) is a progressive spine disease and the most common cause of spinal cord dysfunction in adults worldwide. Patients with DCM may present with common signs and symptoms of neurological dysfunction, such as paresthesia, abnormal gait, decreased hand dexterity, hyperreflexia, increased tone, and sensory dysfunction. Clinicians across several specialties encounter patients with DCM, including primary care physicians, rehabilitation specialists, therapists, rheumatologists, neurologists, and spinal surgeons. Currently, there are no guidelines that outline how to best manage patients with mild (defined as a modified Japanese Orthopedic Association (mJOA) score of 15-17), moderate (mJOA = 12-14), or severe (mJOA <= 11) myelopathy, or nonmyelopathic patients with evidence of cord compression. This guideline provides evidencebased recommendations to specify appropriate treatment strategies for these populations. The intent of our recommendations is to (1) help identify patients at high risk of neurological deterioration, (2) define the role of nonoperative and operative management in each patient population, and (3) determine which patients are most likely to benefit from surgical intervention. The ultimate goal of these guidelines is to improve outcomes and reduce morbidity in patients with DCM by promoting standardization of care and encouraging clinicians to make evidence-informed decisions

Does the Spine Surgeon’s Experience Affect Fracture Classification, Assessment of Stability, and Treatment Plan in Thoracolumbar Injuries?

Study Design: Prospective survey-based study. Objectives: The AO Spine thoracolumbar injury classification has been shown to have good reproducibility among clinicians. However, the influence of spine surgeons’ clinical experience on fracture classification, stability assessment, and decision on management based on this classification has not been studied. Furthermore, the usefulness of varying imaging modalities including radiographs, computed tomography (CT) and magnetic resonance imaging (MRI) in the decision process was also studied. Methods: Forty-one spine surgeons from different regions, acquainted with the AOSpine classification system, were provided with 30 thoracolumbar fractures in a 3-step assessment: first radiographs, followed by CT and MRI. Surgeons classified the fracture, evaluated stability, chose management, and identified reasons for any changes. The surgeons were divided into 2 groups based on years of clinical experience as \u3c10 years (n = 12) and \u3e10 years (n = 29). Results: There were no significant differences between the 2 groups in correctly classifying A1, B2, and C type fractures. Surgeons with less experience hadmore correct diagnosis in classifyingA3 (47.2% vs 38.5%in step 1, 73.6% vs 60.3% in step 2 and 77.8% vs 65.5% in step 3), A4 (16.7% vs 24.1% in step 1, 72.9% vs 57.8% in step 2 and 70.8% vs 56.0%in step3) and B1 injuries (31.9% vs 20.7% in step 1, 41.7% vs 36.8% in step 2 and 38.9% vs 33.9% in step 3). In the assessment of fracture stability and decision on treatment, the less and more experienced surgeons performed equally. The selection of a particular treatment plan varied in all subtypes except in A1 and C type injuries. Conclusion: Surgeons’ experience did not significantly affect overall fracture classification, evaluating stability and planning the treatment. Surgeons with less experience had a higher percentage of correct classification in A3 and A4 injuries. Despite variations between them in classification, the assessment of overall stability and management decisions were similar between the 2 groups. © The Author(s) 2017

Efficacy, Safety, and Timing of Anticoagulant Thromboprophylaxis for the Prevention of Venous Thromboembolism in Patients With Acute Spinal Cord Injury: A Systematic Review

Study Design: Systematic review. Objectives: The objective of this study was to answer 5 key questions: What is the comparative effectiveness and safety of (1a) anticoagulant thromboprophylaxis compared to no prophylaxis, placebo, or another anticoagulant strategy for preventing deep vein thrombosis (DVT) and pulmonary embolism (PE) after acute spinal cord injury (SCI)? (1b) Mechanical prophylaxis strategies alone or in combination with other strategies for preventing DVT and PE after acute SCI? (1c) Prophylactic inferior vena cava filter insertion alone or in combination with other strategies for preventing DVT and PE after acute SCI? (2) What is the optimal timing to initiate and/or discontinue anticoagulant, mechanical, and/or prophylactic inferior vena cava filter following acute SCI? (3) What is the cost-effectiveness of these treatment options? Methods: A systematic literature search was conducted to identify studies published through February 28, 2015. We sought randomized controlled trials evaluating efficacy and safety of antithrombotic strategies. Strength of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Results: Nine studies satisfied inclusion criteria. We found a trend toward lower risk of DVT in patients treated with enoxaparin. There were no significant differences in rates of DVT, PE, bleeding, and mortality between patients treated with different types of low-molecular-weight heparin or between low-molecular-weight heparin and unfractionated heparin. Combined anticoagulant and mechanical prophylaxis initiated within 72 hours of SCI resulted in lower risk of DVT than treatment commenced after 72 hours of injury. Conclusion: Prophylactic treatments can be used to lower the risk of venous thromboembolic events in patients with acute SCI, without significant increase in risk of bleeding and mortality and should be initiated within 72 hours. © 2017, © The Author(s) 2017

Impact of Baseline Magnetic Resonance Imaging on Neurologic, Functional, and Safety Outcomes in Patients With Acute Traumatic Spinal Cord Injury

Study Design: Systematic review. Objective: To perform a systematic review to evaluate the utility of magnetic resonance imaging (MRI) in patients with acute spinal cord injury (SCI). Methods: An electronic search of Medline, EMBASE, the Cochrane Collaboration Library, and Google Scholar was conducted for literature published through May 12, 2015, to answer key questions associated with the use of MRI in patients with acute SCI. Results: The literature search yielded 796 potentially relevant citations, 8 of which were included in this review. One study used MRI in a protocol to decide on early surgical decompression. The MRI-protocol group showed improved outcomes; however, the quality of evidence was deemed very low due to selection bias. Seven studies reported MRI predictors of neurologic or functional outcomes. There was moderate-quality evidence that longer intramedullary hemorrhage (2 studies) and low-quality evidence that smaller spinal canal diameter at the location of maximal spinal cord compression and the presence of cord swelling are associated with poor neurologic recovery. There was moderate-quality evidence that clinical outcomes are not predicted by SCI lesion length and the presence of cord edema. Conclusions: Certain MRI characteristics appear to be predictive of outcomes in acute SCI, including length of intramedullary hemorrhage (moderate-quality evidence), canal diameter at maximal spinal cord compression (low-quality evidence), and spinal cord swelling (low-quality evidence). Other imaging features were either inconsistently (presence of hemorrhage, maximal canal compromise, and edema length) or not associated with outcomes. The paucity of literature highlights the need for well-designed prospective studies. © 2017, © The Author(s) 2017

The need for clinical practice guidelines in assessing and managing perioperative neurologic deficit: results from a survey of the AOSpine international community

Objectives: There is no standardized approach to assess and manage perioperative neurologic deficit (PND) in patients undergoing spinal surgery. This survey aimed to evaluate the awareness and usage of clinical practice guidelines (CPGs) as well as investigate how surgeons performing spine surgeries feel about and manage PND, and how they perceive the value of developing CPGs for the management of PND. Methods: An invitation to participate was sent to the AOSpine International community. Questions were related to the awareness, usage of CPGs and demographics. Results from the entire sample and subgroups were analyzed. Results: Of 770 respondents, 659 (85.6%) reported being aware of the existence of guideline(s), and among those, 578 (87.7%) acknowledged using guideline(s). Overall, 58.8% of surgeons reported not feeling comfortable managing a patient who wakes up quadriplegic after an uneventful multilevel posterior cervical decompression with instrumented fusion. While 22.9% would consider an immediate return to the operating room, the other 77.1% favored conducting some kind of investigation/medical intervention first, such as obtaining a MRI (85.9%), administrating high-dose corticosteroids (50.2%) or increasing the MAP (44.7%). Overall, 90.6% of surgeons believed that CPGs for the management of PND would be useful and 94.4% would be either likely or extremely likely to use these CPGs in their clinical practice. Conclusions: The majority of respondents are aware and routinely use CPGs in their practice. Most surgeons performing spine surgeries reported not feeling comfortable managing PND. However, they highly value the creation and are likely to use CPGs in its management

Anterior Cervical Infection: Presentation and Incidence of an Uncommon Postoperative Complication.

STUDY DESIGN: Retrospective multi-institutional case series. OBJECTIVE: The anterior cervical discectomy and fusion (ACDF) affords the surgeon the flexibility to treat a variety of cervical pathologies, with the majority being for degenerative and traumatic indications. Limited data in the literature describe the presentation and true incidence of postoperative surgical site infections. METHODS: A retrospective multicenter case series study was conducted involving 21 high-volume surgical centers from the AOSpine North America Clinical Research Network, selected for their excellence in spine care and clinical research infrastructure and experience. Medical records for 17 625 patients who received cervical spine surgery (levels from C2 to C7) between January 1, 2005, and December 31, 2011, inclusive, were reviewed to identify the occurrence of 21 predefined treatment complications. Patients who underwent an ACDF were identified in the database and reviewed for the occurrence of postoperative anterior cervical infections. RESULTS: A total of 8887 patients were identified from a retrospective database analysis of 21 centers providing data for postoperative anterior cervical infections (17/21, 81% response rate). A total of 6 postoperative infections after ACDF were identified for a mean rate of 0.07% (range 0% to 0.39%). The mean age of patients identified was 57.5 (SD = 11.6, 66.7% female). The mean body mass index was 22.02. Of the total infections, half were smokers (n = 3). Two patients presented with myelopathy, and 3 patients presented with radiculopathic-type complaints. The mean length of stay was 4.7 days. All patients were treated aggressively with surgery for management of this complication, with improvement in all patients. There were no mortalities. CONCLUSION: The incidence of postoperative infection in ACDF is exceedingly low. The management has historically been urgent irrigation and debridement of the surgical site. However, due to the rarity of this occurrence, guidance for management is limited to retrospective series

The graded redefined assessment of strength sensibility and prehension: reliability and validity.

Abstract With the advent of new interventions targeted at both acute and chronic spinal cord injury (SCI), it is critical that techniques and protocols are developed that reliably evaluate changes in upper limb impairment/function. The Graded Redefined Assessment of Strength Sensibility and Prehension (GRASSP) protocol, which includes five subtests, is a quantitative clinical upper limb impairment measure designed for use in acute and chronic cervical SCI. The objectives of this study were to: (1) establish the inter-rater and test-retest reliability, and (2) establish the construct and concurrent validity with the International Standards of Neurological Classification of Spinal Cord Injury (ISNCSCI), Spinal Cord Independence Measure II (SCIM), and the Capabilities of Upper Extremity Questionnaire (CUE). The study protocol included repeated administration of the GRASSP to a cross-section of individuals with tetraplegia who were neurologically stable (n=72). ISNCSCI, CUE, and SCIM assessments were also administered. Two assessors examined the individuals over a 7-day period. Reliability was tested with intra-class correlation coefficients; construct validity was established with agreement/discordance analysis between the GRASSP and ISNCSCI sensory and motor items; and concurrent validity was tested with Spearman correlation coefficients. Inter-rater and test-retest reliability for all subtests within the GRASSP were above the hypothesized value of 0.80 (0.84-0.96 and 0.86-0.98, respectively). The GRASSP is about 50% more sensitive (construct validity) than the ISNCSCI when defining sensory and motor integrity of the upper limb; the subtests showed concurrence with the SCIM, SCIM self-care subscale, and CUE. The strongest concurrence to impairment was with self-perception of function (CUE) (0.57-0.83, p\u3c0.0001). The GRASSP was found to demonstrate reliability, construct validity, and concurrent validity for use as a standardized upper limb impairment measure for individuals with tetraplegia

Misplaced Cervical Screws Requiring Reoperation.

STUDY DESIGN: A multicenter, retrospective case series. OBJECTIVE: In the past several years, screw fixation of the cervical spine has become commonplace. For the most part, this is a safe, low-risk procedure. While rare, screw backout or misplaced screws can lead to morbidity and increased costs. We report our experiences with this uncommon complication. METHODS: A multicenter, retrospective case series was undertaken at 23 institutions in the United States. Patients were included who underwent cervical spine surgery from January 1, 2005, to December 31, 2011, and had misplacement of screws requiring reoperation. Institutional review board approval was obtained at all participating institutions, and detailed records were sent to a central data center. RESULTS: A total of 12 903 patients met the inclusion criteria and were analyzed. There were 11 instances of screw backout requiring reoperation, for an incidence of 0.085%. There were 7 posterior procedures. Importantly, there were no changes in the health-related quality-of-life metrics due to this complication. There were no new neurologic deficits; a patient most often presented with pain, and misplacement was diagnosed on plain X-ray or computed tomography scan. The most common location for screw backout was C6 (36%). CONCLUSIONS: This study represents the largest series to tabulate the incidence of misplacement of screws following cervical spine surgery, which led to revision procedures. The data suggest this is a rare event, despite the widespread use of cervical fixation. Patients suffering this complication can require revision, but do not usually suffer neurologic sequelae. These patients have increased cost of care. Meticulous technique and thorough knowledge of the relevant anatomy are the best means of preventing this complication

Iatrogenic Spinal Cord Injury Resulting From Cervical Spine Surgery.

STUDY DESIGN: Retrospective cohort study of prospectively collected data. OBJECTIVE: To examine the incidence of iatrogenic spinal cord injury following elective cervical spine surgery. METHODS: A retrospective multicenter case series study involving 21 high-volume surgical centers from the AOSpine North America Clinical Research Network was conducted. Medical records for 17 625 patients who received cervical spine surgery (levels from C2 to C7) between January 1, 2005, and December 31, 2011, were reviewed to identify occurrence of iatrogenic spinal cord injury. RESULTS: In total, 3 cases of iatrogenic spinal cord injury following cervical spine surgery were identified. Institutional incidence rates ranged from 0.0% to 0.24%. Of the 3 patients with quadriplegia, one underwent anterior-only surgery with 2-level cervical corpectomy, one underwent anterior surgery with corpectomy in addition to posterior surgery, and one underwent posterior decompression and fusion surgery alone. One patient had complete neurologic recovery, one partially recovered, and one did not recover motor function. CONCLUSION: Iatrogenic spinal cord injury following cervical spine surgery is a rare and devastating adverse event. No standard protocol exists that can guarantee prevention of this complication, and there is a lack of consensus regarding evaluation and treatment when it does occur. Emergent imaging with magnetic resonance imaging or computed tomography myelography to evaluate for compressive etiology or malpositioned instrumentation and avoidance of hypotension should be performed in cases of intraoperative and postoperative spinal cord injury