Validation of the AO Spine Sacral Classification System: Reliability Among Surgeons Worldwide.

OBJECTIVES: To (1) demonstrate that the AO Spine Sacral Classification System can be reliably applied by general orthopaedic surgeons and subspecialists universally around the world and (2) delineate those injury subtypes that are most difficult to classify reliably to refine the classification before evaluating clinical outcomes. DESIGN: Agreement study. SETTING: All-level trauma centers, worldwide. PARTICIPANTS: One hundred seventy-two members of the AO Trauma and AO Spine community. INTERVENTION: The AO Sacral Classification System was applied by each surgeon to 26 cases in 2 independent assessments performed 3 weeks apart. MAIN OUTCOME MEASUREMENTS: Interobserver reliability and intraobserver reproducibility. RESULTS: A total of 8097 case assessments were performed. The kappa coefficient for interobserver agreement for all cases was 0.72/0.75 (assessment 1/assessment 2), representing substantial reliability. When comparing classification grading (A/B/C) regardless of subtype, the kappa coefficient was 0.84/0.85, corresponding to excellent reliability. The kappa coefficients for interobserver reliability were 0.95/0.93 for type A fractures, 0.78/0.79 for type B fractures, and 0.80/0.83 for type C fractures. The overall kappa statistic for intraobserver reliability was 0.82 (range 0.18-1.00), representing excellent reproducibility. When only evaluating morphology type (A/B/C), the average kappa value was 0.87 (range 0.18-1.00), representing excellent reproducibility. CONCLUSION: The AO Spine Sacral Classification System is universally reliable among general orthopaedic surgeons and subspecialists worldwide, with substantial interobserver and excellent intraobserver reliability.

Establishing the Injury Severity of Subaxial Cervical Spine Trauma: Validating the Hierarchical Nature of the AO Spine Subaxial Cervical Spine Injury Classification System.

STUDY DESIGN: Global cross-sectional survey. OBJECTIVE: The aim of this study was to validate the AO Spine Subaxial Cervical Spine Injury Classification by examining the perceived injury severity by surgeon across AO geographical regions and practice experience. SUMMARY OF BACKGROUND DATA: Previous subaxial cervical spine injury classifications have been limited by subpar interobserver reliability and clinical applicability. In an attempt to create a universally validated scheme with prognostic value, AO Spine established a subaxial cervical spine injury classification involving four elements: injury morphology, facet injury involvement, neurologic status, and case-specific modifiers. METHODS: A survey was sent to 272 AO Spine members across all geographic regions and with a variety of practice experience. Respondents graded the severity of each variable of the classification system on a scale from zero (low severity) to 100 (high severity). Primary outcome was to assess differences in perceived injury severity for each injury type over geographic regions and level of practice experience. RESULTS: A total of 189 responses were received. Overall, the classification system exhibited a hierarchical progression in subtype injury severity scores. Only three subtypes showed a significant difference in injury severity score among geographic regions: F3 (floating lateral mass fracture, P = 0.04), N3 (incomplete spinal cord injury, P = 0.03), and M2 (critical disk herniation, P = 0.04). When stratified by surgeon experience, pairwise comparison showed only two morphological subtypes, B1 (bony posterior tension band injury, P = 0.02) and F2 (unstable facet fracture, P = 0.03), and one neurologic subtype (N3, P = 0.02) exhibited a significant difference in injury severity score. CONCLUSION: The AO Spine Subaxial Cervical Spine Injury Classification System has shown to be reliable and suitable for proper patient management. The study shows this classification is substantially generalizable by geographic region and surgeon experience, and provides a consistent method of communication among physicians while covering the majority of subaxial cervical spine traumatic injuries.Level of Evidence: 4.

The Neuronal Glutamate Transporter EAAT3 in Obsessive-Compulsive Disorder.

Obsessive compulsive disorder (OCD) is a heterogeneous psychiatric disorder affecting 1%-3% of the population worldwide. About half of OCD afflicted individuals do not respond to currently available pharmacotherapy, which is mainly based on serotonin reuptake inhibition. Therefore, there is a critical need to search novel and improved therapeutic targets to treat this devastating disorder. In recent years, accumulating evidence has supported the glutamatergic hypothesis of OCD, and particularly pointing a potential role for the neuronal glutamate transporter EAAT3. This mini-review summarizes recent findings regarding the neurobiological basis of OCD, with an emphasis on the glutamatergic neurotransmission and EAAT3 as a key player in OCD etiology.

Correction: Behavioral and synaptic alterations relevant to obsessivecompulsive disorder in mice with increased EAAT3 expression.

The original version of this Article contained an error in the spelling of the author Anna K Radke, which was incorrectly given as Anna R Radke. This has now been corrected in both the PDF and HTML versions of the Article.

Behavioral and synaptic alterations relevant to obsessive-compulsive disorder in mice with increased EAAT3 expression.

Obsessive-compulsive disorder (OCD) is a severe, chronic neuropsychiatric disorder with a strong genetic component. The SLC1A1 gene encoding the neuronal glutamate transporter EAAT3 has been proposed as a candidate gene for this disorder. Gene variants affecting SLC1A1 expression in human brain tissue have been associated with OCD. Several mouse models fully or partially lacking EAAT3 have shown no alterations in baseline anxiety-like or repetitive behaviors. We generated a transgenic mouse model (EAAT3glo) to achieve conditional, Cre-dependent EAAT3 overexpression and evaluated the overall impact of increased EAAT3 expression at behavioral and synaptic levels. Mice with EAAT3 overexpression driven by CaMKIIα-promoter (EAAT3glo/CMKII) displayed increased anxiety-like and repetitive behaviors that were both restored by chronic, but not acute, treatment with fluoxetine or clomipramine. EAAT3glo/CMKII mice also displayed greater spontaneous recovery of conditioned fear. Electrophysiological and biochemical analyses at corticostriatal synapses of EAAT3glo/CMKII mice revealed changes in NMDA receptor subunit composition and altered NMDA-dependent synaptic plasticity. By recapitulating relevant behavioral, neurophysiological, and psychopharmacological aspects, our results provide support for the glutamatergic hypothesis of OCD, particularly for the increased EAAT3 function, and provide a valuable animal model that may open novel therapeutic approaches to treat this devastating disorder.

Anatomy of the Alar Ligament: Part II: Variations of Its Attachment onto the Dens.

OBJECTIVE: Various authors have described the morphology of the alar ligaments; however, there are no reports of a cadaveric study focusing on their attachments onto the dens. The purpose of this study was to use fresh cadaveric specimens to describe in detail different attachment patterns of the alar ligaments onto the dens. METHODS: This study used 22 sides from 11 fresh frozen cadaveric heads. Specimens were obtained from 8 men and 3 women who were 67-99 years old at death. Dissection of the exact attachment of the alar ligaments onto the dens was observed from posterior, superior, and anterior views under the surgical microscope. RESULTS: From a posterior view, 6 alar ligaments passed over the tip of the dens, and 16 alar ligaments attached onto the posterolateral part of the dens; the right and left ligaments had no continuity. From a superior view, the alar ligament was classified in 2 ways: depending on the covered area of the dens (entirely or posterior two thirds) and continuity of the alar ligament (transversely, separately, or combination). Fourteen alar ligaments covered the posterior two thirds of the dens. From an anterior view, in 1 specimen, the alar ligament extended to the anterior surface of the dens. CONCLUSIONS: Wide posterolateral anchoring to the dens coupled with the nearly horizontal trajectory explains the biomechanical advantage of the alar ligaments in undertaking a stabilizing function in limiting head rotation that would otherwise be ineffective in the case of weaker attachments or a more vertical orientation.

Extraforaminal compression of the L5 nerve: An anatomical study with application to failed posterior decompressive procedures.

This anatomical study was performed to elucidate the pertinent foraminal and lateral L5 nerve anatomy to enhance our understanding of possible neurologic causes of failed decompression surgery. Persistent extraforaminal L5 nerve compression is a possible cause of persistent symptoms following lumbosacral surgery. The amount of extraforaminal space for the L5 ventral ramus was examined in fifty adult human skeletons (100 sides). Based on morphology, the specimens were then categorized (types I-IV) on the basis of the bony space available for the nerve at this location. Next, 25 embalmed adult cadavers (50 sides) underwent bilateral dissection of the lower lateral lumbar region. The type of bony extraforaminal outlet was documented for each cadaver on the basis of our skeletal analysis. Lastly, segments (intra- and extra-foraminal) of the L5 ventral ramus were excised and examined histologically. Types I-IV outlets were found in 43, 31, 20 and 6 skeletal sides, respectively. For cadavers, 22,15, 10 and 3 sides were found to have types I-IV bony outlets, respectively. In cadavers, all type IV outlets and 70% of the type III bony configurations adjacent to the L5 ventral ramus had signs of neural irritation/injury including vascular hyalinization and increased fibrosis distal to the intervertebral foramen. No distal segments of type I and type II outlets showed histological signs of neural compromise. Patients with symptoms referable to L5 nerve compression for whom no proximal pathology is identified could warrant investigation of the more distal extraforaminal segment of this nerve.

Pediatric Hangman's Fracture: A Comprehensive Review.

PURPOSE: Over 170 years ago, traumatic spondylolisthesis of the axis or hangman's fracture was described. Most descriptions of this entity have focused on adult presentations. METHODS: We review the literature on pediatric cases of hangman's fracture emphasizing the embryological as well as presentation aspects. RESULTS: The majority of cervical spine fractures in children occur at C1 and C2 vertebrae. A normal anterolisthesis of C2 can be seen in younger children and can mimic the anterolisthesis seen after traumatic spondylolisthesis. CONCLUSIONS: Traumatic spondylolisthesis of the axis in children requires further investigation due to the current emphasis in the literature on adult clinical findings and diagnostic challenges from the developmental immaturity of the pediatric skeleton.

Hemivertebrae: a comprehensive review of embryology, imaging, classification, and management.

PURPOSE: The purpose of this paper was to comprehensively review hemivertebrae in regard to their classification, embryology, etiology, diagnosis, clinical manifestations, and management of this developmental anomaly. METHODS: This subject review of hemivertebrae was composed after conducting a thorough review of the available literature on this topic using PubMed and other standard search engines. RESULTS: Hemivertebrae are incomplete vertebral column segments that can result in congenital scoliosis and be associated with a range of other structural anomalies. Presentations may differ and based on location and classification, treatments may vary. CONCLUSION: Hemivertebrae are structural anomalies of the vertebral column that can potentially disrupt the spine's normal curvature. Their clinical impact depends on factors such as degree of segmentation and concurrence with other structural anomalies. It is hoped that this review will provide the clinician who treats patients with hemivertebrae a resource in better understanding this finding and its subsequent pathological effects.

Arterial variations around the atlas: a comprehensive review for avoiding neurosurgical complications.

INTRODUCTION: Neurosurgical approaches often involve the atlas. Therefore, the arterial relationships and anatomical variations are of paramount importance to the neurosurgeon. METHODS: Using standard search engines, a literature review of arterial variants near the first cervical vertebra was performed. CONCLUSIONS: Arterial variations around the atlas are surgically significant. Awareness of their existence and course may provide better pre-operative planning and surgical intervention, potentially leading to better clinical outcomes. Three-dimensional computed tomography angiography (3D CTA) is an important tool for identifying and diagnosing such abnormalities and should be used when such vascular anomalies are suspected.

Comprehensive anatomical and immunohistochemical review of the innervation of the human spine and joints with application to an improved understanding of back pain.

BACKGROUND: Pain of spinal origin contributes significantly to cervical, thoracic, and lower back pain presentations. Such pain originates in the nerve fibers supplying the joints or the surrounding ligaments and intervertebral discs. Although there has been little detailed discussion of spinal bony innervation patterns in the literature, the clinical implications of these patterns are anatomically and medically significant. METHODS: The present review provides a detailed analysis of the innervation of the spine, identifying the unique features of each part via online search engines. CONCLUSIONS: The clinical implications of these various studies lie in the importance of the innervation patterns for the mechanism of spinal pain. Immunohistochemical studies have provided further evidence regarding the nature of the innervation of the spine.

The odontoid process: a comprehensive review of its anatomy, embryology, and variations.

BACKGROUND: The odontoid process is a critical component of the cranio-cervical junction. Therefore, clinicians who diagnose, treat, or operate this region need a strong background in regard to the embryology, anatomy, and anatomical variations that may be seen for the odontoid process. METHODS: A literature review was performed, using standard search engines, to explore the morphology, embryology, and anatomical variants of the odontoid process. CONCLUSIONS: A sound understanding of the development of the odontoid process, both in normal and in variant forms, as well as its phenotypical morphology is a prerequisite for the diagnosis and treatment of patients presenting with disorders affecting the cranio-cervical spine.

2DE: the phoenix of proteomics.

Given the rapid developments in mass spectrometry (MS) in terms of sensitivity, mass accuracy, and throughput, some have suggested that two-dimensional gel electrophoresis (2DE) may no longer be a method of choice for proteomic analyses. However, as recognition of issues with these newer shotgun-MS approaches grows, there is a fresh and growing regard for the maturity of 2DE-MS as a genuine top-down analytical approach, particularly as it resolves thousands of intact protein species in a single run, enabling the simultaneous analysis of total protein complement, including isoforms and post-translational modifications. Given the strengths of both, it is most appropriate to view these as complementary or at least parallel approaches: as proteins encompass a myriad of physico-chemical properties, and the real aim is to explore proteomes as deeply as possible, all available resolving strategies must be considered in terms of the complexity encountered. It is time to critically and constructively focus on the optimization and integration of existing techniques rather than simplistically suggesting that one should replace the other. Our intention here is thus to present an overview of protein resolving techniques, focusing on milestones associated with 2DE, including pros, cons, advances and variations, in particular relative to shotgun proteomic approaches. BIOLOGICAL SIGNIFICANCE: Proteomic researchers recognize the importance of 2DE in the history of proteomics. But the latest developments in mass spectrometry-based techniques have led some researchers to retire 2DE in their labs. However, we argue here that 2DE-MS is a genuine top-down analytical approach. The significance of this discussion is to make proteomic researchers aware of the importance of this technique in a proteomic pipeline. This article is part of a Special Issue entitled: Environmental and structural proteomics.

Hypertrophy and neuron loss: structural changes in sheep SCG induced by unilateral sympathectomy.

Recently, superior cervical ganglionectomy has been performed to investigate a variety of scientific topics from regulation of intraocular pressure to suppression of lingual tumour growth. Despite these recent advances in our understanding of the functional mechanisms underlying superior cervical ganglion (SCG) growth and development after surgical ablation, there still exists a need for information concerning the quantitative nature of the relationships between the removed SCG and its remaining contralateral ganglion and between the remaining SCG and its modified innervation territory. To this end, using design-based stereological methods, we have investigated the structural changes induced by unilateral ganglionectomy in sheep at three distinct timepoints (2, 7 and 12 weeks) after surgery. The effects of time, and lateral (left-right) differences, were examined by two-way analyses of variance and paired t-tests. Following removal of the left SCG, the main findings were: (i) the remaining right SCG was bigger at shorter survival times, i.e. 74% at 2 weeks, 55% at 7 weeks and no increase by 12 weeks, (ii) by 7 weeks after surgery, the right SCG contained fewer neurons (no decrease at 2 weeks, 6% fewer by 7 weeks and 17% fewer by 12 weeks) and (iii) by 7 weeks, right SCG neurons were also larger and the magnitude of this increase grew substantially with time (no rise at 2 weeks, 77% by 7 weeks and 215% by 12 weeks). Interaction effects between time and ganglionectomy-induced changes were significant for SCG volume and mean perikaryal volume. These findings show that unilateral superior cervical ganglionectomy has profound effects on the contralateral ganglion. For future investigations, it would be interesting to examine the interaction between SCGs and their innervation targets after ganglionectomy. Is the ganglionectomy-induced imbalance between the sizes of innervation territories the milieu in which morphoquantitative changes, particularly changes in perikaryal volume and neuron number, occur? Mechanistically, how would those changes arise? Are there any grounds for believing in a ganglionectomy-triggered SCG cross-innervation and neuroplasticity?

The heart of the South American rattlesnake, Crotalus durissus.

Most anatomical and physiological studies of the sauropsid heart have focused on species with extraordinary physiologies, and detailed anatomical descriptions of hearts from sauropsids with more common physiologies are therefore warranted. Here, we present a comprehensive study of the cardiac anatomy of the South American rattlesnake (Crotalus durissus). The cardiovascular physiology of this species has been investigated in a number of studies, whereas only a few cursory studies exist on the cardiac anatomy of viperid snakes. The heart of C. durissus is typically squamate in many regards. Both atria are thin-walled sacs, and the right atrium is the most voluminous. The single ventricle contains three major septa; the vertical septum, the muscular ridge (MR), and the bulbuslamelle. These partially divide the ventricle into three chambers; the systemic and left-sided cavum arteriosum (CA), the pulmonary and right-sided cavum pulmonale, and the medial cavum venosum (CV). The MR is the most developed septum, and several additional and minor septa are found within the CA and CV. An extraordinary thin cortical layer encloses the ventricle, and it is irrigated by a remarkably rich arborization of coronary arteries. Previous studies show high degrees of blood flow separation in the Crotalus heart, and this can only be explained by the coordinated actions of the septa and the prominent atrioventricular valves.