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Abstract Cervical spine deformities can have a significant negative impact on the quality of life by causing pain, myelopathy, radiculopathy, sensorimotor deficits, as well as inability to maintain horizontal gaze in severe cases. Many different surgical options exist for operative management of cervical spine deformities. However, selecting the correct approach that ensures the optimal clinical outcome can be challenging and is often controversial. We aim to provide an overview of cervical spine deformity in a 3-part series covering topics including the biomechanics, radiographic parameters, classification, treatment algorithms, surgical techniques, clinical outcome, and complication avoidance with a review of pertinent literature.

This patient and public-involved systematic review originally focused on arachnoiditis, a supposedly rare \"iatrogenic chronic meningitis\" causing permanent neurologic damage and intractable pain. We sought to prove disease existence, causation, symptoms, and inform future directions. After 63 terms for the same pathology were found, the study was renamed Diseases of the Leptomeninges (DLMs). We present results that nullify traditional clinical thinking about DLMs, answer study questions, and create a unified path forward. The prospective PRISMA protocol is published at Arcsology.org. We used four platforms, 10 sources, extraction software, and critical review with ≥2 researchers at each phase. All human sources to 12/6/2020 were eligible for qualitative synthesis utilizing R. Weekly updates since cutoff strengthen conclusions. Included were 887/14286 sources containing 12721 DLMs patients. Pathology involves the subarachnoid space (SAS) and pia. DLMs occurred in all countries as a contributor to the top 10 causes of disability-adjusted life years lost, with communicable diseases (CDs) predominating. In the USA, the ratio of CDs to iatrogenic causes is 2.4:1, contradicting arachnoiditis literature. Spinal fusion surgery comprised 54.7% of the iatrogenic category, with rhBMP-2 resulting in 2.4x more DLMs than no use (p<0.0001). Spinal injections and neuraxial anesthesia procedures cause 1.1%, and 0.2% permanent DLMs, respectively. Syringomyelia, hydrocephalus, and arachnoid cysts are complications caused by blocked CSF flow. CNS neuron death occurs due to insufficient arterial supply from compromised vasculature and nerves traversing the SAS. Contrast MRI is currently the diagnostic test of choice. Lack of radiologist recognition is problematic. DLMs are common. The LM clinically functions as an organ with critical CNS-sustaining roles involving the SAS-pia structure, enclosed cells, lymphatics, and biologic pathways. Cases involve all specialties. Causes are numerous, symptoms predictable, and outcomes dependent on time to treatment and extent of residual SAS damage. An international disease classification and possible treatment trials are proposed.

[This corrects the article DOI: 10.1371/journal.pone.0274634.].

Intervertebral disc (IVD) degeneration is a remodeling process mediated by several growth factors and cytokines. This process has been extensively studied in vitro and with pathologic specimens obtained during surgery for scoliosis or back pain. However, the occurrence and temporal evolution of these molecules during normal aging, particularly in the cervical segment, is not known. Our objective was to study and compare the presence of putative mediators in the IVD of young (<35 years, G1) and elderly (>65 years, G2) presumably asymptomatic individuals. Thirty C4-5 and C5-6 discs and thirty L4-5 and L5-S1 discs per group were collected during the autopsy of individuals whose family members denied a history of neck or back pain. Discs were divided into anterior, central (lumbar only) and posterior sectors for analysis. Immunohistochemistry for TNF-α, IL-1β, VEGF, NGF-β, BDNF, TIMP-1, MMP-1, -2 and -3 was performed and reactivity compared between groups and sectors. All of these molecules were detected in every disc sector of both G1 and G2. Most statistical comparisons (25/45, 55.6%) revealed an increase in mediator expression in G2 in relation to G1. Regional differences in the expression of remodeling enzymes were rare; NGF-β and BDNF had slightly higher expression in the cervical segment of elderly individuals. A senescent profile with elevated VEGF, MMP-2 and MMP-3 was observed across most G2 disc regions and were generally elevated from G1. In conclusion, the mere presence of any of the studied molecules inside the IVD cannot be considered pathologic. Expression of remodeling enzymes and inflammatory mediators is relatively similar across different vertebral segments and disc regions leading to a common degenerated pattern, while neurotrophins have slightly higher expression in cervical discs. These findings support the concept that disc remodeling in different segments follows a similar pathway that can be potentially mediated to avoid structural failure.

The normal aging of the extracellular matrix and collagen content of the human lumbar intervertebral disc (IVD) remains relatively unknown despite vast amounts of basic science research, partly because of the use of inadequate surrogates for a truly normal, human IVD. Our objective in this study was to describe and compare the morphology and ultrastructure of lumbar IVDs in 2 groups of young (G1-<35 years) and elderly (G2->65 years). Thirty L4-5 and L5-S1 discs per group were obtained during autopsies of presumably-asymptomatic individuals and analyzed with magnetic resonance imaging (MRI), a morphological grading scale, light microscopy, scanning electron microscopy (SEM) and immunohistochemistry (IHC) for collagen types I, II, III, IV, V, VI, IX and X. As expected, a mild to moderate degree of degeneration was present in G1 discs and significantly more advanced in G2. The extracellular matrix of G2 discs was significantly more compact with an increase of cartilaginous features such as large chondrocyte clusters. Elastic fibers were abundant in G1 specimens and their presence correlated more with age than with degeneration grade, being very rare in G2. SEM demonstrated persistence of basic structural characteristics such as denser lamellae with Sharpey-type insertions into the endplates despite advanced age or degeneration grades. Immunohistochemistry revealed type II collagen to be the most abundant type followed by collagen IV. All collagen types were detected in every disc sector except for type X collagen. Statistical analysis demonstrated a general decrease in collagen expression from G1 to G2 with an annular- and another nuclear-specific pattern. These results suggest modifications of IVD morphology do not differ between the anterior or posterior annulus but are more advanced or happen earlier in the posterior areas of the disc. This study finally describes the process of extracellular matrix modification during disc degeneration in an unselected, general population and demonstrates it is similar to the same process in the cervical spine as published previously.

Abstract The goals of cervical deformity surgery include deformity correction, restoration of horizontal gaze, decompression of neural elements, spinal stabilization with a biomechanically sound construct, and meticulous arthrodesis technique to prevent pseudoarthrosis and minimizing surgical complications. Many different surgical options exist, but selecting the correct approach that ensures the optimal clinical outcome can be challenging and often controversial. In this last part of the cervical deformity review series, various posterior deformity correction techniques are discussed in detail, along with an overview of surgical outcome and postoperative complications.

Abstract A sound operative plan based on solid understanding of the pathology and biomechanics is the most important part of cervical deformity correction. Many different surgical options exist for operative management of cervical spine deformities. However, selecting the correct approach that ensures the optimal clinical outcome can be challenging and often controversial. In Part 2 of this three-part review series, we discuss the pre-operative planning, management algorithm, and anterior surgical techniques for cervical deformity correction.

ABSTRACT BACKGROUND Anterior cervical discectomy and fusion (ACDF) is being increasingly offered on an outpatient basis. However, the safety profile of outpatient ACDF remains poorly defined. OBJECTIVE To review the medical literature on the safety of outpatient ACDF. METHODS We systematically reviewed the literature for articles published before April 1, 2018, describing outpatient ACDF and associated complications, including incidence of reoperation, stroke, thrombolytic events, dysphagia, hematoma, and mortality. A random-effects analysis was performed comparing complications between the inpatient and outpatient groups. RESULTS We identified 21 articles that satisfied the selection criteria, of which 15 were comparative studies. Most of the existing studies were retrospective, with a lack of level I or II studies on this topic. We found no statistically significant difference between inpatient and outpatient ACDF in overall complications, incidence of stroke, thrombolytic events, dysphagia, and hematoma development. However, patients undergoing outpatient ACDF had lower reported reoperation rates (P < .001), mortality (P < .001), and hospitalization duration (P < .001). CONCLUSION Our meta-analysis indicates that there is a lack of high level of evidence studies regarding the safety of outpatient ACDF. However, the existing literature suggests that outpatient ACDF can be safe, with low complication rates comparable to inpatient ACDF in well-selected patients. Patients with advanced age and comorbidities such as obesity and significant myelopathy are likely not suitable for outpatient ACDF. Spine surgeons must carefully evaluate each patient to decide whether outpatient ACDF is a safe option. Higher quality, large prospective randomized control trials are needed to accurately demonstrate the safety profile of outpatient ACDF.

Several studies describing the ultrastructure and extracellular matrix (ECM) of intervertebral discs (IVDs) involve animal models and specimens obtained from symptomatic individuals during surgery for degenerative disease or scoliosis, which may not necessarily correlate to changes secondary to normal aging in humans. These changes may also be segment-specific based on different load patterns throughout life. Our objective was to describe the ECM and collagen profile of cervical IVDs in young (G1 - <35 years) and elderly (G2 - >65 years) presumably-asymptomatic individuals. Thirty cervical discs per group were obtained during autopsies of presumably-asymptomatic individuals. IVDs were analyzed with MRI, a morphological grading scale, light microscopy, scanning electron microscopy (SEM) and immunohistochemistry (IHC) for collagen types I, II, III, IV, V, VI, IX and X. Macroscopic degenerative features such as loss of annulus-nucleus distinction and fissures were found in both groups and significantly more severe in G2 as expected. MRI could not detect all morphological changes when compared even with simple morphological inspection. The loose fibrocartilaginous G1 matrix was replaced by a denser ECM in G2 with predominantly cartilaginous characteristics, chondrocyte clusters and absent elastic fibers. SEM demonstrated persistence of an identifiable nucleus and Sharpey-type insertion of cervical annulus fibers even in highly-degenerated G2 specimens. All collagen types were detected in every disc sector except for collagen X, with the largest area stained by collagens II and IV. Collagen detection was significantly decreased in G2: although significant intradiscal differences were rare, changes may occur faster or earlier in the posterior annulus. These results demonstrate an extensive modification of the ECM with maintenance of basic ultrastructural features despite severe macroscopic degeneration. Collagen analysis supports there is not a \"pathologic\" collagen type and changes are generally similar throughout the disc. Understanding the collagen and ultrastructural substrate of degenerative changes in the human disc is an essential step in planning restorative therapies.

Abstract BACKGROUND Although advances in implant materials, such as polyetheretherketone (PEEK), have been developed aimed to improve outcome after anterior cervical discectomy and fusion (ACDF), it is essential to confirm whether these changes translate into clinically important sustained benefits. OBJECTIVE To compare the radiographic and clinical outcomes of patients undergoing up to 3-level ACDF with PEEK vs structural allograft implants. METHODS In this cohort study, radiographic and symptomatic nonunion rates were compared in consecutive patients who underwent 1 to 3 level ACDF with allograft or PEEK implant. Prospectively collected clinical data and patient-reported outcome (PRO) scores were compared between the allograft and PEEK groups. Regression analysis was performed to determine the predictors of nonunion. RESULTS In total, 194 of 404 patients met the inclusion criteria (79% allograft vs 21% PEEK). Preoperative demographic variables were comparable between the 2 groups except for age. The rate of radiographic nonunion was higher with PEEK implants (39% vs 27%, P = .0035). However, a higher proportion of nonunion in the allograft cohort required posterior instrumentation (14% vs 3%, P = .039). Patients with multilevel procedures and PEEK implants had up to 5.8 times the risk of radiographic nonunion, whereas younger patients, active smokers, and multilevel procedures were at higher risk of symptomatic nonunion. CONCLUSION Along with implant material, factors such as younger age, active smoking status, and the number of operated levels were independent predictors of fusion failure. Given the impact of nonunion on PRO, perioperative optimization of modifiable factors and surgical planning are essential to ensure a successful outcome.