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Spinal stenosis (SS) is frequently caused by spinal ligament abnormalities, such as ossification and hypertrophy, which narrow the spinal canal and compress the spinal cord or nerve roots, leading to myelopathy or sciatic symptoms; however, the underlying pathological mechanism is poorly understood, hampering the development of effective nonsurgical treatments. Our study aims to investigate the role of co-expression hub genes in patients with spinal ligament ossification and hypertrophy. To achieve this, we conducted an integrated analysis by combining RNA-seq data of ossification of the posterior longitudinal ligament (OPLL) and microarray profiles of hypertrophy of the ligamentum flavum (HLF), consistently pinpointing CTSD as an upregulated hub gene in both OPLL and HLF. Subsequent RT-qPCR and IHC assessments confirmed the heightened expression of CTSD in human OPLL, ossification of the ligamentum flavum (OLF), and HLF samples. We observed an increase in CTSD expression in human PLL and LF primary cells during osteogenic differentiation, as indicated by western blotting (WB). To assess CTSD's impact on osteogenic differentiation, we manipulated its expression levels in human PLL and LF primary cells using siRNAs and lentivirus, as demonstrated by WB, ALP staining, and ARS. Our findings showed that suppressing CTSD hindered the osteogenic differentiation potential of PLL and LF cells, while overexpressing CTSD activated osteogenic differentiation. These findings identify CTSD as a potential therapeutic target for treating spinal stenosis associated with spinal ligament abnormalities., Competing Interests: Declaration of competing interest The authors declare no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To investigate the relationship between the severity and morphology of heterotopic ossification in the spinal ligaments including sacroiliac (SI) joints, and serum interleukin-17 (IL-17) levels in patients with ossification of the posterior longitudinal ligament (OPLL) with or without diffuse idiopathic skeletal hyperostosis (DISH), as well as a non-OPLL group., Methods: A total of 103 patients with OPLL [DISH (-), n = 50; DISH (+), n = 53] and 53 age- and gender-matched controls were included. The serum levels of IL-17 were analysed, and the severity of ectopic ossification and the morphology of ectopic bone formation were evaluated. The SI joint morphological variations were categorized into four types., Results: No significant differences were found in serum IL-17 levels between the OPLL and control groups. However, the DISH (+) group showed higher IL-17 levels than the DISH (-) group, especially in female patients (P = 0.003). Additionally, IL-17 levels were positively correlated with the number of flat vertebral units, this being one of the characteristic DISH ossification types (R2 = 0.199, P = 0.012). IL-17 levels in the type showing bridging osteophyte and bone fusion were significantly higher in the DISH (+) group than in the DISH (-) group., Conclusion: The morphological characteristics of paravertebral bone formation in the entire spine, including the SI joint, are likely associated with serum IL-17 levels in OPLL. These findings provide pathological and serological evidence of local inflammation contributing to paravertebral ossification of OPLL patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Cervical spondylotic myelopathy (CSM) is a prevalent cause of spinal cord dysfunction in adults, primarily from degenerative changes. The efficacy of treatment strategies, especially surgical approaches, remains debated., Objective: This study aimed to assess the long-term impact of posterior fusion laminectomy on the posterior longitudinal ligament (PLL) thickness, disc complex, and myelomalacia signal changes in CSM patients., Methods: A single-centre, prospective study from January 2020 to December 2021 included CSM patients without ossified posterior longitudinal ligament (OPLL). Magnetic resonance imaging (MRI) data from baseline, 6, and 12 months postoperatively were collected. Measurements on the MRI were performed using the Osirix MD software, focusing on the PLL width, myelopathic foci dimensions, and canal diameter., Results: Out of the 82 initially enrolled patients, 64 were considered for analysis. Postoperatively, a significant reduction in PLL width and myelopathic foci dimensions was observed, alongside a considerable increase in the canal diameter. Clinical outcomes based on the Modified Japanese Orthopaedic Association (mJOA) scale also showcased marked improvements post-surgery., Conclusions: Posterior fusion laminectomy effectively reduces anterior pressure in CSM patients. This treatment may represent an optimal surgical approach for selected CSM cases. Furthermore, more extensive studies with extended follow-up are advocated., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Study Design: Retrospective cohort study., Objective: We aimed to develop and validate a convolutional neural network (CNN) model to distinguish between cervical ossification of posterior longitudinal ligament (OPLL) and multilevel degenerative spinal stenosis using Magnetic Resonance Imaging (MRI) and to compare the diagnostic ability with spine surgeons., Summary of Background Data: Some artificial intelligence models have been applied in spinal image analysis and many of promising results were obtained; however, there was still no study attempted to develop a deep learning model in detecting cervical OPLL using MRI images., Materials and Methods: In this retrospective study, 272 cervical OPLL and 412 degenerative patients underwent surgical treatment were enrolled and divided into the training (513 cases) and test dataset (171 cases). CNN models applying ResNet architecture with 34, 50, and 101 layers of residual blocks were constructed and trained with the sagittal MRI images from the training dataset. To evaluate the performance of CNN, the receiver operating characteristic curves of 3 ResNet models were plotted and the area under the curve were calculated on the test dataset. The accuracy, sensitivity, and specificity of the diagnosis by the CNN were calculated and compared with 3 senior spine surgeons., Results: The diagnostic accuracies of our ResNet34, ResNet50, and ResNet101 models were 92.98%, 95.32%, and 97.66%, respectively; the area under the curve of receiver operating characteristic curves of these models were 0.914, 0.942, and 0.971, respectively. The accuracies and specificities of ResNet50 and ResNet101 models were significantly higher than all spine surgeons; for the sensitivity, ResNet101 model achieved better values than that of the 2 surgeons., Conclusion: The performance of our ResNet model in differentiating cervical OPLL from degenerative spinal stenosis using MRI is promising, better results were achieved with more layers of residual blocks applied., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Numerous studies have demonstrated an association between ethnic identity and the prevalence rate of cervical ossified posterior longitudinal ligament (C-OPLL). To date, its prevalence rate in the Jewish population has not been determined. The aim of this historical prospective study is to evaluate the prevalence and characteristics of C-OPLL in the Jewish population., Methods: We performed a retrospective evaluation of imaging studies of all adult patients who underwent both cervical computed tomography and magnetic resonance imaging for all clinical indications within a span of 36 months between January 2017 and July 2020 at a single tertiary referral hospital located in central Israel. Identified C-OPLL carriers were interviewed by telephone. All the patients provided informed consent and then were questioned for current symptoms and demographics, including religion, Jewish ethnic identity, birthplace, parental birthplace and ethnic identity, and family history of spinal disorders., Results: Overall, 440 participants were radiographically evaluated. The prevalence of C-OPLL in the Jewish population was 7.5% (33 of 440). The mean age of the C-OPLL carriers was 65.8 years. All the C-OPLL carriers were symptomatic at analysis. The carriers had an increased proportion with a Sephardic Jewish ethnic identity (65.4%), with a significantly high rate of homogeneous parental Jewish identity (92.4%), suggesting a prominent genetic contribution to the development of this condition., Conclusions: The prevalence of C-OPLL in the Jewish population in central Israel was 7.5%. This rate is significantly higher than that in other previously studied populations. To the best of our knowledge, this is the first study to identify the Jewish population as experiencing an increased prevalence of C-OPLL., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background Context: Obesity and visceral fat have been implicated as potential factors in the pathogenesis of the ossification of the posterior longitudinal ligament (OPLL); the details of the factors involved in OPLL remain unclear., Purpose: We aimed to determine the association between dyslipidemia and symptomatic OPLL., Study Design: Single institution cross-sectional study., Patient Sample: Data were collected from Japanese patients with OPLL (n=92) who underwent whole-spine computed tomography scanning. Control data (n=246) without any spinal ligament ossification were collected from 627 Japanese participants who underwent physical examination., Outcome Measures: Baseline information and lipid parameters, including triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) from fasting blood samples were collected to assess the comorbidity of dyslipidemia., Methods: Patient data were collected from 2020 to 2022. Patients with dyslipidemia were defined as those who were taking medication for dyslipidemia and who met one of the following criteria: TG ≥150 mg/dL, LDL-C ≥140 mg/dL, and/or HDL-C <40 mg/dL. The factors associated with OPLL development were evaluated using multivariate logistic regression analysis., Results: The comorbidity of dyslipidemia in the OPLL group was more than twice that in the control group (71.7% and 35.4%, respectively). The mean body mass index (BMI) of the OPLL group was significantly higher than that of the control group (27.2 kg/m 2 and 23.0 kg/m 2 ). Multivariate logistic regression analysis revealed that dyslipidemia was associated with the development of OPLL (regression coefficient, 0.80; 95% confidence interval, 0.11-1.50). Additional risk factors included age, BMI, and diabetes mellitus., Conclusions: We demonstrated a novel association between dyslipidemia and symptomatic OPLL development using serum data. This suggests that visceral fat obesity or abnormal lipid metabolism are associated with the mechanisms of onset and exacerbation of OPLL as well as focal mechanical irritation due to being overweight., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Study Design: We performed histologic, immunohistochemical, immunoblot examination and suspension array analyses of cytokine expression in cultured cells derived from human cervical ossification of the posterior longitudinal ligament (OPLL)., Objective: To determine the roles of interleukin-6 (IL-6) during the maturation of osteoblasts and chondrocytes associated with the development of OPLL., Summary of Background Data: Ectopic OPLL affects ~3% of the general population, with a higher incidence in Asian ethnic groups. Alterations in cytokine profiles may influence osteoblast differentiation, but the mechanisms and signaling pathways associated with the ossification process remain unclear., Methods: Samples were collected from 14 patients with OPLL who had undergone spinal surgery and seven with cervical spondylotic myelopathy without OPLL. Tissue sections were used for histologic and immunohistochemical studies, and primary cells from ligamentum samples were used for cytokine array and immunoblotting. A suspension array was used to measure the concentrations of 27 inflammatory cytokines or growth factors., Results: Suspension array and immunoblot analyses revealed significantly elevated levels of IL-6 in OPLL patients. Alterations in IL-6 concentrations were found to alter the expression of the genes Sox9 , Runx2 , and SIRT1 . In addition, immunohistochemical analysis revealed that these factors are present in mesenchymal cells within the degenerative portion of the ligament matrix that is adjacent to the ossification front., Conclusions: IL-6 plays a profound role in the osteoblast differentiation process along with the induction of chondrocyte hypertrophy and cell apoptosis in the early stages of ossification in OPLL. These changes in cytokine profiles are essential factors for regulation of the ectopic ossified plaque in OPLL., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The association of various morphological features of facet diastasis with posterior ligamentous complex (PLC) injury has not been previously described. This study aims to determine the diagnostic value of facet diastasis subtypes for diagnosing thoracolumbar PLC injury., Methods: We retrospectively reviewed 337 consecutive patients with acute thoracolumbar fractures who had computed tomography (CT) and magnetic resonance imaging (MRI) within 10 days of injury. Three and 5 reviewers evaluated MRI and CT images, respectively. Facet diastasis was subclassified as follows: Dislocated, no articular surface apposition; subluxed, incomplete articular surface apposition; and facet fracture articular process fractures which may be displaced ≥2 mm or otherwise undisplaced, facet joint widening (FJW) ≥ 3 mm. We examined the diagnostic accuracy and the multivariate associations of facet diastasis subtypes with PLC injury in MRI., Results: Facet dislocation, subluxation, and displaced facet fracture yielded a high positive predictive value (PPV) for PLC injury (96%, 88%, and 94%, respectively). In contrast, undisplaced facet fracture and FJW yielded a moderate PPV for PLC injury (78%, and 45%, respectively). Facet dislocation, subluxation, and displaced facet fracture showed independent associations with PLC injury (adjusted odds ratio [AOR] = 38.4, 17.1, 13.4, respectively; P < 0.05). Undisplaced facet fracture and FJW were not associated with PLC injury (AOR = 3.9 [95% confidence interval, 0.49-38.4], P = 0.20) and (AOR = 1.94 [95% confidence interval, 0.48-7.13]; P = 0.20; P = 0.33), respectively., Conclusions: Facet dislocation, subluxation, and displaced facet fracture, but not undisplaced facet fracture or FJW, were independently associated with PLC injury. Therefore, we propose to define facet diastasis as a surrogate marker of PLC injury in MRI based on these morphologies., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Primary spinal ligament-derived cells (SLDCs) from cervical herniated nucleus pulposus tissue (control, Ctrl) and ossification of the posterior longitudinal ligament (OPLL) tissue of surgical patients were analyzed for pathogenesis elucidation. Here, we found that decreased levels of ferritin and increased levels of alkaline phosphatase (ALP), a bone formation marker, provoked osteogenesis in SLDCs in OPLL. SLDCs from the Ctrl and OPLL groups satisfied the definition of mesenchymal stem/stromal cells. RNA sequencing revealed that oxidative phosphorylation and the citric acid cycle pathway were upregulated in the OPLL group. SLDCs in the OPLL group showed increased mitochondrial mass, increased mitochondrial reactive oxygen species (ROS) production, decreased levels of ROS scavengers including ferritin. ROS and ferritin levels were upregulated and downregulated in a time-dependent manner, and both types of molecules repressed ALP. Osteogenesis was mitigated by apoferritin addition. We propose that enhancing ferritin levels might alleviate osteogenesis in OPLL.

Background: Ossification of the posterior longitudinal ligament (OPLL) is a disabling disease whose pathogenesis is still unclear, and there are no effective cures or prevention methods. Exosomal miRNA plays an important role in the osteogenesis of ectopic bone. Therefore, we focused on the downregulation of miR-140-5p in OPLL cell-derived exosomes to explore the mechanism by which exosomal miR-140-5p inhibits osteogenesis in OPLL., Results: Exosomes were isolated by differential centrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis, and exosomal markers. Exosomal RNA was extracted to perform miRNA sequencing and disclose the differentially expressed miRNAs, among which miR-140-5p was significantly downregulated. Confocal microscopy was used to trace the exosomal miR-140-5p delivered from OPLL cells to human mesenchymal stem cells (hMSCs). In vitro, we verified that exosomal miR-140-5p inhibited the osteoblast differentiation of hMSCs by targeting IGF1R and suppressing the phosphorylation of the IRS1/PI3K/Akt/mTOR pathway. In vivo, we verified that exosomal miR-140-5p inhibited ectopic bone formation in mice as assessed by micro-CT and immunohistochemistry., Conclusions: We found that exosomal miR-140-5p could inhibit the osteogenic differentiation of hMSCs by targeting IGF1R and regulating the mTOR pathway, prompting a further potential means of drug treatment and a possible target for molecular therapy of OPLL., (© 2022. The Author(s).)

Study Design: A prospective multicenter study., Objective: This study aims to evaluate patient-reported outcomes using the Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) and clarify clinical factors that affect the therapeutic effects for patients with cervical ossification of the posterior longitudinal ligament (OPLL)., Summary of Background Data: Although previous studies identified factors that affected the surgical outcomes, their assessment was mainly based on the Japanese Orthopedic Association score, which only includes neurological function. Investigating this pathology through multiple functions and quality of life (QOL) is pivotal to understanding the comprehensive clinical pictures of the cervical OPLL and its therapeutic outcomes., Materials and Methods: This study was performed by the Japanese Multicenter Research Organization for Ossification of the Spinal Ligament. A total of 478 patients with myelopathy caused by cervical OPLL from 28 institutions were prospectively registered from 2014 to 2017 and followed up for 2 years. Of the patients, 168 received laminoplasties and fully completed questionnaires. Demographic information, imaging findings, and clinical outcomes were collected. Patients were grouped according to effective or ineffective surgical outcomes as defined by the JOACMEQ using logistic regression analyses., Results: Laminoplasty resulted in functional improvement in the cervical spine and upper extremity around 40% of the patients, while QOL showed only 21.4% ( P <0.01). Multivariable analyses revealed that younger age and a postoperative decrease in arm or hand pain were correlated with significantly improved function of the upper extremities. A reduction in lower limb pain favorably affected the postoperative lower extremity function. A postoperative reduction in upper extremity pain enhanced the QOL recovery., Conclusions: Surgeons should recognize the diversity of surgical outcomes after laminoplasty and understand the necessity of pain management even after the surgery to enhance bodily functions and QOL in patients with cervical OPLL., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Since the first description of paediatric intervertebral disc calcification (IDC) by Báron in 1924, only approximately 400 cases have been reported in the literature. Paediatric IDC combined with ossification of the posterior longitudinal ligament (OPLL) is an even rarer condition, with only 8 cases described in detail to date. In this paper, we present a review of the disease characteristics described in the relevant English language literature and discuss the possible mechanisms of lesion enhancement in contrast-enhanced magnetic resonance imaging (MRI)., Case Presentation: In May 2020, a 6-year-old Han nationality girl presented with the chief complaint of neck pain that had lasted for a week. She did not report a history of trauma or a past illness. On admission, there was no personal and family history, congenital diseases, or non-specific infections such as tuberculosis, among others. Further physical examination revealed that the movement of her cervical spine was limited. Computed tomography (CT) and MRI revealed ossification of the intervertebral discs and posterior longitudinal ligament (PLL) at the C4/5 levels and an absence of obvious spinal cord compression. When contrast-enhanced MRI was performed, significant enhancement was observed in the intervertebral discs and PLL at the C4/5 level. We adopted a non-interventional approach and performed an imaging re-examination 8 months later. Both the plain and contrast-enhanced MRI scans indicated swelling in the C4/5 intervertebral discs and disappearance of the previously observed enhancement in the nucleus pulposus (NP) and PLL at the corresponding levels; CT examination revealed that the ossified lesions had been completely resorbed., Conclusion: Obvious lesion enhancement in contrast-enhanced MRI is an extremely rare manifestation of paediatric IDC combined with OPLL. However, the exact mechanisms of this phenomenon remain unclear. We surmise that it may be caused by a series of biophysical changes related to vertebral endplate injury and repair, but further research will be required for in-depth investigation., (© 2022. The Author(s).)

Ossification of the posterior longitudinal ligament (OPLL) is an emerging spinal disease caused by heterotopic ossification of the posterior longitudinal ligament. The pathological mechanism is poorly understood, which hinders the development of nonsurgical treatments. Here, we set out to explore the function and mechanism of small extracellular vesicles (sEVs) in OPLL. Global miRNA sequencings are performed on sEVs derived from ligament cells of normal and OPLL patients, and we have showed that miR-320e is abundantly expressed in OPLL-derived sEVs compare to other sEVs. Treatment with either sEVs or miR-320e significantly promote the osteoblastic differentiation of normal longitudinal ligament cells and mesenchymal stem cells and inhibit the osteoclastic differentiation of monocytes. Through a mechanistic study, we find that TAK1 is a downstream target of miR-320e, and we further validate these findings in vivo using OPLL model mice. Together, our data demonstrate that OPLL ligament cells secrete ossification-promoting sEVs that contribute to the development of ossification through the miR-320e/TAK1 axis., (© 2022. The Author(s).)

Ossification of the posterior longitudinal ligament (OPLL) is a disease characterized by the replacement of the posterior longitudinal ligament with ectopic bone and cartilage. Historically, the disease was described as highly prevalent in Japanese and other Asian populations. However, recent studies suggest OPLL may have a higher prevalence in non-Asian communities than previously believed. To date, there are no demographic or epidemiologic studies examining OPLL in Native Hawaiian or Polynesian communities. The purpose of this study was to review the demographics and comorbidities of a cohort of patients with OPLL from the author's institution, designated as either Native Hawaiian and/or Polynesian (NHP) or Non-Native Hawaiian and/or Polynesian (NNHP). Demographic findings from this study were similar to previous literature demonstrating higher rates of OPLL in men and older patients with an average age of 56 years in the NHP group and 65 years in the NNHP group. There were no statistically significant differences in the rates of type II diabetes mellitus, coronary vascular disease, chronic kidney disease, or hypertension between NHP and NNHP groups. The NHP group exhibited statistically higher rates of obesity when compared to the NNHP group. Obesity's risk in the development or progression of OPLL in the NHP population has not been examined and requires additional investigation. This study serves as a beginning for further demographic and epidemiologic investigations into OPLL in Native Hawaiian and Polynesian communities to facilitate improved identification of those at risk and guide diagnosis and treatment of these patients., (©Copyright 2022 by University Health Partners of Hawai‘i (UHP Hawai‘i).)

Study Design: A retrospective analysis of prospectively collected data., Objective: This study aimed to create a prognostic model for surgical outcomes in patients with cervical ossification of the posterior longitudinal ligament (OPLL) using machine learning (ML)., Summary of Background Data: Determining surgical outcomes helps surgeons provide prognostic information to patients and manage their expectations. ML is a mathematical model that finds patterns from a large sample of data and makes predictions outperforming traditional statistical methods., Methods: Of 478 patients, 397 and 370 patients had complete follow-up information at 1 and 2 years, respectively, and were included in the analysis. A minimal clinically important difference (MCID) was defined as an acquired Japanese Orthopedic Association (JOA) score of ≥2.5 points, after which a ML model that predicts whether MCID can be achieved 1 and 2 years after surgery was created. Patient background, clinical symptoms, and imaging findings were used as variables for analysis. The ML model was created using LightGBM, XGBoost, random forest, and logistic regression, after which the accuracy and area under the receiver-operating characteristic curve (AUC) were calculated., Results: The mean JOA score was 10.3 preoperatively, 13.4 at 1 year after surgery, and 13.5 at 2 years after surgery. XGBoost showed the highest AUC (0.72) and high accuracy (67.8) for predicting MCID at 1 year, whereas random forest had the highest AUC (0.75) and accuracy (69.6) for predicting MCID at 2 years. Among the included features, total preoperative JOA score, duration of symptoms, body weight, sensory function of the lower extremity sub-score of the JOA, and age were identified as having the most significance in most of ML models., Conclusion: Constructing a prognostic ML model for surgical outcomes in patients with OPLL is feasible, suggesting the potential application of ML for predictive models of spinal surgery.Level of Evidence: 4., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Posterior longitudinal ligament cysts are very rare lesions and do not usually recur. Microscopic resection is commonly performed. The aim of this article was to report a case of recurrent posterior longitudinal ligament cyst that benefited from full-endoscopic resection., Methods: We used the 25° endoscope of the RIWOspine set for interlaminar approach. A step-by-step description of the surgical technique was presented., Results: Clinical evolution was favorable. The patient remained pain-free 1 month after surgery, and postoperative magnetic resonance imaging showed complete resection of the cyst., Conclusions: Endoscopy is a safe and feasible approach for posterior longitudinal ligament cysts, including unusual recurrent cases., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Magnetic resonance imaging (MRI) is effective in identifying cervical spine injury after trauma. However, cervical instability without major bone injury or dislocation is challenging to assess. Hence, the current study aimed to investigate and compare the MRI and radiography findings of segmental instability in patients with cervical spine injury. We investigated 34 participants with cervical spine injury without vertebral fracture. Based on the radiography findings, the participants were categorized into two: group A with segmental instability (n = 11) and group B without segmental instability (n = 23). Both groups were compared in terms of the presence of segmental instability on radiography and MRI. Anterior longitudinal ligament (ALL) injury, disc injury, and bilateral facet effusion were observed in 6/11, 5/11, and 7/11 patients in group A and in 5/23, 2/23 and 7/23 patients in group B, respectively. The results showed significant differences (p < 0.05). Moreover, 2 and 10 of 11 patients in group A and 16 and 7 of 23 patients in group B presented with hemi lateral facet effusion and paravertebral muscle injury, respectively. However, the results did not significantly differ. According to a logistic regression analysis, bilateral facet effusion after trauma was associated with cervical segmental instability (odd ratio: 10.6, 95% confidence interval: 1.31-84.7). Facet joint effusion might be caused by capsule injury during trauma. Most participants with segmental instability had ALL, disc, and flavum injury and bilateral facet effusion. Therefore, we need to consider bilateral facet effusion with other soft tissue damage of the cervical spine as an association factor to show the instability.

Ossification of the posterior longitudinal ligament (OPLL) within the spinal canal sometimes leads to severe myelopathy. Teriparatide (TPD) is a recombinant human parathyroid hormone (PTH) (1-34), which promotes osteogenesis of mesenchymal stem cells (MSCs) via PTH 1 receptor (PTH1R). Although ligamentum flavum (LF)-MSCs from patients with OPLL have a high osteogenic potency, the effect of TPD on them remains unknown. In this study, we determined PTH1R expression in LF-MSCs from patients with OPLL and investigated whether TPD promotes osteogenic differentiation in them. First, LF-MSCs were isolated from patients with OPLL and cervical spondylotic myelopathy (CSM) (controls). Cultured LF-MSCs were treated with different concentrations of TPD on days 0, 7, and 14. On day 21, osteogenic gene expression was quantified. Mineralization was measured based on optical density after Alizarin Red S staining. LF-MSCs from both groups expressed PTH1R at the same level. TPD did not enhance osteogenic gene expression and mineralization in LF-MSCs from both groups. TPD did not promote the osteogenic differentiation of LF-MSCs from patients with OPLL. Thus, it may be safe for patients with OPLL. However, further confirmation of our results with in vivo studies is necessary., Competing Interests: Declaration of competing interest The authors indicated no potential conflicts of interest., (Copyright © 2020 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Study Design: Immunohistochemical and real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis., Objective: The aim of this study was to analyze the expression of five susceptibility genes (RSPO2, HAO1, CCDC91, RHPH9, and STK38L) for human ossification of the posterior longitudinal ligaments (OPLL) identified in a genome-wide association study., Summary of Background Data: Detailed expression and functional studies for the five susceptibility genes are needed to aid in clarification of the etiology and pathogenesis of OPLL., Methods: Immunostaining, cell culture, and real-time RT-PCR were performed on ossified ligament samples collected during anterior cervical decompression for symptomatic OPLL (n = 39 patients) and on control non-OPLL samples (n = 8 patients). Immunohistochemical analysis in spinal hyperostotic mice (ttw/ttw) (n = 25) was also performed. The sample sections were stained for RSPO2, HAO1, CCDC91, RHPH9, STK38L, Runx2, Sox9, and CD90. The mRNA expression levels of the five susceptibility genes were also analyzed in cultured human OPLL and non-OPLL cells subjected to cyclic tensile strain., Results: Immunoreactivity for RSPO2 and Sox9 was evident in proliferating chondrocytes in human OPLL tissues and ttw/ttw mice. Application of cyclic tensile strain to cultured human OPLL cells resulted in increases in mRNA levels for RSPO2, HAO1, and CCDC91. However, individual differences in expression in human OPLL-related samples were seen. HAO1-positive cells were detected only in 3- to 6-week-old ttw/ttw mice that did not simultaneously express RSPO2-positive samples., Conclusion: Among the five susceptibility genes, RSPO2, HAO1, and CCDC91 might be contributory factors in progression of OPLL. RSPO2 may be involved in endochondral ossification, especially in mixed or continuous type OPLL, HAO1 may be an initiation factor for OPLL that is rarely seen in mature human OPLL samples, and CCDC91 may be associated with progression of ossification caused by mechanical stress. These findings provide important insights into the pathogenesis and therapeutic targets for OPLL., Level of Evidence: N/A.

Pediatric thoracolumbar fractures are rare due to the physiological differences which afford greater resilience to the immature spine. Most pediatric thoracolumbar fractures occur as the result of high energy trauma, such as motor vehicle accidents, and modes of reasonable accidental injuries are limited by age and developmental capabilities of the child. These fractures can occur as the result of inflicted blunt force trauma and child abuse, and in most cases, the mechanism of injury to the spine is not known. We report the death of a 29-month-old man due to blunt force trauma to the back and forced hyperextension of the thoracolumbar spine causing fracture of the fourth lumbar (L4) vertebral body. A complete forensic examination revealed a previous healing fracture of the anterior aspect of the L4 vertebral body, with acute disruption of the anterior longitudinal ligament overlying the fracture site, complete fracture of the vertebral body, and fatal retroperitoneal hemorrhage. We present a review of the biomechanical considerations of the pediatric spine, a survey of pediatric spinal fractures, and a review of the literature on pediatric abusive thoracolumbar fractures. In this case, there was never a provided explanation for how the injury occurred; however, understanding the biomechanics of the pediatric spine allowed for the determination of the mechanism, force required to produce this specific pattern of abusive spinal injury, and the manner of death., (© 2020 American Academy of Forensic Sciences.)

Long non-coding RNAs (lncRNAs) have been noted to influence the progression of ossification of posterior longitudinal ligament (OPLL). The work aims to probe the effect of lncRNA SNHG1 on osteogenic differentiation of ligament fibroblastic cells (LFCs). Aberrantly expressed lncRNAs in ossified PLL tissues were screened out by microarray analysis. Gain- and loss-of function experiments of SNHG1 were performed to identify its role in osteogenic differentiation of LFCs. The downstream molecules of SNHG1 were explored. Altered expression of miR-320b was introduced in LFCs as well. The interactions among SNHG1, miR-320b and IFNGR1 were identified. Consequently, SNHG1 was found highly expressed in OPLL patients. Silencing of SNHG1 inhibited BMP-2, RUNX2 and OCN expression and the ALP activity and reduced osteogenic differentiation of LFCs. Importantly, SNHG1 could and upregulate IFNGR1 through serving as a sponge for miR-320b. Over-expression of miR-320b inhibited osteogenic differentiation of LFCs and inactivated the JAK/STAT signaling pathway. Further administration of Fedratinib, a JAK2-specific agonist, increased osteogenic differentiation of LFCs. To conclude, the study suggested that SNHG1 could upregulate IFNGR1 by sequestering miR-320b and activate the JAK/STAT signaling. Silencing of SNHG1 could reduce the osteogenic differentiation and mineralization of LFCs. The study may offer new insights into OPLL treatment.

Background: Ossification of the anterior longitudinal ligament (OALL) of the cervical spine is a common, but rarely symptomatic, condition mostly observed in the geriatric population. Although the condition usually requires no intervention, it could lead to a difficult airway and compromise the patient's safety., Case Presentation: Here, we describe the case of a 50-year-old man with cervical myelopathy and OALL that resulted in difficult endotracheal intubation after induction of anesthesia. Radiography and magnetic resonance imaging findings showed OALL, with prominent osteophytes involving four cervical vertebrae, a bulge in the posterior pharyngeal wall, and a narrow pharyngeal space. Airtraq® laryngoscope-assisted intubation was accomplished with rapid induction under sevoflurane-inhaled anesthesia., Conclusion: Anesthesiologists should understand that OALL of the cervical spine could cause a difficult airway. However, it is difficult to recognize asymptomatic OALL on the basis of routine airway evaluation guidelines. For susceptible populations, a thorough evaluation of the airway, based on imaging studies and a history of compression symptoms, should be considered whenever possible. In case of unanticipated difficult intubation, anesthesiologists should refer to guidelines for unanticipated difficult airway management and identify OALL of the cervical spine as the cause.

Objectives: Ossification of the posterior longitudinal ligament (OPLL) presents as the development of heterotopic ossification in the posterior longitudinal ligament of the spine. The etiology of OPLL is genetically linked, as shown by its high prevalence in Asian populations. However, the molecular mechanism of the disease remains obscure. In this study, we explored the function and mechanism of OPLL-specific microRNAs. Methods: The expression levels of the ossification-related OPLL-specific miR-181 family were measured in normal or OPLL ligament tissues. The effect of miR-181a on the ossification of normal or pathogenic ligament cells was tested using real-time polymerase chain reaction (PCR), Western blot, alizarin red staining and alkaline phosphatase (ALP) staining. The candidate targets of miR-181 were screened using a dual luciferase reporter assay and functional analysis. The link between miR-181a and its target PBX1 was investigated using chromatin immunoprecipitation, followed by real-time PCR detection. Histological and immunohistochemical analysis as well as micro-CT scanning were used to evaluate the effects of miR-181 and its antagonist using both tip-toe-walking OPLL mice and in vivo bone formation assays. Results: Using bioinformatic analysis, we found that miR-181a-5p is predicted to play important roles in the development of OPLL. Overexpression of miR-181a-5p significantly increased the expression of ossification-related genes, staining level of alizarin red and ALP activity, while the inhibition of miR-181a-5p by treatment with an antagomir had the opposite effects. Functional analysis identified PBX1 as a direct target of miR-181a-5p, and we determined that PBX1 was responsible for miR-181a-5p's osteogenic phenotype. By chromatin immunoprecipitation assay, we found that miR-181a-5p controls ligament cell ossification by regulating PBX1-mediated modulation of histone methylation and acetylation levels in the promoter region of osteogenesis-related genes. Additionally, using an in vivo model, we confirmed that miR-181a-5p can substantially increase the bone formation ability of posterior ligament cells and cause increased osteophyte formation in the cervical spine of tip-toe-walking mice. Conclusions: Our data unveiled the mechanism by which the miR-181a-5p/PBX1 axis functions in the development of OPLL, and it revealed the therapeutic effects of the miR-181a-5p antagomir in preventing OPLL development both in vivo and in vitro . Our work is the first to demonstrate that microRNA perturbation could modulate the development of OPLL through epigenetic regulation., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The pathomechanisms of initiation and progression of ossification of the posterior longitudinal ligament (OPLL) are unclear. Indian hedgehog (Ihh) and related signaling molecules are key factors in normal enchondral ossification. The purpose of this study is to investigate the contribution of mechanical strain to OPLL and the relationship of Ihh with OPLL. Sections of the posterior longitudinal ligament (PLL) were obtained from 49 patients with OPLL and from 7 patients without OPLL. Cultured PLL cells were subjected to 24 hours of cyclic tensile strain. To identify differentially expressed genes associated with cyclic tensile strain, microarray analysis was performed. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified upregulation of various genes, particularly of the Hedgehog signaling pathway; Ihh and related genes had increased expression compared with controls after 24-hour cyclic tensile strain. In immunoblotting analysis, Ihh, Runx2, Sox9, Gli2, Gli3, and smoothened (SMO) had significantly increased expression after 6- or 12-hour cyclic tensile strain. OPLL samples were strongly immunopositive for Ihh, Sox9, Runx2, Gli2, Gli3, and SMO in the ossification front of OPLL. These results suggest that cyclic tensile strain induces abnormal activation of Ihh and related signaling molecules, and this might be important in the ossification process in OPLL.

Purpose: In our aging society, the prevalence of degenerative spinal diseases rose drastically within the last years. However, up till now, the origin of cervical pain is incompletely understood. While animal and small cadaver studies indicate that a complex system of sensory and nociceptive nerve fibers in the anterior (ALL) and posterior longitudinal ligament (PLL) at the level of the intervertebral disc might be involved, there is a lack of data exploring whether such a network exists and is equally distributed within the cervical vertebrae (VB). We, therefore, aimed to investigate the spatial distribution of the mentioned nerve networks in human tissue., Methods: We performed macroscopic (Sihler staining, Spalteholz technique, and Plastination) and microscopic (immunohistochemistry for PGP 9.5 and CGRP) studies to characterize spatial differences in sensory and nociceptive innervation patterns. Therefore, 23 human body donors were dissected from level C3-C6., Results: We could show that there is a focal increase in sensory and nociceptive nerve fibers at the level of C4 and C5 for both ALL and PLL, while we observed less nerve fiber density at the level of C3 and C6. An anatomical vicinity between nerve and vessels was observed., Conclusion: To our knowledge, these findings for the first time report spatial differences in sensory and nociceptive nerve fibers in the human cervical spine at VB level. The interconnection between nerves and vessels supports the importance of the perivascular plexus. These findings might be of special interest for clinical practice as many patients suffer from pain after cervical spine surgery.

Objective: To evaluate the etiology of skeletal changes noted in equid vertebrae from a 19 th - century context near Belgrade, Serbia., Materials: A vertebral column consisting of 15 fused thoracic vertebrae (T2-T16), with right ribs fused to T4 and T5 and small remnants of ribs articulating with T4, T5 and T6 on the left side were accidentally recovered during industrial exploitation of sand., Methods: The specimen was subjected to morphological analysis and collagen fingerprinting by mass spectrometry for species identification. In order to determine the absolute temporal context, radiocarbon dating was employed. Pathological changes were analyzed macroscopically and then underwent X-ray and (CT) imaging., Results: Species identification indicates that the vertebral column belonged to a domestic horse (Equus caballus) living in the early 19 th century. Pathological changes included exuberant bone proliferation, fusion of small articulations, enthesopathy formation, complete fusion between the vertebral bodies, and ossification of the anterior longitudinal ligament., Conclusions: Pathological changes represent signs of an advanced stage of vertebral fusion consistent with diffuse idiopathic skeletal hyperostosis (DISH)., Significance: This case study provides a clear distinction between diffuse idiopathic skeletal hyperostosis (DISH) and other vertebral column diseases in equids. It also presents a new and significant contribution to the nascent discipline of animal paleopathology in present-day Serbia., Limitations: Given that only 15 thoracic vertebrae were discovered, the impact of this disease on other parts of the horse skeleton remains unknown, as does the archaeological context of the remains., Suggestions for Further Research: Research into the frequency of DISH in equids, as well as the historical context of equine husbandry in Serbia will allow greater insight into the causes and effects of this pathological condition., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To explore which preoperative radiologic variables have propensity for reherniation and to evaluate whether the inherent annulus splitting procedure during percutaneous endoscopic lumbar diskectomy (PELD) could prompt reherniation, we assessed the correlation between the anatomic location of annular penetration and reherniation., Methods: Three hundred and fifty patients who underwent PELD for central or subarticular disk herniation through a transforaminal approach were followed-up for at least 24 months. Fifty-four subjects that were reoperated for recurrent herniation were allocated as the reherniation group and the other 296 subjects were allocated as the non-reherniation group. The numerical rating scale score, another lumbosacral disk herniation (LDH) lesion in addition to the PELD level (another LDH), location (central or subarticular) and severity of LDH (protrusion or extrusion), and tear of the posterior longitudinal ligament (PLL) were compared between the 2 groups to identify which variables could be predictive factors for reherniation. To assess the influences of PELD on reherniation, location and severity of reherniation were compared with those of initial herniation., Results: The location at the subarticular region and the existence of a concomitant PLL tear during initial LDH were significantly related to subsequent reherniation. The location and severity of these reherniations were significantly retained when compared with those of primary herniation., Conclusions: PLL tear and subarticular herniation were significantly related to recurrent disk herniation. Reherniation patterns after PELD generally matched those of primary herniation. The annulus penetrating step during PELD did not increase the risk of reherniation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: To investigate the association between ossification of the posterior longitudinal ligament (OPLL) and ossification of the nuchal ligament (ONL) in terms of incidence and size., Methods: This retrospective study evaluated 297 patients who underwent CT of the cervical spine (C-spine). Two radiologists worked in consensus. The incidence of OPLL from patients with and without ONL was compared using Chi Square tests. The mean lengths of ONL from patients with and without OPLL were compared using Student t-test. The correlations between the length of ONL and the presence of OPLL and between the length of ONL and the length of OPLL were analyzed with Pearson correlations., Results: We found that OPLL occurred more frequently in patients with ONL than in patients without ONL (odd ratio = 2.524, p = 0.037); however, the mean length of ONL did not differ significantly patients with and without OPLL (p = 0.874). We found no significant correlation between the length of ONL and the length of OPLL (p = 0.233)., Conclusion: The presence of ONL was associated with the presence of OPLL. The length of OPLL and ONL showed no correlation., Competing Interests: The authors have declared that no competing interests exist.

Purpose: The pathogenesis of ossification of posterior longitudinal ligament (OPLL) is not completely clear. Previous study has confirmed a single-pass type I endoplasmic reticulum (ER) membrane protein kinase (PERK), which is a major transducer of the ER stress, participates in the process of OPLL in vitro. This study aimed to demonstrate the role of ER stress in mechanical stress (MS)-induced OPLL., Methods: The posterior longitudinal ligaments were collected intraoperatively. The expression of ER stress markers in ligament tissue samples was compared between OPLL and non-OPLL patients in vivo. Ligament fibroblasts were isolated and cultured. Loaded by MS, the expression of ER stress markers in fibroblasts deriving from non-ossified areas of the ligament tissues from OPLL patients was detected. The influence of inhibition of ER stress on MS-induced OPLL and activation of mitogen-activated protein kinase (MAPK) pathways by MS was also investigated., Results: We confirmed the ER stress markers were highly expressed in non-ossified areas of the ligament tissues from OPLL patients but could barely be detected in the ligaments from non-OPLL patients in vivo. We also found ER stress could be activated by MS during the process of OPLL in vitro. Moreover, inhibition of ER stress could hinder MS-induced OPLL and activation of MAPK signaling pathways by MS in vitro., Conclusion: Activated ER stress was observed in OPLL patients both in vitro and in vivo. Mechanical stress could activate ER stress response in posterior longitudinal ligament fibroblasts and further promote OPLL in vitro. In this process, ER stress might work through the MAPK signaling pathways. These slides can be retrieved under Electronic Supplementary Material.

The thoracic ossification of the posterior longitudinal ligament (T‑OPLL) can cause thoracic spinal stenosis, which results in intractable myelopathy and radiculopathy. Our previous whole‑genome sequencing study first reported rs199772854 in the interleukin 17 receptor C (IL17RC) gene as a potentially pathogenic loci for T‑OPLL. The aim of the present study was to examine the effects of the IL17RC gene rs199772854A site mutation on osteogenesis by establishing a model of osteogenic differentiation. IL17RC gene mutation site and wild‑type site mouse embryonic osteoblast (3T3‑E1) models were constructed in order to induce the differentiation of the cells into osteoblasts. Whether the mutation site causes the abnormal expression of the IL17RC gene and osteogenic markers was analyzed by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis. The IL17RC gene rs199772854A site mutation was demonstrated to play a biological role through the overexpression of its own gene, and also to significantly increase the expression levels of osteogenic markers. Furthermore, the mutation upregulated the expression of the key proteins, tumor necrosis factor receptor (TNFR)‑associated factor 6 (TRAF6) and nuclear factor (NF)‑κB, in the interleukin (IL)‑17 signaling axis. On the whole, the findings of this study suggest that the IL17RC gene rs199772854A loci mutation propels mouse embryonic osteoblasts towards osteogenic differentiation and may play an important role in the pathogenesis of T‑OPLL. The IL17RC gene may promote osteogenesis through the IL‑17 signaling pathway and may thus be involved in the process of ectopic osteogenesis in T‑OPLL.

Background Context: Despite the fact that ossification of posterior longitudinal ligament (OPLL) is a three-dimensional disease, conventional studies have focused mainly on a two-dimensional measurement, and it is difficult to accurately determine the volume of OPLL growth and analyze the factors affecting OPLL growth after posterior decompression (laminoplasty or laminectomy and fusion)., Purpose: The present study aimed to investigate the factors affecting OPLL volume growth using a three-dimensional measurement., Study Design/setting: This was a retrospective case study., Patient Sample: Eighty-three patients with cervical OPLL who were diagnosed as having multilevel cervical OPLL of more than three levels on cervical computed tomography (CT) scans were retrospectively reviewed from June 1, 1998, to December 31, 2015., Outcome Measures: The OPLL volume from the C1 vertebrae to the C7 vertebrae was measured on preoperative and the most recent follow-up CT scans., Methods: Eighty-three patients were retrospectively examined for age, gender, body mass index, hypertension, diabetes, type of OPLL, surgical method, preoperative cervical curvature, and preoperative and postoperative cervical range of motion. Preoperative cervical CT and the most recent follow-up cervical CT scans were converted to Digital Imaging and Communications in Medicine data, and the OPLL volume was three-dimensionally measured using the Mimics program (Materialise, Leuven, Belgium). The OPLL volume growth was analyzed using univariate and multivariate analyses., Results: The average follow-up period was 32.36 (±23.39) months. Patients' mean age was 54.92 (±8.21) years. In univariate analysis, younger age (p=.037) and laminoplasty (p=.012) were significantly associated with a higher mean annual growth rate of OPLL (%/y). In multivariate analysis, only laminoplasty (p=.027) was significantly associated with a higher mean annual growth rate of OPLL (%/y). The mean annual growth rate of OPLL was about seven times faster with laminoplasty (8.00±13.06%/y) than with laminectomy and fusion (1.16±9.23%/y)., Conclusions: Posterior instrumented fusion has the effect of reducing OPLL growth rate compared with motion-preserving laminoplasty. Patients' age and the surgical method need to be considered in surgically managing the multilevel OPLL., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the effects of leptin/leptin receptor (LepR) combined with mechanical stress on the development of ossification of the posterior longitudinal ligament (OPLL), which is a disease characterized by ectopic bone formation of the posterior longitudinal ligament (PLL) and can lead to radiculopathy and myelopathy., Methods: Six human samples of the PLL were analyzed for the expression of leptin and LepR by RT-PCR and western blotting. PLL cells were stimulated with leptin and mechanical stress delivered via a Flexcell tension system, and osteogenic differentiation was evaluated by RT-PCR and western blotting analysis of osteogenic marker expression as well as by alkaline phosphatase (ALP) staining and alizarin red S staining. Activation of mitogen-activated protein kinase (MAPK), Janus kinase (JAK) 2-signal transducer, activator of transcription (STAT) 3 and phosphatidylinositol 3-kinase (PI3K)-Akt was evaluated by western blotting., Results: Samples from the OPLL group had higher LepR mRNA and protein levels and lower leptin levels than those from healthy controls. Exposure to leptin and Flexcell increased the number of ALP-positive cells and calcium nodules in a dose-dependent manner; this effect was accompanied by upregulation of the osteogenic markers osteocalcin, runt-related transcription factor 2 (RUNX2) and osteopontin. Extracellular signal-regulated kinase, P38 MAPK, JAK2, STAT3, PI3K and Akt signaling, was also activated by the combined effects of leptin and mechanical stress., Conclusions: Leptin and LepR are differentially expressed in OPLL tissues, and the combined use of leptin/LepR and mechanical stress promotes osteogenic differentiation of PLL cells via MAPK, JAK2-STAT3 and PI3K/Akt signaling. These slides can be retrieved under Electronic Supplementary Material.

Purpose: The presence of prominent OALL (ossification of anterior longitudinal ligament) in the anterior cervical spine has been implicated as a cause of dysphagia. Surgical resection of the OALL is considered effective for the management of diffuse idiopathic skeletal hyperostosis (DISH)-related dysphagia. Although many reports have been published on DISH-related dysphagia, no cases of postoperative cervical instability have been reported thus far. We present a case in which the patient developed myelopathy associated with instability consequent to resection of OALL in DISH., Methods: A 62-year-old man presented with progressive dysphagia that persisted for a year. The patient's symptoms were successfully resolved by resection of OALL. Five years after the surgery, the dysphagia resurfaced and was found to be caused by the regrowth of the OALL. A repeat surgery was performed, and the dysphagia disappeared. Eleven months after the second surgery, he visited the hospital with progressive quadriparesis and pain in the cervical region., Results: Nine-month follow-up radiologic study revealed cervical instability at the level of C5-6 resulting in myelopathy. The patient underwent decompressive laminectomy and posterior fusion surgery., Conclusion: Surgical resection of DISH-related dysphagia typically yields excellent outcomes, but our experience in this case highlights the possibility of OALL regrowth and subsequent cervical instability after resection of OALL.

Ossification of the anterior longitudinal ligament (OALL) in cervical spine is known to cause dysphagia. However, dyspnoea and obstructive sleep apnoea (OSA) due to OALL is a rare entity. A 50-year-old man presented to our clinic 2 years after anterior cervical discectomy and fusion (ACDF) with complaints of dysphagia, dyspnoea and difficulty in sleeping supine. The clinico-neurological examination of patient was normal without any long tract signs. The diagnosis of OALL was made on plain lateral radiographs. Ultrasonic bone cutter was used to convert sessile osteophyte mass into a pedunculated mass. It was then disconnected from the anterior aspect of vertebral bodies with a chisel. The patient showed immediate relief from dysphagia and OSA. Dyspnoea improved over a week and the postoperative change in voice responded well to speech therapy. To the best of our knowledge, this is the first report of dyspnoea due to OALL after ACDF., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Ossification of the posterior longitudinal ligament (OPLL) presents as pathological heterotopic ossification of the spinal ligaments. However, its underlying molecular mechanism is still unclear. Our previous findings suggested that altered microRNA regulatory network are critical for the development of OPLL. Here, we set out to unveiling the detailed mechanism of those altered OPLL-specific microRNAs. We screened a set of differentially expressed OPLL-specific microRNAs from the previous sequencing data and showed that microRNA-10a actively modulates the ossification of posterior ligament cells in vitro. Using a tissue-engineered scaffold grown from 4-week-old BALB/c homozygous nude mice, we found that altered microRNA-10a expression in posterior ligament cells indeed affected the heterotopic bone formation in vivo. Furthermore, computational analysis showed that the negative ossification regulator ID3 is a functional target gene of microRNA-10a, and its expression was also significantly altered during microRNA-10a modulation both in vitro and in vivo. Also, we have demonstrated that the ossification promoting function of microRNA-10a requires ID3, as ID3 actively inhibits RUNX2. Thus, we identified a critical role for highly altered OPLL-specific microRNA-10a in regulating the development of OPLL by modulating the ID3/RUNX2 axis.

Purpose: Three-dimensional (3D) imaging using computed tomography (CT) has made it possible to accurately evaluate ossification of the posterior longitudinal ligament (OPLL). Recently, we developed a novel technique to measure ossification volume using the 3D analysis. The purpose of this study was to investigate the natural course of OPLL and the risk factors for volume progression., Methods: Forty-one patients (22 males and 19 females) diagnosed with cervical OPLL who had been non-surgically treated were included in this study. We evaluated clinical examination, radiological findings, and the volume of ossified lesions during at least 1-year intervals. Furthermore, we performed risk factor analysis for OPLL volume progression., Results: The mean ossification volume was 2047.4 ± 1437.3 mm 3 in the first examination and 2201.0 ± 1524.1 mm 3 in the final examination, indicating a significant increase during the follow-up period (p < 0.001). The mean annual rate of lesion increase was 4.1 ± 2.7%. Univariate regression analysis demonstrated significant relationships between the annual rate of lesion increase and age (β = -0.48; p = 0.001), body weight (BW) (β = 0.36; p = 0.02), and body mass index (BMI) (β = 0.35; p = 0.03). Furthermore, age was the only significant predictor of OPLL progression (R 2  = 0.23; p = 0.001) in multivariate liner regression analysis., Conclusions: Younger age, higher BW, and higher BMI are predictors of OPLL progression. Younger age is the most significant predictor in non-surgically treated patients.

Background: Spinous processes and posterior ligaments, such as inter- and supraspinous ligaments are often sacrificed either deliberately to harvest osseous material for final spondylodesis e.g. in deformity corrective surgery or accidentally after posterior spinal instrumentation. This biomechanical study evaluates the potential destabilizing effect of a progressive dissection of the posterior ligaments (PL) after instrumented spinal fusion as a potential risk factor for proximal junctional kyphosis (PJK)., Methods: Twelve calf lumbar spines were instrumented from L3 to L6 (L3 = upper instrumented vertebra, UIV) and randomly assigned to one of the two study groups (dissection vs. control group). The specimens in the dissection group underwent progressive PL dissection, followed by cyclic flexion motion (250 cycles, moment: + 2.5 to + 20.0 Nm) to simulate physical activity and range of motion (ROM) testing of each segment with pure moments of ±15.0 Nm after each dissection step. The segmental ROM in flexion and extension was measured. The control group underwent the same loading and ROM testing protocol, but without PL dissection., Results: In the treatment group, the normalized mean ROM at L2-L3 (direct adjacent segment of interest, UIV/UIV + 1, PJK-level) increased to 104.7%, 107.3%, and 119.4% after dissection of the PL L4-L6, L3-L6, and L2-L6, respectively. In the control group the mean ROM increased only to 103.2%, 106.7%, and 108.7%. The ROM difference at L2-L3 with regard to the last dissection of the PL was statistically significant (P = 0.017) and a PL dissection in the instrumented segments showed a positive trend towards an increased ROM at UIV/UIV + 1., Conclusions: A dissection of the PL at UIV/UIV + 1 leads to a significant increase in ROM at this level which can be considered to be a risk factor for PJK and should be definitely avoided during surgery. However, a dissection of the posterior ligaments within the instrumented segments while preserving the ligaments at UIV/UIV + 1 leads to a slight but not significant increase in ROM in the adjacent cranial segment UIV/UIV + 1 in the used experimental setup. Using this experimental setup we could not confirm our initial hypothesis that the posterior ligaments within a long posterior instrumentation should be preserved.

Ossification of the posterior longitudinal ligament (OPLL) is a myelopathy commonly observed in the cervical spine. By contrast, thoracic OPLL (T‑OPLL) is rare but more severe. Previous studies have identified several polymorphisms in osteogenic genes that are associated with the occurrence and development of cervical OPLL. However, few genetic studies have evaluated T‑OPLL. The present study aimed to identify the genetic factors for OPLL by performing whole‑genome sequencing (WGS) in 30 unrelated northern Chinese Han patients with T‑OPLL. Using bioinformatics analyses and damaging‑variant prediction algorithms, two deleterious variants [c.1534G>A(p.Gly512Ser)/collagen, type VI, α1 (COL6A1)] and [c.2275C>A(p.Leu759Ile)/inteleukin-17 receptor C (IL17RC)] were identified in seven unrelated patients. These two mutations resulted in markedly increased gene expression levels in peripheral blood samples. To the best of our knowledge, this is the first report to describe the use of WGS analysis of T‑OPLL in the northern Chinese Han population. The results revealed two novel potentially pathogenic mutations in patients with T‑OPLL.

Objective: To explore the reason of postoperative axial pain (PAP) complication caused by unilaterally open-door cervical laminoplasty with Centerpiece mini-plate fixations for the treatment of multilevel cervical spondylotic myelopathy(CSM)., Methods: The clinical data of 79 patients with CSM who underwent unilaterally open-door cervical laminoplasty from January 2010 to December 2013 were retrospectively analyzed. There were 45 males and 34 females, aged from 48 to 75 years old with an average of (58.7±4.4) years, complicated with ossified posterior longitudinal ligament(OPLL) of 42 cases. Courses of disease were from 2.1 to 3.9 years with an average of (3.0±0.4) years. Decompression segment occurred in C₃-C₆ of 31 cases, C₃-C₇ of 9 cases, C₄-C₇ of 39 cases. The condition of PAP was record. Cervical curvature index, cervical lordosis angle, the rate of cervical instability, the motion of flexion and extension between PAP group and non-PAP group were compared preoperatively. Multivariate non-linear regression analysis was used to verify relationship between aforementioned parameters and incidence of PAP. JOA score of preoperative, postoperative 6 months and initial onset of PAP, the improvement rate of JOA score and Odom criteria at final follow-up were used to evaluate curative efficacy., Results: All the patients were followed up from 26 to 44 months with an average of (36±9) months. Among them, 12 patients occurred PAP who receive the conservative treatment. The rate of preoperative cervical instablility of PAP group were higher than that of non-PAP group( P <0.05). Preoperative cervical instability was the only independent risk factor in predicting occurrence of PAP. There were no significant differences in cervical curvature, cervical lordosis index, the motion of flexion and extension between PAP and non-PAP group before operation. There were no significant differences in the improvement of nerve function and clinical effect between PAP and non-PAP group after operation( P >0.05)., Conclusions: Preoperative cervical instability is prone to inducing the respectively intervertebral motion disorder and imbalance of stress redistribution, which results in PAP after cervical unilateral laminoplasty. Correct treatment of preoperative cervical instability is a key factor to prevent the occurrence of PAP after cervical laminoplasty, which would not affect long-term nerve functional recovery pronouncedly., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2018 by the China Journal of Orthopaedics and Traumatology Press.)

Ossification of the posterior longitudinal ligament (OPLL), ossification of the anterior longitudinal ligament (OALL), and ossification of the ligamentum flavum (OLF) sometimes are seen in the same patients, but the exact coexisting frequencies are not clear especially in the cervical region. The most frequent combination is OPLL and OALL. Cervical OPLL can coexist with thoracic OLF but is rarely associated with cervical OLF. All of these ossifying diseases of the cervical spinal ligaments are influenced by dynamic factors of the spinal column. The most frequent levels in the cervical spine affected by OPLL, OALL, and OLF are different because of anatomic differences inherent to each ligament., (Copyright © 2017 Elsevier Inc. All rights reserved.)

A 73-year-old man who presented with right lumbosciatic pain underwent a neurosurgical operation for a voluminous L2-L3 disc herniation, seen on conventional MRI images. No disc herniation was identified in the epidural space during the surgery. Just after the operation, the patient started to present pain in the left L3 territory and was not able to walk any more. A second MRI including three-dimensional (3D) high-resolution constructive interference in steady state (CISS) sequence showed that the voluminous L2-L3 disc split the posterior longitudinal ligament and the anterior dura mater, extended intradurally and compressed the cauda equina to the right. The patient underwent a second surgery, which permitted to cure the symptoms. 3D high-resolution CISS should be considered to accurately depict intradural disc herniation in order to optimally guide the surgical approach., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The mechanisms of late recurrent neurological deterioration after conservative treatment for acute traumatic central cord syndrome (ATCCS) remain unclear. Seventeen operative cases sustaining late recurrent neurological deterioration after conservative treatment for ATCCS were reviewed to investigate the mechanisms. The assessment of neurological status was based on International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). Gender, age, cause of injury, results of image, conservative treatment and operative data, and neurological status at different time points were recorded. The mean age of 17 patients was 43.8 ± 2.3 years old, and the causes of the cervical injury were 14 vehicle accidents and 3 falls. The neurological deficits of 17 patients on admission were not serious, and patients recovered quickly after conservative treatment. No fractures or dislocation were found in any patient's radiographs or CT scan images. All 17 patients performed first MRI test in 4 days and there was a slight or mild compression on the spinal cord in 16 patients. Eight patients had a second MRI scan ∼6 weeks later, which showed that there was aggravated compression on the spinal cord in six patients. All patients underwent an anterior approach to cervical decompression and internal fixation operation. During the operation, there were loose discs found in all 17 patients, obvious ruptures of disks found in 3 patients, obvious ruptures of anterior longitudinal ligaments (ALLs) found in 8 patients, and obvious ruptures of posterior longitudinal ligaments (PLLs) found in 7 patients. There was serious adhesion between PLLs and cervical disks in 12 patients. In five patients, partial ossification of PLLs was detected. All patients had a good neurological outcome at 6 month follow-up. Ruptures of ALLs, PLLs, and discs resulting in cervical instability and secondary compression on the spinal cord were important causes for recurrent neurological deterioration after conservative treatment for ATCCS. With timely spinal decompression after recurrent neurological deterioration, patients could achieve a good neurological outcome.

Objective To establish a three-dimensional (3D) finite element (FE) model of ankylosing spondylitis (AS) kyphosis that is a digital platform for further studies. Methods A 30-year-old man with AS kyphosis underwent computed tomography transverse scanning from T1 to the sacrococcyx. The images were imported into Mimics® 17.0 software to establish a 3D model of the posterior spine, which was then imported into Studio Geomagic 2013 software. Posterior spine convex geometry was established on the 3D geometric model for subsequent optimization of image processing. Unigraphics NX 8.5 produced the spinal kyphosis surface model. Modeled calcification of ligaments and partial resection of useless sacral bone were added. The model was imported into ANSYS 15.0 FE analysis software. Ligaments were added. Parameters were set to generate a 3D FE model of AS. Results and Conclusion A 3D FE model of AS was successfully established, providing a reliable digital platform for subsequent biomechanical analysis.

Study Design: A prospective clinical study of factors related to myelopathy deterioration caused by thoracic myelopathy because of ossification of the posterior longitudinal ligament (T-OPLL)., Objective: The objective of the study was to investigate factors related to myelopathy deterioration caused by T-OPLL., Summary of Background Data: Detailed analyses of factors related to myelopathy deterioration caused by T-OPLL have not been reported., Methods: Twenty-two patients (group O) received observation therapy because of the absence of or mild myelopathy, which was defined as walking unaided or with support, and a Japanese Orthopedic Association (JOA) score above 7 points; and 24 patients (group S) were treated with posterior decompression and fusion with instrumentation. Age, sex, body mass index (BMI), presence of diabetes mellitus (DM), and JOA score were obtained for all patients. Radiologically, the T-OPLL level, number of T-OPLLs, canal diameter ratio (CDR), morphology, ossification of the ligamentum flavum (OLF), and cervical OPLL were examined on reconstructed CT, and the presence of hyperintense areas (HIAs) on T2-weighted sagittal MR images., Results: In total, the patients included 22 males and 24 females and had an age range from 18 to 80 years. Sex, DM, JOA score in each domain, OPLL location, OPLL number, CDR of OPLL, morphology, OLF, and cervical OPLL did not differ significantly between groups N and S. However, cases in group N had a significantly higher age, lower weight, lower BMI, lower discontinuous rate on sagittal CT, and a lower HIA rate on MRI. Postoperatively, discontinuous segments connected and became continuous across the disc space in all patients in group S without progression of OPLL thickness., Conclusion: Age, weight, BMI, discontinuity between rostral and caudal OPLL lesions, and occurrence of a high intensity area on MRI are likely to be associated with development of myelopathy., Level of Evidence: 3.

Study Design: In vitro molecular research on the posterior longitudinal ligament fibroblasts., Objective: To investigate different expression of old astrocyte specifically induced substance (OASIS) between spinal ligament fibroblasts from the patients with ossification of the posterior longitudinal ligament (OPLL) and from non-OPLL patients and demonstrate knockdown of OASIS protein expression by RNA interference inhibiting expression of type I collagen (COL I) in OPLL cells., Summary of Background Data: OPLL is characterized by ectopic bone formation in spinal ligaments. Some evidence indicates that ligament fibroblasts from OPLL patients have osteogenic characteristics. However, the relevant intracellular signaling pathways remain unclear., Methods: Spinal ligament cells were cultured using tissue fragment cell culture and identified by immunocytochemistry and immunofluorescence. The mRNA expression of osteoblast-specific genes of osteocalcin, alkaline phosphatase, and COL I were detected in OPLL and non-OPLL cells by semiquantitative reverse transcription-polymerase chain reaction. The protein expression of OASIS was detected by Western blotting. And then, after 72 hours, when RNA interference against OASIS was performed in OPLL cells, expression of the osteoblast-specific genes was compared again between the transfection group and the nontransfection group., Results: Spinal ligament fibroblasts were observed 7 to 10 days after cell culture. Immunocytochemistry and immunofluorescence exhibited positive results of vimentin staining. The mRNA expressions of osteocalcin, alkaline phosphatase, and COL I and protein expressions of OASIS from OPLL cells were significantly greater than those from non-OPLL cells. In addition, knockdown of OASIS protein expression inhibited the mRNA expressions of COL I remarkably in the transfection group compared with the nontransfection group, at 72 hours after RNA interference targeting OASIS was performed in OPLL cells., Conclusions: The cultured fibroblasts from OPLL patients exhibited osteogenic characteristics, and OASIS expression plays an important role in the development of OPLL through the expression of COL I.

Study Design: Prospective cohort study., Objective: To investigate whether classification of increased signal intensity (ISI) on magnetic resonance imaging (MRI) of spinal cord in patients with cervical ossification of the posterior longitudinal ligament (C-OPLL) reflects severity of myelopathy and surgical outcome., Summary of Background Data: The relationship between classification of ISI on C-OPLL and severity is unknown., Methods: The 119 consecutive patients (91 men, 28 women) with C-OPLL who underwent surgery were enrolled. T2-weighted MRI was performed before surgery and ISI was classified into three groups as follows, Grade 0, none; Grade 1, light (obscure); and Grade 2, intense (bright). The severity of myelopathy and surgical outcome were evaluated by the Japanese Orthopedic Association score. To determine factors that influence ISI, the change of the spinal cord cross-sectional area (SCA) during flexion and extension was calculated by computed tomography after myelography., Results: The preoperative MRI showed 55 patients in Grade 0, 46 patients in Grade 1, and 18 patients in Grade 2. The preoperative Japanese Orthopedic Association score (Grade 0, 11.2; Grade 1, 10.3; Grade 2, 9.6 points) and surgical outcome got worsened with increasing ISI grade. The patients in Grade 2 had a longer duration of disease, while those in Grade 1 and Grade 2 had a larger change of SCA during flexion and extension (Grade 0, 4.8 mm; Grade 1, 7.3 mm; Grade 2, 7.8 mm). However age, alignment of the cervical spine, range of motion, and occupying ratio of the ossification were not different in the three grades., Conclusion: Grade of ISI correlated with preoperative severity of myelopathy and surgical outcome in patients with C-OPLL. Increased signal intensity of the spinal cord on MRI was associated with a larger change in SCA and longer duration of disease., Level of Evidence: 3.

Introduction: Approximately 1.5-2.5% of all patients treated due to discopathy have anterior longitudinal ligament lesions. An intervertebral disc moving under the anterior longitudinal ligament causes ligament displacement and irritation of the autonomic nervous system structures, resulting in a disturbed function of the organs controlled by this system. Clinical image: Increased sympathetic system activity in the thoracic section may cause symptoms that mimic coronary heart disease while irritation of the autonomic structures in the lumbosacral section of the spine results in a clinical presentation similar to that of gastrointestinal or gynecological disorders. The clinical image of the most common disorders is presented. The diagnosis may be formulated with the use of magnetic resonance imaging., Treatment: pharmacotherapy is ineffective. Physiotherapy and rehabilitation constitute a method of choice in the treatment of this syndrome.

Rationale: Hypertrophy of posterior longitudinal ligament (HPLL) at C1-2 level accompanied with lower cervical spinal stenosis is rare in clinic. No reports have described HPLL at C1-2 level accompanied with lower cervical spinal stenosis treated by posterior decompression, combined with internal fixation in 1 stage., Patient Concerns: A 70-year-old Chinese female complained of numbness and paralysis in both her hands and right leg for 1.5 years; Cervical vertebra x-rays and magnetic resonance imaging revealed a HPLL at C1-2 and cervical spinal stenosis at C3-6., Diagnoses: She was diagnosed with cervical spondylotic myelopathy (CSM)., Interventions: The patient underwent posterior decompression from C1 to C5 level, and fixed with C1-2 vertebral pedicle and C3-5 lateral mass of screw., Outcomes: One week after operation, the patient showed significant improvement in the numbness of her hands. A follow-up cervical vertebra computed tomography showed good location of internal fixation device and correction of cervical spinal stenosis. Twelve months after surgery, the patient showed improvement in preoperative clumsiness and gait disturbance, and no recurrence of the clinical symptoms occurred., Lessons: HPLL at C1-2 level accompanied with lower cervical spinal stenosis caused myelopathy is rare. Cervical posterior decompression and internal fixation is an effective treatment. The surgical outcome is satisfactory., Competing Interests: The authors have no conflicts of interest to disclose.

Ossification of the posterior longitudinal ligament (OPLL) involves ectopic calcification of the spinal ligament preferentially at the cervical spine. OPLL is associated with different diseases and occurs by endochondral ossification, which is associated with the activity of different transcription factors. However, the pathogenesis of OPLL remains unclear. Here, we investigated the role of osterix (Osx), a transcription factor that functions downstream of Runx2 and is an important regulator of osteogenesis, in the process of OPLL in a dexamethasone (Dex)-induced model of spinal ligament ossification. Our results showed that Osx is upregulated in patients with OPLL and during the ossification of ligament cells in parallel with the upregulation of osteogenic markers including osteocalcin (OCN), alkaline phosphatase (ALP) and collagen-1 (Col-1). Dex-induced ossification of ligament cells was associated with the downregulation and inactivation of β-catenin, and these effects were offset by Osx knockdown. Activation of β-catenin signaling abolished the effect of Dex on ossification and the upregulation of osteogenic markers. Taken together, our results suggest that OPLL is mediated by Osx via a mechanism involving the Wnt/β-catenin signaling pathway, providing a basis for further research to identify potential targets for the treatment of OPLL., (Copyright © 2016 Elsevier Inc. All rights reserved.)