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Background context Hypertrophy of the ligamentum flavum (LF) is a major contributor to the development of lumbar spinal canal stenosis (LSS). Although previous studies have identified some factors related to hypertrophy of the LF, the etiology remains unclear. It is well known that myofibroblasts have a key role in the pathology of fibrosis in other tissues, including the skin, liver, kidney, and lung. We hypothesized that myofibroblasts were also important players in the pathology of fibrosis in the LF. Purpose To elucidate the distribution and role of myofibroblasts in the hypertrophic LF. Study design A histological, immunohistochemical, and gene expression analysis of the LF in the human lumbar spine. Patient sample Hypertrophic LF tissue samples were collected from patients with LSS. Outcome Measures Histology, immunohistochemistry, microarray, reverse transcription-quantitative polymerase chain reaction, western blotting and enzyme-linked immunosorbent assay. Methods The degree of fibrosis in the dural and dorsal layers of the LF was evaluated by Masson's trichrome tissue staining. Collagen gene expression was evaluated by quantitative reverse transcription polymerase chain reaction. Immunostaining of αSMA was performed to evaluate localization of myofibroblasts in LF tissue. The association between gene expression of alpha-smooth muscle actin (αSMA) and that of several types of collagen was investigated. The signal activated on the dorsal side of LF was examined by gene set enrichment analysis using microarray data. Expression levels of αSMA and several types of collagen in LF fibroblasts were investigated under hypoxic conditions. Results In the histological study using Masson's trichrome staining, the fibrosis score was significantly higher in the dorsal layer than in the dural layer. Gene expression levels for several types of collagen (COL1A1, COL1A2, COL3A1, COL5A1, COL6A1, and COL11A1) and heat shock protein 47 (a collagen-specific chaperone) were significantly higher in the dorsal layer. Furthermore, immunohistochemistry revealed a significantly greater number of αSMA-stained cells in the dorsal layer. There was a strong correlation of αSMA mRNA expression with COL1A-1 in LF fibroblasts. Gene set enrichment analysis showed that the set of fibrosis-related gene signals, including those for epithelial-mesenchymal transition, hypoxia, and inflammation, were significantly upregulated in the dorsal layer compared with the dural layer. Under hypoxic stimulation, expression of αSMA and several types of collagen was increased in LF fibroblasts. Conclusions This study is the first to reveal that myofibroblast expression levels are higher in the dorsal layer of the LF than in the dural layer. We confirmed that hypertrophy of the LF in LSS is associated with increased expression of myofibroblasts in the dorsal layer. Hypoxia could be a cause of expression of myofibroblasts leading to fibrosis and finally to hypertrophy of the LF. Clinical significance The results of this study partially elucidate the molecular mechanisms of LF hypertrophy and suggest that myofibroblasts may be involved in age-related degeneration of the LF.

Purpose. Ligamentum flavum hypertrophy (HLF) is the most important component of lumbar spinal canal stenosis (LSCS). Analysis of hypertrophied ligamentum flavum (HLF) samples from patients with LSCS can be an important que. The current study analyzed the surgical samples of HLF samples in patients with LCSC using quantitative and qualitative high performance-liquid chromatography and mass spectrometry.Methods. We collected ligamentum flavum (LF) tissue from twelve patients with LSCS and from four patients with lumbar disk herniation (LDH). We defined LF from LSCS patients as HLF and that from LDH patients as non-hypertrophied ligamentum flavum (NHLF). Total lipids were extracted from the LF samples and evaluated for quantity and quality using liquid chromatography and mass spectrometry.Results. The total lipid amount of the HLF group was 3.6 times higher than that of the NHLF group. Phosphatidylcholines (PCs), ceramides (Cers), O-acyl-ω-hydroxy fatty acids (OAHFAs), and triglycerides (TGs) in the HLF group were more than 32 times higher than those of the NHLF group. PC(26:0)+H+, PC(25:0)+H+, and PC(23:0)+H+ increased in all patients in the HLF group compared to the NHLF group. The thickness of the LF correlated significantly with PC(26:0)+H+ in HLF. Conclusion. We identified the enriched specific PCs, Cers, OAHFAs, and TGs in HLF.

Introduction and Importance Neurological deterioration due to buckling of the ligamentum flavum (LF) is an uncommon complication after anterior cervical corpectomy or discectomy with fusion. Case Presentation In this report, we present the case of a 66-year-old male who underwent anterior cervical partial corpectomy of C5 and discectomy of prolapsed C5-C6 with fusion. Postsurgery, the patient displayed signs of neurological deterioration. Upon immediate cervical magnetic resonance imaging (MRI), posterior canal stenosis and severe compression with cord signal due to LF buckling were detected. A posterior laminectomy procedure and canal decompression at the C5-C6 level with bone fusion were performed. Clinical Discussion Patient presented with walking difficulty, then walking disability, followed by bilateral upper and lower limb paresthesia with burning sensation. Examination showed ⅘ muscle strength in both handgrips. Further investigation showed brisk deep tendon reflexes, positive Hoffman sign unilaterally, equivocal Babinski sign, and progressive quadriparesis. Magnetic resonance imaging showed mild and diffuse building of some cervical discs, with spinal cord progression. We performed an anterior cervical corpectomy and fusion (ACCF) and anterior cervical discectomy and fusion (ACDF); a titanium mesh with plates and screws was used for fusion, with removal of a calcified and herniated subligamentous disc. Postoperatively, upper and lower limb strength deteriorated; immediate cervical and thoracic MRI showed LF buckling, which caused canal stenosis and severe compression. Urgent posterior laminectomy and canal decompression with bone fusion was scheduled on the same day. The patient underwent physiotherapy and regained upper and lower limb strength and his ability to walk. Conclusion This indicates the possibility of neurological deterioration as a result of LF buckling, which may be a result of LF thickening accompanied by hyperextension in the cervical region. In this regard, immediate imaging following signs of neurological complications after anterior cervical corpectomy or discectomy warrants early detection, which results in a better prognosis.

Background This study aimed to assess the effects of anterior cervical discectomy and fusion (ACDF) on distraction of the posterior ligamentum flavum (LF) by increasing the intervertebral disc height and positioning a graft in patients with degenerative cervical spine disease. Methods Sixty-eight patients with degenerative cervical diseases who underwent single-level ACDF were included in the analysis. The intervertebral disc height, Cobb angle, and transverse thickness of the LF were measured, and magnetic resonance imaging was performed both preoperatively and 6 weeks postoperatively on each patient. Correlation analyses were performed to evaluate the relationships between age, sex, change in intervertebral disc height, Cobb angle, and position of the intervertebral implant according to the postoperative change in LF thickness. The position of the intervertebral implant was categorized as anterior, middle, or posterior. We also evaluated radiological effects according to the implant position. Results The mean intervertebral disc height increased from 5.88 mm preoperatively to 7.49 mm postoperatively. The Cobb angle was 0.88° preoperatively and 1.43° postoperatively. Age (p = 0.551), sex (p = 0.348), position of cage (p = 0.312), pre- and postoperative intervertebral disc height (p = 0.850, p = 0.900), Cobb angle (p = 0.977, p = 0.460), and LF thickness (p = 0.060, p = 1.00) were not related to changes in postoperative LF thickness. Postoperative increase in disc height was related to Cobb angle (r = 0.351, p = 0.038). No other factors were significantly related. The position of the cage was not related with the change of Cobb angle (p = 0.91), LF thickness (p = 0.31), or disc height (p = 0.54). Conclusions Change in the intervertebral disc height and the position of the intervertebral implant after ACDF did not affect the thickness of the LF after surgery in patients with degenerative cervical spine disease.

Background and objectivesThe ‘loss of resistance’ technique is used to determine entry into the epidural space, often by a midline needle in the interspinous ligament before the ligamentum flavum. Anatomical explanations for loss of resistance without entry into the epidural space are lacking. This investigation aimed to improve morphometric characterization of the lumbar interspinous ligament by observation and measurement at dissection and from MRI.MethodsMeasurements were made on 14 embalmed donor lumbar spines (T12 to S1) imaged with MRI and then dissected along a tilted axial plane aligned with the lumbar interspace.ResultsIn 73 interspaces, median (IQR) lumbar interspinous plus supraspinous ligament length was 29.7 mm (25.5–33.4). Posterior width was 9.2 mm (7.7, 11.9), with narrowing in the middle (4.5 mm (3.0, 6.8)) and an anterior width of 7.3 mm (5.7, 9.8).Fat-filled gaps were present within 55 (75%). Of 51 anterior gaps, 49 (67%) were related to the ligamenta flava junction. Median (IQR) gap length and width were 3.5 mm (2.5, 5.1) and 1.1 mm (0.9, 1.7).Detection of gaps with MRI had 100% sensitivity (95% CI 93.5 to 100), 94.4% specificity (72.7, 99.9), 98.2% (90.4, 100) positive predictive value and 100% (80.5, 100) negative predictive value against dissection as the gold standard.ConclusionsThe lumbar interspinous ligament plus supraspinous ligament are biconcave axially. It commonly has fat-filled gaps, particularly anteriorly. These anatomical features may form the anatomical basis for false or equivocal loss of resistance.

The ligamentum flavum (LF), the inter- and supraspinous ligament (ISLSSL) and the intertransverse ligament (ITL) are relevant spinal structures for segmental stability. The biomechanical effect of degeneration and aging on their biomechanical properties remains largely unknown.The aim of this study was to assess the material properties of the ITL, ISLSSL and LF and to correlate parameters of biomechanical function with LF-thickness, intervertebral disc (IVD) degeneration and age.Biomechanical cadaveric study.MRI- and CT-scans of 50 human lumbar segments (Th12-L5) were used to assess the ISL (acc. to Keorochana), the grade of IVD degeneration (acc. to Pfirrmann) and to quantify LF-thickness. The ITL, ISLSSL and LF were resected in the neutral position of the spinal segment with a specifically developed method to conserve initial strain. Ramp to failure testing was performed (0.5 mm/s) to record initial tension, slack length, stiffness and ultimate strength. The relationship between the biomechanical characteristics and age and radiological parameters were analyzed. There are no study-specific conflicts of interest and no external funding was received for this study.With aging, a significant reduction in initial tension (r=-0.5, p.01) and ultimate strength (r=-0.41, p.01) of the LF was observed, while the effect on LF-stiffness and the characteristics of the other ligaments was non-significant. IVD-degeneration was correlated with a significant reduction in stiffness (r=-0.47, p=.001; r=-0.36, p=.01) and ultimate strength (r=-0.3, p=.04; r=-0.36, p=.01) of the LF and ISLSSL respectively and a significant reduction in initial tension (r=-0.4, p.01) of the LF. For the ITL, no significant correlation was observed. Comparing Pfirrman 2 to 5, this reduction was 40% to 80% for stiffness 60% to 70% for ultimate strength and 88% for initial tension of the LF. ISLSSL-stiffness between Kerorochana grade A and D differed significantly (p=.03), while all other comparisons were non-significant (p.05). LF-thickness did not correlate with the biomechanical properties of the LF (p.05).Aging is primarily related to biomechanical changes to the LF. IVD-degeneration is related to a relevant reduction in stiffness and ultimate strength of the LF and ISLSSL, with a similar trend for the ITL. The ISL-specific Keorochana grading system provides only minimal biomechanical information and LF-thickness does not provide biomechanical information.Patient age and the degenerative state of the IVD can be used to evaluate the biomechanical characteristics of the dorsal spinal ligaments, which can be helpful in selecting the optimal surgical procedure (e.g. in decompression surgery) for a specific situation.

Age-related cardiac amyloidosis results from deposits of wild-type tranthyretin amyloid (ATTRwt) in cardiac tissue. ATTR may play a role in carpal tunnel syndrome (CTS) and in spinal stenosis (SS), indicating or presaging systemic amyloidosis. We investigated consecutive patients undergoing surgery for SS for ATTR deposition in the resected ligamentum flavum (LF) and concomitant risk of cardiac amyloidosis. Each surgical specimen (LF) was stained with Congo red, and if positive, the amyloid deposits were typed by mass spectrometry. Patients with positive specimens underwent standard of care evaluation with fat pad aspirates, serum and urine protein electrophoresis with immunofixation, free light-chain assay

BACKGROUND CONTEXT Ligamentum flavum (LF) hypertrophy plays a dominant role in lumbar spinal stenosis (LSS). A previous study found that fibroblast growth factor 9 (FGF9) was upregulated with mechanical stress in rabbit LF. However, the expression and function of FGF9 are not well understood in human LF. PURPOSE To evaluate FGF9 expression and function in human LF with and without hypertrophy. STUDY DESIGN This study employed a basic research study design utilizing human LF tissue for histological analyses. PATIENT SAMPLES Hypertrophied LF tissue sample from patients with LSS, and nonhypertrophied (control) LFs from patients with lumbar disc herniation or other diseases were obtained during surgery. METHODS LF specimens were histologically analyzed for FGF9 and vascular endothelial growth factor A (VEGF-A) by immunohistochemistry. The number of total and FGF9 immuno-positive cells and blood vessels were counted and compared between LF with and without hypertrophy. For functional analysis, the effect of FGF9 on cell proliferation and migration was examined using a primary cell culture of human LF. RESULTS Histological studies revealed that the total cell number was significantly higher in the LF of patients with LSS than in the LF of control patients. Immunohistochemistry showed that the percentage of FGF9-positive cells was significantly higher in the LF of patients with LSS than in the controls, and it positively correlated with patients’ age, regardless of disease. Double immune-positive cells for FGF9 and VEGF-A were often observed in vascular endothelial cells and fibroblasts in the fibrotic area of hypertrophied LF, and the number of double positive vessels was significantly higher in LF of LSS patients than in the LF of controls. Primary cell culture of human LF revealed that FGF9 promoted the proliferation and migration of LF cells. CONCLUSION The present study demonstrated that FGF9 expression is highly upregulated in hypertrophied human LF. FGF9 potentially plays a pivotal role in the process of hypertrophy of LF, which is associated with mechanical stress, through cell proliferation and migration. CLINICAL SIGNIFICANCE The results from this study partially reveal the molecular mechanisms of LF hypertrophy and suggest that FGF9 may be involved in the process of LF degeneration in elderly patients.

Study design Western blot, reverse transcription-polymerase chain reaction (RT-PCR), radiological, and histological analyses of the rat ossification of ligamentum flavum (OLF) induced by cyclic tensile stress. Objective The aim of this study was to induce the OLF using cyclic tensile stress to rat thoracolumbar ligamentum flavum, and to investigate the possible molecular mechanism of tension-induced OLF. Summary of background data Tensile stress has been considered as an important factor leading to the OLF. So far, however, no OLF induced by tension has been reported. Methods Forty rats were randomly divided into five equal groups. For control groups, the blank and anesthesia groups were not subjected to tension. For experimental groups, the 4-, 8-, and 12-week groups were subjected to cyclic tensile stress of ligamentum flavum after abdominal anesthesia for 4 weeks, 8 weeks, and 12 weeks, respectively, using an original stress apparatus for rats. The radiological and morphological changes of rat spine, as well as the protein and mRNA expressions of CD44, bone morphogenetic protein-2 (BMP-2), integrin β3, collagen protein type I (COL1), osteopontin (OPN), runt-related transcription factor 2 (RUNX-2), and vascular endothelial growth factor (VEGF), were concerned. Results The micro-CT showed OLF in the 4-, 8-, and 12-week group. The axial maximum occupied area of ossifications was 1.42 mm2, 3.35 mm2, and 7.28 mm2, respectively. In histopathology, chondrocytes proliferated in the experimental model; woven bone arose in the 8- and 12-week groups, and was more noticeable in the 12-week group. According to western blot and RT-PCR, the expressions of seven osteogenesis-related molecules were all increased in three experimental groups. Conclusion Cyclic tensile stress to the ligamentum flavum in rats can induce the OLF, and the longer the duration, the more visible the osteogenesis. The upregulation and synergism of osteogenesis-related molecules may contribute to the OLF induced by tensile stress.Level of Evidence: N/A.

Purpose Cervical ossification of ligamentum flavum (COLF) is a rare clinical entity which can occasionally contribute to severe myeloradiculopathy. Many orthopedists are unfamiliar with or underestimate this pathology. Therefore, a comprehensive research is obligatory to reappraise the epidemiological, radiological, clinical and histopathological characteristics of COLF-myeloradiculopathy based on synthesis of individual patient data. Methods Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, PubMed, EMBASE, Scopus and Web of Science databases were searched for studies discussing COLF-myeloradiculopathy from the inception to December 2020. Results A total of 94 cases from 54 studies were identified. The annual publications demonstrated a steady increase, and most reports were from Japan and China. The mean age was 58.76±13.39 years and nearly 60% of cases occurred in the 55-64 and 65-74 years age group. The male-female ratio was 1.4:1. Most cases belonged to East Asian population (60.64%). COLF predominately appeared in the lower cervical and cervicothoracic spine (76.60%) and mainly affected C4-5 (23.29%) and C5-6 (21.23%). Single-segment type ossification accounted for 62.76 and 45.45% of ossification lesions distributed bilaterally. The majority of COLF (81.1%) were spontaneous, and motor disturbance (76.4%), spinal ataxia (62.5%) and sensory disturbance (58.9%) were the most common manifestations. Histopathologically, it's a metaplastic process of endochondral ossification with the formation of mature lamellar bone which was distinguished from calcification of ligamentum flavum. About 21.28% of concurrent COLF and COPLL cases were identified as a separated group, with unique characteristics. Conclusion COLF is an underappreciated but potentially growing pathogeny of myeloradiculopathy in aging population, though its distinct epidemiological, radiological, clinical and histopathological features are not fully supported by current evidence. However, our findings will provide several referential data for future researches to shed light on COLF.

Objective The aim of the present study was to ascertain the independent risk factors of poor preliminary outcome and to reveal the value of these factors in predicting the postoperative prognosis. Methods A total of 165 patients diagnosed with thoracic myelopathy because of thoracic ossification of the ligamentum flavum (TOLF) were enrolled in this retrospective study. All of them underwent posterior decompressive laminectomy surgery in our hospital from May 2016 to June 2019. The postoperative improvement of symptoms was evaluated using the modified Japanese Orthopaedic Association (mJOA) scoring system. Clinical data, such as age, sex, body mass index (BMI), duration of symptoms, history of hypertension and diabetes, tobacco use, history of drinking, symptoms of incontinence, number of compressed segments, and preoperative mJOA score, were respectively recorded. Radiologic features data included sagittal maximum spinal cord compression (MSCC), axial spinal canal occupation ratio (SCOR), grades and extension of increased signal on sagittal T2‐weighted images (ISST2I), types of increased signal on axial T2‐weighted images (ISAT2I), and the classification of ossification on axial CT scan and sagittal MRI. The t‐test, the χ2‐test, Fisher's exact test, binary logistic regression analyses, receiver operating characteristic (ROC) curves, and subgroup analyses were used to evaluate the effects of individual risk predictors on surgical outcomes. Results A total of 76 men and 89 women were enrolled in this study. The mean age of all patients was 58.53 years. After comparison between two groups, we found some risk factors that may be associated with postoperative outcomes, such as age, preoperative mJOA score, BMI, history of hypertension, MSCC, SCOR, grade and extension of ISST2I, type of ISAT2I, axial type of ossification, and sagittal type of ossification (P, In the present study, four independent risk factors (age, grade of ISST2I, types of ossification on axial CT scan, and number of compressed segments) were identified to be associated with poor preliminary postoperative outcome for TOLF. The obscure and bright intramedullary increased signal intensity on sagittal T2‐weighted MRI had the best predictive ability (AUC = 0.817). In addition, risk factors have different values for predicting the clinical outcome in each subgroup.

Spinal cord herniation (SCH) is a rare condition associated with tethering of the spinal cord at the ventral dural defect. Idiopathic dorsal spinal cord herniation (IDSCH) is an extremely rare clinical entity. Here, we report the first case of IDSCH perforating the lamina in a patient with a history of ossification of the ligamentum flavum and diffuse idiopathic skeletal hyperostosis. Untethering of the spinal cord was performed by removing the surrounded ossified dura. Although urological symptoms and impaired proprioception remained, progressive neurological deterioration was prevented. Because this disease condition is extremely rare, it should be differentiated from ventral SCH.

STUDY DESIGN Sequencing and experimental analysis of the expression profile of circular RNAs (circRNAs) in hypertrophic ligamentum flavum (LFH). OBJECTIVES The aim of this study was to identify differentially expressed circRNAs between LFH and nonhypertrophic ligamentum flavum tissues from lumbar spinal stenosis (LSS) patients. SUMMARY OF BACKGROUND DATA Hypertrophy of the ligamentum flavum (LF) can cause LSS. circRNAs are important in various diseases. However, no circRNA expression patterns related to LF hypertrophy have been reported. METHODS A total of 33 patients with LSS participated in this study. LF tissue samples were obtained when patients underwent decompressive laminectomy during surgery. The expression profile of circRNAs was analyzed by transcriptome high-throughput sequencing and validated with quantitative real-time polymerase chain reaction (PCR). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed for the differentially expressed circRNA-associated genes and related pathways. The connections between circRNAs and microRNAs were explored using Cytoscape. The role of hsa_circ_0052318 on LF cell fibrosis was assessed by analyzing the expression of collagen I and collagen III. RESULTS The results showed that 2439 circRNAs of 4025 were differentially expressed between the LFH and nonhypertrophic ligamentum flavum tissues, including 1276 upregulated and 1163 downregulated circRNAs. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that these differentially expressed circRNAs functioned in biological processes, cellular components, and molecular functions. Autophagy and mammalian target of rapamycin were the top two signaling pathways affected by these circRNAs. Five circRNAs (hsa_circ_0021604, hsa_circ_0025489, hsa_circ_0002599, hsa_circ_0052318, and hsa_circ_0003609) were confirmed by quantitative real-time PCR. The network indicated a strong relationship between circRNAs and miRNAs. Furthermore, hsa_circ_0052318 overexpression decreased mRNA and protein expression of collagen I and III in LF cells from LFH tissues. CONCLUSION This study identified circRNA expression profiles characteristic of hypertrophied LF in LSS patients, and demonstrated that hsa_circ_0052318 may play an important role in the pathogenesis of LF hypertrophy.Level of Evidence: N/A.

Wild-type transthyretin (ATTRwt) amyloid deposits have been found in the ligamentum flavum of patients undergoing surgery for spinal stenosis. The relationship between ATTRwt and ligamentum flavum thickness is unclear. We used pre-operative magnetic resonance imaging (MRI) to analyze ligamentum flavum thickness in lumbar spinal stenosis patients with and without ATTRwt amyloid.We retrospectively identified 178 patients who underwent lumbar spine surgery. Ligamentum flavum thickness of 253 specimens was measured on T2-weighted axial MRI. Amyloid presence was confirmed through Congo red staining of specimens, and ATTRwt was confirmed using mass-spectrometry and gene sequencing.Twenty four of the 178 patients (13.5%) were found to have ATTRwt in the ligamentum flavum. Forty ATTRwt specimens and 213 non-ATTRwt specimens were measured. Mean ligamentum flavum thickness was 4.92 (±1.27) mm in the ATTRwt group and 4.00 (±1.21) mm in the non-ATTRwt group (p 0.01). The ligamentum flavum was thickest at L4-L5, with a thickness of 5.15 (±1.27) mm and 4.23 (±1.29) mm in the ATTRwt and non-ATTRwt group, respectively (p = 0.007). There was a significant difference in ligamentum flavum thickness between ATTRwt and non-ATTRwt case for both patients younger than 70 years (p = 0.016) and those older than 70 years (p = 0.004). ATTRwt patients had greater ligamentum flavum thickness by 0.83 mm (95% confidence interval (CI): 0.41-1.25 mm, p 0.001) when controlled for age and lumbar level.Patients with ATTRwt had thicker ligamentum flavum compared to patients without ATTRwt. Further studies are needed to investigate the pathophysiology of ATTRwt in ligamentum flavum thickening.

Objective This report analyzes the significance of osteophytes in the overall pathologic scheme in patients with single-level or multilevel cervical spinal degeneration. Methods From January 2010 to December 2018, 249 patients with cervical spondylosis were surgically treated. The alterations in ventral compression caused by disc bulges, osteophytes, and ligament buckling (disc-osteophye-ligament [DOL] complex) at single or multiple levels were evaluated after surgical treatment that involved only spinal fixation and did not involve any kind of bone or soft tissue decompression. Delayed (≥1 year after surgery) postoperative imaging was available in 165 patients and these patients formed the study group. Forty-five patients underwent facet distraction arthrodesis (group A), 106 patients underwent only-fixation involving transarticular screw insertion (group B), and 14 patients underwent hybrid fixation that involved both intra-articular spacers and transarticular fixation techniques (group C) as the surgical treatment. Results The size of the DOL complex at the segments that underwent fixation was reduced in 136 patients. The size of the DOL complex or its related dural or neural compression did not increase in any of the cases evaluated. Reduction in the size of DOL was more pronounced in patients in group A in both immediate postoperative and delayed images and in patients in group C at spinal levels at which facet distraction was performed using facet distraction spacers. Conclusions Spinal stabilization reduces the size of osteophytes. Facet distraction spacers are more effective in reduction of the size of DOL in both immediate and delayed postoperative periods.

Parathyroid hormone receptors PTH1R and PTH2R are poorly studied in the pathology of the vertebral column and may be involved in both ectopic ossification of the vertebral ligaments and fibrous growth of the extracellular matrix, as well as in other unknown processes occurring in the pathological focus. Aim . To study the expression of genes encoding parathyroid hormone receptors in intraoperative Ligamentum flavum samples of patients with stenosis of the spinal canal and the lumbar dural sac of the spine and to assess the correlation with the expression of other genes active in connective tissue in conditions of developing pathology. Materials and methods. Studies of the Ligamentum flavum were performed in 33 patients (17 women, 16 men) with stenotic processes of the spinal canal and dural sac of the lumbar spine. RNA was isolated from the biopsies using Qiagen reagents (Germany). Then reverse transcription was performed. cDNA was used for setting up a polymerase chain reaction (Promega Reagents, USA) using a CFX96 thermal cycler (Biorad, USA) with specially selected specific primers. Results. The expression of genes encoding parathyroid hormone receptors PTH1R and PTH2R was detected and evaluated for the first time in intraoperative Ligamentum flavum samples of patients with spinal canal and dural sac stenosis, and their relationship with the activity of genes encoding estradiol receptors (ESR1 and ESR2) and FGFR3 was revealed. For the first time, common features of PTH1R and PTH2R gene expression, as well as their differences, were revealed. It is proved that the intensity of expression of parathyroid hormone receptors in intraoperative Ligamentum flavum biopsies does not depend on age, gender, or the presence of bone and cartilage nodes according to MRI results. The interdependence of differential changes in the expression of genes of the receptor apparatus involved in the metabolism of Ligamentum flavum tissues was revealed.

Thoracic ossification of the ligamentum flavum (OLF) is a pathological condition that causes myelopathy, with unilateral lower extremity pain rarely a feature in the presenting complaint. Moreover, most symptomatic cases of thoracic OLF occur in middle-aged men, with younger individuals rarely affected. We present a rare case of severe and chronic unilateral buttock and leg pain mimicking sciatica due to thoracic OLF in a professional baseball pitcher. A 28-year-old, right-handed, Japanese professional baseball pitcher experienced intractable left leg pain with numbness and spasticity. After the initial presentation, extensive testing focusing on lumbar, hip, and pelvis lesions failed to identify a cause for the pain. One year after onset, careful neurological examination showed signs of upper motor neuron disturbance, and thoracic computed tomography and magnetic resonance imaging revealed thoracic OLF at the level of the thoracolumbar junction. After resection of the thoracic OLF, the pain, numbness, and spasticity completely resolved. He resumed full training and was pitching in top condition within four months after surgery. Though rare, thoracic OLF should be considered in the differential diagnosis of lower extremity pain in young athletes, especially amongst high-level baseball pitchers.

Pseudogout, also known as calcium pyrophosphate deposition disease, is an inflammatory arthropathy that primarily occurs in the peripheral joints, such as the knee or elbow. Spinal pseudogout is uncommon, and neck pain is its most common clinical manifestation. However, cervical myeloradiculopathy as an initial presentation of pseudogout attack of the ligamentum flavum has rarely been reported in the literature. We report a case of a 65-year-old woman who presented with neck pain, bilateral finger numbness, and left-sided upper extremity weakness. Magnetic resonance images showed an epidural mass at the C4-5 level, compressing the spinal cord. Following laminectomy with removal of the calcified mass, the profound neurologic deficits gradually recovered. A pathological examination confirmed the diagnosis of cervical pseudogout.

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.

Study design Experimental animal study. Objective The aim of this study was to clarify chronological effects of mechanical stress on ligamentum flavum (LF) using a long-term fusion rabbit model. Summary of background data LF hypertrophy is a major pathology of lumbar spinal stenosis (LSS), but its mechanism remains unclear. We previously demonstrated mechanical-stress-induced LF hypertrophy with a rabbit model. However, we only investigated LFs at a single time point in the short-term; the effects of long-term mechanical stress have not been elucidated. Methods Eighteen-week-old male New Zealand White rabbits were randomly divided into two groups: the mechanical stress group underwent L2-3 and L4-5 posterolateral fusion and resection of the L3-4 supraspinal muscle, whereas the control group underwent only surgical exposure. Rabbits were sacrificed 16 and 52 weeks after the procedure. Axial specimens of LFs at L3-4 were evaluated histologically. Immunohistochemistry for alpha-smooth muscle actin (α-SMA) was performed to assess the numbers of vessels and myofibroblasts. Results In the mechanical stress group, LFs at the L3-4 level exhibited hypertrophy with elastic fiber disruption and cartilage matrix production at 16 and 52 weeks. A trend test indicated that mechanical stress induced LF hypertrophy, elastic fiber disruption, and cartilage matrix production in a time-dependent manner, with the lowest levels before treatment and the highest at 52 weeks. Immunostaining for α-SMA showed similar numbers of vessels in both groups, whereas the percentage of myofibroblasts was significantly larger at 16 and 52 weeks in the mechanical stress group than in the control group. Conclusion We demonstrated that long-term mechanical stress caused LF hypertrophy with progressive elastic fiber disruption and cartilage matrix production accompanied by enhanced myofibroblasts. In addition, the reported rabbit model could be extended to elucidate the mechanism of LF hypertrophy and to develop new therapeutic strategies for LSS by preventing LF hypertrophy.Level of Evidence: SSSSS.

Study Design: Human ligamentum flavum–derived cells (HFCs) were obtained from surgical samples for a basic experimental study.Purpose: We sought to evaluate the inflammatory response of human ligamentum flavum cells to investigate hypertrophic changes occurring in the ligamentum flavum.Overview of Literature: Lumbar spinal stenosis (LSS) is a disease commonly observed in the elderly. The number of patients with LSS has increased over time, yet the pathomechanisms of LSS still have not been fully elucidated. One of the clinical features of LSS is hypertrophy of the ligamentum flavum, which results in narrowing of the lumbar spinal canal. Some reports have suggested that ligamentum flavum hypertrophy is associated with inflammation and fibrosis; meanwhile, the p38 mitogen-activated protein (MAP) kinase is involved in the hypertrophy of human ligamentum flavum cells.Methods: HFCs were obtained from patients with LSS who underwent surgery. HFCs were stimulated by tumor necrosis factor-α (TNF-α) and a p38 MAP kinase inhibitor, SB203580. Phosphorylation of the p38 MAP kinase was analyzed by western blotting. The concentration of interleukin-6 (IL-6) in the conditioned medium was measured by enzyme-linked immunoassay and IL-6 messenger RNA expression levels were determined by real-time polymerase chain reaction.Results: TNF-α induced the phosphorylation of p38 MAP kinase in a time-dependent manner, which was suppressed by the p38 MAP kinase inhibitor, SB203580. TNF-α also stimulated IL-6 release in both a time- and dose-dependent manner. On its own, SB203580 did not stimulate IL-6 secretion from HFCs; however, it dramatically suppressed the degree of IL-6 release stimulated by TNF-α from HFCs.Conclusions: This is the first report suggesting that TNF-α stimulates the gene expression and protein secretion of IL-6 via p38 MAP kinase in HFCs. A noted association between tissue hypertrophy and inflammation suggests that the p38 MAP kinase inflammatory pathway may be a therapeutic molecular target for LSS.

STUDY DESIGN Retrospective case-control study. OBJECTIVE The aim of this study was to describe and compare the sagittal spinal alignment between patients with and without the ossification of the ligamentum flavum in the thoracic spine (TOLF). SUMMARY OF BACKGROUND DATA Although mechanical factors play an important role in the development of TOLF, limited evidence exists on the association of sagittal spinal alignment and TOLF in the literature. METHODS The present study assessed the preoperative sagittal alignment parameters in consecutive patients who underwent posterior decompression for TOLF in a single institution between January 2014 and December 2019. The sagittal parameters of the patients with TOLF were compared to those of the age- and sex-matched control group with lumbar spondylosis. RESULTS The TOLF group (n = 43 [23 men, 20 women]), with a mean age of 69.5 (range: 41-86) years, and the control group (n = 86) were compared. The TOLF group had a significantly smaller sacral slope (27.60 ± 7.49 vs. 30.61 ± 8.15, P = 0.045) and lumbar lordosis (36.84 ± 13.63 vs. 45.08 ± 9.90, P

O-arm computer navigation-assisted technology (OACNAT) has been widely used in the treatment of thoracic ossification of ligamentum flavum (TOLF) in recent years, but there are few in-depth studies on the safety and effectiveness of this approach. The purpose of this study was to investigate the clinical effect of accurate surgical treatment for TOLF with OACNAT.From January 2010 to January 2018, the clinical data of 64 patients with TOLF who underwent laminectomy and internal fixation in the Third Hospital of Hebei Medical University were retrospectively reviewed. The patients were divided into group A (with OACNAT, n = 33) and group B (without OACNAT, n = 31) according to the application of OACNAT during the operation. The possible operation-related variables, imaging results, and clinical effects were compared between the 2 groups.In terms of demographics, there were no significant differences between group A and group B in age, sex, body mass index, smoking, drinking, heart disease, hypertension and diabetes (P0.05). In terms of operation-related variables, imaging results, and clinical efficacy, there were significant differences in operation time, wound length, postoperative modified Japanese Orthopaedic Association (JOA) score, JOA score improvement rate, accuracy of screw placement, number of intraoperative fluoroscopy procedures, and cerebrospinal fluid leakage between group A and group B (P0.05). There were no significant differences in other variables between the 2 groups (P0.05). In contrast to group A, in group B, 2 patients had incorrect segmental localization, 3 patients had residual ossified ligamentum flavum after the operation, and 1 patient had postoperative neurologic impairment. On further analysis, compared with group B, group A had a shorter operation time, more accurate screw placement, fewer fluoroscopy procedures, higher JOA score improvement rate, and lower incidence of complications.The use of OACNAT accurately located the position, size, shape, and boundary of ossification of the ligamentum flavum during the operation, which could guide accurate decompression and improve the accuracy of pedicle screw placement. This approach not only reduced the incidence of incorrect segmental localization and incomplete or excessive decompression but also reduced the risk of related complications and improved the accuracy, safety, and effectiveness of the operation.

Study design Technical case report. Objective To describe a novel technique of decompression through single-stage mini-thoracotomy for removing concurrent ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF) at the same thoracic level simultaneously. Summary of background data Concurrent OPLL and OLF at the same thoracic level is not common. Because these conditions lead to severe thoracic myelopathy, however, they require surgical decompression.To date, several cases with concurrent OPLL and OLF at the same thoracic level and surgical methods to treat these conditions have been described. However, no consensus on the surgical methods for the treatment these conditions has been established and these surgical methods have been also reported to be linked with the incidence of complication like neurological deterioration and the requirement of bone grafting and instrumentation. Methods Three consecutive patients who presented with thoracic myelopathy caused by concurrent OPLL and OLF at the same thoracic level were treated by our novel surgical technique of decompression through single-stage mini-thoracotomy. Results Simultaneous complete removal of OPLL and OLF through single-stage mini-thoracotomy was performed successfully in the three patients. All patients' preoperative symptoms gradually improved during the follow-up period, and no additional complications were associated with removal of OLF through thoracotomy. And there was no kyphotic change or instability in the thoracic spine after more than a year of follow-up although both bone grafting and instrumentation were not performed. Conclusion This novel surgical technique is considered to be able to be a safe and effective alternative to the conventional treatment of selective cases of thoracic myelopathy caused by concurrent OPLL and OLF at the same thoracic level.Level of Evidence: 4.

Objective To study the distribution of sympathetic nerves of the ligamentum flavum (LF), confirm its existence by histological observation and nuclear magnetic resonance spectroscopy, and analyze the relationship between sympathetic nerve fibers and the biomechanical structure of the LF. Methods Randomly controlled scientific research selected 15 cases of posterior surgery in the affiliated hospital of Qingdao University from January 2013 to December 2019. The average age was 67.5 ± 14.5 years old, eight males and seven females. The LF specimens (completely separated fresh tissue) of different segments (C3‐7) were taken during the operation. Two pages of LF specimens on the left and right sides of the same segment are randomly allocated by the pairing method for formalin fixation and cryopreservation in liquid nitrogen. LF specimens extracted from seven other adult cadaver specimens (average age at death of about 56.8 ± 4.0 years, three males and four females) were used as a control group; together with formalin‐ fixed specimens obtained during surgery, 3D slices were given layer by layer. The distribution of sympathetic nerves in different parts of the LF was analyzed by glyoxylic acid‐induced biological monoamine fluorescent technique (SPG) and hematoxylin–eosin (HE) staining. Fifteen liquid nitrogen storage specimens were divided into the back of the LF and the spinal canal through frozen sections, and were analyzed by nuclear magnetic resonance spectroscopy‐hydrogen spectrum (1H ‐NMR) for neurotransmitters and neurometabolites. Results There were type C sympathetic nerve fibers in the LF, which were divided into linear shape (α) and wave shape (β). Experimental group (χ2 = 1.705, P > 0.05) and control group (χ2 = 0.879, P > 0.05) can detect no difference in fluorescence units. Nerve fiber transmitter metabolites choline (Cho), creator (Cr), γ‐aminobutyric acid (GABA) also indicate that the sympathetic nerve is present in the LF. LF sympathetic nerve fibers were mainly distributed in the proximal spinal canal surface, nerve fibers on the medial belt (area II) were fewer than the lateral belt (area I) (W = 210, P, Sympathetic nerve fibers distributed on ligamentum flavum. Their distribution may be correlated with histological and mechanical characteristics of ligamentum flavum. It may also be the anatomical basis of cervical vertigo.

Background Wild-type transthyretin amyloid (ATTRwt) has been noted to deposit in the ligamentum flavum of the spine. Prior studies have focused on ATTRwt in the lumbar region, but studies discussing its presence in other levels of the spine are lacking. We report on the presentation of patients with confirmed amyloid in the cervicothoracic regions and discuss the literature to date. Methods We retrospectively identified patients at a single institution who underwent surgery for spinal stenosis and had pathologic specimens sent for amyloidosis testing with Congo red staining. ATTRwt was confirmed by the presence of transthyretin amyloid by typing and the absence of mutations in the TTR gene sequence. A final study group of patients with ATTRwt and spinal involvement was established (n = 27). Results Of 27 patients with amyloid in the spine, 24 (89%) had amyloid present in the lumbar region, 2 (7%) had amyloid in the cervical region, and 1 (4%) had amyloid in the thoracic region. The median age at which patients in the study underwent surgery was 71 years (interquartile range: 9). Spinal stenosis was the indication for surgery in 26 of 27 (96%) patients. Surgery involved 1 or 2 spinal levels in 24 of 27 (89%) patients. Conclusions ATTRwt amyloid predominantly deposits in the lumbar region, but it can also be present in the cervical and thoracic regions. While the lumbar regions should remain a focus for evaluation of ATTRwt amyloidosis, the cervicothoracic region should not be ignored.

Objective A prospective, randomized, controlled clinical study was conducted with surgery performed by the same surgeon. The aim was to present a new technique for preserving the ligament flavum during lumbar microdiscectomy, and to evaluate whether this helps prevent postoperative fibrosis and improve outcome. Methods From January to December 2017, 251 patients with indication for microdiscectomy were randomly divided into test group using ligament flavum preservation technique and control group using conventional procedures. Visual analogue scale (VAS) scores and Oswestry Disability Index (ODI) were assessed before the surgery, and 3 days, 1 month, 6 months, 1 year and 2 years after the operation respectively. The grade of epidural fibrosis on MRI after 6 months was evaluated by two radiologists independently and double-blindly. Results Both groups’ VAS and ODI were significantly improved after surgery, but there was no significant difference between two groups at 3d and 1 month after operation. The grade of epidural fibrosis in test group was significantly lower than that in control group at 6 months postoperative. The VAS and ODI were significantly lower in test group than that in control group at 6 months,1 year and 2 years after operation. Conclusion Preservation of more ligament flavum is practicable during the procedure of microdiscectomy. It can prevent postoperative epidural fibrosis, and is helpful to achieve a better clinical outcome.

Ossification of the posterior longitudinal ligament (OPLL) and ligamentum flavum (OLF) are not uncommon independent causes of thoracic myelopathy (TM); however, concomitant OPLL and OLF at the same segment is rare. The ideal surgical strategy remains controversial, and it is difficult for surgeons to balance sufficient neural decompression while simultaneously reducing the occurrence of postoperative neurological defect after circumferential decompression (CD). Aiming to solve this dilemma, we investigated a CD-based surgery using intraoperative ultrasound (IOU) assistance to evaluate spinal decompression sufficiency.The aims of this study are to evaluate the surgical outcomes and identify prognostic factors of one-stage posterior surgery with IOU assistance in patients with concomitant OPLL and OLF.Retrospective study of a single-center TM database with long-term follow-up.Twenty-four patients with TM and concomitant OPLL and OLF.Japanese Orthopaedic Association (JOA) score system for TM, recovery rate (RR), complication rate.Twenty-four patients' data were retrospectively reviewed. All patients initially underwent en bloc excisions of posterior spinal canal elements, and IOU was then used to evaluate spinal decompression sufficiency. If any compression of OPLL was confirmed in IOU, further CD procedure was performed. The JOA score was used to evaluate health-related quality of life. RR was calculated using the Hirabayashi formula. A RR ≥50% was considered favorable, and a RR50% was considered unfavorable. The paired t test was performed to statistically compare the preoperative and postoperative JOA scores. The chi-squared test, rank sum test, and logistic regression analyses were performed to find variants associated with unfavorable surgical outcomes The prognostic factors were analyzed by Spearman correlation and Pearson correlation analyses.The invasive CD procedure were avoided in 9 of 28 segments were avoided, with a mean blood loss of 1,458 mL. Seventeen patients experienced cerebrospinal fluid leakage, and 5 experienced immediate postoperative paralysis. The mean JOA score improved from 4.25±2.2 (preoperative) to 8.16±1.9 (final follow-up). The mean RR was 57.7%±29.4%. There was a significant difference (p.01) between the preoperative and final follow-up JOA score. A comparison between the favorable and the unfavorable groups showed no significant differences in the evaluated factors, but the considerable blood loss was a significant risk factor for poor RR (p=.036, b=-0.43).One-stage CD-based surgery via a posterior approach with IOU assistance for the treatment of concomitant OPLL and OLF led to significant functional improvement in the majority of patients. Under the premise of sufficient decompression, the postoperative paralysis rate reduced compared to that in previous studies. However, there were still high cerebral spinal fluid leakage rates. Considerable blood loss is a risk factor for poor RR.

Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease is characterized by chondrocalcinosis, which mainly affects the knees, wrists, pelvis, and rarely, the spine. According to previous reports, CPPD crystal deposits display heterogeneous enhancement on MRI. When combined with inflammation of the surrounding soft tissue, strong enhancement by CPPD crystal deposition may appear similar to imaging features of other conditions such as infectious spondylitis. In these conditions, CT plays an important role in differential diagnosis. Here, we present a case of CPPD crystal deposition disease in the ligamentum flavum of the cervical spine that showed intense enhancement on MRI.

Case The patient was a 62-year-old woman presenting with low-back pain of 3 years’ duration and numbness in the right leg. Diagnosis She was diagnosed with lumbar spinal stenosis based on combined magnetic resonance imaging, physical examination, and symptoms. Interventions Treatment with computed tomography–guided percutaneous release of the ligamentum flavum was delivered. Outcomes Relief of symptoms immediately after treatment and complete resolution of symptoms after 1 month were achieved. At follow-up, there was no recurrence of symptoms after 2, 4, 6, and 12 months. Conclusion Lumbar ligamentum flavum hypertrophy is an important cause of degenerative lumbar spinal stenosis. The hypertrophic ligamentum flavum can directly compress the spinal canal, squeeze the cauda equina, and simultaneously lead to a reduction in the anteroposterior diameter of the intervertebral foramen, which compresses the nerve roots and causes numbness and other symptoms of lower extremities. In clinical practice, doctors should combine imaging findings with patient symptoms for diagnosis and an individualized treatment plan for each patient with lumbar spinal stenosis, and conduct gradual stepwise treatment using conservative minimally invasive surgery to prevent excessive surgery., Video Abstract Point your mobile at the code above. If you have a QR code-reader, the video abstract will appear. Or use: https://youtu.be/xUgzwLiZT5c

BACKGROUND CONTEXT Ligamentum flavum (LF) induced lumbar spinal stenosis (LSS) is conditioned not only by its "gathering" but especially by hypertrophy. Previous studies have examined the pathophysiology and biochemical changes that cause the hypertrophy. Some studies have described a link between chronic LF inflammation and neovascularization but others have reported highly hypovascular LF tissue in LSS patients. Currently, there is no practical application for our knowledge of the pathophysiology of the LF hypertrophy. Considerations for future treatment include influencing this hypertrophy at the level of tissue mediators, which may slow the development of LSS. To our knowledge, there is no study of micromechanical properties of native LF to date. PURPOSE (1) To clarify the changes in vascularization, chondroid metaplasia, and the presence of inflammatory cell infiltration in LF associated with LSS. (2) To quantify changes in the micromechanical properties associated with LF degenerative processes. STUDY DESIGN/SETTING Vascular density analysis of degenerated and healthy human LF combined with measurement of micromechanical properties. METHODS The study involved 35 patients who underwent surgery between November 1, 2015 and October 1, 2016. The LSS group consisted of 20 patients and the control group consisted of 15 patients. LF samples were obtained during the operation and were used for histopathological and nanoindentation examinations. Sample vascularization was examined as microvascular density (Lv), which was morphometrically evaluated using semiautomatic detection in conjunction with NIS-Elements AR image analysis software. Samples were also histologically examined for the presence of chondroid metaplasia and inflammation. Mechanical properties of native LF samples were analyzed using the Hysitron TI 950 TriboIndenter nanomechanical testing system. RESULTS Vascular density was significantly lower in the LSS group. However, after excluding the effect of age, the difference was not significant. There was high association between Lv and age. With each increasing year of age, Lv decreased by 11.5 mm2. Vascular density decreased up to the age of 50. Over the age of 50, changes were no longer significant and Lv appeared to stabilize. No correlation was observed between Lv and the presence of inflammation or metaplasia; however, LSS patients had a significantly increased incidence of chondroid metaplasia and inflammatory signs. The mechanical properties of control group samples showed significantly higher stiffness than those samples obtained from the LSS group. Conclusion This study showed that Lv changes were not dependent on LSS but were age-dependent. Vascular density was found to decrease up to the age of 50. A significantly higher incidence of chondroid metaplasia and inflammation was observed in LSS patients. The mechanical property values measured by nanoindentation showed high microstructural heterogeneity of the tested ligaments. Our results showed that healthy ligaments were significantly stiffer than LSS ligaments. CLINICAL SIGNIFICANCE Prevention of the loss of LF vascularization during aging may influence stiffness of LF which in turn may slow down the LF degenerative processes and delay onset of LSS.

Study Design: Prospective, comparative.Purpose: To compare the histopathological and electron microscopic changes in the ligamentum flavum (LF) between degenerative lumbar canal stenosis (LCS) and lumbar disk herniation (LDH).Overview of Literature: The LF has been implicated as a key structure in the pathogenesis of LCS. With aging, the LF undergoes morphological changes–a decrease in the elastic component and an increase in the collagen component, in addition to other focal changes. By comparing the histopathological and electron microscopic picture of the LF in elderly patients with LCS with that in young patients with LDH, the role of this ligament in the pathogenesis of LCS may be clarified.Methods: Forty patients were prospectively recruited and divided into two groups: group 1 included 20 patients with degenerative LCS aged >55 years and group 2 included patients with LDH aged

Background Although previous studies have reported the expression of JAK1, STAT3, and phosphorylated STAT3 in hypertrophied ligamentum flavum (LF), the role of the Janus kinase–signal transducer and activator of transcription (JAK/STAT) signaling pathway in hypertrophied LF has not been fully elucidated. The aim of this study was to identify the important JAK/STAT gene expression patterns of the 3 main receptors involved in this pathway: interferon (IFN)-γ receptor (IFN-γR), IFN-α receptor (IFNAR), and interleukin (IL)-6 receptor (IL-6R). Methods The human LF specimens were obtained from 28 patients who underwent lumbar spine surgery for either degenerative lumbar canal stenosis (DLCS) (n = 28) or lumbar disc herniation (LDH) (n = 20). In this design, patients with LDH served as the control group. The degree of fibrosis was demonstrated by Masson's trichrome staining. The location and expression profiling of the JAK/STAT pathway were analyzed by quantitative real-time polymerase chain reaction and Western blotting. The thickness of the LF was measured with axial T1-weighted magnetic resonance imaging. Results The most severe fibrotic changes were on the dorsal side of the LF. IL-6 and IFN-I expression levels were significantly increased on the dorsal side of the LF. While expression levels of IL-6R and IFNAR on the dural and dorsal side were significantly higher in the DLCS samples, IFN-γR and endothelial epidermal growth factor receptor in LF samples showed a significant increase only on the dorsal side. JAK/STAT genes were significantly expressed, especially on the dorsal side. Conclusions Our data suggest that IFNAR- and IL-6R-dependent JAK/STAT signaling pathways may be significant targets in drug development strategies for the treatment of LF hypertrophy.

Ligamentum flavum is one of the structures that could compress the spinal canal. Few studies have reported atrophy of ligamentum flavum after spinal fusion. The purpose of this study was to demonstrate the reduction of ligamentum flavum size after oblique lumbar interbody fusion (OLIF) using magnetic resonance imaging (MRI). Seventeen patients who underwent OLIF without direct decompression were included. The MRI was obtained at the preoperative period, immediate postoperative period, and the follow-up period. Disc height (DH) was measured in plain radiograph. MRI measurements were spinal canal cross-sectional area (SCSA), ligamentum flavum thickness (LFT), ligamentum flavum area (LFA), and foraminal area (FA). Mean age of the patients was 68.5 ± 10.8. Mean times between postoperative MRI and follow-up MRI were 20.2 ± 11.9 months. Mean disc height increased from 7.6 ± 1.6 to 11.6 ± 1.7 mm at an immediate postoperative period but decreased to 10.1 ± 1.6 mm during follow-up (p

Conventional laminectomy for spine decompression involves inherent complications resulting from perioperative traumatization of posterior structures. Minimally invasive decompression was developed to address these issues. Full endoscopic spine surgery has shifted the paradigm from disc pathology to spinal stenosis by overcoming the limitation of bony procedures with evolving endoscopic instruments. However, a steep learning curve restricts the development of endoscopic decompression. The purpose of this study is to describe full endoscopic uniportal unilateral laminotomy for bilateral decompression through the interlaminar approach and to evaluate its efficacy and safety in 2 years of follow-up.A total of 106 patients (45 men, 61 women) with degeneration lumbar stenosis involving 165 segments were enrolled from April 2015 to June 2017, and treated by full endoscopic uniportal unilateral laminotomy for bilateral decompression. We made an 8-mm incision and used a general-size endoscope (working channel 4.3 mm) to avoid neurological compromise during the demonstration.The visual analogue scale (VAS) results for back pain revealed a significant reduction from preoperative 6.8 ± 2.1 to 1.7 ± 1.7 after 2 years (P0.001). The VAS results for leg pain revealed a significant reduction from preoperative 7.6 ± 1.3 to 1.3 ± 1.6 after 2 years (P0.001). The Oswestry Disability Index showed significant improvement from preoperative 62.0 ± 13.9 to 14.6 ± 15.7 after 2 years (P 0.001). The average operation time was 68.9 ± 10.0 minutes per level. One case had iatrogenic durotomy, 1 case underwent revision surgery due to incomplete decompression, and 2 cases had delayed wound healing.This procedure obtained successful and satisfactory outcomes for patients, and was more feasible for surgeons.

STUDY DESIGN Prospectively collected, multicenter, nationwide study. OBJECTIVE The aim of this study was to investigate recent surgical methods and trends, outcomes, and perioperative complications in surgery for thoracic ossification of the ligamentum flavum (T-OLF). SUMMARY OF BACKGROUND DATA A prospective multicenter study of surgical complications and risk factors for T-OLF has not been performed, and previous multicenter retrospective studies have lacked details for these items. METHODS Surgical methods, pre- and postoperative thoracic myelopathy (Japanese Orthopedic Association [JOA] score), symptoms, and intraoperative neurophysiological monitoring were investigated prospectively in 223 cases. Differences in these factors between fusion and nonfusion procedures for T-OLF were examined. The minimum follow-up period was 2 years after surgery RESULTS.: The mean JOA score was 6.2 points preoperatively, and 7.9, 8.2, and 8.2 points at 6 months, 1, and 2 year postoperatively, giving mean recovery rates of 35.0%, 40.9%, and 41.4% respectively. Posterior decompression and fusion with instrumentation was performed in 109 cases (48.9%). There were 45 perioperative complications in 30 cases (13.5%), with aggravation of motor disturbance in the lower extremities being most common (4.0%, n = 9). Patients treated with fusion had a significantly higher BMI, rate of gait disturbance, ossification occupation rate of OLF at computed tomography, and intramedullary high intensity area at magnetic resonance imaging (P

Aim This study aimed to histopathologically evaluate and compare bone morphogenetic protein (BMP)-2, vascular endothelial growth factor (VEGF), and vitamin D receptor (VDR) levels in the ligamentum flavum (LF) of patients with lumbar spinal stenosis (LSS) and lumbar disc herniation (LDH). Material and methods Surgical specimens of the LF in 25 patients who underwent surgery for LDH and 25 patients who underwent surgery for LSS were examined histopathologically. The prevalence and severity of BMP-2, VEGF, and VDR immunoreactivity were evaluated to create histoscores (prevalence × severity), which were compared between groups. Results The mean BMP-2 histoscore was similar in both groups. In the LSS group, the mean VEGF histoscore was significantly higher and the mean VDR histoscore was significantly lower. Conclusion Elevated VEGF and decreased VDR levels in the LF in LSS are associated with more intense inflammation and chronic process of the disease. The prominent expression of BMP-2 in the LF in both diseases suggests that BMP-2 might be affected by inflammation regardless of chronic pressure and degeneration.

Background Involvement in cervical ligamentum flavum is a rare manifestation of the calcium pyrophosphate dihydrate deposition disease. Only few cases of this condition have been reported. We revealed eighteen cases of CPPD in cervical ligamentum flavum that diagnosed at a single medical center. In our case series, clinical characteristics and magnetic resonance imaging findings of patients are described. Methods We retrospectively reviewed the medical charts and imaging studies of the eighteen patients with pseudogout attack of the cervical ligamentum flavum. In addition, we discussed the differences between this disease and ossification of ligamentum flavum in image manifestations. Results There were fourteen men and four women aged between 59 and 87 years. Diabetes mellitus and hypertension were the most common comorbidities. Myelopathy and neck pain were presented in most patients. C4–5 and C5–6 were attacked most frequently, and multiple- rather than single-level involvement could be observed in our series. “Acute on chronic phenomenon” was a specific magnetic resonance image finding in patients whose symptom durations were between 2 to 5 months. Compared to ossification of ligamentum flavum, calcium pyrophosphate dihydrate crystal deposition had different image signs, including morphology, side of the involved ligament, no continuity with the lamina, acute on chronic phenomenon, and presence of retro-odontoid mass. Conclusions Nodular calcifications in cervical ligamentum flavum raise highly suspicion for calcium pyrophosphate dihydrate deposition and must be diagnosed by histological examination and polarized light microscopy. This disease is different from ossification of ligamentum flavum, and it could be recognized by specific image features.

This study aimed to validate previously published computed tomography (CT) derived mathematical equations with the true skin to lumbosacral epidural distance (SLED) in dog cadavers. Phase 1: The lumbar region of 11 dog cadavers were scanned in sternal recumbency to determine the effect of cranial, neutral, and caudal pelvic limb positioning on the CT derived lumbosacral epidural distance (CLED). Phase 2: The epidural space was determined using contrast epidurography, and the SLED was analysed against the mathematical equations using a body condition score (BCS) and either the cadaveric occipital-coccygeal length (OCL) (Equation (1): = 7.3 + 0.05*OCL + 16.45*BCS) or the ilium wing distance (IWD) (Equation (2): = 3.5 + 0.56*IWD + 16.6*BCS). There were no differences detected between the pelvic limb positions and the CLED. Both equations demonstrated strong correlations (Equation (1): r = 0.7196, Equation (2): r = 0.7590) with the SLED. The level of agreement was greater for Equation (1) than with Equation (2) (concordance coefficient 0.6061 and 0.3752, respectively). Equation (1) also demonstrated a closer fit to the concordance line compared with Equation (2) (bias correction factor 0.8422 and 0.4960, respectively). Further studies in live anaesthetised dogs will help to determine the usefulness of the pre-procedural knowledge when performing lumbosacral epidurals.

Ossification of the ligamenta flava (OLF) is a rare and likely multifactorial condition that most commonly affects the lower thoracic spine. It can result in chronic pain and neurological deficits and has a higher prevalence in men of Japanese descent. We present the case of OLF of the lumbar spine in a Caucasian man with a history of multiple sports-related injuries. To treat his severe lumbar spinal stenosis, the patient underwent endoscopic intralaminar laminotomy with partial facetectomy and complete resection of OLF with lateral recess decompression, which immediately resolved his symptoms. We noted signs of OLF based on T1 and T2 signal changes upon re-evaluation of MRI.

Background Currently, decompressive laminectomy with or without concomitant fusion is a standard treatment for ossification of the ligamentum flavum (OLF). However, conventional thoracic decompressive laminectomy is not free of the inevitable destruction of the posterior ligamentous complex, and facet injury may lead to various sequelae. Method We used the biportal endoscopic technique for posterior thoracic decompression (BE-PTD) and describe the steps with discussion regarding the indications, advantages, possible complications, and ways to overcome complications. Conclusion BE-PTD can obtain endoscopic visualizations of all the boundaries of the OLF lesion and achieve direct neural decompression of thoracic OLF.

STUDY DESIGN A retrospective cohort analysis. OBJECTIVE The aim of this study was to investigate the impact of piecemeal versus en bloc laminectomies on spinal cord in thoracic ossification of ligamentum flavum (TOLF) through intraoperative changes of motor-evoked potentials (MEPs) and somatosensory-evoked potentials (SEPs). SUMMARY OF BACKGROUND DATA Surgical treatment is indicated for symptomatic TOLF, and both piecemeal and en bloc laminectomies are commonly used methods. However, few studies compared both intraoperative interference and prognostic impact of these two laminectomies on spinal cord in TOLF patients. METHODS MEPs were recorded from abductor hallucis (AH) and tibialis anterior, and SEPs were performed on tibial nerve in 55 TOLF patients (piecemeal vs. en bloc: 23 vs. 32). Patients were categorized based on MEP/SEP improvement, deterioration, and no change, and MEP/SEP improvement rates were measured in the improvement group. Additionally, all patients were assessed by American Spinal Injury Association (ASIA) scores, Ashworth scores, and modified Japanese Orthopedic association (mJOA) scores before and after operation. RESULTS The incidences of both MEP/SEP improvement and deterioration were similar between the two laminectomy groups (P > 0.05), and no significant difference is noted in both MEP and SEP amplitudes between the baseline and different critical manipulations in both laminectomy groups (P > 0.05). In the improvement group, patients receiving en bloc laminectomy exhibited increased improvement rates of both MEPs in bilateral AH and left-side SEPs compared to piecemeal laminectomy (P

Background It is imperative to preoperatively distinguish dural ossification (DO) and thus anticipate the risks and outcome of the surgery for patients with ossification of ligamentum flavum (OLF). However, studies have disagreed as to the efficacy of the radiographic signs or factors to predict DO and surgical outcome. In additon, the association between the cerebrospinal fluid cross-section area ratio (CCAR) and DO or clinical outcome had not been reported. The purpose of this study was to analyse CCAR and its role in prediction of DO and neurological function recovery rate in patients with OLF. Methods Fifty-two consecutive patients with OLF, who underwent posterior thoracic decompression and fusion between September 2012 and March 2019 at a single institution, were retrospectively reviewed. Demographic data, radiographic signs of DO, CCAR, pre- and postoperative modified Japanese Orthopedic Association (mJOA) score were recorded. Results There were 27 patients in the DO group and 25 patients in the non-DO group, with a mean age at surgery of 57.4 years and 53.9 years, respectively. No significant differences were found in sex, age, segment of maximum compression and preoperative mJOA score between the two groups. The receiver operating characteristic curve showed that the value of CCAR had a relatively high value for diagnosis of DO and prediction of neurological function recovery rate (P = .000). According to the value of CCAR, three zones were defined as DO zone (≤14.3%), non-DO zone (≥44.5%), and gray zone (14.3 to 44.5%). When the value of CCAR≤14.3%, the recovery rate was poor or fair, while it had good or excellent recovery when CCAR≥45.2%. Conclusion The value of CCAR had a high diagnostic value for prediction of DO and neurological function recovery rate in patients with OLF.

Cervical laminoplasty is a valuable procedure for myelopathy but it is associated with complications such as increased kyphosis. The effect of ligament damage during cervical laminoplasty on biomechanics is not well understood. We developed the C2–C7 cervical spine finite element model and simulated C3–C6 double-door laminoplasty. Three models were created (a) intact, (b) laminoplasty-pre (model assuming that the ligamentum flavum (LF) between C3–C6 was preserved during surgery), and (c) laminoplasty-res (model assuming that the LF between C3–C6 was resected during surgery). The models were subjected to physiological loading, and the range of motion (ROM), intervertebral nucleus stress, and facet contact forces were analyzed under flexion/extension, lateral bending, and axial rotation. The maximum change in ROM was observed under flexion motion. Under flexion, ROM in the laminoplasty-pre model increased by 100.2%, 111.8%, and 98.6% compared to the intact model at C3–C4, C4–C5, and C5–C6, respectively. The ROM in laminoplasty-res further increased by 105.2%, 116.8%, and 101.8% compared to the intact model at C3–C4, C4–C5, and C5–C6, respectively. The maximum stress in the annulus/nucleus was observed under left bending at the C4–C5 segment where an increase of 139.5% and 229.6% compared to the intact model was observed for laminoplasty-pre and laminoplasty-res model, respectively. The highest facet contact forces were observed at C4–C5 under axial rotation, where an increase of 500.7% and 500.7% was observed compared to the intact model for laminoplasty-pre and laminoplasty-res, respectively. The posterior ligaments of the cervical spine play a vital role in restoring/stabilizing the cervical spine. When laminoplasty is performed, the surgeon needs to be careful not to injure the posterior soft tissue, including ligaments such as LF.

INTRODUCTION: Achondroplasia is a rare autosomal dominant condition characterized by stenosis in spinal canal. Multilevel Ossification of the ligamentum flavum in the spine is a rare occurrence which too can contribute to stenosed canal. CASE PRESENTATION: We report a case of an Indian achondroplasic dwarf with multilevel ossification of ligamentum flavum (OLF) at thoracic and lumbar segment. She presented in the outpatient department with bilateral weakness in legs with complete foot drop on the left side and was non-ambulatory. She was managed surgically by instrumentation with multiple interbody fusions with wide decompression and excision of OLF. The patient responded well to the surgery and became a walker after 2-year follow-up. DISCUSSION: Achondroplasic patients may present rarely with multiregional and multilevel OLF. It is important to identify them preoperatively so as to have good surgical outcome. Wide laminectomy, removal of the ossified ligament, and fusion with instrumentation resulted in the improvement of the patient’s neurological symptoms and functions.

INTRODUCTION: Acute spinal cord injury without tomographic evidence of vertebral fracture or dislocation in patients post trauma can represent a diagnostic challenge for the treating physician. The ossification of thoracic ligamentum flavum has been widely published as a cause of thoracic myelopathy, however its association with acute traumatic spinal cord injury is limited to isolated cases. CASE PRESENTATION: we report a Caucasian 37-year-old man who suffered a high-energy thoracolumbar spine trauma in a motorcycle accident with acute paraplegia. He presented ossification of the ligamentum flavum between the thoracic vertebrae T10 and T11 with a decrease in the diameter of the vertebral canal as the only pathological finding. We treated the patient with early surgical release before 72 h of trauma. We performed a posterior approach with hemilaminectomy and T10–T11 flavectomy. Arthrodesis was done with T10–T11 pedicle screws. Postoperative neurological status improved from ASIA Impairment Scale (AIS) A to C with severe functional dependence. DISCUSSION: Ossification of the ligamentum flavum should be considered in the differential diagnosis in patients presenting with acute traumatic spinal cord injury without tomographic evidence of trauma. A proper diagnosis in time is the key to decision making and treatment of spinal cord injury. Especially in adult patients, we must consider nontraumatic associated factors that could be involved in the spinal cord injury mechanism, such as ossification of the ligamentum flavum.

Background. Mechanisms are known that allow partial local regulation of the thyroid status of tissues using peripheral conversion of iodothyronines, which determines the local level of metabolic activity. The molecular mechanisms of degenerative-dystrophic changes in the ligamentum flavum are not well understood; only a few studies on the expression of genes in this substrate have been published. The aim of the study was to identify key factors in the peripheral conversion of iodothyronines in ligamentum flavum in patients with stenosis of spinal canal and dural sac in the lumbar spine and to evaluate the features of the expression of deiodinase genes depending on the severity of ossification processes of ligamentum flavum . Methods. A group of patients with stenotic processes of the spinal canal was examined: 31 people (15 men, 16 women). The average age was45.73 ± 1.95years. In intraoperatively collected samples of ligamentum flavum , the expression ofdeiodinase genes (real time PCR) was studied and the severity of ossification processes was evaluated using a histopathological study. Results. The key factors of peripheral conversion of iodothyronines in intraoperative bioptates of the ligamentum flavum of patients (n = 31) with stenosis of the spinal canal at the lumbar level were revealed. Information was obtained on the local level of metabolic activity in the focus of pathology. The intensity and variability of deiodinase gene expression in ligamentum flavum samples were evaluated. The distribution of deiodinase gene expression patterns in groups formed on the basis of presence/absence of ossification of ligamentum flavum was found. Various variants of peripheral conversion of iodothyronines in biopsy samples of the yellow ligament of the operated patients were determined and the frequency of their occurrence was estimated. Conclusion. The key factors ofperipheral conversion of iodothyronines in intraoperative biopsy samples of the ligamentum flavum of patients with degenerative diseases of the spine were revealed for the first time. The reasons for the differences in tissue metabolism of iodothyronines and the place in the pathogenesis of stenotic processes are yet to be found.

BACKGROUND The bridge crane technique is a novel surgical technique for the treatment of thoracic ossification of the ligamentum flavum (TOLF), but its preoperative planning has not been studied well, which limits the safety and efficacy of surgery to some extent. The purpose of this study was to investigate the method of application and effect of computer-aided preoperative planning (CAPP) on the bridge crane technique for TOLF. MATERIAL AND METHODS This retrospective multi-center included 40 patients with TOLF who underwent the bridge crane technique from 2016 to 2018. According to the utilization of CAPP, patients were divided into Group A (with CAPP, n=21) and Group B (without CAPP, n=19). Comparisons of clinical and radiological outcomes were carried out between the 2 groups. RESULTS The patients in Group A had higher post-mJOA scores and IR of neurological function than those in Group B (p0.05). Group A had shorter surgery time, fewer fluoroscopic images, and lower incidence of complications than Group B. In Group A, there was a high consistency of all the anatomical parameters between preoperative simulation and postoperative CT (p0.05). In Group B, there were significant differences in 3 anatomical parameters between postoperative simulation and postoperative CT (p0.05). In Group B, the patients with no complications had higher post-SVOR and lower SVRR and height of posterior suspension of LOC in postoperative CT than those in postoperative simulation (p0.05). CONCLUSIONS CAPP can enable surgeons to control the decompression effect accurately and reduce the risk of related complications, which improves the safety and efficacy of surgery.

Background General anesthesia (GA), which is routinely applied in patients who undergo percutaneous endoscopic interlaminar lumbar discectomy (PEILD) of L5-S1 disc herniation, is closely associated with postoperative cognitive dysfunction (POCD) in the elderly. Local anesthesia (LA) is an alternative pain control protocol that has not yet been fully evaluated. Objectives To evaluate the feasibility of LA in PEILD compared with GA. Study design A retrospective study. Setting This study took place at the First Affiliated Hospital of Harbin Medical University. Methods A total of 120 patients (aged 60-85 years) diagnosed with L5-S1 disc herniation and with American Society of Anesthesiologists fitness grade I or II between March 2016 and August 2017 were enrolled in the current study. Patients were randomly divided into LA group and GA group. For LA, 0.25% lidocaine was injected layer-by-layer into skin, subcutaneous tissue, fasciae, lumbar facet joint, muscle, and ligamentum flavum followed by injection of 1.33% lidocaine into epidural space; for GA, propofol, sufentanil, and cisatracurium were infused intravenously at 1 to 2 mg/kg, 0.3 µg/kg, and 0.15 mg/kg, respectively. Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and MacNab Criteria (MNC) evaluated the feasibility of LA as pain control protocol in comparison to GA before and after operation. The development of POCD was assessed by the Mini-Mental State Examination 1 and 7 days postsurgery. Feasibility of LA as a pain control protocol was also evaluated by patient's willingness to receive the same surgical procedure immediately and 24 hours after the surgery, and intraoperative fluoroscopy use, blood loss, surgery duration, postoperative bed confinement, and duration and cost of hospital stay were also evaluated. Results Patients in both LA and GA groups had comparable VAS grade, ODI, and MNC pre- and post-PEILD, with significant pain reduction after operation. However, POCD developed only in GA group but not in LA group. In addition, compared with GA, LA group did not require postoperative bed confinement, had significantly shorter hospital stay, and lower hospital cost. Low intraoperative VAS grade and willingness to receive the same procedure reflected the acceptance of LA by patients. Limitations The development of POCD was examined only 7 days after operation. The follow-up should be extended to 3 months and 2 years postoperation. Conclusions LA has satisfactory pain control and low-risk of POCD in PEILD and is well accepted by patients. The benefits of LA are no postoperative bed confinement, faster recovery, shorter hospital stay, and lower hospital cost. Key words L5-S1 disc herniation, older patients, percutaneous endoscopic interlaminar lumbar discectomy, local anesthesia, general anesthesia, postoperative cognitive dysfunction, American Society of Anesthesiologists grade, Oswestry Disability Index, MacNab Criteria, Mini-Mental State Examination.