N6-methyladenosine-modified circCDK14 promotes ossification of the ligamentum flavum via epigenetic modulation by targeting AFF4.

BACKGROUND: The ligamentum flavum (LF) is an important anatomical structure of the spine. Ossification of the LF (OLF) has become the leading cause of thoracic spinal stenosis. Circular RNAs (circRNAs) and N6-methyladenosine (m6A) modification are reported to be associated with several human diseases. However, the role of circRNAs and m6A modification in the pathogenesis of OLF has not been fully investigated. Here, we aimed to explore the vital function of circRNAs and m6A modification in OLF. MATERIALS AND METHODS: We analysed the circRNA expression of 4 OLF tissues and 4 normal LF tissues using bioinformatic analysis and identified circCDK14 for further analysis. We investigated the effects of circCDK14 on the osteogenic differentiation of LF cells. We observed that circCDK14 regulated its target genes by binding to miRNAs as a miRNA sponge. Moreover, the circRNA pull-down assay indicated that RNA-binding proteins might regulate the expression of circCDK14 via m6A modification. RESULTS: CircCDK14 was significantly upregulated in OLF tissues compared to normal LF tissues. Overexpression of circCDK14 promoted the osteogenic differentiation of LF cells. Mechanistically, CircCDK14 promoted the expression of ALF transcription elongation Factor 4 (AFF4) by serving as a sponge for miR-93-5p. Moreover, Wilms tumour 1-associated protein (WTAP) increased the stability of circCDK14 via N6-methyladenosine modification. CONCLUSION: The m6A-modified CircCDK14 binding to miR-93-5p played an important role in the osteogenesis of LF cells by targeting AFF4, providing a promising therapeutic target for OLF.

Periostin increased by mechanical stress upregulates interleukin-6 expression in the ligamentum flavum.

Ligamentum flavum (LF) hypertrophy is a major cause of lumbar spinal canal stenosis. Although mechanical stress is thought to be a major factor involved in LF hypertrophy, the exact mechanism by which it causes hypertrophy has not yet been fully elucidated. Here, changes in gene expression due to long-term mechanical stress were analyzed using RNA-seq in a rabbit LF hypertrophy model. In combination with previously reported analysis results, periostin was identified as a molecule whose expression fluctuates due to mechanical stress. The expression and function of periostin were further investigated using human LF tissues and primary LF cell cultures. Periostin was abundantly expressed in human hypertrophied LF tissues, and periostin gene expression was significantly correlated with LF thickness. In vitro, mechanical stress increased gene expressions of periostin, transforming growth factor-ß1, α-smooth muscle actin, collagen type 1 alpha 1, and interleukin-6 (IL-6) in LF cells. Periostin blockade suppressed the mechanical stress-induced gene expression of IL-6 while periostin treatment increased IL-6 gene expression. Our results suggest that periostin is upregulated by mechanical stress and promotes inflammation by upregulating IL-6 expression, which leads to LF degeneration and hypertrophy. Periostin may be a pivotal molecule for LF hypertrophy and a promising therapeutic target for lumbar spinal stenosis.

Circular RNA PDK1 targets miR-4731-5p to enhance TNXB expression in ligamentum flavum hypertrophy.

Hypertrophic ligamentum flavum (LF) is a main factor responsible for lumbar spinal stenosis (LSS); however, the exact mechanisms of the pathogenesis of these processes remain unknown. This study aimed to elucidate whether circular RNAs and microRNAs regulate the pathogenesis of LF and LSS, especially focusing on circPDK1 (hsa_circ_0057105), a circRNA targeting pyruvate dehydrogenase kinase 1 and differentially expressed in LF tissues between lumbar disk herniation and LSS patients. The circPDK1/miR-4731 and miR-4731/TNXB (Tenascin XB) interactions were predicted and validated by luciferase reporter assay. Colony formation, wound-healing, and MTT assays were used for estimating cell proliferation and migration. Protein expression levels were evaluated using Western blotting. TNXB expression was verified using immunohistochemistry (IHC). Overexpressing circPDK1 promoted the proliferation, migration, and expression of fibrosis-related protein (alpha smooth muscle actin (α-SMA), lysyl oxidase like 2 (LOXL2), Collagen I, matrix metalloproteinase-2 (MMP-2) and TNXB) in LF whereas miR-4731-5p showed opposite effects. The expression of TNXB was promoted by circPDK1; contrary results were observed with miR-4731-5p. Co-overexpression of miR-4731-5p partially reversed the proliferative and fibrosis-prompting effects of circPDK1 or TNXB. The circPDK1-miR-4731-TNXB pathway may be proposed as a regulatory axis in LF hypertrophy, which might shed light on in-depth research of LSS, as well as providing a novel therapeutic target for LF hypertrophy-induced LSS.

Cysts of the ligamentum flavum are often linked to ischemic conditions: A morphological study.

"Cysts of the ligamentum flavum (cysts-LF)" is the term for non-neoplastic cystic lesion involving LF. The aim of the present study was to elucidate the histopathological characteristics and pathogenesis of "cysts-LF". Herein, we defined cysts-LF as spinal cysts containing degenerative LF components. From archival cases, we investigated 18 symptomatic cysts-LF surgically removed from 18 patients (13 males and five females; median age 68.5 years [range, 42-86 years]). The elastic fibers of LF components in the wall were separated and/or torn, and cyst walls were accompanied by chondroid metaplasia (17 cases), myxoid changes (13 cases), ossification (11 cases), amyloid deposits (14 cases), hemosiderosis (six cases), granular/smudgy calcification (four cases), synovial cell linings (three cases), and severe inflammatory infiltrates (one case). These histologic features of our cysts-LF were shared by previously reported "cysts-LF." Fourteen cysts-LF demonstrated vascular stenosis/occlusion, and eight showed thick hyalinized vessels, suggesting local circulatory insufficiency. Eight cases (44%) exhibited lipomembranous fat necrosis, accompanied by hyalinized vascular changes (p = 0.003). Ischemic conditions were observed in nearly half of the present cysts-LF, and may be one of the main contributing factors for the formation of cysts-LF, via degeneration and cystic changes in the LF.

Comparison of endoscopic decompression to open laminectomy in patients with thoracic ossified ligamentum flavum - a systematic review and meta-analysis.

In recent years, there has been growing interest in an alternative approach for treating TOLF, such as endoscopic decompression, which minimizes the disruption of surrounding tissues. It is important to understand the advantages, disadvantages, and potential differences in outcomes associated with each approach. This comparative study aims to evaluate and contrast the effectiveness, safety, and outcomes of these two surgical techniques, open laminectomy and endoscopic decompression, in the management of thoracic OLF. The literature review was conducted on Embase, PubMed, Scopus and Google Scholar databases. After a thorough screening of all search results, 14 studies were shortlisted, from which data was extracted, and statistical analysis was done. Pooled analysis was done to ascertain the intra-operative and post-operative outcomes after surgery for TOLF. Overall, 351 patients were included in the study for evaluation. 174 patients were operated on by open laminectomy, and 177 patients were seen in the endoscopy group. Decreased operative time was seen in the endoscopic subgroup. The mean length of hospital stay of 6.6 days. Both groups showed improvement in mJOA and VAS score. The recovery rate for the reported study cohort was 66.8%, with the Endoscopic surgical approach showing a positive correlation with the mean recovery rate. The dural tear was the most common complication, with a rate of 6.6%. The mean estimated infection rate was 2.7% and postoperative CSF leak was 3.7%, with a trend of significantly higher rates in the open subgroup. Both of the groups showed improvement in functional scores, VAS scores, and cross-sectional area. However, the Endoscopic decompression group experienced reduced hospital stays, operating times, and intraoperative blood loss. The most frequent side effects were CSF leak and dural tear. A few cases showed revision and infection. None of the problems differed between the groups.

Macrophage polarization and macrophage-related factor expression in hypertrophy of the ligamentum flavum.

PURPOSE: Owing to the unknow types of infiltrating macrophages and the corresponded factors, we aimed to investigate the specific types of infiltrating macrophages involved in HLF and the expression of macrophage-related factors. METHODS: The ligamentum flavum was obtained from patients with lumbar spinal stenosis (HLF group; n = 15) and lumbar disc herniation (non-hypertrophic ligamentum flavum [NLF] group; n = 15). Ligamentum flavum specimens were paraffin embedded, followed by histological and immunohistochemical staining to identify the macrophage type and expression of macrophage-related factors. RESULTS: The HLF group demonstrated CD206 marker expression, while the NLF group did not (P < 0.0001; n = 11). CD68 marker was expressed in both groups (P > 0.05; n = 11). CCR7 was not expressed in either group. The expression levels of the extracellular matrix proteins aggrecan (Agg), type I collagen (Coll1), and type II collagen (Coll2) were higher in the HLF group than in the NLF group (P < 0.0001; n = 11). The aging markers p21, p16, and p53 were expressed in the HLF group, but not in the NLF group (P < 0.0001; n = 11). The expression levels of the inflammatory factors TNF-α and IL-1ß were higher in the HLF group than in the NLF group (P < 0.0001; n = 11). Similarly, the expression level of the fibrosis factor TGF-ß1 was higher in the HLF group than in the NLF group (P < 0.0001; n = 11). CONCLUSIONS: The infiltration of M2 macrophages may be involved in HLF, while involvement of M1 macrophages may only occur early in inflammation. The expression of extracellular matrix proteins and macrophage-related factors was increased. Aging may also be associated with HLF.

Imaging anatomy study related to unilateral biportal endoscopic lumbar spine surgery.

PURPOSE: To provide lumbar spine anatomical parameters relevant to the UBE technique and explore their intraoperative application. METHODS: CT imaging data processed by Mimics for parametric measurements, including laminar abduction angle (LAA), laminar slope angle (LSA), minimum laminar height (MLH), distance between the inferior margin of the lamina and attachment of the ligamentum flavum onto the cephalad lamina (DLL), distance between the initial point and the middle of the articular process (DIA), and distance from the inferior margin of the lamina to the inferior border of the vertebral body (DLV), and were manually measured. RESULTS: LAA and DIA gradually increase from L1 to L5. At L1, the DIA is approximately the length of 2 drill bits with a diameter of 3 mm (male: 7.77 ± 1.39 mm, female: 7.22 ± 1.09 mm), while at L5, it can reach the length of 4-5 drill bits (male: 14.96 ± 2.24 mm, female: 13.67 ± 2.33 mm). MLH, DLL, and DLV reach their maximum values at the L3 and decrease toward the cranial and caudal ends. The DLL is smallest at L5 (male: 9.58 ± 1.90 mm, female: 9.38 ± 2.14 mm), equivalent to the length of 3 drill bits, while the DLL at L3 is the length of 4-5 drill bits (male: 14.17 ± 2.13 mm, female: 14.01 ± 2.07 mm). CONCLUSION: Referring to the drill diameter during surgery can mark the extent of laminotomy. The characteristics of vertebral plate angles at different lumbar levels can provide references for preoperative incision design.

Open posterior approach versus endoscopic approach for thoracic ligamentum flavum ossification: a systematic review and meta-analysis.

BACKGROUND: Thoracic ossification of the ligamentum flavum (TOLF), a rare condition more prevalent in East Asia, is managed through open and endoscopic surgical approaches. Determining the superior surgical option remains unclear. This study assesses the safety and clinical outcomes associated with these approaches in TOLF patients. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic literature search up to August 5, 2023, across PubMed, Scopus, EMBASE, Web of Science, Cochrane, and ClinicalTrials.gov. We included randomized controlled trials and cohort studies reporting complication rates, mJOA (modified Japanese Orthopedic Association) scores, JOA scores, VAS (Visual Analog Scale) scores, or hospitalization duration for both open and endoscopic surgeries in TOLF patients. RESULTS: We analyzed 37 studies encompassing 1,646 TOLF patients using a random-effects model. Our findings revealed a significant difference in complication rates (overall complication rates: 0.12; 95% CI: 0.07, 0.19; p < 0.01; I2: 69%; quality of evidence: moderate), with lower complication rates in the endoscopy group. However, no significant differences were observed in JOA scores (overall JOA: 8.35; 95% CI: 7.16, 9.54; p = 0.12; I2: 99%; quality of evidence: very low), VAS scores (overall VAS: 1.31; 95% CI: 1.03, 1.59; p = 0.35; I2: 91%; quality of evidence: very low), or hospitalization duration (hospital stay: 10.83 days; 95% CI: 6.86, 14.80; p = 0.35; I2: 91%; quality of evidence: very low) between the open and endoscopic groups. CONCLUSIONS: This meta-analysis reports lower complication rates and improved postoperative mJOA scores for endoscopic surgery in TOLF patients compared to open surgery. It represents the first comprehensive evaluation of clinical outcomes and safety of different surgical approaches for TOLF patients. Further randomized controlled trials are essential to validate these findings.

Perioperative complications and cost of posterior decompression with fusion in thoracic spine for ossification of the posterior longitudinal ligament and ossification of the ligamentum flavum -a comparative study using a national inpatient database.

BACKGROUND: Although posterior decompression with fusion (PDF) are effective for treating thoracic myelopathy, surgical treatment has a high risk of various complications. There is currently no information available on the perioperative complications in thoracic ossification of the longitudinal ligament (T-OPLL) and thoracic ossification of the ligamentum flavum (T-OLF). We evaluate the perioperative complication rate and cost between T-OPLL and T-OLF for patients underwent PDF. METHODS: Patients undergoing PDF for T-OPLL and T-OLF from 2012 to 2018 were detected in Japanese nationwide inpatient database. One-to-one propensity score matching between T-OPLL and T-OLF was performed based on patient characteristics and preoperative comorbidities. We examined systemic and local complication rate, reoperation rate, length of hospital stays, costs, discharge destination, and mortality after matching. RESULTS: In a total of 2,660 patients, 828 pairs of T-OPLL and T-OLF patients were included after matching. The incidence of systemic complications did not differ significantly between the T-OPLL and OLF groups. However, local complications were more frequently occurred in T-OPLL than in T-OLF groups (11.4% vs. 7.7% P = 0.012). Transfusion rates was also significantly higher in the T-OPLL group (14.1% vs. 9.4%, P = 0.003). T-OPLL group had longer hospital stay (42.2 days vs. 36.2 days, P = 0.004) and higher medical costs (USD 32,805 vs. USD 25,134, P < 0.001). In both T-OPLL and T-OLF, the occurrence of perioperative complications led to longer hospital stay and higher medical costs. While fewer patients in T-OPLL were discharged home (51.6% vs. 65.1%, P < 0.001), patients were transferred to other hospitals more frequently (47.5% vs. 33.5%, P = 0.001). CONCLUSION: This research identified the perioperative complications of T-OPLL and T-OLF in PDF using a large national database, which revealed that the incidence of local complications was higher in the T-OPLL patients. Perioperative complications resulted in longer hospital stays and higher medical costs.

miR-29b-3p Affects the Hypertrophy of Ligamentum Flavum in Lumbar Spinal Stenosis and its Mechanism.

To explore the effect of miR-29b-3p on fibrosis and hypertrophy of ligamentum flavum (LF) in lumbar spinal stenosis (LSS) and its underlying mechanism. Patients with LSS and lumbar disc herniation (LDH) (control) undergoing posterior lumbar laminectomy were included in this study. Human LF samples were obtained for LF cell isolation, RNA, and protein extraction. Histomorphological analysis of LF was performed using hematoxylin-eosin (HE) staining. After isolation, culture, and transfection of primary LF cells, different transfection groups were constructed: NC-mimic, miR-29b-3p-mimic, NC-inhibitor, and miR-29b-3p-inhibitor. Quantitative real time polymerase chain reaction (qRT-PCR) was performed to detect the expression of miR-29b-3p in LF and LF cells. Western blot analysis detected the protein expressions of P16 and CyclinD1. ELISA detected the protein expressions of TGF-ß1, Smad2, Smad3, TLR4, Type I collagen, and Type III collagen. Finally, LF cell viability was detected using the Cell Counting Kit-8 (CCK8) assay. The thickness of LF was significantly thicker in the LSS group compared to the LDH group (p < 0.05), accompanied by a higher calcification degree, more fibroblasts, and a larger area of collagen fiber proliferation. miR-29b-3p expression was significantly lower in LSS-derived LF tissues and cells than in LDH-derived tissues and cells (both p < 0.05). Compared to the NC-mimic group, the miR-29b-3p-mimic group exhibited significantly higher miR-29b-3p expression, decreased protein expressions of Type I collagen, Type III collagen, TGF-ß1, Smad2, Smad3, TLR4, P16, and CyclinD1, and inhibited LF cell proliferation (all p < 0.05). As expected, the miR-29b-3p-inhibitor group displayed contrasting expression patterns (all p < 0.05). Compared to the phosphate buffer saline (PBS) group, the Trimethylamine-N-Oxide (TMAO) group showed significantly increased expressions of TGF-ß1, Smad2, Smad3, TLR4, Type I collagen, Type III collagen, P16, and CyclinD1, as well as enhanced LF cell proliferation (all p < 0.05). However, there was no significant difference between the TMAO group and the Ang II group (all p > 0.05). Upregulation of miR-29b-3p expression may play a role in improving LF fibrosis and hypertrophy in LSS by inhibiting P16 expression and suppressing the activation of the TGF-ß/Smad signaling pathway. This finding offers new insights into future gene modification therapy for this patient population.

Comparative Gene-Expression Analysis of the Ligamentum Flavum of Patients with Lumbar Spinal Canal Stenosis: Comparison between the Dural and Dorsal Sides of the Thickened Ligamentum Flavum.

Thickening of the ligamentum flavum is the main factor in the development of lumbar spinal canal stenosis (LSCS). Although previous studies have reported factors related to ligamentum flavum thickening, its etiology has not been clarified. Furthermore, it is often difficult to set proper controls to investigate the pathologies of thickening due to differences in patient characteristics, such as age, sex, obesity, and comorbidities. This study aimed to elucidate the pathologies of ligamentum flavum thickening by comparing the dural and dorsal sides of the thickened ligamentum flavum in patients with LSCS. Ligamentum flavum samples were collected from 19 patients with LSCS. The samples were divided into the dural and dorsal sides. The dural side was used as a control to assess the pathologies occurring on the dorsal side. Elastic Masson staining was used to assess the elastic fibres. Gene expression levels were comprehensively assessed using quantitative reverse transcription polymerase chain reaction and DNA microarray analyses. Gene ontology analysis was used to identify biological processes associated with differentially expressed genes. The elastic fibres were significantly decreased on the dorsal side of the thickened ligamentum flavum. Genes related to fibrosis, inflammation, tissue repair, remodeling, and chondrometaplasia, such as COL1A2, COL3A1, COL5A1, TGFB1, VEGFA, TNFA, MMP2, COL10A1, and ADAMTS4, were highly expressed on the dorsal side of the thickened ligamentum flavum. The biological processes occurring on the dorsal side of the thickened ligamentum flavum were extracellular matrix organization, cell adhesion, extracellular matrix disassembly, and proteolysis.These are considered important pathologies of ligamentum flavum thickening.

Quantitative evaluation of the lumbar ligamentum flavum using MRI T2-mapping: Efficacy of its clinical application in patients with lumbar spinal stenosis.

OBEJECTIVE: To perform a magnetic resonance imaging T2-mapping of the ligamentum flavum in healthy individuals and patients with lumbar spinal stenosis scheduled for surgery and compare the T2 relaxation times. SUBJECTS AND METHODS: The T2 relaxation time of the ligamentum flavum was compared among 3 groups, healthy young individuals (H group (age< 50)), healthy middle-aged and older individuals (H group (age≥50)), and patients with lumbar spinal stenosis (L group). Additionally, the thickness of the ligament was measured in the axial image plane, and the occupied area ratio of each fiber was measured by staining the surgically obtained ligament, and each was correlated with the T2 relaxation time. We also evaluated the adhesion of the ligamentum flavum with the dura mater during the surgery. RESULTS: The T2 relaxation times were significantly prolonged in H group (age ≥50) and L group (P < 0.001) compared to H group (age<50). The relationship between collagen fiber and T2 relaxation times was significantly positive (r = 0.720, P < 0.001). Moreover, the relaxation times were significantly prolonged in those with adhesion of the ligamentum flavum with the dura mater (P < 0.05). The cut-off for the relaxation time was 50 ms (sensitivity: 62.50%, false positive rate: 10.8%). CONCLUSION: Healthy middle-aged and older individuals and patients with lumbar spinal stenosis and adhesion of the ligamentum flavum with the dura mater have prolonged T2 relaxation times. Hence, the adhesion between the ligamentum flavum and dura mater should be considered in cases with a relaxation time ≥50 ms.

The MOTION study: Two-year results of a real-world randomized controlled trial of the mild® procedure for treatment of lumbar spinal stenosis.

OBJECTIVE: The MOTION study is designed to measure the impact of percutaneous image-guided lumbar decompression as a first-line therapy on patients otherwise receiving real-world conventional medical management for lumbar spinal stenosis with neurogenic claudication secondary to hypertrophic ligamentum flavum. This prospective, multicenter randomized controlled trial uses objective and patient-reported outcome measures to compare the combination of the mild® percutaneous treatment and nonsurgical conventional medical management (CMM) to CMM-Alone. METHODS: Test group patients received the mild procedure after study enrollment. Test and control groups were allowed conventional conservative therapies and low-risk interventional therapies as recommended by their physicians. Subjective outcomes included the Oswestry Disability Index, Numeric Pain Rating Scale, and Zurich Claudication Questionnaire. Objective outcomes included a validated Walking Tolerance Test, the rate of subsequent lumbar spine interventions, and safety data. RESULTS: Two-year follow-up included 64 mild + CMM and 67 CMM-Alone patients. All outcome measures showed significant improvement from baseline for mild + CMM, whereas the majority of CMM-Alone patients had elected to receive mild treatment or other lumbar spine interventions by 2 years, precluding valid 2-year between-group comparisons. Neither group reported any device- or procedure-related adverse events. CONCLUSIONS: The durability of mild + CMM for this patient population was demonstrated for all efficacy outcomes through 2 years. Improvements in walking time from baseline to 2 years for patients treated with mild + CMM were significant and substantial. The lack of reported device or procedure-related adverse events reinforces the strong safety profile of the mild procedure. These results provide support for early interventional treatment of symptomatic LSS with the mild procedure.

Novel therapeutic strategy in the treatment of ossification of the ligamentum flavum associated with dural ossification.

PURPOSE: To investigate the imaging characteristics of thoracic ossification of ligamentum flavum (OLF) combined with dural ossification (DO) and the clinical efficacy of zoning laminectomy. METHOD: The clinical data of 48 patients with thoracic OLF combined with DO who underwent zoning laminectomy between June 2016 and May 2020 were retrospectively analyzed. The modified Japanese Orthopedic Association (mJOA) score was used to evaluate neurological function before and after surgery, and the clinical efficacy was evaluated according to the improvement rate. RESULTS: The symptoms of all patients significantly improved after the operation, and the average follow-up time was 27.8 (10-47) months. In addition, the average mJOA score had increased from 5.0 (2-8) preoperatively to 8.7 (6-11) postoperatively (t = 18.880, P < 0.05). The average improvement rate was 62.6% (25-100%), with 16 patients graded as excellent, 21 as good, and 11 as fair. Cerebrospinal fluid leakage occurred in 12 cases (25.0%), and all of them healed well after treatment. No postoperative aggravation of neurological dysfunction, wound infection or hematoma occurred. At the last follow-up, there was no recurrence of symptoms and kyphosis. CONCLUSION: The Zoning laminectomy described here is both safe and effective.

Clinical progression of ossification of the ligamentum flavum in thoracic spine: a 10- to 11-year follow-up study.

BACKGROUND: Thoracic ossification of ligamentum flavum (TOLF) can be asymptomatic and progress insidiously. But, long-term follow-up results of clinical progression of TOLF are still unknown. METHODS: The clinical progression of 81 patients with TOLF at our center, followed for 10 to 11 (mean, 10.3) years from May 2010 to November 2021, were analyzed. Among them, 51 patients with thoracic myelopathy were caused by single- or multi-segment TOLF, and received partial TOLF resection (30 patients) or total TOLF resection (21 patients). The remaining 30 patients showed TOLF on imaging examinations, but TOLF was not the responsible compressing factor causing myelopathy and with no TOLF resection. The mJOA score (total 11 scores) and spinal operation were used to evaluate the clinical progression at follow-up. RESULTS: During the 10- to 11-year follow-up of 81 TOLF patients, 71 (87.7%) had no deterioration of neurological function, and 10 (12.3%) patients had deterioration of neurological function and had another spinal operation, including only 4 (4.9%) suffered thoracic myelopathy caused by the progression of TOLF; 6 (7.4%) for other spinal diseases: 2 (2.5%) had fall damage and acute spinal cord injury at the TOLF level; 2 (2.5%) had thoracic myelopathy caused by ossification of posterior longitudinal ligament (OPLL); 2 (2.5%) had cervical spondylosis and received cervical operation. CONCLUSIONS: Most TOLF (87.7%) patients had no clinical progression and received no reoperations for TOLF in the ten-year dimension (mean, 10.3 years). Narrow spinal canal for TOLF increases the risk of traumatic paraplegia.

Prevalence, diagnosis, and impact on clinical outcomes of dural ossification in the thoracic ossification of the ligamentum flavum: a systematic review.

STUDY DESIGN: Systematic review. BACKGROUND CONTEXT: Thoracic ossification of the ligamentum flavum (TOLF) has become the principal cause of thoracic spinal stenosis. Dural ossification (DO) was a common clinical feature accompanying with TOLF. However, on account of the rarity, we know little about the DO in TOLF so far. PURPOSE: This study was conducted to elucidate the prevalence, diagnostic measures, and impact on the clinical outcomes of DO in TOLF by integrating the existing evidence. METHODS: PubMed, Embase, and Cochrane Database were comprehensively searched for studies relevant to the prevalence, diagnostic measures, or impact on the clinical outcomes of DO in TOLF. All retrieved studies meeting the inclusion and criterion were included into this systematic review. RESULTS: The prevalence of DO in TOLF treated surgically was 27% (281/1046), ranging from 11 to 67%. Eight diagnostic measures have been put forward to predict the DO in TOLF using the CT or MRI modalities, including "tram track sign", "comma sign", "bridge sign", "banner cloud sign", "T2 ring sign", TOLF-DO grading system, CSAOR grading system, and CCAR grading system. DO did not affect the neurological recovery of TOLF patients treated with the laminectomy. The rate of dural tear or CSF leakage in TOLF patients with DO was approximately 83% (149/180). CONCLUSION: The prevalence of DO in TOLF treated surgically was 27%. Eight diagnostic measures have been put forward to predict the DO in TOLF. DO did not affect the neurological recovery of TOLF treated with laminectomy but was associated with high risk of complications.

Manipulation of osteogenic and adipogenic differentiation of human degenerative disc and ligamentum flavum derived progenitor cells using IL-1ß, IL-19, and IL-20.

PURPOSE: To elucidate whether pro-inflammatory cytokines might influence the commitment of intervertebral disc (IVD)- and ligamentum flavum (LF)-derived progenitor cells toward either osteogenesis or adipogenesis, specifically Interleukin-1ß (IL-1ß), IL-19, and IL-20. METHODS: Sixty patients with degenerative spondylolisthesis and lumbar or lumbosacral spinal stenosis were included in the study. Injuries to the spine, infections, and benign or malignant tumors were excluded. From nine patient samples, IVD- and LF-derived cells were isolated after primary culture, and two clinical samples were excluded due to mycoplasma infection. The effects of IL-1ß, IL-19, as well as IL-20 in regulating osteogenic and adipogenic differentiation in vitro were investigated. RESULTS: Primary IVD- and LF-derived cells were found to have a similar cell morphology and profile of surface markers (CD44, CD90, and CD105) as placenta-derived mesenchymal stem cells (MSCs). Primary IVD/LF cells have a high capacity to differentiate into osteocytes and adipocytes. IL-19 had a tendency to promote adipogenesis. IL-20 inhibited osteogenesis and promoted adipogenesis; IL-1ß promoted osteogenesis but inhibited adipogenesis. CONCLUSION: IL-1ß, IL-19, and IL-20 impact the adipogenic and osteogenic differentiation of IVD-derived and LF-derived cells. Modulating the expression of IL-1ß, IL-19, and IL-20 provides a potential avenue for controlling cell differentiation of IVD- and LF-derived cells, which might have beneficial effect for degenerative spondylolisthesis and spinal stenosis.

Surgical outcomes of percutaneous endoscopic thoracic decompression in the treatment of multi-segment thoracic ossification of the ligamentum flavum.

BACKGROUND: Previous studies have demonstrated satisfactory outcomes of percutaneous endoscopic thoracic decompression (PETD) for single-segment thoracic ossification of the ligamentum flavum (TOLF). However, the clinical outcomes of PETD in patients with multi-segment TOLF (mTOLF) remain unclear. The aim of the present study was to evaluate the efficacy and safety of PETD for patients with multi-segment mTOLF. METHODS: Eighteen consecutive patients (41 segments) with mTOLF were treated with PETD between January 2020 and December 2021. The clinical outcomes were evaluated using the modified Japanese Orthopaedic Association (mJOA) score and Visual Analog Scale (VAS), whereas radiographic parameters were measured by cross-section area of the spinal canal and anteroposterior diameter of the spinal cord. RESULTS: The follow-up period ranged from 14 to 34 months. The mean operation time and blood loss were 154.06 ± 32.14 min and 61.72 ± 12.72 ml, respectively. Hospital stay after first-stage operation was 10.89 ± 2.42 days. The mJOA score and VAS score significantly improved at the final follow-up, with a mean mJOA recovery rate of 63.3 ± 21.90%. The incidence of complications was 12.2% per level. The radiographic outcomes showed adequate decompression of the spinal cord. CONCLUSIONS: The present study demonstrates that PETD is effective and safe as a minimally invasive procedure to treat patients with mTOLF. All patients showed relief of their symptoms and improvement in neurological function.

CT-based radiographic measurements and effectiveness estimates of full-endoscopic surgery in thoracic myelopathy caused by ossification of ligamentum flavum.

BACKGROUND: Evaluate the effectiveness of posterior percutaneous full-endoscopic technique for patients with thoracic myelopathy caused by ossification of ligamentum flavum (TOLF). METHODS: A prospective study was conducted for 16 patients with TOLF, who were treated with posterior endoscopic technique from 2017 to 2019. The sagittal and cross-sectional CT images are used to measure the area of ossified ligamentum and evaluate the decompression of surgery, respectively. The effectiveness was evaluated with visual analog scale (VAS), modified Japanese Orthopedic Association scale (mJOA), The Oswestry Disability Index (ODI), and Macnab efficacy evaluation. RESULTS: The average area of TOLF on sagittal and cross-sectional CT images in the 16 patients was (116.62 ± 32.72) mm2 and (141.59 ± 27.25) mm2 preoperatively, (15.99 ± 12.54) mm2 and (11.72 ± 8.64) mm2 at 3 days after the operation, (16.78 ± 11.49) mm2 and (10.82 ± 7.57) mm2 postoperative 1 year, respectively. The invasive proportion of spinal canal at preoperative sagittal and cross-sectional CT images was (48.10 ± 10.04) % and (57.58 ± 11.37) %, which decreased to (6.83 ± 4.48) % and (4.40 ± 3.01) % at the final follow-up. The average score of mJOA, VAS and ODI improved. The excellent and good rate was 87.50% according to Macnab evaluation. Compared with preoperative, differences in areas of TOLF, proportions of spinal canal, and clinical assessments of postoperative 3 days and 1 year were all statistically significant. Two cases of dural tear were observed. CONCLUSION: Endoscopic surgery has a good clinical effect on TOLF, which has the advantage of less trauma to the paraspinal muscles and no impact on the spinal structure. The CT-based radiographic measurements can quantitatively evaluate the degree of spinal canal stenosis in TOLF.

Post-surgical thoracic spinal cord herniation following an unrepaired dural defect: a rare complication.

Surgery for ossification of the ligamentum flavum (OLF) comes with a relatively high risk of dural tear. We report a 50-year-old woman, who presented with symptomatic spinal stenosis from OLF at T11-T12 and lower lumbar spondylosis for which a single stage posterior decompression and instrumented fusion of both sites was done. Removal of the OLF resulted in a small dural tear with intact arachanoid which was covered using a fibrin sealant. In the first post-operative day, the patient's neurology started deteriorating. An MR scan was done to look for hematoma. It showed the spinal cord herniating out of the thecal sac at the operated level. Emergency re-operation was done to reduce the herniation and the dural defect was repaired. The patient gradually recovered to her best functional status. Based on this experience, we advise primary repair of inadvertent durotomies.