Hypertrophied posterior longitudinal ligament and ligamentum flavum causing myelopathy: a case report and literature review.

INTRODUCTION: The occurrence of concurrent hypertrophied posterior longitudinal ligament (HPLL) and hypertrophied ligamentum flavum (HLF) in the thoracic spine is a very rare presentation. This case report describes a young female who developed thoracic myelopathy secondary to a combination of both thoracic HPLL and HLF. CASE PRESENTATION: A 30-year-old previously well female was referred for an MRI scan of the thoraco-lumbar spine. She was having lower limb weakness and difficulty in walking, which had progressed over 3 months. On examination, she was found to have spastic lower limbs with associated motor weakness. Her biochemical investigations were unremarkable. The MRI scan showed HPLL, which was uniformly hypointense on T2W images and was isointense on T1W images. The hypertrophied segment was extending from T2 level to T7 level. Similarly, the ligamentum flavum was hypertrophied from T1 level to T8 level. The thoracic spinal cord was seen compressed between the hypertrophied ligaments. The compressed cord showed central hyperintense signal pattern in T2W images. CT scan of the thoracic spine did not show any calcifications or ossifications along the ligaments. Patient underwent posterior decompressive surgery and she had an uneventful recovery. DISCUSSION: Although few cases of HPLL and HLF were reported in older patients in literature, both these conditions were found in this patient at a younger age. HPLL and HLF are thought to be precursors of ossification of these ligaments and these patients need long-term follow-up.

Ligamentum flavum analysis in patients with lumbar discus hernia and lumbar spinal stenosis.

The normal ligamentum flavum (LF) is a well-defined elastic structure with specific innervation. Several studies investigated LF in patients with lumbar spinal stenosis (LSS) and used lumbar discus hernia (LDH) patients as control group, only on the presumed thesis that LF in this patients have normal morphology. In patients with LSS thickening of the LF is the main cause of stenosis, which is most often presented with neurogenic claudication, whose pathophysiological mechanism is not completely understood. We conducted observational cohort study of 60 operated patients divided into two groups. The first group of 30 patients underwent micro-discectomy (LSH group), and second group with 30 patients underwent decompression, after which analysis of harvested LF was performed. Patients from the LDH group and LSS group differed significantly in the frequencies of chief complaints, duration of symptoms, physical examination, and specific morphological/radiological parameters. The LF analysis showed that the groups differed significantly in the amount of collagen and elastic fibers, as well as in the histological appearance/architectonics of elastic fibers. Also, groups differ in the presence of LF nerve fibers. Our findings speak in favor of the recently postulated inflammatory theory in the origin of spinal neurogenic claudication's.

LC-MS/MS analysis of elastin crosslinker desmosines and microscopic evaluation in clinical samples of patients with hypertrophy of ligamentum flavum.

Ligamentum flavum (LF) pathologies often lead to severe myelopathy or radiculopathy characterized by reduced elasticity, obvious thickening, or worsened ossification. Elastin endows critical mechanical properties to tissues and organs such as vertebrae and ligaments. Desmosine (DES) and isodesmosine (IDES) are crosslinkers of elastin monomers called tropoelastin. These crosslinkers are potential biomarkers of chronic obstructive pulmonary disease. As a biological diagnostic tool that supplements existing symptomatic, magnetic resonance imaging scanning or radiological imaging diagnostic measures for LF hypertrophy and associated pathologies, an isotope-dilution liquid chromatography-tandem mass spectrometry method with selected reaction monitoring mode for the quantitation of DESs in human plasma, urine, cerebrospinal fluid (CSF), and yellow ligamentum was investigated. Isotopically labeled IDES-13C3,15N1 was used as an internal standard (ISTD) for DES quantitation for the first time. The samples plus ISTD were hydrolyzed with 6 N hydrochloric acid. Analytes and ISTD were extracted using a solid phase extraction cellulose cartridge column. The assays were repeatable, reproducible, and accurate with % CV ≤ 7.7, ISTD area % RSD of 7.6, and % AC ≤ (101.2 ± 3.90) of the calibrations. The ligamentum samples gave the highest average DES/IDES content (2.38 µg/mg) on a dry-weight basis. A high percentage of the CSF samples showed almost no DESs. Urine and plasma samples of patients showed no significant difference from the control (p-value = 0.0519 and 0.5707, respectively). Microscopy of the yellow ligamentum samples revealed dark or blue-colored zones of elastin fibers that retained the hematoxylin dye and highly red-colored zones of collagen after counterstaining with van Gieson solution. Thus, we successfully developed a method for DES/IDES quantitation in clinical samples.

Ligamentum Flavum Rupture by Epidural Injection Using Ultrasound with SMI Method.

The loss of resistance (LOR) method has been used exclusively to identify epidural space. It is difficult to find the epidural space without the risk of dural puncture. Various devices have been developed to improve the accuracy of the LOR method; however, no method has overcome the problems completely. Therefore, we devised a ligamentum flavum rupture method (LFRM) in which the needle tip is placed only on the ligamentum flavum during the epidural injection, and the injection pressure is used to rupture the ligamentum flavum and spread the drug into the epidural space. We confirmed the accuracy of this method using ultrasound with superb microvascular imaging (SMI) to visualize the epidural space. Here, we report two cases of 63-year-old and 90-year-old males. The 63-year-old patient presented with severe pain in his right buttock that extended to the posterior lower leg. The 90-year-old patient presented with intermittent claudication every 10 min. LFRM was performed, and SMI was used to confirm that the parenteral solution had spread into the epidural space. Our results indicate that LFRM can be used for interlaminar lumbar epidural steroid injections.

Repeated Recurrence of Ligamentum Flavum Ossification After Posterior Spinal Surgery: A Case Report and Literature Review.

CASE: Patients with myelopathy due to narrowing of the spinal canal with ossification of the ligamentum flavum (OLF) generally require surgical intervention, but surgical methods for OLF remain controversial. We discuss our experience regarding posterior fusion surgery with instrumentation for a patient with recurrent OLF at the same level after decompression surgery as well as describe the preoperative and postoperative course of this rare case. CONCLUSION: Posterior decompression and fusion surgery is recommended as revision surgery for recurrent OLF at the same level after decompression surgery. A detailed surgical planning should be developed before surgery.

Full-Endoscopic Decompression for Thoracic Ossification of the Ligamentum Flavum Combined with Dural Ossification.

Ossification of the ligamentum flavum (OLF) can result in spinal stenosis. Thoracic spinal cord compression due to spinal stenosis is a common cause of progressive thoracic myelopathy in Asian countries. The incidence of complications is high in open decompression surgeries for thoracic OLF. With dural ossification (DO), the risk of complications is even higher in thoracic OLF. We introduce a full-endoscopic decompression surgery for thoracic OLF combined with DO under local anesthesia. Hemilaminectomy is performed using a high-speed burr under the endoscopy first, and then decompression of the contralateral spinal canal is completed using an "over the top" technique. DO resection uses the eggshell technique; after the base of the DO is cut from the lamina, forceps or lamina rongeurs are typically used for removal. The dural defect left after resection does not need repair. Neurological function was improved, and no complications such as hematoma or neck pain occurred. On imaging, no pseudodural cyst, cerebrospinal fluid leakage, or wound complications were observed after the operation. Endoscopic surgery causes less damage to the posterior ligament complex, so no cases of persistent back pain complaints or secondary internal fixation requirements were found in this study. Full-endoscopic decompression can achieve good imaging and clinical effects in the treatment of thoracic OLF with DO.

[Application of unilateral biportal endoscopy technique in single-segment thoracic ossification of ligamentum flavum].

Objective: To investigate the safety and effectiveness of unilateral biportal endoscopy (UBE) technique in the treatment of single-segment thoracic ossification of ligamentum flavum (TOLF). Methods: Between August 2020 and December 2021, 11 patients with single-segment TOLF were treated with UBE technique. There were 6 males and 5 females, with an average of 58.2 years (range, 49-72 years). The responsible segment was T 6, 7 in 1 case, T 7, 8 in 1 case, T 8, 9 in 2 cases, T 9, 10 in 2 cases, T 10, 11 in 2 cases, and T 11, 12 in 3 cases. Imaging examination showed that the ossification were located on the left side in 4 cases, on the right side in 3 cases, and on bilateral sides in 4 cases. The main clinical symptoms were chest and back pain or lower limb pain, all accompanied by lower limb numbness and fatigue. The disease duration ranged from 2 to 28 months (median, 17 months). The operation time, postoperative hospital stay, and complications were recorded. Visual analogue scale (VAS) score was used to evaluate the chest and back pain and low limb pain, and Oswestry disability index (ODI) and Japanese Orthopedic Association (JOA) score were used to evaluate functional recovery before operation and at 3 days, 1 month, 3 months after operation, and last follow-up. The anteroposterior diameter of the coronal spinal canal was measured by CT before and after operation to evaluate the effect of surgical decompression. Results: All operations were successfully completed. The operation time was 50-105 minutes, with an average of 80.0 minutes. No postoperative complication such as dural sac tear, cerebrospinal fluid leakage, spinal nerve injury, or infection occurred. The postoperative hospital stay was 2-5 days, with an average of 3.1 days. All incisions healed by first intention. All patients were followed up 6-22 months, with an average of 14.8 months. CT measurement at 3 days after operation showed that the anteroposterior diameter of the spinal canal was (8.63±1.61) mm, which was significantly larger than that before operation [(3.67±1.37) mm] ( t=-12.181, P<0.001). The VAS score of chest and back pain and lower limb pain and ODI at each time point after operation were significantly lower than those before operation ( P<0.05). The above indexes were further improved after operation, except that there was no significant difference between at 3 months after operation and at last follow-up ( P>0.05), the differences between other time points were significant ( P<0.05). There was no recurrence during the follow-up period. Conclusion: UBE technique is a safe and effective method to treat single-segment TOLF, but its long-term effectiveness needs to be further studied.

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.

An unusual obstacle to the thoracic interlaminar epidural injection for the treatment of post-herpetic neuralgia.

Interlaminar epidural steroid injections corresponding to dermatomes affected by post-herpetic neuralgia (PHN) were found effective in reducing pain. Diffuse idiopathic skeletal hyperostosis (DISH) is a non-inflammatory condition that mainly occurs with calcification and ossification of spinal ligaments such as anterior and posterior longitudinal, interspinous, supraspinous ligament, and ligamentum flavum. In this case, it is presented that the failure of the access to the T7-T8 interlaminar space due to the supra/interspinous ligament calcification and ossification accompanied by thoracic DISH in a 73-year-old male for the treatment of PHN.

Lumbar ossification of the ligamentum flavum reflects a strong ossification tendency of the entire spinal ligament.

Patients with ossification of the ligamentum flavum (OLF) in the lumbar spine may be at high risk of developing concomitant ossification of the entire spinal ligament, but the etiology remains unclear. We investigated the propensity for spinal ligament ossification in asymptomatic subjects with lumbar OLF using the data of 595 Japanese individuals receiving medical check-ups, including computed tomography (CT) scanning. The severity of OLF (total number of intervertebral segments with OLF) of the entire spine on CT was quantified using an OLF index. Subjects with OLF were grouped according to this index: localized OLF (n = 138), intermediate OLF (n = 70), and extensive OLF (n = 31). The proportion of subjects with lumbar OLF increased with increasing OLF index (localized 13.7%, intermediate 41.4%, and extensive 70.9%). Multiple regression analysis found that lumbar OLF index was associated with thoracic OLF index, and co-existence of ossification of the posterior longitudinal ligament (OPLL) of the thoracic and lumbar spine. This study showed that subjects with more multilevel lumbar OLF were more likely to develop multilevel thoracic OLF and to have coexisting OPLL. Patients with lumbar OLF may be a distinctive subgroup with a strong tendency to ossification of the entire spinal ligament.

En bloc resection of ligamentum flavum with laminotomy of the caudal lamina in the minimally invasive laminectomy: surgical anatomy and technique.

OBJECTIVE: A CSF leak is a potential complication in a lumbar laminectomy. An analysis of the author's surgical experience identified inadvertent durotomies that occurred when resecting the ligamentum flavum at its insertion into the superior aspect of the caudal lamina. Anatomical analyses of the lumbar canal diameter demonstrate that the insertion point of the caudal ligamentum flavum is the most constrained area of the canal. The surgical technique was modified to eliminate the need for direct action in that anatomical region after the author compared the efficacy of piecemeal resection of the ligamentum flavum with en bloc resection with a laminotomy of the caudal lamina beyond the insertion point of the ligamentum flavum in the lumbar laminectomy. METHODS: An analysis of a single surgeon's experience managing 147 consecutive patients with lumbar stenosis who underwent single-level lumbar hemilaminectomies over a 4-year period was performed. Patients were managed with either piecemeal resection (cohort 1) or en bloc resection with a laminotomy beyond the caudal insertion (cohort 2) of the ligamentum flavum. RESULTS: Seventy-seven patients underwent piecemeal resection (cohort 1), and 70 underwent en bloc resection (cohort 2). There were 5 CSF leaks (6.4%) in cohort 1. There were no CSF leaks in cohort 2. There was a statistically significant difference in operative times between the two groups (p = 0.04), but there was no statistically significant difference in patient-reported outcomes at 6 months between the groups. CONCLUSIONS: En bloc resection of the ligamentum flavum with a laminotomy below the caudal insertion point appears to decrease the risk of a CSF leak by working beyond the most constrained diameter of the lumbar canal to release the caudal insertion of the ligamentum flavum.

Retrodural space of Okada in the posterior ligamentous complex region: clinical and anatomical findings relevant to lumbar interlaminar epidural injection.

BACKGROUND: The retrodural space of Okada is a potential space posterior to the ligamentum flavum that allows communication with the bilateral facet joints. However, the actual anatomy of this space has not been clearly visualized to date. We sought to investigate the characteristics of patients showing contrast spreading to the facet joint space during epidural injection and to clarify the anatomical structures of the retrodural space and adjacent ligamentous tissues in cadaveric specimens. METHODS: Fluoroscopic images of patients who underwent fluoroscopy-guided lumbar interlaminar epidural injection were assessed for contrast flow to the facet joints. Patient demographics, preprocedural imaging study findings, and epidural approaches were analyzed. The anatomical study included the sectional dissection, micro-CT imaging, and histological evaluation of lumbar spine specimens from 16 embalmed cadavers. RESULTS: Fluoroscopic images of 605 epidural injections were analyzed. Among them, 36 with inadvertent spread into the facet joints (5.9%) were identified. Multivariate analysis revealed that facet joint pathologies were significantly associated with inadvertent spread into the facet joints (OR 4.382; 95% CI 1.160 to 16.558; p=0.029). Micro-CT and histological findings consistently showed a retrodural space between the ligamentum flavum and interspinous ligament. Various anatomical communication routes in the posterior ligamentous complex leading to this space were observed in specimens with degenerative and pathological changes. CONCLUSION: Degenerative and pathological facet joint changes were associated with a higher incidence of spread into the retrodural space during epidural injection. Our findings confirm anatomical evidence for a false loss of resistance before the needle enters the epidural space.

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.

Strong relationship between dyslipidemia and the ectopic ossification of the spinal ligaments.

Obesity and metabolic disturbances are prevalent in ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF); however, the involvement of dyslipidemia (DL) in OPLL/OLF remains uncertain. We investigated the association between dyslipidemia and OPLL/OLF using a dataset of 458 individuals receiving health screening tests, including computed tomography. Subjects were grouped according to the presence or location of OPLL/OLF: controls (no OPLL/OLF, n = 230), OLF (n = 167), cervical OPLL (n = 28), and thoracic OPLL (n = 33). They were also grouped according to the presence of dyslipidemia (DL[+], n = 215; DL[-], n = 243). The proportion of dyslipidemia in the OLF and OPLL groups was 1.6-2.2 times higher than that in the control group. The proportion of OLF and OPLL in the DL(+) group was significantly higher than that in the DL(-) group (OLF, 43% vs. 29%; cervical OPLL, 14.4% vs. 3.2%; thoracic OPLL, 11.1% vs. 3.7%). Multivariate logistic regression analysis showed an association between all ossification types and dyslipidemia. This study demonstrated an association of dyslipidemia with OPLL/OLF; further investigation on the causal relationship between dyslipidemia and ectopic spinal ligament ossification is warranted to develop a therapeutic intervention for OPLL/OLF.

Factors Predicting Poor Surgical Outcome in Patients with Thoracic Ossified Ligamentum Flavum - Analysis Of 106 Patients in a Tertiary Care Hospital in South India.

Background: Ossified ligamentum flavum (OLF) is the major cause of thoracic myelopathy in our locality. Surgical outcomes and their related factors for patients with thoracic OLF (T-OLF) remain unclear because of the few studies on this condition. Objectives: The present study aimed to examine the factors predicting poor surgical outcomes and the effectiveness of decompressive laminectomy and OLF resection in patients with T-OLF. Material and Methods: A total of 106 patients with T-OLF operated at our institute from 2007 to 2018 were included. The mJOA score was used in neurological assessment preoperatively and during the follow-up. Multiple regression analysis was conducted to know the best correlation between factors and surgical outcomes. Results: The mean mJOA score was 5.67 ± 2.13 preoperatively and 7.50 ± 2.60 postoperatively at the end of follow-up. The recovery rate was 43.29 ± 30.55%. After decompressive laminectomy, the mean mJOA score, modified Nurick score, and Ashworth's grade showed significant improvement (P < 0.001). Multiple regression analysis showed that the age of the patient, associated trauma, OLF level, tuberous type OLF, intramedullary signal change on T2WI, preoperative severity of myelopathy, pre-op mJOA score, and pre-op Nurick grade were significantly correlated with the surgical outcome (P < 0.001). No correlation was identified with the duration of symptoms, dural ossification, dural tear, and CSF leak (P > 0.05). Conclusion: It is important to identify preventable risk factors for poor surgical outcomes for T-OLF. Age of the patient, associated trauma, OLF level, tuberous type OLF, intramedullary signal change on T2WI, preoperative severity of myelopathy, preoperative mJOA score, and Nurick grade were important predictors of surgical outcome in our study series.

Administration of N-Acetylcysteine to Regress the Fibrogenic and Proinflammatory Effects of Oxidative Stress in Hypertrophic Ligamentum Flavum Cells.

Ligamentum flavum hypertrophy (LFH) is a major cause of lumbar spinal stenosis (LSS). In hypertrophic ligamentum flavum (LF) cells, oxidative stress activates intracellular signaling and induces the expression of inflammatory and fibrotic markers. This study explored whether healthy and hypertrophic LF cells respond differently to oxidative stress, via examining the levels of phosphorylated p38 (p-p38), inducible nitric oxide synthase (iNOS), and α-smooth muscle actin (α-SMA). Furthermore, the efficacy of N-acetylcysteine (NAC), an antioxidant, in reversing the fibrogenic and proinflammatory effects of oxidative stress in hypertrophic LF cells was investigated by assessing the expression levels of p-p38, p-p65, iNOS, TGF-ß, α-SMA, vimentin, and collagen I under H2O2 treatment with or without NAC. Under oxidative stress, p-p38 increased significantly in both hypertrophic and healthy LF cells, and iNOS was elevated in only the hypertrophic LF cells. This revealed that oxidative stress negatively affected both hypertrophic and healthy LF cells, with the hypertrophic LF cells exhibiting more active inflammation than did the healthy cells. After H2O2 treatment, p-p38, p-p65, iNOS, TGF-ß, vimentin, and collagen I increased significantly, and NAC administration reversed the effects of oxidative stress. These results can form the basis of a novel therapeutic treatment for LFH using antioxidants.

Molecular and Genetic Mechanisms of Spinal Stenosis Formation: Systematic Review.

Spinal stenosis (SS) is a multifactorial polyetiological condition characterized by the narrowing of the spinal canal. This condition is a common source of pain among people over 50 years old. We perform a systematic review of molecular and genetic mechanisms that cause SS. The five main mechanisms of SS were found to be ossification of the posterior longitudinal ligament (OPLL), hypertrophy and ossification of the ligamentum flavum (HLF/OLF), facet joint (FJ) osteoarthritis, herniation of the intervertebral disc (IVD), and achondroplasia. FJ osteoarthritis, OPLL, and HLF/OLFLF/OLF have all been associated with an over-abundance of transforming growth factor beta and genes related to this phenomenon. OPLL has also been associated with increased bone morphogenetic protein 2. FJ osteoarthritis is additionally associated with Wnt/ß-catenin signaling and genes. IVD herniation is associated with collagen type I alpha 1 and 2 gene mutations and subsequent protein dysregulation. Finally, achondroplasia is associated with fibroblast growth factor receptor 3 gene mutations and fibroblast growth factor signaling. Although most publications lack data on a direct relationship between the mutation and SS formation, it is clear that genetics has a direct impact on the formation of any pathology, including SS. Further studies are necessary to understand the genetic and molecular changes associated with SS.

EGF Contributes to Hypertrophy of Human Ligamentum Flavum via the TGF-ß1/Smad3 Signaling Pathway.

Background: The most common spinal disorder in elderly is lumbar spinal canal stenosis (LSCS). Previous studies showed that ligamentum flavum hypertrophy (LFH) with fibrosis as the main pathological change is one of the pathogenic factors leading to LSCS. Epidermal Growth Factor (EGF) is known to have an intimate relationship with fibrosis in various tissues. Nevertheless, currently, there are few studies regarding EGF in LFH. The effect of EGF on the development of LFH is unknown, and the underlying pathomechanism remains unclear. In this study, we investigated the role of EGF in LFH and its potential molecular mechanism. Methods: First, the expression levels of EGF, phosphorylation of EGF receptor (pEGFR), Transforming growth factor-ß1 (TGF-ß1), Phosphorylated Smad3 (pSmad3), collagen I and collagen III were examined via immunohistochemistry and Western blot in LF tissues from patients with LSCS or Non-LSCS. Second, primary LF cells were isolated from adults with normal LF thickness and were cultured with different concentrations of exogenous EGF with or without erlotinib/TGF-ß1-neutralizing antibody. Results: The results showed that EGF, pEGFR, TGF-ß1, pSmad3, collagen I and collagen III protein expression in the LSCS group was significantly higher than that in the Non-LSCS group. Meanwhile, pEGFR, TGF-ß1, pSmad3, collagen I and collagen III protein expression was significantly enhanced in LF cells after exogenous EGF exposure, which can be notably blocked by erlotinib. In addition, pSmad3, collagen I and collagen III protein expression was blocked by TGF-ß1-neutralizing antibody. Conclusions: EGF promotes the synthesis of collagen I and collagen III via the TGF-ß1/Smad3 signaling pathway, which eventually contributes to LFH.

Relationship between Severity of Lumbar Spinal Stenosis and Ligamentum Flavum Hypertrophy and Serum Inflammatory Factors.

Objective: This study is aimed at investigating the correlation between lumbar spinal stenosis (LSS) severity, ligamentum flavum hypertrophy, and the upregulation of inflammatory markers. Methods: From March 2019 and May 2022, eighty-five inpatients with LSS were enlisted as the study's research group, while sixty-five patients hospitalized for lumbar intervertebral disc herniation over the same time period served as the study's control group. Moreover, mild, moderate, and severe subgroups of patients were created within the research population based on their LSS severity. The ligamentum flavum thickness and the positive expression rates of TNF-α, TGF-ß1, and IL-1α were compared between the study group and the control group. The levels of TNF-α, TGF-ß1, and IL-1α that were found to be positively expressed were compared between the mild, moderate, and severe groups. Patients with LSS had their ligamentum flavum thickness and their positive expression rates of TNF-α, TGF-ß1, and IL-1α analyzed using Spearman correlation analysis. We evaluated the diagnostic utility of the positive expression rates of IL-α1, TGF-ß1, and TNF-α and ligamentum flavum thickness in distinguishing the severity of LSS using a receiver operating characteristic (ROC) curve. Results: The rates of both lower limb pain (40.00%) and intermittent claudication (80.00%) in the LSS group were higher than those in the lumbar disc herniation group (15.38%, 12.31%), with statistical significance (P < 0.05). However, no substantial disparity was observed in left lower limb pain, right lower limb pain, low back pain, lower limb sensation, muscle strength, and reflex abnormalities between the two groups (P > 0.05). Positive expressions of TGF-ß1, TNF-α, and IL-1α and thicker ligamentum flavum were more prevalent in the LSS group than in the lumbar intervertebral disc herniation group. All indexes were significantly (P < 0.05) higher in the moderate stenosis group than in the severe stenosis group. Additionally, the thickness of the ligamentum flavum and the positive expression rates of TNF-α, TGF-ß1, and IL-1α were higher in the mild and moderate stenosis groups than in the severe stenosis group. The expression levels of TNF-α, TGF-ß1, and IL-1α were favorably linked with ligamentum flavum thickness (P < 0.05). ROC curve analysis showed that the thickness of ligamentum flavum, the expression of IL-1α, the expression of TGF-ß1, and the expression of TNF-α could effectively diagnose mild, moderate, and severe LSS (P < 0.05). Conclusion: Ligamentum flavum hypertrophy and positive expression rates of IL-1α, TGF-ß1, and TNF-α are closely linked to LSS, which can effectively identify mild, moderate, and severe LSS.

Elucidating the effect of mechanical stretch stress on the mechanism of ligamentum flavum hypertrophy: Development of a novel in vitro multi-torsional stretch loading device.

OBJECTIVE: We developed a novel multi-torsional mechanical stretch stress loading device for ligamentum flavum cells and evaluated its influence on the development of ligamentum flavum hypertrophy, a common cause of lumbar spinal canal stenosis. MATERIALS AND METHODS: Stretch strength of the device was optimized by applying 5% and 15% MSS loads for 24, 48, and 72 h. A cytotoxicity assay of human ligamentum flavum cells was performed and the results were compared to control (0% stress). Inflammatory markers (interleukin [IL]-6, IL-8), vascular endothelial growth factor [VEGF], and extracellular matrix (ECM)-regulating cytokines (matrix metalloproteinase [MMP]-1, MMP-3 and MMP-9, and tissue inhibitor of metalloproteinase [TIMP]-1 and TIMP-2) were quantified via enzyme-linked immunosorbent assay. RESULTS: Using our multi-torsional mechanical stretch stress loading device, 5% stress for 24 hour was optimal for ligamentum flavum cells. Under this condition, the IL-6 and IL-8 levels, VEGF level, and MMP-1, MMP-3, and TIMP-2 were significantly increased, compared to the control. CONCLUSION: Using the novel multi-torsional mechanical stretch stress loading device we confirmed that, mechanical stress enhances the production of inflammatory cytokines and angiogenic factors, and altered the expression of ECM-regulating enzymes, possibly triggering ligamentum flavum hypertrophy.