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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. [ABSTRACT FROM AUTHOR]

Background: Accumulation of transthyretin amyloids (ATTR) is detected in ligamentum flavum in about 1/3 of patients underwent surgery for spinal stenosis. However, the significance of this finding is not known. The aim of this systematic review and meta-analysis is to analyze the incidence and importance of ATTR in patients with spinal stenosis who underwent spinal surgery. Methods: The primary outcome measure was incidence of ATTR in patients with spinal stenosis. English language observational studies published within 10 years period were searched in Pubmed and Taylor and Francis databases. Results: Nine articles were included in the systematic review. The incidence of positive ATTR among patients who underwent lumbar spinal surgery was 48% (95%CI 38-58%). ATTR deposits were found in the lumbar region the most frequently. Seven studies showed that patients with positive ATTR were older than those with negative. Five studies investigated and found a significant relationship between the ligamentum flavum thickness and positive ATTR. Five studies investigated cardiac involvement among patients with positive ATTR. Conclusion: ATTR deposits are frequently found in older patients with spinal stenosis, especially in the lumbar region. The presence of ATTR deposits is related to ligamentum flavum thickness. [ABSTRACT FROM AUTHOR]

Hypertrophy of the ligamentum flavum (HLF) is a common contributor to lumbar spinal stenosis (LSS). Fibrosis is a core pathological factor of HLF resulting in degenerative LSS and associated low back pain. Although progress has been made in HLF research, the specific molecular mechanisms that promote HLF remain to be defined. The molecular factors involved in the onset of HLF include increases in inflammatory cytokines such as transforming growth factor (TGF)-β, matrix metalloproteinases, and pro-fibrotic growth factors. In this review, we discuss the current understanding of the mechanisms involved in HLF with a particular emphasis on aging and mechanical stress. We also discuss in detail how several pathomechanisms such as fibrosis, proliferation and apoptosis, macrophage infiltration, and autophagy, in addition to several molecular pathways involving TGF-β1, mitogen-activated protein kinase (MAPKs), and nuclear factor-κB (NF-κB) signaling, PI3K/AKT signaling, Wnt signaling, micro-RNAs, extracellular matrix proteins, reactive oxygen species (ROS), etc. are involved in fibrosis leading to HLF. We also present a summary of the current advancements in preclinical animal models for HLF research. In addition, we update the current and potential therapeutic targets/agents against HLF. An improved understanding of the molecular processes behind HLF and a novel animal model are key to developing effective LSS prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

BACKGROUND: It has been proved clinically that adhesion of fibrous scar with the dura mater or nerve root after lumbar operation is an important factor for postoperative symptoms, such as postoperative pain and numbness. OBJECTIVE: To verify the inhibitory effect of autologous ligamentum flavum on the formation of epidural fibrous scar after lumbar surgery and explore the possible molecular biological mechanism. METHODS: Forty-eight Japanese white rabbits (6-8 months old) were randomly divided into three groups: a ligamentum flavum preservation group, a ligamentum flavum non-preservation group, and an autologous fat reposition group. A lumbar laminectomy model was established in all the three groups of rabbits, and rabbit epidural tissues were collected at 3 and 6 weeks after modeling. Hematoxylin-eosin staining was used to observe histological changes and the number and density of fibroblasts, VG staining was used to observe the percentage of collagen fiber area, and immunohistochemistry was used to observe the expression of transforming growth factor β1 and Smad3 proteins. RESULTS AND CONCLUSION: Hematoxylin-eosin staining results revealed that fibroblasts in the ligamentum flavum preservation group were few and loosely arranged, while the cells in the ligamentum flavum non-preservation and autologous fat reposition groups were more numerous and closely arranged. The number density of fibroblasts in the ligamentum flavum preservation group was lower than that in the ligamentum flavum non-preservation and autologous fat reposition groups at 3 and 6 weeks after surgery (P < 0.05); however, there was no significant difference between the latter two groups. VG staining results showed that the collagen fibers in the ligamentum flavum preservation group were sparse and distributed unevenly, while a lot of red collagen fibers were gathered in the ligamentum flavum non-preservation and autologous fat reposition groups. The area percentage of collagen fibers in the ligamentum flavum preservation group was lower than that in the ligamentum flavum non-preservation and autologous fat reposition groups at 3 and 6 weeks after surgery (P < 0.05), but there was no significant difference between the latter two groups. The results of immunohistochemistry showed that the degree of positive staining of retained histone the ligamentum flavum preservation group was significantly lower than that of the other two groups. The absorbance value of transforming growth factor β1 and Smad3 in the ligamentum flavum preservation group was significantly lower than that in the other two groups at 3 and 6 weeks after surgery (P < 0.05), but there was no significant difference between the latter two groups. To conclude, there are different degrees of epidural fibrous scar formation after lumbar surgery. If the ligamentum flavum is preserved, it can help to reduce the number of epidural fibroblasts as well as the formation of collagen fibers, thus reducing the adhesion of the fibrous scar tissue to the dural sac and nerve root. The mechanism is not only a purely mechanical blockade, but also to reduce the formation of epidural fibrous scar by interfering with the transforming growth factor β1/Smad3 signaling pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: Needle-knife release of the ligamentum flavum can effectively improve symptoms in patients with lumbar degeneration, and ultrasound guidance can increase the precision of needle-knife release; however, the specific effects of needle-knife release of the ligamentum flavum on the degenerated intervertebral discs and the possible mechanisms remain to be clarified. OBJECTIVE: To investigate the effect of ultrasound-guided needle-knife release of the ligamentum flavum. METHODS: Twenty-four New Zealand rabbits were randomized into control (n=6) and model (n=18) groups. A rabbit model of lumbar disc degeneration model was established in the model group by cutting the supraspinous and interspinous ligaments of the L5/6 and L6/7 segments to maintain a standing posture and apply axial load to the lumbar spine. After successful modeling, the model rabbits were subdivided into a control group, a model group, an ultrasonic needleknife group, and a sham needle-knife group according to a random number table method, with six animals in each group. The ultrasonic needle-knife group underwent ultrasound-guided needle-knife release of the right yellow ligament of L7/S1, once every week, for a total of four times. The needle-knife approach in the sham needle-knife group was the same as that in the ultrasound needle-knife group, but the ligamentum flavum was not released. At 30 days after the intervention, MRI was used to observe the changes in the signal intensity of the nucleus pulposus within the L7/S1 segment. Hematoxylin-eosin staining was used to observe the morphological changes of the L7/S1 segment. Immunohisto-chemical staining was used to detect the expression of type I and II collagen in the nucleus pulposus of the L7/S1 segment. RT-PCR and western blot were used to detect the expression of integrin α5 and β1, p38, and nuclear factor κB in the L7/S1 segment. RESULTS AND CONCLUSION: MRI findings indicated that the nucleus pulposus of the intervertebral disc of rabbits in the model group was gray-black in color, and the gray value of the nucleus pulposus was significantly lower than that of the control group (P < 0.01). The brightness of the nucleus pulposus of the intervertebral disc of the rabbits in the ultrasonic needle-knife group was elevated compared with that of the model group, and the gray value of the nucleus pulposus was higher than that of the model group (P < 0.01). Results from hematoxylin-eosin staining showed that in the model group, the shape of the nucleus pulposus was irregular, the number of nucleus pulposus cells was reduced, the extracellular matrix was compressed, the fibrous ring was ruptured, the structure and boundary of the end plate were unclear, and the chondrocytes were arranged disorderly. Compared with the model group, the ultrasonic needle-knife group showed an increase in the number of the nucleus pulposus, an improvement in the rupture of the fibrous ring, and more regular arrangement of cartilage endplate cells. Results from immunohisto-chemical staining showed an increase in positive expression of type I collagen (P < 0.01) and a decrease in positive expression of type II collagen in the nucleus pulposus of the model group compared with the control group as well as a decrease in positive expression of type I collagen and an increase in positive expression of type II collagen in the nucleus pulposus of the ultrasonic needle-knife group compared with the model group (P < 0.01). RT-PCR and western blot assays showed that the mRNA and protein expression of integrin α5, integrin β1, p38, and nuclear factor κB in the intervertebral discs of rabbits in the model group were increased compared with that in the control group (P < 0.01); the mRNA and protein expression of integrin α5, integrin β1, p38, and nuclear factor κB in the intervertebral discs of rabbits in the ultrasonic needle-knife group was decreased compared with that in the model group (P < 0.01). To conclude, ultrasound-guided needle-knife release of the ligamentum flavum can improve the degree of lumbar disc degeneration in rabbits, which may be related to the inhibition of p38 and nuclear factor-κB expression by modulating integrin α5 and β1 expression. [ABSTRACT FROM AUTHOR]

The study aimed to examine matrix metalloproteinase‐2 (MMP‐2) expression in a rat ligamentum flavum (LF) hypertrophy model in vivo, and the effect of elastin‐derived peptides (EDPs) on MMP‐2 and tissue inhibitors of metalloproteinases (TIMPs) in rat LF cells in vitro. Surgical destabilization was performed at the rat spinal L3/4 level to induce increased mechanical stress. Rats were killed at 6‐ and 12‐weeks postsurgery for histological staining, immunohistochemical staining, RT‐qPCR and western blot. 100 µg/mL EDPs were applied to isolated normal rat LF cells, with or without pretreatment of elastin receptor complex (ERC) inhibitors, to assess the expression of MMP‐2, TIMP‐1, and TIMP‐2. Spinal destabilization led to LF hypertrophy, observed through increased LF thickness and area, along with histological changes of chondrometaplasia and elastic fiber degradation. LF was also stained positively for Col I and Col II, where elastic fiber has broken down. MMP‐2 expression was notably elevated in the hypertrophied LF, accompanied by increased TIMP‐2 and TIMP‐3 levels. EDPs were found to suppress MMP‐2 expression and reduce TIMP‐1 and TIMP‐2 levels in rat LF cells. Interestingly, exposure to EDPs led to a significant rise in MMP‐2/TIMP‐1 and MMP‐2/TIMP‐2 ratios, dependent on the ERC. Collectively, the study suggests that increased MMP‐2 activity contributes to elastic fiber degradation in hypertrophied LF, generating EDPs that further enhance the MMP‐2/TIMPs ratio in LF cells in an ERC‐dependent manner. Further research is essential to delve into the mechanisms of EDPs in LF hypertrophy. [ABSTRACT FROM AUTHOR]

Study Design. Experimental study. Objective. We sought to elucidate the association between ligamentum flavum thickening and tissue buckling, and the clinical and imaging factors related to buckling by comparing the ligamentum flavum thickness on MRI images and within the actual tissue. Summary of Background Data. Ligamentum flavum thickening is a main contributor to lumbar spinal canal stenosis. Buckling of the tissue may contribute to ligamentum flavum thickening along with tissue hypertrophy; however, this association has not been established conclusively. Materials and Methods. Ligamentum flavum samples (135 ligament samples) from 70 patients with lumbar spinal canal stenosis were evaluated. The ligamentum flavum thicknesses on magnetic resonance imaging (MRI) and in the tissue samples were compared to assess for the presence of buckling. The ligamentum flavum samples were divided into groups with or without buckling based on the difference between their thicknesses on MRI and in the tissues. The Pearson correlation coefficient test was used to assess the relationships between the LF thicknesses on MRI and in the tissues, MRI-tissue difference and LF thickness in the tissues, and MRI-tissue difference and LF thickness on MRI. Further, differences between the buckling+ and buckling-groups were compared using the unpaired t-test (LF thickness on MRI, LF thickness in the tissues, age, disc angle, and disc height) and χ² (disc level, disc degeneration, and receival/nonreceival of dialysis) test. Results. The ligamentum flavum thickness on MRI and in the tissues had a positive linear relationship, although the thickness was estimated to be significantly larger on MRI than in the tissues themselves. The ligamentum flavum with buckling had a larger thickness on MRI, less tissue hypertrophy, more severe disc degeneration, and was present in patients with a higher rate of dialysis. There were no differences in age and disc height, angle, or level between the two groups. Conclusions. Buckling of the ligamentum flavum coexists with tissue hypertrophy and contributes to perceived ligamentum thickening on imaging. Buckling of the ligamentum flavum tends to occur in less hypertrophied tissues and is associated with the grade of disc degeneration and the presence of other characteristics associated with spinal degeneration. [ABSTRACT FROM AUTHOR]

Background: The ligamentum flavum (LF) degeneration is a critical factor in spinal stenosis, leading to nerve compression and pain. Even with new treatment options becoming available, it is vital to have a better understanding of LF degeneration to ensure the effectiveness of these treatments. Objective: This study aimed to provide insight into LF degeneration by examining the connections between various aspects of LF degeneration, including histology, microstructure, chemical composition, and biomechanics. Method: We analyzed 30 LF samples from 27 patients with lumbar vertebrae, employing magnetic resonance imaging (MRI) to link lumbar disc degeneration grades with fibrosis levels in the tissue. X‐ray diffraction (XRD) analysis assessed microstructural alterations in the LF matrix component due to degeneration progression. Instrumented nanoindentation combined with Raman spectroscopy explored the spatial microbiomechanical and biochemical characteristics of the LF's ventral and dorsal regions. Results: Our outcomes revealed a clear association between the severity of LF fibrosis grades and increasing LF thickness. XRD analysis showed a rise in crystalline components and hydroxyapatite molecules with progressing degeneration. Raman spectroscopy detected changes in the ratio of phosphate, proteoglycan, and proline/hydroxyproline over the amide I band, indicating alterations in the extracellular matrix composition. Biomechanical testing demonstrated that LF tissue becomes stiffer and less extensible with increasing fibrosis. Discussion: Notably, the micro‐spatial assessment revealed the dorsal side of the LF experiencing more significant mechanical stress, alongside more pronounced biochemical and biomechanical changes compared to the ventral side. Degeneration of the LF involves complex processes that affect tissue histology, chemical composition, and biomechanics. It is crucial to fully understand these changes to develop new and effective treatments for spinal stenosis. These findings can improve diagnostic accuracy, identify potential biomarkers and treatment targets, guide personalized treatment strategies, advance tissue engineering approaches, help make informed clinical decisions, and educate patients about LF degeneration. [ABSTRACT FROM AUTHOR]

Hypertrophy of ligamentum flavum (LF) is a significant contributing factor to lumbar spinal canal stenosis (LSCS). lncRNA plays a vital role in organ fibrosis, but its role in LF fibrosis remains unclear. Our previous findings have demonstrated that Hedgehog- Gli1 signaling is a critical driver leading to LF hypertrophy. Through the RIP experiment, our group found lnc-RMRP was physically associated with Gli1 and exhibited enrichment in Gli1-activated LF cells. Histological studies revealed elevated expression of RMRP in hypertrophic LF. In vitro experiments further confirmed that RMRP promoted Gli1 SUMO modification and nucleus transfer. Mechanistically, RMRP induced GSDMD-mediated pyroptosis, proinflammatory activation, and collagen expression through the Hedgehog pathway. Notably, the mechanical stress-induced hypertrophy of LF in rabbit exhibited analogous pathological changes of LF fibrosis occurred in human and showed enhanced levels of collagen and α-SMA. Knockdown of RMRP resulted in the decreased expression of fibrosis and pyroptosis-related proteins, ultimately ameliorating fibrosis. The above data concluded that RMRP exerts a crucial role in regulating GSDMD-mediated pyroptosis of LF cells via Gli1 SUMOylation, thus indicating that targeting RMRP could serve as a potential and effective therapeutic strategy for LF hypertrophy and fibrosis. [ABSTRACT FROM AUTHOR]

"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. [ABSTRACT FROM AUTHOR]

Study Design. Prospective cohort study. Objective. This study aimed to evaluate the risk factors and prevalence of intraoperative contamination (IoC) through the microbial culture of superficial and deep samples obtained during surgery. Summary of Background Data. Surgical site infection (SSI) in spinal surgery is a serious complication. The prevalence of IoC may differ based on surgical approach and technique, even in the setting of the same procedure. Materials and Methods. In this in vivo study, microbial cultivation was performed with superficial (ligamentum flavum, LF) and deep (nucleus pulposus, NP) surgical specimens to evaluate IoC in 132 patients undergoing single-level transforaminal lumbar interbody fusion (TLIF). Biportal endoscopic --TLIF was performed under continuous wound irrigation (group A, n=66), whereas open microscopic (OM) TLIF was performed under intermittent wound irrigation (group B, n=66). LF and NP specimens were homogenized, gram stained, and cultured in aerobic and anaerobic media for 14 days. Microbial culture results and the occurrence of SSI in the two groups were assessed. The χ² test and Fisher exact test were used to determine significant differences among categorical variables. Logistic regression analysis was used to assess the influence of patient characteristics on the prevalence of positive microbial cultures. Results. Of the 132 patients, 34 (25.8%) had positive microbial cultures, and positive culture required an incubation period of 72 hours to 2 weeks in all these patients except for three. Overall, positive culture was significantly higher in group B than in group A P=0.029). The subgroups of LF- and NP-positive cultures were 18.18% (n=24) and 12.88% (n=17), respectively; the SSI was 0.76% (n=1). Group A had a significantly lower subgroup of NP-positive culture than group B (P=0.035). OM technique was an independent risk factor associated with overall positive culture (P<0.05). The most common microorganism was Cutibacterium acnes (C. acnes). Conclusions. Biportal endoscopic--TLIF with continuous wound irrigation showed significantly lower overall and NP-positive cultures than OM-TLIF with intermittent irrigation. The most common strain of positive culture was C. acnes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: A condition known as ligamentum flavum (LF) hypertrophy occurs when the ligamentum flavum (LF) swells as a result of pressures applied to the spine. Among the elderly population, lumbar spinal stenosis is a major cause of pain and disabilities. Numerous studies indicate that lumbar spinal stenosis etiology involves the ligamentum flavum in a major way. This study looks into the relationship between low back pain and ligamentum flavum thickening. PATIENTS AND METHODS: The imaging tests and case histories of all patients with low back pain who had consecutive magnetic resonance imaging exams performed at the Prince Sattam University and King Khalid hospitals in Al Kharj City will serve as the basis for this retrospective observational study. A radiologist utilized the Pfirrmann grading system, which is based on spinal levels starting from the first lumbar to the first sacral vertebrae, to measure the thickness of the ligamentum flavum in all cases who underwent magnetic resonance imaging (MRI). A correlation between age, hypertrophy of LF, and low back pain was investigated. RESULTS: There were 79 participants in the study, ages ranging from 21 to 82, 49 of which were men. The patients' average age was 54 years, and 62% of them were men. We found no appreciable variations in LF thickness according to gender. At the L4-L5 and L5-S1 levels, the left LF was noticeably thicker than the right. Moreover, there was a significant difference (p < 0.05) in the bilateral LF thicknesses at L5-S1 compared to the comparable sides at L4-L5. CONCLUSIONS: By evaluating the thickness of LF on magnetic resonance images, we discovered that it may be closely associated with the etiology of pain processes in the spine. [ABSTRACT FROM AUTHOR]

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BackgroundAccumulation of transthyretin amyloids (ATTR) is detected in ligamentum flavum in about 1/3 of patients underwent surgery for spinal stenosis. However, the significance of this finding is not known. The aim of this systematic review and meta-analysis is to analyze the incidence and importance of ATTR in patients with spinal stenosis who underwent spinal surgery.MethodsThe primary outcome measure was incidence of ATTR in patients with spinal stenosis. English language observational studies published within 10 years period were searched in Pubmed and Taylor and Francis databases.ResultsNine articles were included in the systematic review. The incidence of positive ATTR among patients who underwent lumbar spinal surgery was 48% (95%CI 38–58%). ATTR deposits were found in the lumbar region the most frequently. Seven studies showed that patients with positive ATTR were older than those with negative. Five studies investigated and found a significant relationship between the ligamentum flavum thickness and positive ATTR. Five studies investigated cardiac involvement among patients with positive ATTR.ConclusionATTR deposits are frequently found in older patients with spinal stenosis, especially in the lumbar region. The presence of ATTR deposits is related to ligamentum flavum thickness.

Abstract Background Ossification of ligamentum flavum (OLF) is a prevalent degenerative spinal disease, typically causing severe neurological dysfunction. Kruppel-like factor 5 (KLF5) plays an essential role in the regulation of skeletal development. However, the mechanism KLF5 plays in OLF remains unclear, necessitating further investigative studies. Methods qRT-PCR, immunofluorescent staining and western blot were used to measure the expression of KLF5. Alkaline Phosphatase (ALP) staining, Alizarin red staining (ARS), and the expression of Runt-related transcription factor 2 (RUNX2), osteopontin (OPN), and osteocalcin (OCN) were used to evaluate the osteogenic differentiation. Luciferase activity assay and ChIP-PCR were performed to investigate the molecular mechanisms. Results KLF5 was significantly upregulated in OLF fibroblasts in contrast to normal ligamentum flavum (LF) fibroblasts. Silencing KLF5 diminished osteogenic markers and mineralized nodules, while its overexpression had the opposite effect, confirming KLF5’s role in promoting ossification. Moreover, KLF5 promotes the ossification of LF by activating the transcription of Connexin 43 (CX43), and overexpressing CX43 could reverse the suppressive impact of KLF5 knockdown on OLF fibroblasts’ osteogenesis. Conclusion KLF5 promotes the OLF by transcriptionally activating CX43. This finding contributes significantly to our understanding of OLF and may provide new therapeutic targets.

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. [ABSTRACT FROM AUTHOR]

Objective: We aimed to radiologically evaluate the clinical and demographic features accompanying ligamentum flavum hypertrophy and possible accompanying differences in anatomical structures. Materials and Methods: We evaluated vertebral alignment, integrity of neural structures, diameter of the central canal, posterior longitudinal ligament, ligamentum flavum integrity, and position of the facet joints in patients with lumbar disk herniation and lumbar spinal canal stenosis using magnetic resonance imaging (MRI). Furthermore, we examined the age, body mass index (BMI), and employment status of the patients and the status of the vertebral and paravertebral anatomical structures using MRI. Age, BMI, employment status, ligamentum flavum thickness at the L4-L5 level, interspinous ligament thickness, facet joint diameter, posterior longitudinal ligament integrity, psoas muscle diameter, erector spina muscle diameter, and mean multifidus muscle diameter were also analyzed. Results: Significant differences were found in age, BMI, employment status, ligamentum flavum thickness, interspinous ligament thickness, mean facet diameter, mean multifidus muscle diameter, mean erector spina muscle diameter, and mean psoas muscle diameter. In addition, separate statistical analyses were conducted between sex, age, employment status, BMI, and lumbar anatomical parameters. Significant correlations were found between lumbar disk herniation and spinal stenosis pathologies based on radiological measurements of lumbar structures, such as the ligamentum flavum, interspinous ligament, and facet diameter, and demographic parameters, such as age, sex, employment status, and BMI. Conclusion: We examined changes in the anatomical structures accompanying the vertebral column and existing discal or stenotic pathologies. In addition to the demographic characteristics of the patients, changes in the accompanying lumbar spinal anatomical structures, such as degeneration, hypertrophy, and atrophy, may be important. These factors and changes will help plan the treatment process and guide the results. [ABSTRACT FROM AUTHOR]

Hypertrophy of the ligamentum flavum (HLF) is a common contributor to lumbar spinal stenosis (LSS). Fibrosis is a core pathological factor of HLF resulting in degenerative LSS and associated low back pain. Although progress has been made in HLF research, the specific molecular mechanisms that promote HLF remain to be defined. The molecular factors involved in the onset of HLF include increases in inflammatory cytokines such as transforming growth factor (TGF)-β, matrix metalloproteinases, and pro-fibrotic growth factors. In this review, we discuss the current understanding of the mechanisms involved in HLF with a particular emphasis on aging and mechanical stress. We also discuss in detail how several pathomechanisms such as fibrosis, proliferation and apoptosis, macrophage infiltration, and autophagy, in addition to several molecular pathways involving TGF-β1, mitogen-activated protein kinase (MAPKs), and nuclear factor-κB (NF-κB) signaling, PI3K/AKT signaling, Wnt signaling, micro-RNAs, extracellular matrix proteins, reactive oxygen species (ROS), etc. are involved in fibrosis leading to HLF. We also present a summary of the current advancements in preclinical animal models for HLF research. In addition, we update the current and potential therapeutic targets/agents against HLF. An improved understanding of the molecular processes behind HLF and a novel animal model are key to developing effective LSS prevention and treatment strategies.

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. 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. 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%). 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. [ABSTRACT FROM AUTHOR]

Study Design This experimental study was performed using human ligamentum flavum–derived cells (HFCs). Purpose To investigate the intracellular signaling mechanism of interleukin-6 (IL-6) secretion in transforming growth factor-β (TGF-β)-stimulated HFCs. Overview of Literature Lumbar spinal stenosis (LSS) is a prevalent disease among the elderly, characterized by debilitating pain in the lower extremities. Although the number of patients with LSS has increased in recent years, the underlying pathomechanism remains unclear. Clinical examinations typically rely on magnetic resonance imaging to diagnose patients, revealing ligamentum flavum hypertrophy. Some studies have suggested an association between ligamentum flavum hypertrophy and inflammation/fibrosis, and expression of TGF-β and IL-6 has been observed in surgically obtained ligamentum flavum samples. However, direct evidence linking TGF-β and IL-6 expression in HFCs is lacking. Methods HFCs were obtained from patients with LSS who had undergone decompression surgery. The cells were stimulated with TGF-β and pretreated with either the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580 or the p44/42 MAP kinase inhibitor FR180204. IL-6 secretion in the cell culture medium and IL-6 messenger RNA (mRNA) expression levels were analyzed using an enzyme-linked immunoassay and real-time polymerase chain reaction, respectively. Results TGF-β administration resulted in a dose- and time-dependent stimulation of IL-6 release. Treatment with SB203580 and FR180204 markedly suppressed TGF-β–induced IL-6 secretion from HFCs. Moreover, these inhibitors suppressed IL-6 mRNA expression in response to TGF-β stimulation. Conclusions Our findings indicate that TGF-β induces IL-6 protein secretion and gene expression in HFCs through the activation of p38 or p44/42 MAP kinases. These results suggest a potential association between IL-6–mediated inflammatory response and tissue hypertrophy in LSS, and we provide insights into molecular targets for therapeutic interventions targeting LSS-related inflammation through our analysis of the MAP kinase pathway using HFCs.

Hongjie Yuan,1 Xiaobin Yi2 1Department of Pain Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Pain Division, Department of Anesthesiology, Washington University in St Louis, St Louis, MO, USACorrespondence: Xiaobin Yi, Email yix@wustl.eduBackground: Lumbar spinal stenosis (LSS) is a common pain condition that causes lumbar back pain, radiating leg pain, and possible functional impairment. MILD is an emerging minimally invasive treatment for LSS. It is an image-guided percutaneous procedure designed to debulk hypertrophied ligamentum flavum. However, the exact short- and long-term efficacy, safety profile, indication criteria, and certain procedure details reported in medical literature vary.Objective: This narrative review was to elucidate efficacy, safety profile, certain procedure details, advantages, and limitations of MILD.Study Design: This is a narrative review.Setting: All included articles are clinic trials including analytic studies and descriptive studies.Methods: PubMed, Cochrane Library, and Scopus were searched. Only clinical trials of MILD procedure were included. Information of indications, contraindications, VAS scores, ODI scores, effective rate, efficacy durations, and certain procedure details was focused on.Results: According to the literature, for the MILD procedure, the VAS score could be reduced from a pre-treatment level of 6.3– 9.6 to a post-treatment level of 2.3– 5.8. The ODI score could be reduced from a pre-treatment level of 38.8– 55.3 to a post-treatment level of 27.4– 39.8. The effective rate of the MILD procedure was reported to be 57.1%– 88%. A 2-year postoperative stability of efficacy was also supported. One RCT study testified superior efficacy of MILD over epidural steroid injection.Limitations: There is few high-quality literature in the review. Moreover, the long-term efficacy of MILD cannot be revealed according to the current literature.Conclusion: Based on the reviewed literature, MILD is an effective and safe procedure. MILD can reduce pain intensity and improve functional status significantly. Therefore, it is a preferable option for LSS patients who failed conservative treatments, but not for those who require immediate invasive decompression surgery.Keywords: lumbar spinal stenosis, minimally invasive lumbar decompression, mild ®, low back pain, lumbar radiculopathy, neurogenic claudication, ligamentum flavum

Hyperparathyroidism (HPT) is a rare endocrine disorder in the pediatric population. Patients often present with bone pain and abnormal gait along with biochemical findings of hypercalcemia, hypophosphatemia, and elevated parathyroid hormone (PTH). HPT is most commonly due to the unregulated secretion of PTH from a parathyroid adenoma. Diagnosis is usually identified with sonography and scintigraphy to localize parathyroid anomalies. Treatment traditionally involves parathyroidectomy with postoperative monitoring of serum calcium and phosphate levels. Here we present a case of a preadolescent girl with metabolic bone disease secondary to hyperparathyroidism.

Liyu Yang,1,&ast; Long Zhou,1,&ast; Guanqi Wang,2 Min Qiu,1 Feng Liang,1 Changqing Jia,1 Weibing Xu,3 Qin Fu,1 Liqing Yang,1 Gen Ba1 1Department of Orthopedic, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 2Rehabilitation Center, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 3Spinal Surgery, Dalian Central Hospital Affiliated to Dalian Medical University, Dalian, Liaoning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gen Ba, Department of Orthopedic, Shengjing Hospital of China Medical University, Sanhao Street 36, He Ping District, Shenyang, Liaoning Province, People’s Republic of China, 110004, Tel +86 18940259116, Email bagen1983@163.comObjective: This article aims to discuss a novel surgical strategy, referred to as unilateral bi/multi-portal endoscopy (UME), which used a uniaxial spinal endoscope instead of an arthroscope in the traditional unilateral biportal endoscopy (UBE) surgical procedure in our study of the treatment of complicated lumbar degenerative diseases.Methods: This retrospective study included 42 patients diagnosed with high-migrated lumbar disc herniation and bilateral spinal stenosis who underwent UME surgery from January 2021 to December 2021. Patients included 20 men and 22 women, with an average age of 55.97± 14.92 years. The average follow-up period was 13.19 months. The demographic data, operation time (min), and complications were recorded and analyzed. The visual analogue scale (VAS), Oswestry Disability Index (ODI) scores were used to evaluate the surgical outcomes. Three-dimensional CT scans and MRI were conducted to evaluate the radiographic improvement.Results: A total of 26 patients were diagnosed with lumbar disc herniation and 16 with lumbar spinal stenosis. All 42 patients underwent UME surgery and achieved satisfactory outcomes. The operation time was 154.46± 46.09 min. The average follow-up time was 13.19± 1.33 months. The preoperative back pain (VAS-Back) and the last follow-up VAS-Back were 3.84± 1.00 and 0.70± 0.46, respectively (P < 0.05). The preoperative leg pain (VAS-Leg) and the last follow-up VAS-Leg were 6.46± 1.08 and 1.03± 0.64, respectively (P < 0.05). Significant differences existed between preoperative ODI scores (58.70± 11.22%) and the last follow-up ODI scores (9.24± 3.04%; P< 0.05). All patients achieved significant pain relief and functional improvement after the surgery. No severe complications occurred, except for two cases of postoperative dysesthesia and one case suffered from vertebral compression fractures induced by a postoperative accidental injury. Symptoms of numbness disappeared within one week with treatment using dexamethasone and neurotrophic drugs. The vertebral fracture case recovered with percutaneous kyphoplasty treatment.Conclusion: This study suggests that UME is a promising treatment strategy for high-migrated disc herniation and bilateral spinal stenosis.Keywords: unilateral bi/multi-portal endoscopy, lumbar degenerative diseases, high-migrated disc herniation, bilateral spinal stenosis, ligamentum flavum, spinal endoscope

Purpose The effects of weight bearing on lumbar spinal canal dimensions are not well reported the low back pain (LBP) literature. Since axial loading induces changes in anatomical configuration of the lumbar spine, supine spine imaging may not uncover dimensional changes associated with physiological weight bearing that could be demonstrated in imaging in the upright position. Methods This study compared anteroposterior spinal canal dimensions measured at the level of the intervertebral discs in the supine and upright lumbar spine magnetic resonance images in adults without a history or current back pain. Additionally, interlaminar distances were measured between the centers of adjacent laminae involving a spinal segment. These parameters were utilized to ascertain the deformation incurred at the ligamentum flavum due to load bearing. Results Within and between-sessions t-tests, factorial and repeated-measures analysis of variance showed significant alterations in canal dimensions at certain levels, secondary to the upright positioning of the spine. Measurement reliability assessed between sessions and scanning positions using intraclass correlation coefficients demonstrated strong agreement. Conclusion Imaging studies involving physiological weight bearing may be useful to understand the potential etiological effects of such changes in mechanical LBP.

Background: Transthyretin (ATTR) amyloidosis is often diagnosed in an advanced stage, when irreversible cardiac damage has occurred. Lumbar spinal stenosis (LSS) may precede cardiac ATTR amyloidosis by many years, offering the opportunity to detect ATTR already at the time of LSS surgery. We prospectively assessed the prevalence of ATTR in the ligamentum flavum by tissue biopsy in patients aged >50 years undergoing surgery for LSS. Methods: Ligamentum flavum thickness was assessed pre-operatively on axial T2 magnetic resonance imaging (MRI) slices. Tissue samples from ligamentum flavum were screened centrally by Congo red staining and immunohistochemistry (IHC). Results: Amyloid in the ligamentum flavum was detected in 74/94 patients (78.7%). IHC revealed ATTR in 61 (64.9%), whereas amyloid subtyping was inconclusive in 13 (13.8%). Mean thickness of ligamentum flavum was significantly higher at all levels in patients with amyloid (p < .05). Patients with amyloid deposits were older (73.1 ± 9.2 vs. 64.6 ± 10.1 years, p = .01). No differences in sex, comorbidities, previous surgery for carpal tunnel syndrome or LSS were observed. Conclusions: Amyloid, mostly of the ATTR subtype, was found in four out of five patients with LSS and is associated with age and ligamentum flavum thickness. Histopathological work-up of ligamentum flavum might inform future decision making. [ABSTRACT FROM AUTHOR]

Study Design. Retrospective cohort study. Objective. To clarify whether outcomes of anterior cervical discectomy and fusion (ACDF) differ according to the presence of posterior cord compression from the ligamentum flavum (CCLF) Summary of Background Data. Although ACDF effectively addresses anterior cord compression from disc material and bone spurs, it cannot address posterior compression. Whether ACDF could result in favorable outcomes when CCLF is present remains unclear. Patients and Methods. A total of 195 consecutive patients who underwent ACDF and were followed up for >2 years were included. CCLF was graded based on magnetic resonance imaging findings. Patients with CCLF grade 2 were classified as such, whereas patients with CCLF grades 0 to 1 were classified as the no- CCLF group. Patient characteristics, cervical sagittal parameters, neck pain visual analog scale, arm pain visual analog scale, and Japanese Orthopedic Association (JOA) score were assessed. Categorical variables were analyzed using a χ² test, whereas continuous variables were analyzed using the Student t test. Multivariable logistic regression analysis was performed to elucidate factors associated with JOA recovery rates of > 50%. Results. One hundred sixty-seven patients (85.6%) were included in the no-CCLF group, whereas the remaining 28 patients (14.4%) were included in the CCLF group. Among patients in the CCLF group, 14 patients (50.0%) achieved clinical improvement. JOA score significantly improved in the no-CCLF group after the operation (P < 0.001), whereas improvement was not appreciated in the CCLF group (P = 0.642). JOA scores at 3 months (P = 0.037) and 2 years (P = 0.001) postoperatively were significantly higher in the no-CCLF group. Furthermore, the JOA recovery rate at 2 years after surgery was significantly higher in the no-CCLF group (P = 0.042). Logistic regression demonstrated that CCLF was significantly associated with a JOA recovery rate of >50% at 2 years after surgery (odds ratio: 2.719; 95% CI: 1.12, 6.60). Conclusion. ACDF performed for patients with CCLF grade 2 showed inferior JOA score improvement compared with those with CCLF grade 0 or 1. ACDF cannot remove posterior compressive structures, which limits its utility when ligamentum flavum significantly contributes to cord compression. [ABSTRACT FROM AUTHOR]

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-1β (IL-1β), 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-1β, 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-1β promoted osteogenesis but inhibited adipogenesis. Conclusion: IL-1β, IL-19, and IL-20 impact the adipogenic and osteogenic differentiation of IVD-derived and LF-derived cells. Modulating the expression of IL-1β, 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. [ABSTRACT FROM AUTHOR]

Objective Uniportal full endoscopic thoracic endoscopic surgery can be performed through transforaminal and interlaminar approaches. The interlaminar approach is commonly described as thoracic endoscopic unilateral laminotomy for bilateral decompression (TE-ULBD), which is typically indicated for pathologies such as ossified ligamentum flavum and other posteriorly based compressive pathologies. TE-ULBD decompresses the central and lateral recesses of the thoracic spinal canal. Both the outside-in (over the top of ligamentum flavum) and inside-out (under the ligamentum flavum) approaches can decompress the thoracic spinal canal through the uniportal interlaminar endoscopic route. Methods A retrospective clinical cohort evaluation of patients who underwent TE-ULBD was performed from January 2018 to December 2021 Results A cohort of 50 cases of TE-ULBD with a mean age of 65 years old were evaluated. The complication rate was 5.4% and the reoperation rate was 2%. Statistically significant mean VAS improvements were found at 1 week, 6 months, and the final follow-up, with changes of 3.95±1.49, 4.95±1.7, and 5.2±1.8 points, respectively. Likewise, the mean Oswestry Disability Index improvements at 1 week, 3 months, and the final follow-up were 33.8±9.05, 40.12±10.38, and 41.92±11.26, respectively (p

Spinal stenosis is one of the most common neurosurgical diseases and a leading cause of pain and disability. Wild-type transthyretin amyloid (ATTRwt) has been found in the ligamentum flavum (LF) of a significant subset of patients with spinal stenosis who undergo decompression surgery. Histologic and biochemical analyses of LF specimens from spinal stenosis patients, normally discarded as waste, have the potential to help elucidate the underlying pathophysiology of spinal stenosis and possibly allow for medical treatment of stenosis and screening for other systemic diseases. In the present review, we discuss the utility of analyzing LF specimens after spinal stenosis surgery for ATTRwt deposits. Screening for ATTRwt amyloidosis cardiomyopathy through LF specimens has led to the early diagnosis and treatment of cardiac amyloidosis in several patients, with more expected to benefit from this process. Emerging evidence in the literature also point to ATTRwt as a contributor to a previously unrecognized subtype of spinal stenosis in patients who might, in the future, benefit from medical therapy. In the present report, we review the current literature regarding the early detection of ATTRwt cardiomyopathy via LF screening and the possible contribution of ATTRwt deposits in the LF to spinal stenosis development. [ABSTRACT FROM AUTHOR]

Multi‐joint disease pathologies in the lumbar spine, including ligamentum flavum (LF) hypertrophy and intervertebral disc (IVD) bulging or herniation contribute to lumbar spinal stenosis (LSS), a highly prevalent condition characterized by symptomatic narrowing of the spinal canal. Clinical hypertrophic LF is characterized by a loss of elastic fibers and increase in collagen fibers, resulting in fibrotic thickening and scar formation. In this study, we created an injury model to test the hypothesis that LF needle scrape injury in the rat will result in hypertrophy of the LF characterized by altered tissue geometry, matrix organization, composition and inflammation. An initial pilot study was conducted to evaluate effect of needle size. Results indicate that LF needle scrape injury using a 22G needle produced upregulation of the pro‐inflammatory cytokine Il6 at 1 week post injury, and increased expression of Ctgf and Tgfb1 at 8 weeks post injury, along with persistent presence of infiltrating macrophages at 1, 3, and 8 weeks post injury. LF integrity was also altered, evidenced by increases in LF tissue thickness and loss of elastic tissue by 8 weeks post injury. Persistent LF injury also produced multi‐joint effects in the lumbar IVD, including disc height loss at the injury and adjacent to injury level, with degenerative IVD changes observed in the adjacent level. These results demonstrate that LF scrape injury in the rat produces structural and molecular features of LF hypertrophy and IVD height and histological changes, dependent on level. This model may be useful for testing of therapeutic interventions for treatment of LSS and IVD degeneration associated with LF hypertrophy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Degenerative spondylolisthesis burdens the future economy. Elderly individuals with this condition suffer from back pain, limb paralysis, reduced activity, and diminished quality of life. Surgery offers relief but is risky and expensive. As healthcare improves, the aging population grows, and spondylolisthesis incidence rises. Early detection and risk factor management are vital for prevention. Therefore, this study aimed to evaluate the correlation of the risk factors for degenerative lumbar spondylolisthesis. Methods: A retrospective observational study was done in Dr Soetomo General Academic Hospital, Surabaya from January 2018 to December 2019. Forty-five subjects with degenerative spondylolisthesis diagnosed by MR Imaging enrolled in this study. Intervertebral disc, facet joint, multifidus muscle, and ligamentum flavum at level L1 until level L5 were examined using MR imaging. Correlation analysis was measured using the Spearman correlation test and risk factor analysis was measured using the logistic regression test. Results: There are significant correlations between intervertebral disc degeneration, facet joint osteoarthritis, multifidus muscle fatty infiltration, and thickening of ligamentum flavum with degenerative spondylolisthesis. The risk factors at levels L3-4 and L5-S1 are intervertebral disc degeneration and L4-5 is multifidus muscle fatty infiltration and facet joint osteoarthritis. Conclusion: This study confirmed the risk factors that correlated with degenerative lumbar spondylolisthesis. [ABSTRACT FROM AUTHOR]

Purpose The effects of weight bearing on lumbar spinal canal dimensions are not well reported the low back pain (LBP) literature. Since axial loading induces changes in anatomical configuration of the lumbar spine, supine spine imaging may not uncover dimensional changes associated with physiological weight bearing that could be demonstrated in imaging in the upright position. Methods This study compared anteroposterior spinal canal dimensions measured at the level of the intervertebral discs in the supine and upright lumbar spine magnetic resonance images in adults without a history or current back pain. Additionally, interlaminar distances were measured between the centers of adjacent laminae involving a spinal segment. These parameters were utilized to ascertain the deformation incurred at the ligamentum flavum due to load bearing. Results Within and between-sessions t -tests, factorial and repeated-measures analysis of variance showed significant alterations in canal dimensions at certain levels, secondary to the upright positioning of the spine. Measurement reliability assessed between sessions and scanning positions using intraclass correlation coefficients demonstrated strong agreement. Conclusion Imaging studies involving physiological weight bearing may be useful to understand the potential etiological effects of such changes in mechanical LBP. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE: Minimally invasive lumbar decompression (mild ®) is an effective long-term therapy for patients with symptomatic lumbar spinal stenosis (LSS) resulting primarily from hypertrophic ligamentum flavum (HLF). Most subjects in clinical studies of the mild procedure have been older adults (age≥65). While the incidence of LSS increases with age, a substantial number of adults (age

Study Design This is a retrospective cohort study. Purpose This study aimed to clarify the role of crosstalk between discoidin domain receptors (DDRs) and matrix metalloproteinases (MMPs) in the ligamentum flavum (LF) fibrosis obtained from patients with degenerative lumbar canal stenosis (DLCS). Overview of Literature The DDRs, DDR1 and DDR2, are cell surface receptors and have an essential role in collagen fiber accumulation in several fibrotic diseases. MMPs are one of the critical factors in extracellular matrix remodeling and elastic fiber degradation in LF tissues. However, the crosstalk between DDRs and MMPs and the role of this molecular signal in LF fibrosis remain unclear. Methods A total of 35 patients were divided into two groups in this study. Spinal surgery was performed in 23 of these patients with the diagnosis of DLCS. Twelve patients with lumbar disk herniation (LDH) were included in the control group. On axial T2-weighted magnetic resonance imaging, LF thickness was measured bilaterally at the level of the facet joint. Histology, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot analyses were performed on LF tissue samples. LF tissues were stained with hematoxylin and eosin. In addition, the grade of fibrosis was histologically assessed using Masson trichrome triple staining. DDR1 and DDR2 Western blot analyses were performed. DDR1, DDR2, MMP2, MMP3, MMP9, and MMP13 expression levels were measured using qRT-PCR analysis. Results The grade of fibrosis and LF thickness were significantly higher in the DLCS patients than in the LDH patients. DDR1 and DDR2 gene expression and protein levels in LF tissues are significantly greater in DLCS samples than in control samples, according to both qRT-PCR and Western blot analyses. In addition, we detected a significant expression of the MMP3, MMP9, and MMP13, which are known to have important roles in extracellular matrix remodeling in DLCS. Furthermore, we discovered a link between DDR protein levels and LF thickness, fibrosis, and MMP3/MMP9. Conclusions Our results indicate that DDR1, DDR2, and MMP3 and MMP9 signals can be correlated with each other in LF tissues and be promoted LF fibrosis leading to spinal canal narrowing in patients with DLCS.

In order to find out the mechanisms of pathogenesis of degenerative-dystrophic diseases of the spine, it is of particular interest to search for body parameters which are directly or indirectly interrelated with the key factors of peripheral conversion of nidus iodothyronines and constitute a system of network interactions, affecting metabolic indicators at the local and systemic level.The aim. To search for correlations of local key factors of peripheral conversion of Ligamentum flavum iodothyronines with indicators of biochemical, hematological and hormonal blood profiles of patients with stenosing processes of the spinal canal and dural sac in the lumbar spine.Materials and methods. 33 patients (15 males, 18 females) with stenosing processes of the spinal canal and dural sac in the lumbar spine were examined (mean age – 45.73 ± 1.95 years). The expression of deiodinase genes and other candidate genes was determined in Ligamentum flavum biopsies collected during surgical treatment. Biochemical, hematological and hormonal parameters were determined in peripheral blood. The resulting data array was processed in order to find correlations between the parameters of systemic and local metabolism.Results. The relationships of deiodinases with the expression of GDF5, MMP1, MMP3 and TIMP1 in Ligamentum flavum (p < 0.05) were found. Of the hormonal profile of the blood serum, the most significant indicators were thyreotropin, free triiodothyronine and thyroperoxidase antibodies. In the biochemical profile, levels of direct bilirubin, total cholesterol, HDL and LDL cholesterol and triglycerides changed along with the expression of deiodinases. Correlative relationships with the expression of deiodinases were found for the following hematological analytes of whole peripheral blood: hemoglobin, mean corpuscular hemoglobin concentration, numbers of granulocytes, lymphocytes, eosinophils, monocytes, band neutrophils, red cell distribution width and platelet crit. The data obtained indicate the involvement of peripheral conversion factors in the pathogenetic process and provide information to form a new view on the pathogenesis of degenerative-dystrophic processes in the Ligamentum flavum of patients with stenosing processes of the spinal canal and the dural sac in the lumbar spine.

Abstract Objectives To identify age-related radiographic risk factors for degenerative lumbar spinal stenosis (DLSS) and analyze correlations among them. Methods A total of 180 cases were enrolled in this study, and lumbar magnetic resonance was performed. Among them, 93 cases suffered DLSS and lumbar dynamic X-ray was examined. And following parameters were measured and evaluated: intervertebral disk height (IDH), the ratio of IDH(IDHL4-5/L3-4), initial IDH of L4-5(iIDHL4-5) in the DLSS group, disk degeneration (DD), cartilaginous endplate failure (CEF), Modic changes, the thickness of ligamentum flavum (LF), range of intervertebral motion (ROM), facet joint opening (FJO), facet joint angle (FJA), the standard cross-sectional area (SCSA) of the multifidus, erector spinae, and psoas major muscles. The data of two groups were compared, and the possible risk factors of DLSS were analyzed. Results Compared with the control group, the DLSS group had higher IDH except for L4-5 and larger iIDHL4-5 (P

Background: Calcification of the ligamentum flavum is a rare cause of spinal stenosis. The process can occur at any level in the spine, often presents with local pain or radicular symptoms, and is a distinct process from ossification of the spinal ligaments in pathogenesis and treatment approach. Few case reports have described multiple level involvement in the thoracic spine that results in sensorimotor deficits and myelopathy. Case Report: A 37-year-old female presented with progressive sensorimotor deficits from T3 distally that resulted in complete sensory deficits and diminished lower extremity strength. Computed tomography and magnetic resonance imaging demonstrated calcification of the ligamentum flavum from T2-T12 with severe spinal stenosis at T3-T4. She underwent T2-T12 posterior laminectomy with ligamentum flavum resection. Postoperatively, she had complete motor strength return and was discharged home for outpatient therapy. Her residual sensory deficits continued to improve with time after decompression and excision of the calcified ligamentum flavum. Conclusion: This case is unique in that the calcific process involved nearly the entire thoracic spine. The patient had dramatic improvement in her symptoms following resection of the involved levels. The case adds a severe manifestation of calcification of the ligamentum flavum with a surgical outcome to the literature. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective cross-sectional study. Objectives: There is insufficient data on the clinical features of ossification of the ligamentum flavum (OLF) of the thoracic spine and the risk of progression of ossified lesions. The link between obesity and ossification of the posterior longitudinal ligament (OPLL), which frequently coexists with OLF, has been demonstrated. However, the link between obesity and OLF has not been recognized. We aimed to determine the prevalence of obesity in thoracic OLF and whether the severity of OLF is associated with the degree of obesity. Methods: A total of 204 symptomatic Japanese subjects with thoracic OLF and 136 subjects without spinal ligament ossification as controls were included. OLF subjects were divided into 3 groups: 1) localized OLF (OLF <2-intervertebral regions); 2) multilevel OLF (OLF ≥3-intervertebral regions); and 3) OLF + OPLL. The severity of OLF was quantified using the OLF index using computed tomography imaging of the entire spine. Results: The proportion of severely obese subjects (BMI ≥ 30 kg/m2) was significantly higher both in the multilevel OLF group (25.5%) and the OLF + OPLL group (44.3%) than in the localized OLF group (3.6%) and the control group (1.4%) (P < 0.01). BMI, age, and coexistence of cervical OPLL and lumbar OLF were associated with thoracic OLF index in the multiple regression analysis. Conclusions: Our findings demonstrated that obesity is a distinct feature of multilevel OLF in the thoracic spine and that the severity of OLF is associated with the degree of obesity. [ABSTRACT FROM AUTHOR]

A muscle-preserving, spinous process-splitting approach may be a less invasive approach to conventional laminectomy in patients with thoracic ossification of the ligamentum flavum. Few reports have discussed the usefulness of this procedure for thoracic lesions in professional athletes who need highly active thoracic spinal function after surgery. The treatment of thoracic ossification of the ligamentum flavum using a spinous process-splitting approach in 3 professional athletes is presented. In all three cases the patients could return to play within 3 months after surgery without complications, and in two of the cases, there was no spinal deformity or local recurrence of ossification of the ligamentum flavum at the final follow-up at least 8 years after surgery. The spinous process-splitting approach could be a safe procedure for multi-level and all other forms of ossification of the ligamentum flavum and is less invasive to the paraspinal muscles, relieves back symptoms, and restores function for athletes. [ABSTRACT FROM AUTHOR]

Abstract Multi‐joint disease pathologies in the lumbar spine, including ligamentum flavum (LF) hypertrophy and intervertebral disc (IVD) bulging or herniation contribute to lumbar spinal stenosis (LSS), a highly prevalent condition characterized by symptomatic narrowing of the spinal canal. Clinical hypertrophic LF is characterized by a loss of elastic fibers and increase in collagen fibers, resulting in fibrotic thickening and scar formation. In this study, we created an injury model to test the hypothesis that LF needle scrape injury in the rat will result in hypertrophy of the LF characterized by altered tissue geometry, matrix organization, composition and inflammation. An initial pilot study was conducted to evaluate effect of needle size. Results indicate that LF needle scrape injury using a 22G needle produced upregulation of the pro‐inflammatory cytokine Il6 at 1 week post injury, and increased expression of Ctgf and Tgfb1 at 8 weeks post injury, along with persistent presence of infiltrating macrophages at 1, 3, and 8 weeks post injury. LF integrity was also altered, evidenced by increases in LF tissue thickness and loss of elastic tissue by 8 weeks post injury. Persistent LF injury also produced multi‐joint effects in the lumbar IVD, including disc height loss at the injury and adjacent to injury level, with degenerative IVD changes observed in the adjacent level. These results demonstrate that LF scrape injury in the rat produces structural and molecular features of LF hypertrophy and IVD height and histological changes, dependent on level. This model may be useful for testing of therapeutic interventions for treatment of LSS and IVD degeneration associated with LF hypertrophy.

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. [ABSTRACT FROM AUTHOR]