Ligamentum Flavum Thickness Research Articles

Thickening of spine ligamentum flavum and facet tropism

OBJECTIVE: This study investigated the thickening of the ligamentum flavum (LF) and its correlation with facet tropism and its severity at different levels of the spine. METHOD: This retrospective study was performed with patients with chronic back pain consecutively admitted to a specialized spinal surgery service between January 2012 and January 2013. All patients underwent magnetic resonance imaging (MRI) to measure the thickness of the LF and facet tropism severity (severe, moderate or absent) according to the spine levels (L3 -L4, L4-L5, L5-S1). The association between the thickness of LF and facet tropism was analyzed. RESULTS: During the study period, 98 consecutive patients were enrolled with a mean age of 53.6 years, most women (59.2%). There was no significant difference between the thicknesses of the ligament and the presence of tropism in different spinal levels (p > 0.05). The thickness of LF was significantly associated with the severity of tropism only in L5-S1 level (p < 0.03). CONCLUSIONS: Our results show that there is a positive relationship between severe facet tropism and increased thickness of the LF in the L5-S1 level.

Angiopoietin-Like Protein 2 Induced by Mechanical Stress Accelerates Degeneration and Hypertrophy of the Ligamentum Flavum in Lumbar Spinal Canal Stenosis

Chronic inflammation and subsequent fibrosis induced by mechanical stress play an important role in ligamentum flavum (LF) hypertrophy and degeneration in patients with lumbar spinal canal stenosis (LSCS). Angiopoietin-like protein 2 (Angptl2) is a chronic inflammatory mediator induced under various pathological conditions and increases the expression of TGF-β1, which is a well-characterized mediator in LF hypertrophy. We investigated whether Angptl2 is induced by mechanical stress, and whether it contributes to LF hypertrophy and degeneration by activating the TGF-β1 signaling cascade. In this study, we investigated human LF tissue and LF fibroblasts isolated from patients who underwent lumbar surgery. We found that Angptl2 was abundantly expressed in fibroblasts of hypertrophied LF tissues at both the mRNA and protein levels. This expression was not only positively correlated with LF thickness and degeneration but also positively correlated with lumbar segmental motion. Our in vitro experiments with fibroblasts from hypertrophied LF tissue revealed that mechanical stretching stress increases the expression and secretion of Angptl2 via activation of calcineurin/NFAT pathways. In hypertrophied LF tissue, expression of TGF-β1 mRNA was also increased and TGF-β1/Smad signaling was activated. Angptl2 expression in LF tissue was positively correlated with the expression of TGF-β1 mRNA, suggesting cooperation between Angptl2 and TGF-β1 in the pathogenesis of LF hypertrophy. In vitro experiments revealed that Angptl2 increased levels of TGF-β1 and its receptors, and also activated TGF-β1/Smad signaling. Mechanical stretching stress increased TGF-β1 mRNA expression, which was partially attenuated by treatment with a calcineurin/NFAT inhibitor or Angptl2 siRNA, indicating that induction of TGF-β1 expression by mechanical stretching stress is partially mediated by Angptl2. We conclude that expression of Angptl2 induced by mechanical stress in LF fibroblasts promotes LF tissue degeneration by activation of TGF-β1/Smad signaling, which results in LF hypertrophy in patients with LSCS.

Hypertrophy of ligamentum flavum in lumbar spine stenosis is associated with increased miR-155 level.

Hypertrophy of ligamentum flavum (LF) contributes to lumbar spinal stenosis (LSS) and is caused mainly by fibrosis. Recent data indicate that miR-155 plays a crucial role in the pathogenesis of different fibrotic diseases. This study aimed to test the hypothesis that miR-155 exerts effects on LF thickness by regulating collagen expression. We found that LF thickness and the expression of collagen I and, collagen III were higher in LF from LSS patients than in LF from lumbar disc herniation (LDH) patients (P < 0.01). The expression of miR-155 was significantly higher in LF from LSS group than in LF from LDH group (P < 0.01). miR-155 level was positively correlated with LF thickness (r = 0.958, P < 0.01), type I collagen level (r = 0.825, P < 0.01), and type III collagen level (r = 0.827, P < 0.01). miR-155 mimic increased mRNA and protein expression of collagen I and collagen III in fibroblasts isolated from LF, while miR-155 sponge decreased mRNA and protein expression of collagen I and III in fibroblasts. In conclusions, miR-155 is a fibrosis-associated miRNA and may play important role in the pathogenesis of LF hypertrophy.

Thickness of the ligamentum flavum of the spine and its relationship with disc degeneration

Objective: This study investigates whether the thickening of the ligamentum flavum (LF) is correlated with disc degeneration. Methods: This retrospective study was conducted with 98 patients with chronic low back pain treated in a spinal surgery service between January 2012 and January 2013. All patients underwent magnetic resonance imaging (MRI) and the images were evaluated by a spinal surgeon to measure the thickness of the LF and evaluate the degree of disc degeneration by the Pfirrmann grading system, according to the spinal levels (L3 -L4, L4-L5, L5-S1). An association was sought between LF hypertrophy and disc degeneration, age, sex and disc height. Results: The mean age of the patients was 53.6 years, and the majority were women (59.2%). The thickness of the LF and disc height varied according to the spinal level, the greatest LF thickness being found between L4-L5, and the greatest disc height at L5-S1. Women had statistically thicker ligaments in L3/L4 than men. The degree of disc degeneration was inversely correlated with the height at all the levels evaluated, i.e., the greater the degree of degeneration, the lower the disc height. Conclusions: The thickening of LF is not related to disc height or degree of disc degeneration. Therefore, there is no deformation of the LF within the spinal canal secondary to disc degeneration.

Expression of Hypoxia-inducible Factor-1α, Vascular Endothelial Growth Factor, and Matrix Metalloproteinases 1, 3, and 9 in Hypertrophied Ligamentum Flavum

Immunohistological study. To elucidate the role of matrix metalloproteinases (MMPs), hypoxia-inducible factor-1α (HIF), and vascular endothelial growth factor (VEGF) in the hypertrophied ligamentum flavum (LF) obtained from patients with lumbar spinal stenosis (LSS). The most common spinal disorder in the elderly is LSS, which results in part from LF hypertrophy. Although prior histologic and immunochemical studies have been performed in this area, the pathophysiology of loss of elasticity and hypertrophy is not completely understood. LF samples of 38 patients with LSS were harvested during spinal decompression. Twelve LF samples obtained from patients with disk herniation and no visible degeneration on preoperative magnetic resonance imaging were obtained as controls. Samples were dehydrated and paraffin embedded. For immunohistochemical determination of VEGF, HIF, and MMPs 1, 3, and 9 expression, slices were stained with VEGF, HIF, and MMP antibody dilution. Neovessel density and number of elastic fibers were counted after Masson-Goldner staining. LF hypertrophy and cross-sectional area (CSA) were measured on T1-weighted magnetic resonance imaging. MMPs 1, 3, 9 and VEGF expression were significantly increased in the hypertrophy group (P<0.05). HIF expression was negative in both groups. Vessel density was increased in the hypertrophy group, although this was not statistically significant. The number of elastic fibres was significantly higher in the control group. In the hypertrophy group, LF thickness was significantly increased, whereas CSA was significantly decreased. There was a statistical correlation between LF thickness, CSA, MMP, and VEGF expression in the hypertrophy group (P<0.05). LF hypertrophy is accompanied by increased MMPs 1, 3, 9 and VEGF expression. Neovessel density is increased in hypertrophied LF. HIF is not expressed in hypertrophied LF.

Hypertrophy of the ligament flavum in degenerative lumbar stenosis associated with the increased expression of fractalkine (CX3CL1)/CX3CR1 chemokine

Fractalkine (CX3CL1) and its receptor (CX3CR1) comprise a chemokine system involved in leukocyte recruitment and adhesion in chronic inflammatory disease, but its role in spinal diseases is unknown. The purpose of this study is to investigate the role of CX3CL1/CX3CR1 chemokine on hypertrophy of the ligamentum flavum (LF) in degenerative lumbar stenosis (DLS) compared with that of non-degenerative spinal condition (NDS) of the lumbar spine and correlation between expression of CX3CL1/CX3CR1 chemokine and thickness of LF. The mRNA concentrations of CX3CL1/CX3CR1 chemokine were analyzed in the surgically obtained LF specimens from DLS (n = 10) and NDS (n = 11) by real-time PCR. The localization of CX3CL1/CX3CR1 chemokine within the LF was determined using immunohistochemical study. Plasma levels of soluble FKN (sFKN) were measured by enzyme-linked immunosorbent assay, respectively. The thickness of the LF was measured with axial T1-weighted MRI. The cells that express CX3CL1/CX3CR1 chemokine ratio in the LF observed in DLS group were substantially higher than in NDS group. In ELISA, the plasma levels of sFKN was significantly increased in DLS compared with patients in the other groups (p = 0.006). There was greater CX3CL1/CX3CR1 expression in DLS as quantified by RT-PCR (p = 0.004, 0.010). Thickness of LF in patients was significantly correlated with serum CX3CL1 level (R2 = 0.824, p = 0.003) and with mRNA expression of CX3CL1/CX3CR1 (R2 = 0.671, p = 0.000) (R2 = 0.514, p = 0.001). This study identified for the first time that increases in CX3CL1 and CX3CR1-expressing cells are significantly related to LF hypertrophy.

Socioeconomic and Physical Characteristics of Individuals With Degenerative Lumbar Spinal Stenosis

A descriptive study of the association between demographic factors, and physical characteristics, and degenerative lumbar spinal stenosis (DLSS).To shed light on the association between socioeconomic parameters, physical characteristics, and DLSS.Lumbar spinal stenosis is a prevalent and disabling condition in the aging population. DLSS is considered to be the most common type and is essentially associated with disc disease, facet joint arthrosis, ligamentum flavum thickening, and osteophyte formation. Although there is ample information regarding the association between body mass index, cardiovascular disorders, smoking habits, and disc disease, very little is known about their association with DLSS. Data on the association of body physique (e.g., height and weight) and DLSS are limited.Two sample populations were studied. The first included 165 individuals with DLSS (mean age, 64 ± 9.9 yr) and the second 180 individuals without spinal stenosis related symptoms (mean age, 62.5 ± 12.6 yr). An evaluation of the cross-sectional area of the dural sac and degenerative listhesis for all participants was performed using computed tomographic lumbar spine images, obtained by Philips EBW station (Brilliance 64, Philips Medical System, Cleveland, OH). All participants were interviewed to obtain demographic, physical, and health data. Independent t test, Mann-Whitney and χ tests were used to determine the association between parametric and nonparametric variables and DLSS. Logistic regression analysis was carried out to reveal predicting variables for DLSS.Females with stenosis were significantly heavier and shorter than their counterparts in the control group. We also noticed that they delivered babies more often than those in the control group. Prevalence of individuals experiencing diabetes mellitus was significantly higher in the males with stenosis than control group. In the stenosis group, the frequencies of individuals engaged in heavy manual labor (males) and housekeeping (females) were significantly higher than that of their counterparts in the control group.Heavy manual labor and diabetes mellitus in males and housekeeping (females) play major roles in the genesis of DLSS.

Hypertrophy of the ligamentum flavum in lumbar spinal canal stenosis is associated with increased bFGF expression

A prospective study was undertaken to investigate basic fibroblast growth factor (bFGF) expression in hypertrophic ligamentum flavum (LF) from patients with lumbar spinal canal stenosis (LSCS) and to determine whether there was a correlation of bFGF expression with LF thickness. Twenty patients with lumbar spinal canal stenosis were enrolled in this study. bFGF mRNA and protein expressions in LF were analyzed using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA), respectively. The thickness of LF was measured by axial T1-weighted magnetic resonance imaging. Expression of bFGF was substantially higher in the hypertrophic LF group than in the control group (P < 0.001) as quantified by quantitative real-time PCR. In immunohistochemical study, bFGF was positively stained on the fibroblasts within hypertrophic LF compared to nonpathologic LF of controls. Subsequent ELISA analysis revealed that bFGF concentration in the hypertrophic LF group was remarkably higher than that in the control group (P = 0.003). The thickness of LF in the hypertrophic LF was significantly greater than that in the control group (P < 0.001). LSCS patients with greater severity of LF hypertrophy had significantly higher bFGF levels in the LF tissues (P < 0.001). Furthermore, the bFGF concentration exhibited a positive correlation with the LF thickness (r = 0.974, P < 0.001). These findings suggest that the increased expression of bFGF is associated with the hypertrophy of ligamentum flavum in patients with LSCS.

Dynamic Changes of the Ligamentum Flavum in the Cervical Spine Assessed with Kinetic Magnetic Resonance Imaging

The purpose of this article is to quantify changes in thickness of the ligamentum flavum (LF) associated with motion of the cervical spine and to compare the thickness of the LF at each cervical level using kinetic magnetic resonance imaging (kMRI). Two hundred fifty-seven symptomatic patients (129 men; 128 women) underwent kMRI in neutral, flexion, and extension positions. Midsagittal images were digitally marked and electronically analyzed by spine surgeons. Thickness of LF in the cervical region from C2–3 to C7–T1 was measured in all three positions. LF at C7–T1 was significantly thicker than C2–3 to C6–7 in neutral, flexion, and extension positions (p < 0.05). LF was significantly thicker in extension than in flexion at C3–4 to C6–7. LF thickness increases with extension and decreases with flexion. LF is uniquely thick at C6–7 and at C7–T1 in the extension position, which may predispose these levels to cord compression syndromes and associated neuropathies.

Functional and Patient‐Reported Outcomes in Symptomatic Lumbar Spinal Stenosis Following Percutaneous Decompression

Neurogenic claudication due to symptomatic lumbar spinal stenosis (LSS) is a painful condition causing significant functional disability. While the cause of LSS is multifactorial, thickened ligamentum flavum (LF) accounts for up to 85% of spinal canal narrowing. mild percutaneous lumbar decompression allows debulking of the hypertrophic LF while avoiding the morbidities frequently associated with more invasive surgical procedures. In this prospective case series study, consecutive LSS patients presenting with neurogenic claudication were treated with percutaneous lumbar decompression. Efficacy was evaluated using the Pain Disability Index (PDI) and Roland-Morris Disability Questionnaire. Pre- and postprocedure Standing Time, Walking Distance, and Visual Analog Score (VAS) were also monitored. Significant device- or procedure-related adverse events were reported. The mild procedure was successfully performed on forty patients. At twelve months, both PDI and Roland-Morris showed significant improvement of 22.6 points (ANOVA, P<0.0001) and 7.7 points (ANOVA, P<0.0001), respectively. Walking Distance, Standing Time, and VAS improvements were also statistically significant, increasing from 246 to 3,956 feet (ANOVA, P<0.0001), 8 to 56 minutes (ANOVA, P<0.0001), and 7.1 to 3.6 points (ANOVA, P<0.0001), respectively. Tukey HSD test found improvement in all 5-outcome measures to be significant from baseline at each follow-up interval. No significant device- or procedure-related adverse events were reported. This study demonstrated significant functional improvement as well as decreased disability secondary to neurogenic claudication after mild procedure. Safety, cost-effectiveness, and quality-of-life outcomes are best compared with comprehensive medical management in a randomized controlled fashion and, where ethical, to open lumbar decompression surgery.

Assessment of ligamentum flavum thickness correlation with demographic variables and disc degeneration in Erbil governorate population sample

Background and objectives: This study aimed to investigate the correlation between the ligamentum flavum thickness and age, sex, body mass index and type of disc degeneration. Method: 126 consecutive patients were examined prospectively. The sample included all the patients who had an MRI examination after they presented to Rizgary teaching hospital complaining of lower back and/or leg pain. The LF thickness was measured by using lumbo-sacral spine MRI. Results: The mean thickness of LF was more at L4-L5 (right: 0.27mm, left 0.25mm), L5-S1 (right: 0.25 mm, left 0.25 mm) levels, and was thicker on the right side. LF was thicker in females than males with a statistically significant measurement at L2-L3, L3-L4 and L4-L5 levels. The mean thickness of LF was more at older age group than the younger age groups, and the results were statistically different at left side of L2-L3 and right side of L4-L5 level. Thickness of LF was more among those with higher BMI for all levels except for L5-S1. In most cases, LF was thicker in patients with advanced disc degeneration. Conclusion: Thickening of the LF is associated to some extent with sex, age, BMI and disc degeneration. Thickening of the LF is potentially due to its buckling into the spinal canal secondary to disc degeneration more than to LF hypertrophy. Further research is needed to confirm these associations.

Cellularity and Cartilage Matrix Increased in Hypertrophied Ligamentum Flavum

Histopathological and immunohistochemical analysis. To investigate the histological changes and expression of bone morphogenetic protein (BMP) signaling component in hypertrophied ligamentum flavum (LF), and to clarify the effect of mechanical stress on them. Hypertrophic changes of the LF are a major factor in degenerative lumbar canal stenosis (DLCS), but their mechanism remains unclear. BMPs are growth factors that regulate many cellular processes including proliferation, differentiation, and extracellular matrix synthesis. However, a few studies have investigated the expressions of BMP signaling in the hypertrophied LF. A total of 133 LF specimens from patients with DLCS and 17 control LF specimens from patients with lumbar disc herniation were analyzed histologically using hematoxylin and eosin, elastica van Gieson, and toluidine blue staining. To analyze the influence of mechanical stress, the DLCS specimens were divided into 2 groups: DLCS with and DLCS without hypermobility groups. The LF thickness was measured by magnetic resonance image, and the correlations between the thickness and the histological data were analyzed. Immunohistochemical analyses were carried out to confirm the expressions and localizations of BMP signaling components. The cell number and cartilage matrix area were significantly increased in the hypertrophied LF, and those changes were more obvious in DLCS with hypermobility than in DLCS without hypermobility. The cellularity and percentage of cartilage matrix area had positive linear correlations with the LF thickness. BMP receptors and BMP ligands were both expressed by many cells of the hypertrophied LF, and some of these cells were positive for Sox9, CD105, and Msx2. The percentage of immunopositive cells for each BMP receptor type was significantly higher in DLCS with hypermobility than in DLCS without hypermobility. Higher cellularity and increased cartilage matrix area are important changes in LF hypertrophy. These results suggest that BMP signaling and mechanical stress may play a role in the hypertrophied LF.

Radiological Significance of Ligamentum Flavum Hypertrophy in the Occurrence of Redundant Nerve Roots of Central Lumbar Spinal Stenosis

ObjectiveThere were previous reports of redundant nerve roots (RNRs) focused on their clinical significance and pathogenesis. In this study, we investigated the significant radiologic findings that correlate with RNRs occurrence. These relations would provide an advanced clue for clinical significance and pathogenesis of RNRs.MethodsRetrospective research was performed with data from 126 patients who underwent surgery for central lumbar spinal stenosis (LSS). Finally, 106 patients with common denominators (inter-observer accuracy : 84%) were included on this study. We divided the patients into two groups by MRI, patients with RNRs and those with no RNRs (NRNRs). Comparative analyses were performed with clinical and radiologic parameters.ResultsRNRs were found in 45 patients (42%) with central LSS. There were no statistically significant differences between the two groups in severity of symptoms. On the other hand, we found statistically significant differences in duration of symptom and number of level included (p<0.05). In the maximal stenotic level, ligamentum flavum (LF) thickness, LF cross-sectional area (CSA), dural sac CSA, and segmental angulation are significantly different in RNRs group compared to NRNRs group (p<0.05).ConclusionRNRs patients showed clinically longer duration of symptoms and multiple levels included. We also confirmed that wide segmental angulation and LF hypertrophy play a major role of the development of RNRs in central LSS. Together, our results suggest that wide motion in long period contribute to LF hypertrophy, and it might be the key factor of RNRs formation in central LSS.

The Ligamentum Flavum at L4-5: Relationship With Anthropomorphic Factors and Clinical Findings in Older Persons With and Without Spinal Disorders

To examine the relationship between ligamentum flavum thickness and clinical spinal stenosis. A validation study. Clinical research laboratory. A total of 119 subjects from the Michigan Spinal Stenosis Study (MSSS). Two new measurement techniques were compared by use of magnetic resonance images of 4 asymptomatic subjects by 2 examiners. The technique with the best interrater reliability was then used to measure the ligamentum flavum at L4-L5 in 119 subjects in the MSSS who, on the basis of clinical examination without imaging, were thought to have lumbar stenosis, mechanical back pain, or no pain. These findings were related to other radiologic findings, demographics, clinical severity, and electrodiagnostic findings. Perpendicular on the inside of the spinal canal from the deepest point of concavity of the lamina to the edge of the ligament. The ligamentum flavum width measurement had high interrater (r = 0.774) and intrarater (r = 0.768) reliability. In 28 asymptomatic volunteers, ligamentum flavum width averaged 5.72 ± 0.95 mm, with the left side significantly thinner than the right (t = 2.117, P = .044), and thicker ligaments with age (r = 0.653, P < .001). Asymptomatic persons whom radiologists thought had stenosis had thicker ligaments (t = 2.273, P = .032). Persons with clinical stenosis (n = 48) and mechanical pain (n = 43) had ligament thickness similar to that of asymptomatic volunteers. Among patients with clinical stenosis, ligamentum flavum thickness did not relate to symptom severity (pedometer and laboratory ambulation tests, Pain Disability Index, and visual analog scale for pain). Most neurophysiological findings had no relationship with ligamentum flavum width, except the presence of limb fibrillation potentials related to a thinner ligament (t = 2.915, P = .004). The measurement technique is standardized for the ligamentum flavum for future use. Although the ligamentum flavum appears to get thicker with age, other factors, including clinical diagnosis, pain, and function, do not appear to relate to the ligamentum flavum width.

Increased expression of CD44 in hypertrophied ligamentum flavum and relevance of splice variants CD44v5 and CD44v6

The most common spinal disorder in the elderly is lumbar spinal stenosis (LSS), which results in part from ligamentum flavum (LF) hypertrophy. Although prior histologic and immunochemical studies have been performed in this area, the pathophysiology of loss of elasticity and hypertrophy is not completely understood. The purpose of this immunohistological study is to elucidate the role of CD44 and its splice variants CD44v5 and CD44v6 in the hypertrophied LF obtained from patients with lumbar spinal stenosis (LSS). LF samples of 38 patients with LSS were harvested during spinal decompression. Twelve LF samples obtained from patients with disc herniation and no visible degeneration on preoperative MRI were obtained as controls. Samples were dehydrated and embedded in paraffin. For immunohistochemical determination, slices were stained with antibodies against CD44, Cd44v4, and CD44v6 stained with DAB. LF hypertrophy and cross-sectional area (CSA) were measured with T1-weighted MRI. CD44 and CD44v5 expression were significantly increased in the hypertrophy group (p < 0.05). CD44v6 expression was not significantly increased. The number of elastic fibers was significantly higher in the hypertrophy group. In the hypertrophy group, LF thickness was significantly increased while CSA was significantly decreased. There was a statistical correlation between LF thickness, CSA, CD44, and CD44v5 expression in the hypertrophy group (p < 0.05). LF hypertrophy is accompanied by increased CD44 and CD44v5 expression. CD44v6 expression is not enhanced in LF hypertrophy.

Matrix metalloproteinase 13 in the ligamentum flavum from lumbar spinal canal stenosis patients with and without diabetes mellitus

BackgroundLumbar spinal canal stenosis (LSCS) is one of the most common spinal disorders in the elderly, and ligamentum flavum (LF) hypertrophy is an important cause of LSCS. Matrix metalloproteinase 13 (MMP13) can degrade fibrillar collagens and elastic microfibrils, and is involved in inflammation and fibrosis. The purpose of this study was to compare the expression of MMP13 in the LF from LSCS patients with diabetes mellitus [DM (+)] with that in the LF from patients without DM [DM (−)] and to analyze the relationship among DM, MMP13 expression, and LF hypertrophy. MethodsLFs from 11DM (+) and 24DM (−) LSCS patients were analyzed in this study. Histology analysis using hematoxylin and eosin and Masson's trichrome stain was performed for each LF. The expression of MMP13 was analyzed by quantitative real-time PCR. The thickness of LF was measured by CT. ResultsIn the LF from DM (+) LSCS patients, the elastic fibers were more disorganized and had lower volumes than in the LF from DM (−) LSCS patients, while more fibrotic tissue was observed in the LF from DM (+) than from DM (−) LSCS patients. MMP13 expression was significantly higher in the LF from DM (+) LSCS patients (0.46 ± 0.61 vs. 0.05 ± 0.09, P = 0.002). The LF from the DM (+) LSCS patients was significantly thicker than that from the DM (−) LSCS patients (5.0 ± 0.9 vs. 3.1 ± 0.8 mm, P < 0.01), and the thickness was correlated with the expression of MMP13 (correlation coefficient = 0.43, P = 0.01, Pearson's correlation test). ConclusionDM-related MMP13 expression can be one of the factors contributing to fibrosis and hypertrophy of the LF. Further research on the mechanism of this process may lead to new therapies for LF hypertrophy.

Factors Associated With the Thickness of the Ligamentum Flavum

Ligamentum flavum (LF) thickness was measured by using lumbar magnetic resonance imaging in patients with low back or leg pain. This study investigated whether LF thickening is due to hypertrophy or buckling related to disc degeneration and examined the correlations between the thickness of the LF and age, sex, body mass index (BMI), degree of pain, lumbar spinal stenosis (LSS), and disc herniation. "LF thickness" and "LF hypertrophy" are used interchangeably in the literature, although they are not necessarily the same thing. Thickness may increase by buckling without a change in the mass of the LF, and whether LF thickening is due to tissue hypertrophy or buckling remains controversial. The thickness of 896 LFs at the L2-L3, L3-L4, L4-L5, and L5-S1 levels of 224 (mean age, 47.8 ± 16.7 yrs) patients was measured prospectively on axial T1-weighed magnetic resonance images, obtained at the facet joint level. The presence of disc degeneration, spinal stenosis, and disc herniation was evaluated. At all of the levels investigated, LF thickness was significantly greater in patients with grades IV to V degeneration compared with the patients with grades I to III degeneration (P < 0.05). LF thickness at all levels increased significantly with age (P < 0.05). Sex and the degree of pain were not correlated with the thickness of the LF. Patients with a BMI of 25 kg/m or greater had the thickest LF at the L3-L4 level (P < 0.01). LF thickness was significantly greater at the L2-L3, L3-L4, and L4-L5 levels in subjects with LSS and significantly greater at all levels in subjects with disc herniation (P < 0.05). Thickening of the LF is correlated with disc degeneration, aging, BMI, LSS, spinal level, and disc herniation. The authors concluded that thickening of the LF is due to buckling of the LF into the spinal canal secondary to disc degeneration more than to LF hypertrophy. Sex and the degree of pain were not correlated with the thickness of the LF.

Hypertrophy of ligamentum flavum in lumbar spine stenosis associated with the increased expression of connective tissue growth factor

Hypertrophy of the ligamentum flavum (LF) contributes to lumbar spinal stenosis (LSS), and results mainly from fibrosis. Connective tissue growth factor (CTGF) is a profibrotic factor involved in the fibrotic process. This study aimed to evaluate CTGF expression in hypertrophied lumbar LF and the involvement of CTGF in LF hypertrophy. Ten patients with LSS were enrolled in this study. The control group included 10 patients with lumbar disc herniation. LF thickness was measured on the preoperative axial T1-weighted MRI. LF samples were collected during surgery. LF fibrosis was scored by Masson's trichrome staining. CTGF expression was determined by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. Correlation between LF thickness and CTGF expression was analyzed. Human LF cells were cultured and treated with recombinant human (rh) CTGF. Expression of types I and III collagen was determined by real-time PCR and ELISA. The thickness and fibrosis scores of LF in the LSS group were higher than that in the control group (all P < 0.001). CTGF was expressed in the extracellular matrix of all ligament samples, and was significantly higher in the LSS group than that in the control group (P < 0.001). The increase of CTGF expression was positive correlation with the LF thickness (r = 0.969, P = 0.000). rhCTGF treatment increased the mRNA expression and protein synthesis of types I and III collagen of the LF cells (all P < 0.001). Our results suggest that the increased expression of CTGF is associated with hypertrophy of the LF in patients with LSS.

Ligamentum Flavum Thickness in Normal and Stenotic Lumbar Spines

A descriptive computed tomography (CT) study of the ligamentum flavum (LF) thickness in individuals with normal and stenotic lumbar spines. To establish standards for normal and pathologic range of LF thickness and its asymmetry as indicated in CT images and to examine its association with vertebral body size, age, and gender. LF lines a considerable part of the posterior and lateral walls of the spinal canal and is a major role contributor to spinal canal stenosis. Due to methodologic deficiencies (e.g., small sample size, lack of control for vertebral body size, gender, and age), the normal range of LF thickness is still controversial. Furthermore, data on important aspect of LF thickness such as left-right differences are missing. Two groups of individuals were studied. The first group included 65 individuals with lumbar spinal stenosis (LSS) (mean age: 66 +/- 9.7 years) and the second, 150 individuals (mean age: 52 +/- 19 years) without LSS-related symptoms. LF thickness was measured on CT images (Philips Brilliance 64), obtained from axial plane scan at the intervertebral disc level. Measurements were performed at the levels of L3-L4, L4-L5, and L5-S1. Analysis of variance and t test were carried out to evaluate the association between LF thickness and demographic factors. Absolute and relative LF thickness were significantly greater in the LSS group at the levels of L3-L4 and L4-L5 on both sides, compared to control group (P < 0.05). LF thickness was independent of gender (absolute and relative thickness). Even though LF thickness at all levels significantly increases with age, significant changes after the age of 60 occurred only at L3-L4. Significant asymmetry in LF thickness was found at L3-L4 (2.9 +/- 0.90 mm on the right vs. 2.76 +/- 0.90 mm on the left) and L5-S1 (3.42 +/- 1.1 mm on the right vs. 3.22 +/- 1.22 mm on the left) (P < 0.05). LF thickness is an age-dependent and gender-independent phenomenon. LF is significantly thicker on the right side. The borderline between normal and pathologic LF thickness should not be set at 4 mm.

Cervical myelopathy from calcium pyrophosphate dihydrate crystal deposition: a case report

Calcification of the ligamentum flavum secondary to calcium pyrophosphate dihydrate (CPPD) deposition may be a rare cause of cervical myelopathy. We present a 56-year-old man with spinal stenosis secondary to CPPD disease and subacute cervical myelopathy following minor trauma. The patient had no history of CPPD disease. Posterior C4-C6 decompression and instrumented fusion were performed. Intraoperative findings were densely thickened ligamentum flavum and distortion of the cervical dura mater due to impingement. Histological sections of discs and ligamentum flavum specimens showed CPPD crystals. Postoperatively, neck pain and paresthesias improved immediately. At 2 weeks after spinal surgery, the patient experienced acute right knee swelling. Standard radiographs showed chondrocalcinosis of the knee menisci.