Lumbar Ligamentum Flavum Research Articles

MicroRNA-221 Regulates Hypertrophy of Ligamentum Flavum in Lumbar Spinal Stenosis by Targeting TIMP-2.

A study of lumbar ligamentum flavum (LF). The aim of this study was to identify LF hypertrophy related microRNAs (miRNAs) expression profile and to investigate the role of miRNAs in the development of LF hypertrophy in lumbar spinal stenosis (LSS). Although histologic and biologic literature on LF hypertrophy is available, the pathomechanism is still unknown. Accumulating evidence suggests that microRNAs (miRNAs) participate in many physiologic processes, including cell proliferation, differentiation, and fibrosis, but the role of specific miRNAs involved in LF hypertrophy remains elusive. An initial screening of LF tissues miRNA expression by miRNA microarray was performed using samples from 10 patients and 10 controls, respectively. Subsequently, differential expression was validated using qRT-PCR. Then, functional analysis of the miRNAs in regulating collagens I and III expression was carried out. Western blotting and luciferase reporter assay were also used to detect the target gene. In addition, the thickness of the LF at the level of the facet joint was measured on axial T1-weighted magnetic resonance images. We identified 18 miRNAs that were differentially expressed in patients compared with controls. Following qRT-PCR confirmation, miR-221 was significantly lower in LF tissues of patients than controls. The LF was significantly thicker in patients than that in controls. Bioinformatics target prediction identified tissue inhibitors of matrix metalloproteinase (TIMP)-2 as a putative target of miR-221. Furthermore, luciferase reporter assays demonstrated that miR-221 directly targets TIMP-2 and affects the protein expression of TIMP-2 in fibroblasts isolated from LF. Of note, miR-221 mimic reduced mRNA and protein expression of collagens I and collagen III in fibroblasts isolated from LF. The downregulation of miR-221 might contribute to LF hypertrophy by promoting collagens I and III expression via the induction of TIMP-2. Our study also underscores the potential of miR-221 as a novel therapeutic target in LSS. 3.

A case report of the lumbar ligamentum flavum hematoma, treatment by minimum invasive surgery

A case report of the lumbar ligamentum flavum hematoma, treatment by minimum invasive surgery

Hematoma in the lumbar ligamentum flavum report of four cases

Hematoma in the lumbar ligamentum flavum report of four cases

Lateral extent and ventral laminar attachments of the lumbar ligamentum flavum: cadaveric study

Background contextCadaveric descriptions of the deep layer of the lumbar ligamentum flavum (LF), extending between contiguous borders of adjacent laminae and into the lateral spinal canal region are limited. PurposeTo provide detailed descriptions of the lumbar LF. Study designCadaveric dissection. MethodsThe deep ligamentum flava of 14 formalin-fixed human cadaver lumbar spines (140 levels) were examined to assess their laminar attachments and lateral extents in relation to the intervertebral foramen. ResultsThe variable attachment of the deep layer of the LF with respect to the cephalad and caudad laminae was identified and described. At each successive caudal level of the lumbar spine, the deep layer appeared to become a more prominent feature of the posterior vertebral column, lining more of the laminae to which it is attached and encroaching further into the posteroinferior region of the intervertebral foramen at its lateral margins. ConclusionsWe describe our observations of the deep LF in the human lumbar spine. These observations have clinical relevance for the interpretation of radiologic imaging and the performance of adequate decompression in the setting of spinal stenosis.

Spinal cord compression by hematoma in the cervical ligamentum flavum: a case report

There have been some reports describing hematoma in the thoracic and lumbar ligamentum flavum, but there have been only three reports of hematoma in the cervical ligamentum flavum. We describe another case of the ligamentum flavum hematoma in the cervical spine with a different feature of occurrence that required surgical treatment. Case report. Patient with ligamentum flavum hematoma in the cervical spine. Preoperative magnetic resonance imaging and pathologic finding from operative specimen confirmed the diagnosis. A 69-year-old man insidiously presented with pain in his left upper arm and difficulty in left shoulder abduction. Neurologic examination demonstrated a cervical myelopathy with diffuse muscle weakness of left upper extremity and sensory disturbance. Imaging studies revealed a mass of high intense on T1-weighted images and isointense on T2-weighted images posterior to the dura at C4 lower end level. The patient underwent C4-C5 hemilaminectomy and the removal of the mass. The mass existed within the ligamentum flavum and was connected toward the pedicle like the beads of a rosary. Histopathologic examination of the surgical specimen showed that the hematoma was present within the ligamentum flavum and contained macrophages that had phagocytosed red blood cells and hemosiderin. After surgery, the patients' symptoms immediately improved, and no recurrence was observed at 2 years postoperatively. We reported a very rare case of hematoma in the ligamentum flavum of the cervical spine that required surgery. Because the patient was without the history of trauma, it was suggested that the use of antiplatelet drugs was responsible for the occurrence of the disease.

血腫形成を伴った腰椎黄色靱帯内ガングリオン嚢胞の病理・免疫組織化学的検討

血腫形成を伴った腰椎黄色靱帯内ガングリオン嚢胞の病理・免疫組織化学的検討

Lumbar Ligamentum Flavum Hematoma Treated With Endoscopy

Hematoma of the ligamentum flavum is a rare cause of neural compression, for which treatment has consisted of excising the hematoma via open surgical approaches, including total laminectomy or bilateral partial laminectomy. This article presents the first report of a microscope-assisted endoscopic decompression to resect a hematoma of the ligamentum flavum.A 52-year-old man presented with back and leg pain, as well as difficulty initiating micturation. Magnetic resonance imaging demonstrated an epidural mass at L5/S1 that was continuous with the facet joint. Visualization was obtained via an endoscope, and a reddish tan-brown solid mass was found beneath the ligamentum flavum. Thorough decompression of the cauda equine and nerve roots was undertaken. The patient's radicular leg pain and bladder function improved soon after the decompression. Histological examination of the ligamentum flavum revealed a consolidated hematoma with granulomatous change.A review of the English literature revealed 29 cases of hematoma in the lumbar ligamentum flavum. Surgical decompression in these patients was accomplished with a standard open approach through hemilaminectomy (n=11), total laminectomy (n=10), or laminectomy followed by posterior fixation (n=3). The literature review did not identify any case of hematoma of the lumbar ligamentum flavum that was treated endoscopically. We expect our case may expand the indications for the endoscope in spine surgery.

Is Platelet-Derived Growth Factor-BB Expression Proportional to Fibrosis in the Hypertrophied Lumber Ligamentum Flavum?

A clinical and experimental assessment using human samples of lumbar ligamentum flavum (LF). To identify platelet-derived growth factor-BB (PDGF-BB) expression in hypertrophied LF of patients with lumbar spinal canal stenosis (LSS) and relate it to fibrosis. Recent studies showed that fibrosis in LF hypertrophy was due to accumulation of inflammation-related scar tissue. PDGF-BB participates in scar formation and collagen development in wound healing and fibrosis diseases. However, it is unclear whether PDGF-BB expression is associated with fibrosis of the hypertrophied LF in LSS. In all, 10 patients of LSS was enrolled in this study, while 10 patients of lumbar disc herniation (LDH) as a control group. LF thickness was measured by axial T1-weighted magnetic resonance imaging. Fibrosis was graded and type of collagen was identified. The location and the expression of PDGF-BB were analyzed using immunohistochemical stains, real-time polymerase chain reaction, and Western Blotting. Correlation among LF thickness, fibrosis, and PDGF-BB expression was analyzed. LF thickness was 5.3 ± 1.0 mm (range from 3.9 to 7.5 mm) in the LSS group and 2.8 ± 0.7 mm (range from 1.69 to 3.8 mm) in the LDH group. Obvious fibrosis was observed in all samples of the LSS group, and correlated to LF thickness of the dural, middle, and dorsal layers (P < 0.05), respectively. PDGF-BB was detected in the hypertrophied LF, particularly in the dorsal layer. PDGF-BB expression was higher in the LSS group than that in the LDH group (P < 0.05), and in the dorsal layer than the dural layer in the LSS group (P < 0.05). PDGF-BB mRNA correlated significantly to thickness of LF (r = 0.41) and the severity of fibrosis (r = 0.69) (P < 0.05). A higher PDGF-BB expression existed in the hypertrophied LF of patients with LSS and could be a risk factor of the fibrosis.

Hypertrophy of the lumbar ligamentum flavum is associated with inflammation-related TGF-β expression

Despite the significance of hypertrophy of the ligamentum flavum (HLF) in the disease progress of neurogenic claudication, the cellular mechanisms underlying the gradual fibrotic thickening of the ligamentum flavum remain poorly understood. The aim of our study was to get insight into the contribution of inflammatory mechanisms to the development of hypertrophy. Specimens of hypertrophied ligamenta flava were obtained at surgery from 20 patients with acquired lumbar osteoligamentous spinal canal stenosis from the central part of the ligament. Paraffin sections were stained with hematoxylin and eosin and Elastica van Gieson to evaluate extracellular matrix architecture, and immunohistochemistry was performed to characterize the inflammatory reaction and the sources of transforming growth factor beta (TGF-β) expression. Sections of normal ligamenta flava obtained from corresponding anatomical sites and stained in parallel served as a control. HLF was characterized by a considerable distortion of the elastic matrix and fibrotic transformation by extracellular collagen deposition. All specimens showed highly inflammatory cellular infiltrates confined to regions exhibiting marked degeneration of the elastic matrix composed mainly of macrophages, scattered T lymphocytes, and neovascularization, thus representing a chronic inflammation. Surprisingly, macrophages as well as vascular endothelial cells but not fibroblasts showed a strong expression of TGF-β, a strong inducer of extracellular collagen deposition. Macrophages were identified as a major cellular source of TGF-β in advanced HLF and may perpetuate further hypertrophy. This finding suggests that modulating the immune response locally or systemically could prove to be effective for impeding the disease progress.

Microsurgical excision of hematoma of the lumbar ligamentum flavum

Hematoma of the lumbar ligamentum flavum is a very rare cause of sciatica. A 72-year-old man presented with left-sided sciatica and paresthesia of the lateral aspect of his left foot. From CT and MRI findings, he was diagnosed as having a hematoma embedded in the ligamentum flavum, which compressed the dura mater at the L5/S1 disc level. After an adequate surgical field was obtained with a microscope and a Casper retractor, the hematoma of the ligamentum flavum could be excised via a unilateral approach and satisfactory decompression of the cauda equina and nerve roots were obtained.

Foot Drop of Sudden Onset Caused by Acute Hematoma in the Lumbar Ligamentum Flavum

A case report. To describe an unusual case of acute hematoma in the lumbar ligamentum flavum causing foot drop. There have been several reports of hematoma in the lumbar ligamentum flavum causing compression of the cauda equina and/or nerve root. However, the majority of these cases were chronic hematomas, based on clinical history and histologic findings. A 64-year-old man presented with right foot drop of sudden onset and severe sciatica. Magnetic resonance imaging (MRI) on the 10th day after the onset of symptoms revealed spinal stenosis at L4/5 caused by a posterior mass that was isointense on T1-weighted images and hyperintense on T2-weighted images, but was hyperintense on T1-weighted images and hypointense on T2-weighted images 5 days later. Because of these neurologic findings, surgical exploration and excision of the intraspinal mass were performed on the 18th day after onset. Surgical treatment was uneventful, and the severe sciatica improved immediately after surgical treatment. Histologic examination revealed recent extravasation of blood in the degenerated ligamentum flavum. These findings were supported by the 2 consecutive preoperative MRI examinations. At 1 year after surgery, manual muscle testing of the tibialis anterior on the affected side had recovered to grade 4. Consecutive MRI examinations performed 5 days apart in the early stage after the onset of symptoms clearly demonstrated intensity change, indicating acute hematoma of ligamentum flavum as a cause of foot drop of sudden onset.

Pathomechanism of Loss of Elasticity and Hypertrophy of Lumbar Ligamentum Flavum in Elderly Patients With Lumbar Spinal Canal Stenosis

A histologic, biologic, and immunohistochemical assessment using human samples of lumbar ligamentum flavum. To clarify the pathomechanism of loss of elasticity and hypertrophy of the lumbar ligamentum flavum (LF) in the elderly population. The most common spinal disorder in elderly patients is lumbar spinal canal stenosis, causing low back and leg pain, and paresis. Canal narrowing, in part, results from hypertrophy of the LF. Although histologic and biologic literature on this topic is available, the pathomechanism of loss of elasticity and hypertrophy of the LF is still unknown. One fetus, 5 young, and 5 elderly LF were obtained for histologic study. Hematoxylin and eosin, Alcian blue, Masson Trichrome, and Elastica Van Gieson stains were performed for each LF. Nine LF were collected and were used for biologic study of real time RT-PCR to quantitatively measure mRNA expression of Type I collagen and elastin in each LF. In the LF of the fetus, elastic fibers accounted for about 75% of the entire area. In the dural aspect of the LF in the young and elderly group, the ratio was also around 75%; however, the ratio of the dorsal aspect decreased with age. Almost half of the area showing loss of elastic fibers was shown to be converted to cartilaginous tissue producing Type II collagen and proteoglycan by Alcian blue and Type II collagen immunohistochemistry. The area, which did not stain black with EV nor blue with AB stain, was positively stained blue with T stain, indicating scarring. The area of the normal dural layer was 18.0 +/- 2.3 and 33.8 +/- 4.3 (mm2), for young and elderly group, respectively. Accordingly, it was 3.2 +/- 0.8 and 18.0 +/- 10.2 (mm2), for the dorsal abnormal layer. Elastin mRNA showed a relatively strong correlation (r = 0.44) with age; however, the slope was very gentle. Type I collagen mRNA showed a very strong correlation (r = 0.80) with age. The slope was steeper, and the value reached at 1000% (10-fold) around 65 years old when compared with the LF from younger patient. Elastin mRNA showed a weak correlation (r = 0.36) with thickness, and the slope was gentle. Type I collagen mRNA showed relatively strong correlation (r = 0.52) with thickness. The slope was steeper, and the line reached at 1000% (10-fold) around 6.5 (mm) when compared with a thin LF. Decreased elasticity of LF in the elderly is due to the loss of elastic fibers and a concomitant increase of collagenous fibers in the dorsal aspect. LF hypertrophy could be due to the thickening of the normal elastic layer as well as of the abnormal collagenous layer.

Calcium pyrophosphate crystal deposition in the ligamentum flavum of degenerated lumbar spine: histopathological and immunohistological findings

We investigated the histological and immunohistochemical features of degenerative changes in the ligamentum flavum of the lumbar spine with calcium crystal deposition. We investigated degenerative changes in 270 ligamentum flavum specimens harvested from 198 patients who underwent decompressive surgeries for lumbar spinal canal stenosis. En bloc sections of the ligamentum flavum were examined histologically. We also examined immunoreactivity for transforming growth factor (TGF)-beta, vascular endothelial growth factor (VEGF), CD34, and CD68; immunoblot analysis for VEGF; and terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick end-labeling (TUNEL) method. The ligamentum flavum showed fragmented and disorganized elastic fiber bundles with increased collagen fibrils in the matrix. Calcium deposition, which was identified as calcium pyrophosphate dihydrate crystals, was evident in 72 of 198 patients and in 99 of 270 samples, and was associated with appearance of hypertrophic chondrocytes and new blood vessel formation. Areas of calcium deposits were surrounded by abundant hypertrophic chondrocytes (with marked immunoreactivity to TGF-beta and VEGF) and a significant number of TUNEL-positive chondrocytes. Calcium crystal deposition in the lumbar ligamentum flavum progresses with reduction in elastic fibers and accumulation of collagen fibrils in the matrix as well as expansion of chondrometaplastic areas.

Lumbar Ligamentum Flavum Hypertrophy Is Due to Accumulation of Inflammation-Related Scar Tissue

A histologic, biologic, and immunohistochemical assessment using human samples of the lumbar ligamentum flavum. To prove our hypothesis that hypertrophy of the ligamentum flavum is caused by accumulation of inflammation-related scar tissue. Lumbar spinal canal stenosis is 1 of the most common spinal disorders in elderly patients. Canal narrowing, in part, results from hypertrophy of the ligamentum flavum. The hypertrophy mechanism remains unclear. Based on our preliminary analyses, we have previously proposed that the hypertrophy may be due to accumulation of scar tissue in the ligament. Scar tissue is reported to develop after inflammation; however, there is no report, including our previous study, on inflammation in the ligamentum flavum. There is a need for an in-depth investigation of any relationship between inflammation and scar formation in the ligamentum flavum. If inflammation is related to hypertrophy, we may control/delay the hypertrophy by inhibiting the inflammation. Twenty-one ligamentum flavum samples were obtained for the histologic study. Trichrome and Verhoeff-van Gieson stains were used to assess the degree of fibrosis (scarring) and content of elastic fibers, respectively. Two ligamentum flavum samples, hypertrophied and thin control ligaments, were used for a global genetic assessment by oligonucleotide gene array technology with gene chips. Messenger ribonucleic acid expression of cyclooxygenase (COX)-2 was quantitatively measured from 16 ligamentum flavum samples using real-time reverse transcriptase polymerase chain reaction. Immunohistochemistry evaluated the cellular location of COX-2 in ligamentum flavum. In the hypertrophied ligament, severe fibrosis (scarring) was observed in the entire area of the ligamentum flavum, and the severity of scarring showed a significant (r = 0.79; P < 0.0001) and positive linear correlation with ligamentum flavum thickness. Gene array results showed in both thin/control and hypertrophied ligaments expression of inflammation-related genes such as COX-2, tumor necrosis factor-alpha, and interleukin-1, 6, 8, and 15. Real-time polymerase chain reaction showed COX-2 messenger ribonucleic acid expression in all ligamentum flavum samples. Its expression showed weak positive linear correlation with the thickness of ligament. COX-2 was released from vascular endothelial cells in ligamentum flavum as per the immunohistochemical analysis. Accumulation of fibrosis (scarring) causes hypertrophy of the ligamentum flavum. Inflammation-related gene expression is found in the ligamentum flavum. It might be possible to prevent the hypertrophy of ligamentum flavum with antiinflammatory drugs.

Case Reports: A Rare Cause of Radicular Complaints

Hematomas in the lumbar ligamentum flavum are rare and may generate signs and symptoms of lumbar nerve root compression or neurogenic claudication similar to the far more common degenerative diseases. The pathogenesis of these hematomas is unclear. Ruptured irregular vessels of the degenerated and hypertrophic ligamentum flavum were assumed. We diagnosed three patients with a flavum hematoma intraoperatively leading to radicular complaints and spinal claudication. One occurred as a complication of local infiltration therapy, and the other two patients reported minor trauma as the releasing factor. Using spinal magnetic resonance imaging, a preoperative diagnosis is possible but the differentiation to synovial cysts is difficult. Surgical resection of the ligamentum flavum, including the hematoma, provided adequate treatment in these patients.

HISTOLOGICAL CHANGES OF LIGAMENTA FLAVA IN ‎LUMBAR DISC HERNIATION AND SPINAL CANAL ‎STENOSIS

‏ ‏Samples of ligamenta flava were obtained after surgical operations from 50 patients with a ‎lumbar disc herniation, another 50 patients with a lumbar canal stenosis, and 25 patients with ‎spinal fractures who were used as control group. ‎ ‎ Ligamenta flava from control patients aged below 46 years consisted of large elastic fibers, ‎thin bundles of collagen fibers, and few spindle-shaped fibroblast cells.‎ In close proximity to the laminal insertion, the ligamentum flavum had fibrocartilagineous ‎features. in the control patients who were aged 46 or older, the areas that had fewer and thinner ‎elastic fibers and a more abundant collagen component were visible occasionally. The spindle-‎shaped fibroblast cells were fewer compared with control patients aged below 46 years. Also ‎remnants of necrotic cells and few, short, thin, interwoven, fragmented, non-branching elastic ‎fibers, as well as small calcified areas, were occasionally visible. ‎ ‎ In close proximity to the laminal insertion, the ligamentum flavum had larger fibrocartilaginous ‎features with more collagen fibers compared with younger patients. ‎ ‎ In patients with disc herniation, the ligamenta flava had nearly similar morphologic features to ‎those of the control patients of similar ages. The ligamenta flava from patients with lumbar ‎spinal stenosis aged below 46 years showed areas of fibrosis in which the cells were often ‎represented by fibroblast cells and in stenotic patients older than 46 years, central portion of ‎ligamentum flavum showed areas of fibrosis, in which the elastic fibers appear normal in some ‎areas, showed little changes in others and in most of these areas showed great changes. ‎Fibrous septa, degenerating elastic fibers as well as small calcified areas were observed often.‎ ‎ In conclusion, Lumbar ligamentum flavum as any tissue in human body undergo degenerative ‎changes during aging. In lumbar canal stenosis, the degenerative changes were more obvious ‎compared with normal spine or lumbar disc herniation. In stenotic patients, ligamenta flava ‎show a significant decrease in the elastic component as a result of fibrosis and chondroid ‎metaplasia of the tissue, as well as degeneration of the elastic fibers. These changes, and the ‎presence of calcified areas within the tissue, decrease the elasticity of the ligaments. An elastic ‎tissue can be deformed under traction and gradually return to its normal size, proportional to ‎the decrease of the elastic tension. Ligamenta flava do not normally bulge into the spinal canal ‎when spine is in the neutral position.‎

The incidence of lumbar ligamentum flavum midline gaps.

Lumbar epidural anesthesia and analgesia has gained increasing importance in perioperative pain therapy for abdominal and lower limb surgery. The loss-of-resistance technique, used to identify the epidural space, is thought to rely on the penetration of the ligamentum flavum. However, the exact morphology of the ligamentum flavum at different vertebral levels remains controversial. Therefore, in this study, we directly investigated the incidence of lumbar ligamentum flavum midline gaps in embalmed cadavers. Vertebral column specimens were obtained from 45 human cadavers. On each dissected level, ligamentum flavum midline gaps were recorded. The incidence of midline gaps per number of viable specimens at the following levels was: L1-2 = 10 of 45 (22.2%), L2-3 = 5 of 44 (11.4%), L3-4 = 5 of 45 (11.1%), L4-5 = 4 of 43 (9.3%), L5/S1 = 0 of 33 (0%). In conclusion, the present study determined the frequency of lumbar ligamentum flavum midline gaps. Gaps in the lumbar ligamentum flavum are most frequent between L1 and L2 but are more rare below this level. When using the midline approach, the ligamentum flavum may not impede entering the epidural space in all patients. The ligamentum flavum is a crucial anatomical landmark for the safe performance of epidural anesthesia. However, the present study demonstrates some failure of the lumbar ligamentum flavum as a landmark. This may mean that, using a midline approach, one cannot always rely on the ligamentum flavum as a perceptible barrier to epidural needle advancement.

Calcium Crystal Deposition in the Ligamentum Flavum of the Lumbar Spine: Role of Sex Hormones and Transforming Growth Factor-.BETA.

We investigated histopathological and immunohistochemical properties of the ligamentum flavum of the lumbar spine with calcium crystal deposition. Ligamentum flavum of the lumbar spine containing calcium deposits were harvested from 41 surgical cases. Sections of the ligaments were immunostained for estrogen receptor (ER), progesterone receptor (PR), and transforming growth factor (TGF)-β. The results were compared with those of ligaments without calcium deposits. The elastic fibers of the ligament with calcium deposits showed marked degeneration (irregular arrangement and fragmentation of fiber bundles) and nodular lesions. Deposits of calcium crystals were present in these areas where elastic fibers were degenerated. Immunostaining for ER was positive in these areas, and PR as well as TGF-β-containing chondrocytes were detected around and within the calcified areas. TGF-β, ER and PR-containing chondrocytes appeared to precipitate deposition of calcium crystals in the nodular lesions of the degenerated lumbar ligamentum flavum. Our results suggest that TGF-β and sex hormones play a role in the calcification of the lumbar ligamentum flavum.

Sciatica caused by tumor in lumbar ligamentum flavum

Sciatica caused by tumor in lumbar ligamentum flavum

Point of View: Calcification of Lumbar Ligamentum Flavum and Facet Joints Capsule

Point of View: Calcification of Lumbar Ligamentum Flavum and Facet Joints Capsule