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1.  Serum Levels of TGF-β1, TIMP-1 and TIMP-2 in Patients with Lumbar Spinal Stenosis and Disc Herniation 
Asian Spine Journal  2007;1(1):8-11.
Study Design
The serum levels of transforming growth factor-beta 1 (TGF-β1), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-2 were measured by enzyme-linked immunosorbent assay.
Purpose
To compare the serum levels of TGF-β1, TIMP-1 and TIMP-2 between patients with lumbar spinal stenosis and disc herniation.
Overview of Literature
It has been reported that increased concentrations of TGF-β1, TIMP-1 and TIMP-2 in the ligamentum flavum might be a possible pathogenesis for ligamentum flavum hypertrophy in spinal stenosis. However, it is not determined whether this phenomenon in spinal stenosis is a local or systemic problem.
Methods
The concentrations of TGF-β1, TIMP-1 and TIMP-2 were quantitatively analyzed by ELISA in the ligamentum flavum and serum of patients with lumbar spinal stenosis (n=16) and disc herniation (n=16). The thickness of ligamentum flavum was measured on axial T1-weigted magnetic resonance image. The biochemical and radiological results were compared for the two conditions.
Results
The thickness of the ligamentum flavum was larger in patients with spinal stenosis compared with that with disc herniation (p=0.001). The mean concentrations of TGF-β1, TIMP-1, and TIMP-2 in the ligamentum flavum were significantly higher in patients with spinal stenosis than those with disc herniation (all, p < 0.05). However, the difference in serum levels of TGF-β1 (p=0.464), TIMP-1 (p=0.146) and TIMP-2 (p=0.794) was not significant between the lumbar spinal stenosis and disc herniation patients.
Conclusions
Despite increased levels of TGF-β1, TIMP-1, and TIMP-2 in the ligamentum flavum of spinal stenosis patients compared to disc herniation patients, the serum levels of TGF-β1, TIMP-1 and TIMP-2 were very similar in both groups. These results indicate that the role of TGF-β1, TIMP-1 and TIMP-2 on hypertrophy of the ligamentum flavum in spinal stenosis patients is a local phenomenon, not systemic.
doi:10.4184/asj.2007.1.1.8
PMCID: PMC2857497  PMID: 20411146
Spinal stenosis; Hypertrophy of ligamentum flavum; TGF-β1; TIMPs; Local phenomenon
2.  Ligamentum flavum cyst in the lumbar spine: a case report and review of the literature 
Degenerative changes in the lumbar spine can be followed by cystic changes. Most reported intraspinal cysts are ganglion or synovial cysts. Ligamentum flavum pseudocyst, as a cystic lesion in the lumbar spine, is a rare and unusual cause of neurologic signs and symptoms and is usually seen in elderly persons (due to degenerative changes). They are preferentially located in the lower lumbar region, while cervical localization is rare. Complete removal of the cyst leads to excellent results and seems to preclude recurrence. We report the case of a right-sided ligamentum flavum cyst occurring at L3–L4 level in a 70-year-old woman, which was surgically removed with excellent postoperative results and complete resolution of symptoms. In addition, we discuss and review reports in the literature.
doi:10.1007/s10195-010-0094-y
PMCID: PMC2896575  PMID: 20582448
Ligamentum flavum cyst; Pseudocyst; Radiculopathy; Lumbar spine
3.  Ligamentum flavum cyst in the lumbar spine: a case report and review of the literature 
Degenerative changes in the lumbar spine can be followed by cystic changes. Most reported intraspinal cysts are ganglion or synovial cysts. Ligamentum flavum pseudocyst, as a cystic lesion in the lumbar spine, is a rare and unusual cause of neurologic signs and symptoms and is usually seen in elderly persons (due to degenerative changes). They are preferentially located in the lower lumbar region, while cervical localization is rare. Complete removal of the cyst leads to excellent results and seems to preclude recurrence. We report the case of a right-sided ligamentum flavum cyst occurring at L3–L4 level in a 70-year-old woman, which was surgically removed with excellent postoperative results and complete resolution of symptoms. In addition, we discuss and review reports in the literature.
doi:10.1007/s10195-010-0094-y
PMCID: PMC2896575  PMID: 20582448
Ligamentum flavum cyst; Pseudocyst; Radiculopathy; Lumbar spine
4.  Posterior epidural fibrotic mass associated with Baastrup’s disease 
European Spine Journal  2010;19(Suppl 2):165-168.
A few reports have demonstrated rare cases of Baastrup’s disease that involve epidural cysts that cause dural compression. However, there have been no reports of a midline epidural fibrotic mass being associated with Baastrup’s disease. A 60-year-old man presented with neurogenic claudication that had lasted for 5 years. Radiography showed anterolisthesis at the L4–L5 level, magnetic resonance imaging demonstrated severe stenosis due to a posterior noncystic mass, and the linear fluid signal tracked into the posterior epidural space at the L4–L5 level. A cleft in the ligamentum flavum was identified by probe at surgery, and this enabled the probe to be inserted into the epidural space without excising ligamentum flavum. Histological analysis showed that the fibrotic mass consisted of a collagen matrix that had a cystic component and exhibited a peripheral inflammatory reaction. This report shows that it is possible for an extended epidural cystic mass that occurs in Baastrup’s disease to change over time through peripheral inflammation into a cyst-containing fibrotic mass.
doi:10.1007/s00586-009-1262-8
PMCID: PMC2899643  PMID: 20063020
Baastrup’s disease; Spinal stenosis; Epidural mass; Fibrosis
5.  Dynamic Lumbar Spinal Stenosis : The Usefulness of Axial Loaded MRI in Preoperative Evaluation 
Two cases of dynamic lumbar spinal stenosis were identified by the authors using axial loaded magnetic resonance image (MRI). In both cases, the patients presented with neurogenic claudication but MRI in decumbency showed no definite pathologic condition associated with their symptoms. In contrast, axial loaded MRI demonstrated constrictive spinal stenosis and a significantly decreased dural sac caused by epidural fat buckling and thickening of the ligamentum flavum in both cases. In the second case, a more prominent disc protrusion was also demonstrated compared with decumbent MRI. After decompressive surgery, both patients had satisfactory outcomes. Axial loaded MRI can therefore give decisive information in dynamic spinal disorders by allowing simulation of an upright position.
doi:10.3340/jkns.2009.46.3.265
PMCID: PMC2764028  PMID: 19844630
Axial loaded MRI; Dynamic lumbar spinal stenosis; Neurogenic claudication
6.  Rare ligamentum flavum cyst causing incapacitating lumbar spinal stenosis: Experience with 3 Chinese patients 
Three Chinese patients suffered from severe lumbar spinal stenosis with debilitating symptoms due to a rare condition of ligamentum flavum cysts in the midline of the lumbar spine. This disease is distinct from synovial cyst of the facet joints or ganglion cysts, both intraoperatively and histopathologically. Magnetic Resonance imaging features of the ligamentum flavum cyst are also demonstrated. We share our surgical experiences of identification of the ligamentum flavum cysts, decompression and excision for two of the patients with demonstrably good recovery. This disease should be considered in the differential diagnosis of an extradural instraspinal mass in patients with lumbar spinal stenosis.
doi:10.1186/1749-799X-5-81
PMCID: PMC2988014  PMID: 21047439
7.  Thoracic myelopathy caused by ossification of ligamentum flavum of which fluorosis as an etiology factor 
Purpose
To evaluate the clinical feature, operative method and prognosis of thoracic ossification of ligamentum flavum caused by skeletal fluorosis.
Methods
All the patients with thoracic OLF, who underwent surgical management in the authors' hospital from 1993–2003, were retrospectively studied. The diagnosis of skeletal fluorosis was made by the epidemic history, clinical symptoms, radiographic findings, and urinalysis. En bloc laminectomy decompression of the involved thoracic levels was performed in all cases. Cervical open door decompression or lumbar laminectomy decompression was performed if relevant stenosis existed. The neurological statuses were evaluated with the Japanese Orthopaedic Association (JOA) scoring system preoperatively and at the end point of follow up. Also, the recovery rate was calculated.
Results
23 cases have been enrolled in this study. Imaging study findings showed all the cases have ossification of ligamentum flavum together with ossification of many other ligaments and interosseous membranes, i.e. interosseous membranes of the forearm in 18 of 23 (78.3%), of the leg in 14 of 23 (60.1%) and of the ribs in 11 of 23 (47.8%). Urinalysis showed markedly increased urinary fluoride in 14 of 23 patients (60.9%). All the patients were followed up from 12 months to 9 years and 3 months, with an average of 4 years and 5 months. The JOA score increased significantly at the end of follow up (P = 0.0001). The recovery rate was 51.83 ± 32.36%. Multiple regression analysis revealed that the preoperative JOA score was an important predictor of surgical outcome (p = 0.0022, r = 0.60628). ANOVA analysis showed that patients with acute onset or too long duration had worse surgical result (P = 0.0003).
Conclusion
Fluorosis can cause ossification of thoracic ligamentum flavum, as well as other ligaments. En bloc laminectomy decompression was an effective method. Preoperative JOA score was the most important predictor of surgical outcome. Patients with acute onset or too long duration had worse surgical outcome.
doi:10.1186/1749-799X-1-10
PMCID: PMC1636628  PMID: 17150117
8.  Cervical cyst of the ligamentum flavum and C7-T1 subluxation: case report 
European Spine Journal  2005;14(8):807-809.
A patient with progressive gait disturbance resulting from a cyst of the cervical ligamentum flavum associated with C7-T1 listhesis is reported. Surgical removal of the cyst improved the patient’s myelopathy. Intraspinal degenerative cysts are preferentially located in the lumbar region:unusual is the cervical localization. Differential diagnosis includes ligamentum flavum cyst, synovial and ganglion cysts. Association between degenerative intraspinal cysts and listhesis is discussed. To our knowledge, this is the first case of cyst of the ligamentum flavum associated with cervical subluxation.
doi:10.1007/s00586-005-0913-7
PMCID: PMC3489245  PMID: 15981000
Cyst; Ligamentum flavum; Cervical spine; Subluxation
9.  The narrowing of the lumbar spinal canal during loaded MRI: the effects of the disc and ligamentum flavum 
European Spine Journal  2009;18(5):679-686.
Load and activity changes of the spine typically cause symptoms of nerve root compression in subjects with spinal stenosis. Protrusion of the intervertebral disc has been regarded as the main cause of the compression. The objective was to determine the changes in the size of the lumbar spinal canal and especially those caused by the ligamentum flavum and the disc during loaded MRI. For this purpose an interventional clinical study on consecutive patients was made. The lumbar spines in 24 supine patients were examined with MRI: first without any external load and then with an axial load corresponding to half the body weight. The effect of the load was determined through the cross-sectional areas of the spinal canal and the ligamentum flavum, the thickness of ligamentum flavum, the posterior bulge of the disc and the intervertebral angle. External load decreased the size of the spinal canal. Bulging of the ligamentum flavum contributed to between 50 and 85% of the spinal canal narrowing. It was concluded that the ligamentum flavum, not the disc had a dominating role for the load induced narrowing of the lumbar spinal canal, a finding that can improve the understanding of the patho-physiology in spinal stenosis.
doi:10.1007/s00586-009-0919-7
PMCID: PMC3234003  PMID: 19277726
Ligamentum flavum; Intervertebral disc; Spinal stenosis; Cauda equina; Loaded MRI
10.  Ochronosis in a murine model of alkaptonuria is synonymous to that in the human condition 
Osteoarthritis and Cartilage  2012;20(8):880-886.
Objective
Alkaptonuria (AKU) is a rare genetic disease which results in severe early onset osteoarthropathy. It has recently been shown that the subchondral interface is of key significance in disease pathogenesis. Human surgical tissues are often beyond this initial stage and there is no published murine model of pathogenesis, to study the natural history of the disease. The murine genotype exists but it has been reported not to demonstrate ochronotic osteoarthropathy consistent with the human disease. Recent anecdotal evidence of macroscopic renal ochronosis in a mouse model of tyrosinaemia led us to perform histological analysis of tissues of these mice that are known to be affected in human AKU.
Design
The homogentisate 1,2-dioxygenase Hgd+/−Fah−/− mouse can model either hereditary tyrosinaemia type I (HT1) or AKU depending on selection conditions. Mice having undergone Hgd reversion were sacrificed at various time points, and their tissues taken for histological analysis. Sections were stained with haematoxylin eosin (H&E) and Schmorl’s reagent.
Results
Early time point observations at 8 months showed no sign of macroscopic ochronosis of tissues. Macroscopic examination at 13 months revealed ochronosis of the kidneys. Microscopic analysis of the kidneys revealed large pigmented nodules displaying distinct ochre colouration. Close microscopic examination of the distal femur and proximal fibula at the subchondral junctions revealed the presence of numerous pigmented chondrocytes.
Conclusions
Here we present the first data showing ochronosis of tissues in a murine model of AKU. These preliminary histological observations provide a stimulus for further studies into the natural history of the disease to provide a greater understanding of this class of arthropathy.
doi:10.1016/j.joca.2012.04.013
PMCID: PMC3406176  PMID: 22542924
Alkaptonuria; Mouse model; Arthropathy; Arthritis; Ochronosis
11.  Natural history of the aging spine 
European Spine Journal  2003;12(Suppl 2):S86-S89.
The unrelenting changes associated with aging progressively affects all structures of the spinal units. The degenerative process starts early during the first decade of life at the disc level. Discal degeneration is associated with biochemical changes followed by macroscopic alterations including tears and fissures, which may lead to discal herniation, the main cause of radiculopathy in the young adult. Moreover, nociceptive nerve fibers have been demonstrated in degenerated discs. They may be a source of nociception and of pure low-back pain. Facet joint changes are usually secondary to discal degeneration. They include subluxation, cartilage alteration and osteophytosis. Facet hypertrophy and laxity, associated with discal degeneration, and enlargement of the ligamentum flavum progressively create narrowing of the spinal canal as well as degenerative instabilities such as spondylolisthesis and scoliosis, which are the main causes of neurogenic claudication and radiculopathy in old persons. Vertebral bodies are the static elements of the spinal unit. With advancing age, osteoporosis weakens the bony structures and facilitates bone remodeling and rotatory deformities. Finally, aging of bone, discs, facets, ligaments, and muscles may ultimately lead to rotatory scoliosis, destabilization, and rupture of equilibrium.
doi:10.1007/s00586-003-0593-0
PMCID: PMC3591827  PMID: 12961079
Lumbar disc degeneration; Age-related intervertebral changes; Disc herniation; Stenosis; Low-back pain
12.  Homogentisate 1,2 Dioxygenase is Expressed in Human Osteoarticular Cells: Implications in Alkaptonuria 
Journal of Cellular Physiology  2011;227(9):3254-3257.
Alkaptonuria (AKU) results from defective homogentisate1,2-dioxygenase (HGD), causing degenerative arthropathy. The deposition of ochronotic pigment in joints is so far attributed to homogentisic acid produced by the liver, circulating in the blood and accumulating locally. Human normal and AKU osteoarticular cells were tested for HGD gene expression by RT-PCR, mono- and 2D-Western blotting. HGD gene expression was revealed in chondrocytes, synoviocytes, osteoblasts. Furthermore, HGD expression was confirmed by Western blotting, that also revealed the presence of five enzymatic molecular species. Our findings indicate that AKU osteoarticular cells produce the ochronotic pigment in loco and this may strongly contribute to induction of ochronotic arthropathy. J. Cell. Physiol. 227: 3254–3257, 2012. © 2011 Wiley Periodicals, Inc.
doi:10.1002/jcp.24018
PMCID: PMC3427883  PMID: 22105303
13.  Morphological changes of the ligamentum flavum as a cause of nerve root compression 
European Spine Journal  2004;14(3):277-286.
The ligamentum flavum is considered to be one of the important causes of radiculopathy in lumbar degenerative disease. Although there have been several reports anatomically examining the positional relationship between the ligamentum flavum and nerve root, there are few reports on ventral observation. The purpose of this study is to clarify the shape of the ligamentum flavum seen ventrally, and to obtain anatomic findings related to nerve root compression. The subjects were 18 adult embalmed cadavers, with an average age of 78 years at the time of death. The ventral shapes of the ligamentum flavum were observed. The relationships between the morphological change of the ligamentum flavum and nerve root compression or radiographic findings were statistically evaluated. Among the shapes of the ligamentum flavum, bulging of the ligament was most frequently observed. Proximal bulging indicates the type with the cranial portion bulging from the subarticular zone to the foraminal zone of the ligamentum flavum. In this type associated with a decrease in disc height, nerve root compression was frequently observed. Thus, we could more realistically grasp the relationship between bulging morphology of the ligamentum flavum and nerve root compression.
doi:10.1007/s00586-004-0782-5
PMCID: PMC3476746  PMID: 15583951
Lumbar spine; Ligamentum flavum; Anatomy; Nerve root compression; Disc height
14.  Spontaneous Ligamentum Flavum Hematoma in the Rigid Thoracic Spine : A Case Report and Review of the Literature 
Ligamentum flavum hematoma is a rare condition. Twenty cases including present case have been reported in English-language literature. Among them, only one case reported in pure thoracic spine. A 72-year-old man presented with thoracic myelopathy without precedent cause. Magnetic resonance images revealed a posterior semicircular mass which was located in T7 and T8 level compressing the spinal cord dorsally. T7-8 total laminectomy and extirpation of the mass was performed. One month later following surgery, the patient fully recovered to normal state. Pathologic result was confirmed as ligamentum flavum hematoma. Ligamentum flavum hematoma of rigid thoracic spine is a very rare disease entity. Most reported cases were confined to mobile cervical and lumbar spine. Surgeons should be aware that there seems to be another different pathogenesis other than previously reported cases of mobile cervical and lumbar spine.
doi:10.3340/jkns.2008.44.1.47
PMCID: PMC2588285  PMID: 19096657
Ligamentum flavum; Hematoma; Thoracic spine; Myelopathy
15.  Intraspinal Ganglion Cyst 
Chonnam Medical Journal  2012;48(3):183-184.
The pathogenesis of juxtafacet cysts is closely related to degenerative instability of the lumbar spine and degenerative changes in the ligamentum flavum and the facet joint. A 56-year-old man presented with severe right thigh pain and numbness for 1 month after a laminar fracture of the L4 spine. Magnetic resonance imaging revealed a heterogenous cystic mass surrounding the facet joint between the fourth and fifth lumbar vertebrae on the right side. Conservative therapy was unsuccessful and the lesion was removed by surgical decompression alone without fusion. The histological examination showed a fragmented, cystic wall-like structure composed of myxoid degenerative tissue without lining epithelium. Here we present this case of a ganglion cyst that appeared to be associated with facet joint instability.
doi:10.4068/cmj.2012.48.3.183
PMCID: PMC3539101  PMID: 23323226
Ganglion cysts; Synovial cyst; Spine
16.  The Increased Expression of Matrix Metalloproteinases Associated with Elastin Degradation and Fibrosis of the Ligamentum Flavum in Patients with Lumbar Spinal Stenosis 
Clinics in Orthopedic Surgery  2009;1(2):81-89.
Background
One of the characteristics of spinal stenosis is elastin degradation and fibrosis of the extracellular matrix of the ligamentum flavum. However, there have been no investigations to determine which biochemical factors cause these histologic changes. So we performed the current study to investigate the hypothesis that matrix metalloproteinases (MMPs), which possess the ability to cause extracellular matrix remodeling, may play a role as a mediator for this malady in the ligamentum flavum.
Methods
The ligamentum flavum specimens were surgically obtained from thirty patients with spinal stenosis, as well as from 30 control patients with a disc herniation. The extents of ligamentum flavum elastin degradation and fibrosis were graded (grade 0-4) with performing hematoxylin-eosin staining and Masson's trichrome staining, respectively. The localization of MMP-2 (gelatinase), MMP-3 (stromelysin) and MMP-13 (collagenase) within the ligamentum flavum tissue was determined by immunohistochemistry. The expressions of the active forms of MMP-2, MMP-3 and MMP-13 were determined by western blot analysis, and the blots were quantified using an imaging densitometer. The histologic and biochemical results were compared between the two conditions.
Results
Elastin degradation and fibrosis of the ligamentum flavum were significantly more severe in the spinal stenosis samples than that in the disc herniation samples (3.14 ± 0.50 vs. 0.55 ± 0.60, p < 0.001; 3.10 ± 0.57 vs. 0.76 ± 0.52, p < 0.001, respectively). The expressions of the active form of MMPs were identified in all the ligamentum flavums of the spinal stenosis and disc herniation patients. The expressions of active MMP-2 and MMP-13 were significantly higher in the spinal stenosis samples than that in the disc herniation samples (both p < 0.05). The expression of active MMP-3 was slightly higher in the spinal stenosis samples than that in the disc herniation samples, but the difference was not statistically significant (p = 0.131). MMP-2, -3, and -13 were positively stained on the ligamentum flavum fibroblasts.
Conclusions
The current results suggest that the increased expression of active MMPs by the ligamentum flavum fibroblasts might be related to the elastin degradation and fibrosis of the ligamentum flavum in the patients who suffer with lumbar spinal stenosis.
doi:10.4055/cios.2009.1.2.81
PMCID: PMC2766760  PMID: 19885059
Spinal stenosis; Ligamentum flavum; Elastin degradation; Fibrosis; Matrix metalloproteinases
17.  Upper Thoracic Myelopathy Caused by Delayed Neck Extensor Weakness in Myotonic Dystrophy 
Annals of Rehabilitation Medicine  2012;36(4):569-572.
Myotonic dystrophy is the most common autosomal dominant myopathy in adults. Our patient, a 41 year-old female suffering from myotonic muscular dystrophy, developed upper thoracic myelopathy due to hypertrophy of the ligamentum flavum and the posterior longitudinal ligament. She had a typical hatchet face and ptosis with "head hanging forward" appearance caused by neck weakness. Motor weakness, sensory changes and severe pain below T4 level, along with urinary incontinence began 3 months ago. Genetic and electrodiagnostic studies revealed myotonic dystrophy type 1. Magnetic resonance imaging of the spine showed loss of cervical lordosis and spinal cord compression due to hypertrophied ligamentum flavum and posterior longitudinal ligament at T1 to T3 level. We concluded that her upper thoracic myelopathy was likely related to the thickness of the ligamentum flavum and posterior longitudinal ligament due to repetitive mechanical stress on her neck caused by neck muscle weakness with myotonic dystrophy.
doi:10.5535/arm.2012.36.4.569
PMCID: PMC3438427  PMID: 22977786
Myotonic dystrophy; Neck weakness; Thoracic myelopathy
18.  Ligamentum Flavum Hematoma in the Adjacent Segment after a long Level Fusion 
Ligamentum flavum hematoma (LFH) is a very rare condition of dural compression; most are observed in the mobile cervical and lumbar spine regions. A 67-year-old man who had a long level interbody fusion at L3-S1 four years ago presented with symptoms suggestive of dural compression. Magnetic resonance imaging showed a posterior semicircular mass located at the adjacent L2-L3 level. After decompression of the spinal canal and removal of the mass lesion, pathological examination of the surgical specimen revealed a hematoma within the ligamentum. The patient fully recovered to normal status after surgery. Here, we report our experience with a LFH in the adjacent segment after a long level fusion procedure and discuss the possible associated mechanisms.
doi:10.3340/jkns.2011.49.1.58
PMCID: PMC3070897  PMID: 21494365
Ligamentum flavum; Hematoma; Adjacent segment
19.  Ossification process involving the human thoracic ligamentum flavum: role of transcription factors 
Arthritis Research & Therapy  2011;13(5):R144.
Introduction
Ossification of the ligamentum flavum (OLF) of the spine is associated with serious neurologic compromise, but the pathomechanism of this process remains unclear. The objective of this study was to investigate the pathomechanism of the ossification process, including the roles of various transcriptional factors in the ossification of human thoracic ligamentum flavum.
Methods
Sections of the thoracic ligamentum flavum were obtained from 31 patients with OLF who underwent posterior thoracic decompression, and from six control patients free of OLF. Cultured ligamentum flavum cells (n = 6, each) were examined with real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis for Sry-type high-mobility group box 9 (Sox9), runt-related transcription factor 2 (Runx2), muscle segment homeobox 2 (Msx2), Osterix, distal-less homeobox 5 (Dlx5), and AP-1. The harvested sections were examined with hematoxylin-eosin, the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method, and immunohistochemistry for the transcriptional factors.
Results
Compared with the control, the OLF showed disorganization of the elastic fiber bundles and abundant hypertrophic chondrocytes in the ossification front. TUNEL-positive chondrocytes were found near the ossified plaques. The mRNA expression levels of Sox9, Runx2, Msx2, and AP-1 in cultured cells from the ligamentum flavum of OLF patients were significantly different from those of the control. OLF samples were strongly immunoreactive to Sox9, Runx2, and Msx2 at proliferating chondrocytes in the fibrocartilage area. Hypertrophic chondrocytes were positive for Runx2, Osterix, Dlx5, and AP-1.
Conclusions
The ossification process in OLF seems to involve chondrocyte differentiation under the unique expression of transcriptional factors. Accumulation of hypertrophic chondrocytes was evident around the calcified area at the ossification front, and we suggest that the differentiation of these cells seems to be concerned with the ossification process.
doi:10.1186/ar3458
PMCID: PMC3308072  PMID: 21914169
20.  Numerical Simulation of Asymmetrically Altered Growth as Initiation Mechanism of Scoliosis 
Annals of Biomedical Engineering  2007;35(7):1206-1215.
The causes of idiopathic scoliosis are still uncertain; buckling is mentioned often, but never proven. The authors hypothesize another option: unilateral postponement of growth of MM Rotatores or of ligamentum flavum and intertransverse ligament. In this paper, both buckling and the two new theories of scoliotic initiation are studied using a new finite element model that simulates the mechanical behavior of the human spine. This model was validated by the stiffness data of Panjabi et al. (J. Biomech. 9:185–192, 1976). After a small correction of the prestrain of some ligaments and the MM Rotatores the model appeared to be valid. The postponement in growth was translated in the numerical model in an asymmetrical stiffness. The spine was loaded axially and the resulting deformation was analyzed for the presence of the coupling of lateral deviation and axial rotation that is characteristic for scoliosis. Only unilateral postponement of growth of ligamentum flavum and intertransverse ligament appeared to initiate scoliosis. Buckling did not initiate scoliosis.
doi:10.1007/s10439-007-9256-3
PMCID: PMC1914297  PMID: 17415662
Scoliosis; Biomechanics; Idiopathic; Finite element method; Buckling; Numerical simulation; Growth postponement
21.  A less invasive surgical approach in the lumbar lateral recess stenosis: direct approach to the medial wall of the pedicle 
European Spine Journal  2008;17(12):1745-1751.
The lateral recess is one of the main compression sites in lumbar spinal canal stenosis. Lumbar nerve root is mainly entrapped by bony tissue in compression syndrome. The patient has a long history of back pain in conjunction with claudication symptoms. Besides laminotomy and facetectomy techniques, several specific surgical approaches to treat the lateral recess stenosis have been described. The surgical technique of bilateral lateral recess decompression via subarticular fenestrations used in this study is a less invasive technique, which enables to decompress the neural structures while preserving as much of the bony structures and ligamentum flavum as preferred. In 16 patients, we measured lateral recess heights with computerized tomography. The number of involved lumbar segments was one in 11 patients and two in 5 patients. The visual analogue scale (VAS) results were maintained before, 3 and 12 months after the operation. All patients benefited from the operations. Mean VAS scores were 7.0, 5.5, and 4.0, respectively. There were not any surgery-related complications. Mean follow-up period is 22.6 months. The surgical technique described and used in this study provides easy access to every zone of lateral recess and is safe and effective in treating the lumbar lateral recess stenosis syndrome.
doi:10.1007/s00586-008-0801-z
PMCID: PMC2587672  PMID: 18830635
Lumbar spine; Spinal stenosis; Subarticular fenestration
22.  Comparison of Magnetic Resonance Imaging and Computed Tomography-Myelography for Quantitative Evaluation of Lumbar Intracanalar Cross-Section 
Yonsei Medical Journal  2010;52(1):137-144.
Purpose
A comparison of MRI and computed tomography-myelography (CTM) for lumbar intracanalar dimensions. To compare the capability and reproducibility of MRI and CTM in measuring the cross-sectional morphology of intracanalar lesions of the lumbar spine.
Materials and Methods
MRI and CTM of lumbar disc levels from 61 subjects with various lumbar spinal diseases were studied. Dural area, dural anteroposterior (AP) diameter, dural right-left diameter, and thickness of the ligamentum flavum were measured by two orthopedic surgeons. Each section was graded by degree of stenosis. Absolute value and intra- and inter-observer correlation coefficients (ICC) of these measurements and the associations between MRI and CTM values were determined.
Results
Except for MRI determination of ligament flavum thickness, CTM and MRI and intra- and ICC suggested sufficient reproducibility. When measurements of dural area, dural AP diameter, and RL diameter were compared, values in CTM were significantly (p = 0.01-0.004) larger than those in MRI (CTM/MRI ratios, 119%, 111%, and 105%, respectively). As spinal stenosis became more severe, discrepancies between CTM and MRI in measurements of the dural sac became larger.
Conclusion
Both CTM and MRI provided reproducible measurements of lumbar intracanalar dimensions. However, flavum thickness may be more accurately measured by CTM. Because the differences in the measurements between CTM and MRI are very slight and there is very little data to suggest that the precise degree of stenosis is related to symptoms or treatment outcome, the usefulness of the CTM over MRI needs to be confirmed in future studies.
doi:10.3349/ymj.2011.52.1.137
PMCID: PMC3017689  PMID: 21155046
Magnetic resonance imaging; computed tomography; myelography; CTM; lumbar spine; lumbar spinal canal stenosis; diagnosis
23.  Thoracic ossification of ligamentum flavum caused by skeletal fluorosis 
European Spine Journal  2006;16(8):1119-1128.
Thoracic ossification of ligamentum flavum (OLF) caused by skeletal fluorosis is rare. Only six patients had been reported in the English literature. This study reports findings from the first clinical series of this disease. This was a retrospective study of patients with thoracic OLF due to skeletal fluorosis who underwent surgical management at the authors’ hospital between 1993 and 2003. Diagnosis of skeletal fluorosis was made based on the epidemic history, clinical symptoms, radiographic findings, and urinalysis. En bloc laminectomy decompression of the involved thoracic levels was performed in all cases. Cervical open door decompression or lumbar laminectomy decompression was performed if relevant stenosis was present. Neurological status was evaluated preoperatively, at the third day postoperatively, and at the end point of follow-up using the Japanese Orthopaedic Association (JOA) scoring system of motor function of the lower extremities. A total of 23 cases were enrolled, 16 (69.6%) males and 7 (30.4%) females, age ranging from 42 to 72 years (mean 54.8 years). All patients came from a high-fluoride area, and 22 (95.7%) had dental fluorosis. Medical imaging showed OLF together with ossification of many ligaments and interosseous membranes, including interosseous membranes of the forearm (18/23 patients 78.3%), leg (14/23 patients 60.9%), and ribs (11/23 patients 47.8%). OLF was classified into five types based on MRI findings: localized (4/23 patients 17.4%), continued (12/23 patients 52.2%), skip (3/23 patients 13.0%), combining with anterior pressure (2/23 patients 8.7%), and combining with cervical and/or lumbar stenosis (2/23 patients, 8.7%). Urinalysis showed a markedly high urinary fluoride level in 14 of 23 patients (60.9%). Patients were followed up for an average duration of 4 years, 5 months. Paired t-test showed that the JOA score was slightly but nonsignificantly increased relative to preoperative measurement 3 days after surgery (P = 0.0829) and significantly increased at the end of follow-up (P = 0.0001). In conclusion, Fluorosis can cause ossification of thoracic ligamentum flavum, as well as other ligaments. Comparing with other OLF series, a larger number of spinal segments were involved. The diagnosis of skeletal fluorosis was made by the epidemic history, clinical symptom, imaging study findings, and urinalysis. En bloc laminectomy decompression was an effective method.
doi:10.1007/s00586-006-0242-5
PMCID: PMC2200777  PMID: 17075705
Ossification of ligamentum flavum; Thoracic spinal stenosis; Skeletal fluorosis; Operation; Classification
24.  Contributing factors affecting the prognosis surgical outcome for thoracic OLF 
European Spine Journal  2005;15(4):485-491.
The thoracic ossification of ligamentum flavum (OLF) is a disease that produces spastic paraparesis, and there are various factors that may affect the surgical outcome of thoracic OLF patients. The authors of this study treated 19 of these thoracic OLF patients from 1998 to 2002, and retrospectively reviewed the patients′ age, sex, symptom duration, involved disease level, preoperative clinical features, neurological findings, radiological findings, the other combined spinal diseases and the surgical outcomes. There were excellent or good surgical outcomes in 16 patients, but 3 patients did not improve after thoracic OLF surgery: this included 1 patient, whose motor function worsened after decompressive thoracic OLF surgery. The favorable contributing factors of surgical outcome in thoracic OLF are a short preoperative symptom duration, single-level lesion, and unilateral lesion type on CT axial scan. On the contrary, the poor prognostic factors are beak type lesion and intramedullary signal changes on T2-weighted sagittal MRI. The complete preoperative evaluation including radiologic findings will provide valuable aid in presuming the surgical outcome for the thoracic OLF patients.
doi:10.1007/s00586-005-0903-9
PMCID: PMC3489313  PMID: 15902507
Thoracic Spine; Stenosis; Ossification of ligament flavum; Myelopathy; Surgical Outcome
25.  Perioperative management of patient with alkaptonuria and associated multiple comorbidities 
Alkaptonuria is a rare inherited genetic disorder of tyrosine metabolism characterized by a triad of homogentisic aciduria, ochronosis, and arthritis. The most common clinical manifestations of ochronosis involve the musculoskeletal, respiratory, airway, cardiovascular, genitourinary, cutaneous, and ocular systems. We report the perioperative anesthetic management of a 56-year-old alkaptonuric patient, with multiple comorbidities scheduled, for revision total hip replacement. A review of her medical history revealed alkaptonuria, hypothyroidism, rheumatoid arthritis, hypertension, diabetes mellitus, and Pott's spine with disc prolapse. We want to highlight the need of thorough preoperative evaluation in patients of alkaptonuria, as it is associated with multiple comorbidities. The systemic involvement should determine the anesthetic plan. Caution should be exercised during positioning to prevent injury to the joints and the spine.
doi:10.4103/0970-9185.81839
PMCID: PMC3127314  PMID: 21772695
Alkaptonuria; anesthesia; comorbidities

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