Expression of the JAK/STAT signaling pathway in the ligamentum flavum of patients with lumbar spinal canal stenosis

Background

Ligamentum flavum (LF) hypertrophy is an important cause of lumbar spinal canal stenosis (LSS), one of the most common spinal disorders in the elderly. Although many cytokines are reported to be associated with LF hypertrophy, the intracellular signaling system is rarely discussed. The purpose of this study was to identify the JAK/STAT signaling pathway and to examine the role of the JAK/STAT systems in the hypertrophied LF.

Gait analysis does not correlate with clinical and MR imaging parameters in patients with symptomatic lumbar spinal stenosis

Background  

Parameters of MR imaging play a pivotal role in diagnosing lumbar spinal stenosis (LSS), and serve as an important tool in clinical decision-making. Despite the importance of MR imaging, little is known about the correlation between MRI parameters, objective gait analysis, and clinical presentation of patients with lumbar spinal stenosis.     

Predictive factors of cervical spondylotic myelopathy in patients with lumbar spinal stenosis

Objective  

To analyze cervical spondylotic myelopathy (CSM) predictive factors in patients with lumbar spinal stenosis (LSS).     

A non-surgical approach to the management of lumbar spinal stenosis: A prospective observational cohort study

Background  

While it is widely held that non-surgical management should be the first line of approach in patients with lumbar spinal stenosis (LSS), little is known about the efficacy of non-surgical treatments for this condition. Data are needed to determine the most efficacious and safe non-surgical treatment options for patients with LSS. The purpose of this paper is to describe the clinical outcomes of a novel approach to patients with LSS that focuses on distraction manipulation (DM) and neural mobilization (NM).     

Depressive symptoms during rehabilitation period predict poor outcome of lumbar spinal stenosis surgery: A two-year perspective

Background  

Previous research has shown an association between preoperative depressive symptoms and a poorer surgery outcome in lumbar spinal stenosis (LSS). It is not known whether depressive symptoms throughout the recovery period are relevant to the outcome of surgery in LSS. In this prospective clinical study the predictive value of preoperative and postoperative depressive symptoms with respect to the surgery outcome is reported.     

Fluoroscopically guided transforaminal epidural dry needling for lumbar spinal stenosis using a specially designed needle

Background  

This report describes the methodological approach and clinical application of a minimally invasive intervention to treat lumbar spinal stenosis (LSS).     

The effect of the X-Stop implantation on intervertebral foramen,segmental spinal canal length and disc space in elderly patients with lumbar spinal stenosis

Objectives  

To evaluate the biomechanical effect of the X-Stop device on the intervertebral foramen (IVF) and segmental spinal canal length (SSCL), as well as the intervertebral disc space at the implanted and the adjacent segments in patients with lumbar spinal stenosis (LSS).     

Expression and function of fibroblast growth factor 1 in the hypertrophied ligamentum flavum of lumbar spinal stenosis

BackgroundFibrosis is one of the main pathologies caused by hypertrophy of the ligamentum flavum (LF), which leads to lumbar spinal stenosis (LSS). The fibroblast growth factor (FGF) family is a key mediator of fibrosis. However, acidic fibroblast growth factor (FGF-1) expression and function are not well understood in LF. This study sought to evaluate FGF-1 expression in the hypertrophied and non-hypertrophied human LF, and to investigate its function using primary human LF cell cultures.MethodsWe obtained hypertrophied lumbar LF from LSS patients and non-hypertrophied lumbar LF from control patients during surgery. Immunohistochemistry and qPCR were performed to evaluate FGF-1 expression in LF tissue. The function of FGF-1 and transforming growth factor beta 1 (TGF-β1) was also investigated using primary LF cell culture. The effects on cell morphology and cell proliferation were examined using a crystal violet staining assay and MTT assay, respectively. Immunocytochemistry, western blotting, and qPCR were performed to evaluate the effect of FGF-1 on TGF-β1–induced myofibroblast differentiation and fibrosis.ResultsImmunohistochemistry and qPCR showed higher FGF-1 expression in hypertrophied LF compared to control LF. Crystal violet staining and MTT assay revealed that FGF-1 decreases LF cell size and inhibits their proliferation in a dose-dependent manner, whereas TGF-β1 increases cell size and promotes proliferation. Immunocytochemistry and western blotting further demonstrated that TGF-β1 increases, while FGF-1 decreases, α-SMA expression in LF cells. Moreover, FGF-1 also caused downregulation of collagen type 1 and type 3 expression in LF cells.ConclusionFGF-1 is highly upregulated in the LF of LSS patients. Meanwhile, in vitro, FGF-1 exhibits antagonistic effects to TGF-β1 by inhibiting cell proliferation and decreasing LF cell size as well as the expression of fibrosis markers. These results suggest that FGF-1 has an anti-fibrotic role in the pathophysiology of LF hypertrophy.     

The interspinous ligament should be removed for the decompression surgery with the case of lumbar spinal canal stenosis

Introduction  

Retrospective clinical study has done concerning the outcomes of lumbar spinal stenosis (LSS) patients treated with trans-interspinous ligament approach method. The object is to determine the efficacy of this procedure and to confirm that the interspinous ligament could be removed for the decompression surgery.     

Clinical outcome of lumbar spinal stenosis based on new classification according to hypertrophied ligamentum flavum

Background

The ligamentum flavum hypertrophy is considered to be one of the important causes of development of lumbar spinal stenosis (LSS). Several histologic and biologic mechanisms in hypertrophied flavum have proposed. However, no study that investigated the relationship between clinical outcome and ligamentum flavum hypertrophy has been published. The purpose of this study was to identify a new classification of LSS, in ligamentous and nonligamentous stenosis, according to the cutoff value of the area proportion of the ligamentum flavum in the spinal canal, and to assess the value of surgical and conservative treatments for LSS based on the classification of the ligamentous stenosis.

Expression and function of FGF9 in the hypertrophied ligamentum flavum of lumbar spinal stenosis patients

BACKGROUND CONTEXTLigamentum flavum (LF) hypertrophy plays a dominant role in lumbar spinal stenosis (LSS). A previous study found that fibroblast growth factor 9 (FGF9) was upregulated with mechanical stress in rabbit LF. However, the expression and function of FGF9 are not well understood in human LF.PURPOSETo evaluate FGF9 expression and function in human LF with and without hypertrophy.STUDY DESIGNThis study employed a basic research study design utilizing human LF tissue for histological analyses.PATIENT SAMPLESHypertrophied LF tissue sample from patients with LSS, and nonhypertrophied (control) LFs from patients with lumbar disc herniation or other diseases were obtained during surgery.METHODSLF specimens were histologically analyzed for FGF9 and vascular endothelial growth factor A (VEGF-A) by immunohistochemistry. The number of total and FGF9 immuno-positive cells and blood vessels were counted and compared between LF with and without hypertrophy. For functional analysis, the effect of FGF9 on cell proliferation and migration was examined using a primary cell culture of human LF.RESULTSHistological studies revealed that the total cell number was significantly higher in the LF of patients with LSS than in the LF of control patients. Immunohistochemistry showed that the percentage of FGF9-positive cells was significantly higher in the LF of patients with LSS than in the controls, and it positively correlated with patients’ age, regardless of disease. Double immune-positive cells for FGF9 and VEGF-A were often observed in vascular endothelial cells and fibroblasts in the fibrotic area of hypertrophied LF, and the number of double positive vessels was significantly higher in LF of LSS patients than in the LF of controls. Primary cell culture of human LF revealed that FGF9 promoted the proliferation and migration of LF cells.CONCLUSIONThe present study demonstrated that FGF9 expression is highly upregulated in hypertrophied human LF. FGF9 potentially plays a pivotal role in the process of hypertrophy of LF, which is associated with mechanical stress, through cell proliferation and migration.CLINICAL SIGNIFICANCEThe results from this study partially reveal the molecular mechanisms of LF hypertrophy and suggest that FGF9 may be involved in the process of LF degeneration in elderly patients.     

Assessment and management of neurogenic claudication associated with lumbar spinal stenosis in a UK primary care musculoskeletal service: a survey of current practice among physiotherapists

Background  

Neurogenic claudication (NC) is the clinical syndrome commonly associated with lumbar spinal stenosis (LSS). Non-surgical management is recommended as initial treatment, but little is known about current practice in relation to the assessment and management of these patients in the non-surgical setting.     

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. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 1592–1597, 2011     

Correlation of low back pain caused by lumbar spinal stenosis and depression in women: a clinical study

Objective:

Low back pain (LBP) due to spinal stenosis may be one of the most debilitating symptoms to decrease the quality of life. The cause and effect association of LBP and depression is vague. Pain may also be a somatization symptom of depression. This is more frequent in the female population. This clinical study was designed to evaluate the correlation between the level of back pain caused by lumbar spinal stenosis and depression in the female population.

Method:

The study included 50 consecutive female patients with spinal stenosis. The stenosis diagnosis is made by neurological examination and neuro-imaging. The study group was psychiatrically evaluated and grouped as those with and without depression. Visual analog scale (VAS), Oswestry disability index (ODI) and Hamilton Depression Scale (HDS) were utilized in initial evaluation of the group.

Results:

Twenty-one patients with lumbar spinal stenosis had depression (DLS Group) and 29 did not (LSS Group). Mean HDS scores were 8.97 and 32.48 for Group LSS and Group DLS, respectively. There was a statistically significant difference between the VAS scores of the groups (the mean VAS scores were 5.6 and 7.6, for groups LSS and DLS, respectively). The mean ODI values for LSS (65.24?±?4.58) and DLS (75.1?±?6.7) groups were also significantly different. In Group DLS, there were positive correlations between ODI and VAS with HDS (p?Conclusion: Our findings indicated a relationship between lumbar spinal stenosis associated pain levels and depression. However, the cause and result relationship still needs to be established yet.     

Impact of oxidized LDL/LOX-1 system on ligamentum flavum hypertrophy

BackgroundPatients with lumbar spinal canal stenosis (LSS) often have peripheral arterial disease and aortic disease based on atherosclerosis. Oxidized LDL, which is clinically involved in the development of atherosclerosis, may also influence LF hypertrophy, but the function of the oxidized low-density lipoprotein (LDL)/lectin-type oxidized LDL receptor 1 (LOX-1) system in LF hypertrophy is unknown. We aimed to elucidate the potential involvement of oxidized LDL/LOX-1 system in ligamentum flavum (LF) hypertrophy.MethodsA total of 43 samples were collected from LF tissues of the patients who underwent posterior lumbar spinal surgery. Immunohistochemistry for LOX-1 was performed using human LF samples. We treated the cells in vitro with inflammatory cytokines TNF-α and IL-1β, oxidized LDL, and simvastatin. The expressions of LOX-1 and LF hypertrophy markers including type I collagen, Type III collagen, and COX-2 were assessed by real-time RT-PCR and immunocytochemistry. Phosphorylation of MAPKs and NF-κb was evaluated by Western blot after treatment with TNF-α, IL-1β, oxidized LDL, and simvastatin.ResultsA significant weak correlation was observed between the number of positive cells of LOX-1 and cross-sectional area of LF on preoperative axial magnetic resonance imaging. In functional analysis, simvastatin treatment neutralized the oxidized LDL-mediated induction of mRNA expressions of LF hypertrophy markers. Western blot analysis showed that oxidized LDL as well as TNF-α and IL-1β activated the signaling of MAPKs and NF-κb in LF cells, and that simvastatin treatment reduced the phosphorylation of all signaling. The TNF-α and IL-1β treatments increased both mRNA and protein expression of LOX-1 in LF cells.ConclusionWe found a link between the oxidized LDL/LOX-1 system and LF hypertrophy. In addition, our in vitro analysis indicate that oxidized LDL may affect LF hypertrophy through signaling of MAPKs. Our results suggest that the oxidized LDL/LOX-1 system may be a potential therapeutic target for LSS.     

The prevalence of tandem spinal stenosis and its characteristics in a population-based MRI study: The Wakayama Spine Study

Purpose

Tandem spinal stenosis (TSS) is a condition of combined spinal stenosis in the cervical and lumbar regions. The purpose of this study was to determine the prevalence of radiographic TSS and its association with developmental canal stenosis (DCS). The second purpose was to investigate the extent to which radiographic TSS is associated with cervical myelopathy and symptomatic LSS.

Methods

We recruited 1011 (336 men and 675 women) participants in this population-based study. After excluding those with a pacemaker, a history of cervical or lumbar surgery, disqualification, the MRI data of whole spine was analysed in 931 (mean, 67.3 years) participants. Cervical cord compression (CCC) and radiographic lumbar spinal stenosis (LSS) were evaluated by MRI. The canal-to-body ratio was also measured by plain X-ray. DCS was diagnosed as canal-to-body ratio <0.75. The diagnosis of cervical myelopathy and symptomatic LSS was made by presentation of both symptoms and radiographic compression using MRI.

Results

The prevalence of CCC was 24.7%, that of radiographic LSS was 30.2%, and that of radiographic TSS was 11.0% (men, 14.1%; women, 9.4%). The prevalence of TSS was significantly higher in the DCS group than in the non-DCS group (p < 0.001). Among the participants with radiographic TSS, the prevalence of cervical myelopathy and symptomatic LSS was 9.8 and 18.6%, respectively. The coexisting cervical myelopathy and symptomatic LSS was 6.1% in the participants with LSS.

Conclusions

The present study is the first population-based study to clarify TSS characteristic using whole-spine MRI.

     

Image changes of paraspinal muscles and clinical correlations in patients with unilateral lumbar spinal stenosis

Study design

This is a retrospective study.

Purpose

To compare the morphometric parameters of the psoas major and lumbar multifidus muscles in lumbar spinal stenosis (LSS) patients exhibiting different functional performance.

Summary of background data

LSS refers to symptoms related to size reduction of the lumbar spinal canal; however, the degree of stenosis is poorly related to symptom severity and functional impairments. Morphometric changes in the paraspinal muscles have been correlated with chronic lower back pain in previous studies. However, correlations between the functional performance of LSS patients and the morphometric changes in paraspinal muscles have seldom been reported.

Methods

Sixty-six LSS patients without mechanical back pain or segmental instability were enrolled in the study. A review of their medical records and MRI images was performed. Morphometric parameters, including the fatty infiltration (FI) of the lumbar multifidus muscle as well as the relative cross-sectional area (RCSA) of the psoas major and lumbar multifidus muscles, were measured. Subjects were divided into high and low functional performance groups according to their Japanese Orthopedic Association (JOA) scores.

Results

The male LSS patients exhibited a larger psoas RCSA than the female patients, whereas the older patients exhibited a smaller psoas RCSA and higher multifidus FI than the younger patients. LSS patients in the high functional performance group exhibited a significantly larger psoas RCSA and lower multifidus FI.

Conclusion

The psoas RCSA and multifidus FI can be used as predictive factors for functional performance in LSS patients.     

Expression profile of CD44s,CD44v6, and CD44v10 in localized prostate cancer: Effect on prognostic outcomes following radical prostatectomy

ObjectivesTo investigate the expression of CD44 standard form (CD44s) and 2 major variant exons (CD44v6 and CD44v10) in localized prostate cancer (PC) to determine the prognostic significance of these markers following radical prostatectomy (RP).Materials and methodsExpression levels of CD44s, CD44v6, and CD44v10 in RP specimens from 160 consecutive patients with clinically localized PC were evaluated by immunohistochemical staining.ResultsOf these 3 markers, expression level of CD44v6 was closely associated with several conventional prognostic factors. Univariate analysis identified CD44v6 expression in addition to serum prostate-specific antigen level, Gleason score, seminal vesicle invasion, and surgical margin status as significant predictors for biochemical recurrence (BR). Of these significant factors, CD44v6 expression, serum prostate-specific antigen level, and surgical margin status appeared to be independently associated with BR on multivariate analysis. We observed significant differences in BR-free survival according to the positive numbers of these 3 independent factors; i.e., BR occurred in 0 (0%) of 42 patients who had negative results for risk factors, 9 (16.7%) of 54 who had positive results for 1 risk factor, and 31 (48.4%) of 64 who had positive results for 2 or 3 risk factors.ConclusionsAssessment of the expression levels of CD44v6 in RP specimens in addition to conventional prognostic parameters would contribute to the accurate prediction of the biochemical outcome in patients with localized PC who underwent RP.     

Walking ability during daily life in patients with osteoarthritis of the knee or the hip and lumbar spinal stenosis: a cross sectional study

Background  

Degenerative musculoskeletal disorders are among the most frequent diseases occurring in adulthood, often impairing patients' functional mobility and physical activity. The aim of the present study was to investigate and compare the impact of three frequent degenerative musculoskeletal disorders -- knee osteoarthritis (knee OA), hip osteoarthritis (hip OA) and lumbar spinal stenosis (LSS) -- on patients' walking ability.