Lumbar Spinal Canal Stenosis Group Research Articles

Cerebrospinal Fluid Lysophosphatidylcholine Species for Distinguishing Narrowing of the Lumbar Spine

ContextReoperation, sometimes multiple, is common with progressively worse outcomes in patients with degenerative lumbar spine diseases. Lysophosphatidylcholine (LPC), a precursor of lysophosphatidic acid, in the cerebrospinal fluid (CSF) is a possible biomarker for neuropathic pain and discriminating neuropathic pain caused by lumbar spinal canal stenosis (LSCS) from other etiologies. This study aimed to explore this possible use of LPC species in the CSF. DesignUsing liquid chromatography-tandem mass spectrometry, we measured six LPC species, (16:0), (18:0), (18:1), (18:2), (20:4), and (22:6), in the CSF. Setting[Multi-site observational study] ParticipantsPatients with LSCS (n=137) and persistent spinal pain syndrome (PSPS, n=22). InterventionsCSF collection using lumbar puncture. Outcome MeasuresWe compared the LPC values between the groups and determined the cutoff levels that could efficiently discriminate the groups with high accuracy. ResultsThe levels of all measured LPC species were significantly higher in the LSCS group than the PSPS group. Four LPC species demonstrated more than 0.80 area under the curve obtained from the receiver operating characteristic curve analysis. Although the specificity of cutoff levels for the six LPC species was low to moderate, their sensitivity was consistently high. ConclusionThe existing diagnostic protocols combining physical examinations and morphological imaging studies for lumbar spinal pain have limited sensitivity. Measuring LPC species in the CSF is a promising objective laboratory test and could be suitable for detecting the presence of lumbar spinal stenosis and can help indications for surgery.

Differences in preoperative clinical symptoms and radiological findings of degenerative lumbar spondylolisthesis and lumbar canal stenosis

ObjectiveSome reports have referred to differences in preoperative symptoms and radiological findings between lumbar degenerative spondylolisthesis (DS) and lumbar spinal canal stenosis (LCS), while others have reported no differences. We investigated the differences of preoperative clinical and radiological findings between the DS group and LCS group.Methods: We retrospectively reviewed 32 patients in the DS group and 24 patients in the LCS group with regard to preoperative clinical symptoms, dural sac area and spinopelvic parameters.Results: The mean dural sac area of the DS group (40.4 ± 18.7 mm2) was significantly narrower than that of the LCS group (56.0 ± 24.0 mm2) (p = 0.008). As for the spinopelvic parameters, the PI was significantly greater in the DS group with 56.6 ± 11.8° compared to 47.4 ± 11.4° in the LCS group (p = 0.005), and the LL was also significantly different with 45.8 ± 13.8° and 37.1 ± 14.0° respectively (p = 0.023). Japanese Orthopaedic Association Back Pain Questionnaire (JOABPEQ) scores for walking ability was significantly impaired in the DS group compared to the LCS group (p = 0.025).Conclusion. The DS group had a significantly smaller dural sac area than the LCS group, while PI and LL were significantly larger and walking ability was significantly impaired.

Different Profiles of the Triad of Lysophosphatidylcholine, Lysophosphatidic Acid, and Autotaxin in Patients with Neuropathic Pain Diseases: a Preliminary Observational Study.

The mechanisms underlying neuropathic pain remain unclear. Lysophosphatidic acid (LPA) is a bioactive phospholipid derived mainly from lysophosphatidylcholine (LPC) by extracellular autotaxin (ATX), and has attracted attention as a candidate biomarker of neuropathic pain. We aimed to investigate the levels of LPA, LPC, and ATX in patients with lumbar spinal canal stenosis (LSCS) or other neuropathic pain diseases, and to distinguish the underlying mechanism of LSCS from other neuropathic pain conditions. Furthermore, the levels of phosphorylated neurofilament heavy chain (pNF-H), an objective surrogate marker of axonal damage, were also measured. Cerebrospinal fluid (CSF) samples were obtained from 56 patients with LSCS (n = 31) and various etiologies other than LSCS (n = 25). Patients with LSCS complained of pain intensity comparable to that of patients without LSCS. The LPA levels were significantly higher in patients with LSCS than in non-LSCS patients, while the ATX levels were significantly lower. However, the differences in LPC and pNF-H levels between the two patient groups were not significant. The LPA/LPC ratio was significantly higher in the LSCS group. Notably, the difference in LPA between the two groups diminished in the analysis of covariance (ANCOVA) with ATX as a covariate. Thus, it helped to reveal that LPA synthesis in patients with LSCS depends more efficiently on ATX than in non-LSCS neuropathic pain patients with other etiologies. Our findings further suggest that the triad of LPA, LPC, and ATX in LSCS may contribute to the development and maintenance of neuropathic pain in a manner different from non-LSCS neuropathic conditions.

Comparative proteome analysis of the ligamentum flavum of patients with lumbar spinal canal stenosis.

Thickening of the ligamentum flavum is considered to be the main factor for lumbar spinal canal stenosis (LSCS). Although some mechanisms have been speculated in the thickening of the ligamentum flavum, there are only a few comprehensive approaches to investigate its pathology. The objective of this study was to investigate the pathology of thickened ligamentum flavum in patients with LSCS based on protein expression levels using shotgun proteome analysis. Ligamentum flavum samples were collected from four patients with LSCS (LSCS group) and four patients with lumbar disc herniation (LDH) as controls (LDH group). Protein mixtures were digested and analyzed by liquid chromatography/mass spectrometry analysis. To compare protein expression levels between the LSCS and LDH groups, the mean Mascot score was compared. Biological processes were assessed using Gene Ontology analysis. A total of 1151 proteins were identified in some samples of ligamentum flavum. Among these, 145 proteins were detected only in the LSCS group, 315 in the LDH group, and 691 in both groups. The demonstrated biological processes occurring in the LSCS group included: extracellular matrix organization, regulation of peptidase activity, extracellular matrix disassembly, and negative regulation of cell growth. Proteins related to fibrosis, chondrometaplasia, and amyloid deposition were found highly expressed in the LSCS group compared with those in the LDH group. Tissue repair via fibrosis, chondrometaplasia, and amyloid deposits may be important pathologies that occur in the thickened ligamentum flavum of patients with LSCS.

EGF Contributes to Hypertrophy of Human Ligamentum Flavum via the TGF-β1/Smad3 Signaling Pathway.

Background: The most common spinal disorder in elderly is lumbar spinal canal stenosis (LSCS). Previous studies showed that ligamentum flavum hypertrophy (LFH) with fibrosis as the main pathological change is one of the pathogenic factors leading to LSCS. Epidermal Growth Factor (EGF) is known to have an intimate relationship with fibrosis in various tissues. Nevertheless, currently, there are few studies regarding EGF in LFH. The effect of EGF on the development of LFH is unknown, and the underlying pathomechanism remains unclear. In this study, we investigated the role of EGF in LFH and its potential molecular mechanism.Methods: First, the expression levels of EGF, phosphorylation of EGF receptor (pEGFR), Transforming growth factor-β1 (TGF-β1), Phosphorylated Smad3 (pSmad3), collagen I and collagen III were examined via immunohistochemistry and Western blot in LF tissues from patients with LSCS or Non-LSCS. Second, primary LF cells were isolated from adults with normal LF thickness and were cultured with different concentrations of exogenous EGF with or without erlotinib/TGF-β1-neutralizing antibody.Results: The results showed that EGF, pEGFR, TGF-β1, pSmad3, collagen I and collagen III protein expression in the LSCS group was significantly higher than that in the Non-LSCS group. Meanwhile, pEGFR, TGF-β1, pSmad3, collagen I and collagen III protein expression was significantly enhanced in LF cells after exogenous EGF exposure, which can be notably blocked by erlotinib. In addition, pSmad3, collagen I and collagen III protein expression was blocked by TGF-β1-neutralizing antibody.Conclusions: EGF promotes the synthesis of collagen I and collagen III via the TGF-β1/Smad3 signaling pathway, which eventually contributes to LFH.

P134. Midterm clinical and radiological outcomes of lumbar spinal stenosis with concurrent scoliosis and/or spondylolisthesis after minimally invasive lumbar decompression surgery: Minimum 5-year follow-up

<h3>BACKGROUND CONTEXT</h3> Several studies recently have been published about the sagittal spinal alignment of lumbar spinal canal stenosis (LSS) after decompression surgery, however, little is known about these variables of LSS with concurrent degenerative spondylolisthesis (DS) and/or lumbar scoliosis (DLS). With aging of the population, spine surgeons are currently more and more confronted with a wide variety of degenerative changes of the lumbar spine. <h3>PURPOSE</h3> The purpose of this study was to investigate whether the radiological and clinical outcomes differ depend on the concomitance after minimally invasive lumbar decompression surgery. <h3>STUDY DESIGN/SETTING</h3> Retrospective analysis of prospectively collected data. <h3>PATIENT SAMPLE</h3> A total of 244 patients underwent bilateral decompression via unilateral approach using microscope or microendscope at our instituted between 2008 and 2013, and were followed up for more than 5 years postoperatively. A total of 169 patients were included in the final analysis (88 women, 81 men; mean age at surgery, 69.5±9.2years). The patients were divided into three groups: LSS group (without DS and DLS; n=91), DS group (n=59) and DLS group (n=19) <h3>OUTCOME MEASURES</h3> Clinical outcomes were evaluated with the Japanese Orthopaedic Association (JOA) scoring system (29 possible points) and visual analog scale (VAS) score for low back pain (LBP), leg pain, leg numbness and achievement of minimal clinically important difference (MCID) of VAS for low back pain (LBP) or leg pain (LP). Furthermore all spinopelvic parameters such as 1) cervical lordosis (CL): C2–7 angle (positive means lordosis); 2) cervicothoracic kyphosis (CTK): C7–T5 angle (positive means kyphosis); 3) thoracic kyphosis (TK): T5–12 angle (positive means kyphosis); 4) lumbar lordosis: T12–S1 angle (positive means lordosis); 5) C7–S1 sagittal vertical axis (SVA): distance between C-7 plumb line and posterosuperior sacrum; 6) pelvic parameters: sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI) and PI – LL were evaluated. <h3>METHODS</h3> All patients underwent bilateral decompression via a unilateral approach to decompress the central and bilateral lateral recess using a microscope or the METRx Microendoscopic Discectomy System (Medtronic Sofamor Danek, Warsaw, IN, USA). Outcomes were quantified comparatively among Simple LSS group vs DS group (with anterior slip of more than 3mm) and DLS group (with ≥ 20° coronal Cobb angle) using low back pain (LBP) /leg pain/leg numbness visual analog scale (VAS) scores, the JOA scores and variables about sagittal plane alignment before surgery, 2 years and 5 years of follow-up. <h3>RESULTS</h3> In patients coexisting DS, the clinical outcomes at 2year and 5-year after surgery were similar with that of LSS except for VAS leg numbness. In patients coexisting DLS, the VAS leg pain at 2-year after surgery was significantly higher (34.5 vs 14.5, P=0.001) and the achievement rate of the minimal clinically important difference in VAS LBP and leg pain was significantly lower than LSS group (26.3% vs 52.7%; P=0.036, 42.1% vs 72.5%; P=0.01). The reoperation rate of DS group was significantly lower than that of LSS group (3.4% vs16.5%; P=0.01), but the DLS group was comparable to the LSS group (15.8% vs 16.5%; P=0.941). Lumbar lordosis (LL), pelvic tilt and pelvic incidence-LL were significantly improved and maintained for 5 years after surgery, however, sagittal vertical axis improved at 2-year follow-up, but no significantly difference was observed at 5-year follow-up in both the DS and the DLS group. <h3>CONCLUSIONS</h3> Among patients with DS and DLS, the clinical effectiveness and radiological changes after minimally lumbar decompression surgery alone was noninferior to that of LSS without deformity. The less invasive procedure should be considered for most LSS patients. <h3>FDA DEVICE/DRUG STATUS</h3> Unavailable from authors at time of publication.

Surgical outcomes of the thoracic ossification of ligamentum flavum: a retrospective analysis of 61 cases

BackgroundThoracic ossification of ligamentum flavum (T-OLF), as one of the causes of thoracic myelopathy, is often combined with other spinal disorders. Concurrent lumbar spinal canal stenosis (LCS) is often obscured by symptoms due to T-OLF, leading to difficulty in identifying the origin of these neurological findings. It is common to be misdiagnosed or delayed diagnosis due to the complicated nature. We evaluated the prevalence, distribution, and clinical characteristics of OLF, especially in patients with LCS.MethodsThe authors performed a retrospective analysis of the outcomes of 61 patients who underwent thoracic surgeries performed for symptomatic T-OLF. In all the patients, whole spine lesions were evaluated preoperatively. We examined the factors related to poor outcomes (the recovery rate of the Japanese Orthopedic Association score for thoracic myelopathy is less than 40%) following OLF surgeries. We compared the clinical outcomes according to whether there was concurrent LCS, and determined the optimal surgical approach.ResultsThe occurrence of T-OLF increased with age. Forty-six cases (75.4%) were considered to be tandem T-OLF and LCS (LCS group). An advanced age, and concurrent LCS were associated with a poor outcome after the surgery. The LCS group significantly included a greater number of elderly, and more light-weighted patients with Modic change in thoracic spine and a greater sagittal vertical axis, resulting in the lower neurological recovery. Additional lumbar surgery (13cases) effectively improved both the T-JOA and L-JOA scores (from 6.5 ± 2.0 points to 8.0 ± 1.8 points, p = 0.0406, and from 14.5 ± 4.7 points to 20.7 ± 2.6 points, p = 0.001, respectively) in OLF patients with LCS.ConclusionsT-OLF was highly associated with other spinal disorders. Poor outcomes in T-OLF surgery could be associated with age and concurrent LCS, and an additional surgery for another lumbar lesion significantly improved neurological findings in T-OLF patients.

Lomber Pedikül Kalınlığı Lomber Spinal Kanal Darlığını Öngörmede Morfolojik Bir Parametre Olabilir mi?

Background: Lumbar spinal canal stenosis (LSCS) is an important cause of morbidity in the elderly population. Many morphological abnormalities such as facet joint hypertrophy, ligamentum flavum hypertrophy, disc herniation combined with osteophytes associated with LSCS were investigated. Degenerative changes in all the elements of the vertebral bone such as lumbar pedicle thickness (LPT) has not evaluated clearly. The aim of this study to investigate whether LPT can be a morphological parameter to predict LSCS using magnetic resonance imaging (MRI).Materials and Methods: 150 patients diagnosed clinical LSCS and 150 control subjects who did not have LCSC-related symptoms referred to radiology unit to undergo lomber MRI enrolled the study. LPT was measured at the most stenotic level of the L5 vertebra using axial T2-weighted images.Results: The mean LPT value was 14.70±1.94 mm in the LSCS group and 14.23±2.00 mm in the control group and was higher in patient group than the controls but did not reach statistical significance (p=0.082).Conclusion: LPT can not be an effective factor to predict patients with LSCS.

Risk factors of degenerative lumbar scoliosis in patients with lumbar spinal canal stenosis.

Lumbar spinal canal stenosis (LSCS) associated with degenerative scoliosis has being increasingly aware by the public and studied by many researchers. Degenerative changes leading to spinal stenosis can precede a spinal deformity which will develop into the de novo scoliosis. There are few studies focusing on the risk factors contributing to the degenerative lumbar scoliosis (DLS) in lumbar spinal stenosis patients.From September, 2017 to December, 2017, 181 patients who were diagnosed with LSCS in the outpatient department of our hospital were enrolled in this retrospective investigation. The patients were divided into 2 groups: DLS group (Cobb angle >10°) and LSCS group. Sex, age, smoking status (yes or no), occupation (heavy or light labor), body mass index (BMI), bone mineral density (BMD) and radiographic parameters including the lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), thoracic kyphosis (TK), coronal vertical axis, and sagittal vertical axis (SVA) are all evaluated as potential risk factors. Multivariate logistic regression analysis and receiver-operating characteristic curves were used to identify potential risk factors.Forty-five of 181 patients were diagnosed with DLS and involved in the DLS group. There were significant differences between the 2 groups in BMI (P < .001), LL (P = .0046), BMD (P < .001), SVA (P < .001), and TK (P = .047). BMD < −1.85 g/cm2 (adjusted odds ratio [AOR] 0.030, 95% confidence interval [CI] 0.008–0.107, P < .001), BMI >25.57 kg/m2 (AOR 1.270, 95% CI 1.040–1.551, P = .019), and SVA >3.98 cm (AOR 3.651, 95% CI 2.226–5.990, P < .001) had good accuracy to predict the formation of degenerative lumbar scoliosis based on degenerative lumbar spinal stenosis.Degenerative lumbar scoliosis has a high incidence in degenerative lumbar spinal stenosis. BMD <−1.85 g/cm2, BMI >25.57 kg/m2, and SVA >3.98 cm were the potential risk factors for the formation of degenerative lumbar scoliosis based on degenerative lumbar spinal stenosis.

Decreased catalase expression is associated with ligamentum flavum hypertrophy due to lumbar spinal canal stenosis.

Background:This is an immunohistologic study of gene expression between patients and controls.This study aims to evaluate expression of the catalase gene in hypertrophied ligamentum flavum (LF) specimens obtained from patients with lumbar spinal canal stenosis (LSCS).LSCS is one of the most common spinal disorders. It is well known that LF hypertrophy plays an important role in the onset of LSCS. Although degenerative changes, aging, and mechanical stress are all thought to contribute to hypertrophy and fibrosis of the LF, the precise pathogenesis of LF hypertrophy remains unknown. Previous genetic studies have tried to determine the mechanism of LF hypertrophy. However, the association between catalase gene expression and LF hypertrophy has not yet been explored.Methods:LF specimens were surgically obtained from 30 patients with spinal stenosis (LSCS group) and from 30 controls with lumbar disc herniation (LDH group). LF thickness was measured at the thickest point using calipers to an accuracy of 0.01 mm during surgical intervention. The extent of LF elastin degradation and fibrosis were graded (grades 0–4) by hematoxylin and eosin staining and Masson trichrome staining, respectively. The resulting LF measurements, histologic data, and immunohistologic results were then compared between the 2 groups.Results:The average LF thickness was significantly higher in the LSCS group than in the LDH group (5.99 and 2.95 mm, respectively, P = .004). Elastin degradation and fibrosis of the LF were significantly more severe in spinal stenosis samples than in the disc herniation samples (3.04 ± 0.50 vs 0.79 ± 0.60, P = .007; 3.01 ± 0.47 vs 0.66 ± 0.42, P = .009, respectively). Significantly lower expression of catalase was observed in the perivascular area of LF samples obtained from patients with LSCS compared with controls (61.80 ± 31.10 vs 152.80 ± 41.13, respectively, P = .009).Conclusion:Our findings suggest that decreased expression of catalase is associated with LF hypertrophy in patients with LSCS.

Comparison of glutathion-s-transferase A-4 expression values between lumbar spinal canal stenosis and lumbar discal hernia patients

Aim: To compare the glutathione s-transferase α-4 (GSTA4) isoenzymes expression values in patients with lumbar spinal canal stenosis (LSCS) due to ligamentum flavum (LF) hypertrophy with patients no evidence of LF hypertrophy.Material and Methods: 27 LF specimens were obtained from patients with LSCS and 27 LF specimens were obtained from patients with lumbar discal hernia (LDH). Firstly these LF samples were analyzed histologically to identify the fibrosis and elastin degradation values. Then GSTA4 isoenzyme values were measured and compared.Results: The mean LF thickness was significantly higher in the LSCS group than in the LDH group (6.72±0.86 and 3.1±0.7 mm, respectively, p 0.005). Average elastin degradation degree was significantly higher in the LSCS group than LDH group (4.4 ±0.50 vs. 0.18±0.1, respectively, p 0.001). And avarage fibrosis degree was significantly higher in the LSCS group than LDH group (4.41±0.17 vs. 0.96±0.11, respectively, p 0.001). And significantly higherexpression of GSTA4 izoenzyme was observed in the LF samples obtained from patients with LSCS compared with controls (144.1±11.16 vs 51.75±21.53, respectively, p=0.009). Conclusion: Our findings in this study suggest that there is a relationship between LF hypertrophy and GSTA4 isoenzyme expression.

Facet joint hypertrophy is a misnomer: A retrospective study.

One of the major causes of lumbar spinal canal stenosis (LSCS) has been considered facet joint hypertrophy (FJH). However, a previous study asserted that “FJH” is a misnomer because common facet joints are no smaller than degenerative facet joints; however, this hypothesis has not been effectively demonstrated. Therefore, in order to verify that FJH is a misnomer in patients with LSCS, we devised new morphological parameters that we called facet joint thickness (FJT) and facet joint cross-sectional area (FJA).We collected FJT and FJA data from 114 patients with LSCS. A total of 86 control subjects underwent lumbar magnetic resonance imaging (MRI) as part of routine medical examinations, and axial T2-weighted MRI images were obtained from all participants. We measured FJT by drawing a line along the facet area and then measuring the narrowest point at L4-L5. We measured FJA as the whole cross-sectional area of the facet joint at the stenotic L4-L5 level.The average FJT was 1.60 ± 0.36 mm in the control group and 1.11 ± 0.32 mm in the LSCS group. The average FJA was 14.46 ± 5.17 mm2 in the control group and 9.31 ± 3.47 mm2 in the LSCS group. Patients with LSCS had significantly lower FJTs (P < .001) and FJAs (P < .001).FJH, a misnomer, should be renamed facet joint area narrowing. Using this terminology would eliminate confusion in descriptions of the facet joint.

Leptin-induced inflammation by activating IL-6 expression contributes to the fibrosis and hypertrophy of ligamentum flavum in lumbar spinal canal stenosis.

The ongoing chronic inflammation and subsequent fibrosis play an important role in ligamentum flavum (LF) fibrosis and hypertrophy in patients with lumbar spinal canal stenosis (LSCS). Leptin is a chronic inflammatory mediator and involved in the fibrotic process in multiple organ systems. The present study aimed to investigate the role of leptin in LF fibrosis and its related regulatory mechanisms. The LF specimens were obtained during the surgery from 12 patients with LSCS (LSCS group) and 12 control patients with lumbar disc herniation (LDH) group. The morphologic changes and fibrosis score of LF were assessed by Hematoxylin and eosin (H&E) and Masson’s trichrome staining respectively. The location and expression of leptin in LF tissues were determined. Then, the LF cells were cultured and exposed to recombinant human leptin (rhleptin). Collagen I and III were used as fibrosis markers and IL-6 was used as the inflammatory factor. As a result, the LF thickness and fibrosis score in the LSCS group were significantly higher than those in the LDH group (P<0.05). Leptin was detected in the hypertrophied LF and its expression was substantially increased in the LSCS group and positively correlated with LF thickness and fibrosis score (P<0.05). Moreover, our in vitro experiments revealed that rhleptin treated LF cells elevated the expression of collagen I and III. Finally, leptin administration induced IL-6 expression via nuclear factor-κB (NF-κB) pathway in LF cell (P<0.05). Our study demonstrated novel molecular events for leptin-induced inflammation in LF tissue by promoting IL-6 expression and thus might have potential implications for clarifying the mechanism underlying LF fibrosis and hypertrophy.

The tibial nerve compression test for the diagnosis of lumbar spinal canal stenosis—A simple and reliable physical examination for use by primary care physicians

ObjectivesIn the present study, we aimed to evaluate the diagnostic accuracy and suitability of the ‘Tibial Nerve Compression Test (TNCT)’ as a screening tool for lumbar spinal canal stenosis (LSS). MethodsA total of 108 consecutive patients admitted to our hospital for surgical treatment or diagnosis of LSS were included in this study. Fifty healthy volunteers were examined as a control group. The severity of tenderness was scored (tenderness score) and measured on a visual analogue scale (P-VAS score). These scores were compared between the LSS and control groups. Moreover, they were compared before and after the operation among operated patients. ResultsThe positive tenderness rate was significantly higher (92.6% [100/108]) in the LSS group than in the control group (30% [15/50]). The sensitivity and specificity of TNCT (95% confidence interval) were 0.93 (0.88–0.96) and 0.70 (0.61–0.77), respectively. Positive tenderness rates and P-VAS scores were significantly higher in the LSS group (p < 0.0001). Scores on all measures significantly improved post-operatively in operated patients (p < 0.0001). ConclusionThe Tibial Nerve Compression Test is a useful screening tool for LSS diagnosis in a primary care setting. Level of evidenceLevel II, diagnostic study

Diabetes mellitus is associated with increased elastin fiber loss in ligamentum flavum of patients with lumbar spinal canal stenosis: results of a pilot histological study.

Lumbar spinal canal stenosis (LSCS) is associated with fibrosis, decreased elastin-to-collagen ratio, and hypertrophy of the ligamentum flavum (LF). Diabetes mellitus (DM) is known to cause metabolic disturbances within the extracellular matrix in multiple tissues. These alterations may play a major role in the severity of clinical symptoms of LSCS affecting diabetic patients. We aimed to examine the hypothesis that DM may contribute to the LF changes seen in patients with LSCS. The study cohort included 29 patients: 23 with LSCS (10 with DM vs. 13 without DM) as well as six patients with lumbar disc herniation (LDH). Surgical LF specimens were retrieved for histological assessment. Morphologic quantification of confocal microscopy images using fast Fourier transform analysis allowed us to compare anisotropy and elastin fiber orientation between groups. There was a significant positive correlation between fasting plasma glucose values and degree of elastin degradation (r=0.36, p=0.043). The diabetic patients with LSCS showed a significantly greater loss of elastic fibers (2.3±0.9 vs. 1.5±0.55, p=0.009), although fibrosis was shown to be similar (1.44±0.7 vs. 1.43±0.88, p=0.98). There was no significant difference in the degree of calcification in the LSCS group between patients with and without diabetes (1.71 vs. 2.05%, p=0.653). Fiber orientation was found to be less homogenous in the LSCS compared with the LDH group, although not significantly affected by DM. The present study points to a significant contribution of DM to the loss of elastin fibers that occurs in the LF of patients with LSCS.

MiR-21 promotes fibrosis and hypertrophy of ligamentum flavum in lumbar spinal canal stenosis by activating IL-6 expression

The molecular mechanism underlying the fibrosis of ligamentum flavum(LF) in patients with lumbar spinal canal stenosis(LSCS) remains unknown. MicroRNAs are reported to play important roles in regulating fibrosis in different organs. The present study aimed to identify fibrosis related miR-21 expression profile and investigate the pathological process of miR-21 in the fibrosis of LF hypertrophy and associated regulatory mechanisms. 15 patients with LSCS underwent surgical treatment were enrolled in this study. For the control group, 11 patients with lumbar disc herniation(LDH) was included. The LF thickness was measured on MRI. LF samples were obtained during the surgery. Fibrosis score was assessed by Masson's trichrome staining. The expression of miR-21 in LF tissues were determined by RT-PCR. Correlation among LF thickness, fibrosis score, and miR-21 expression was analyzed. In addition, Lentiviral vectors for miR-21 mimic were constructed and transfected into LF cells to examine the role of miR-21 in LF fibrosis. Types I and III collagen were used as indicators of fibrosis. IL-6 expression in LF cells after transfection was investigated by RT-PCR and ELISA. Patients in two groups showed similar outcomes regarding age, gender, level of LF tissue. The thickness and fibrosis score of LF in the LSCS group were significantly greater than those in LDH group (all P < 0.05). Similarly, the expression of miR-21 in LSCS group was substantially higher than that in LDH group(P < 0.05). Furthermore, the miR-21 expression exhibited positive correlations with the LF thickness (r = 0.595, P < 0.05) and fibrosis score (r = 0.608, P < 0.05). Of note, miR-21 over-expression increased the expression levels of collagen I and III (P < 0.05). Also, IL-6 expression and secretion in LF cells was elevated after transfection of miR-21 mimic. MiR-21 is a fibrosis-associated miRNA and promotes inflammation in LF tissue by activating IL-6 expression, leading to LF fibrosis and hypertrophy.

Circulatory dynamics of the cauda equina in lumbar canal stenosis using dynamic contrast-enhanced magnetic resonance imaging

Background contextThere has been no study regarding the cauda equina circulation of patients with neurogenic intermittent claudication (NIC) in lumbar spinal canal stenosis (LSCS) using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). PurposeThe mechanism responsible for the onset of NIC was investigated using DCE-MRI to examine changes in cauda equina blood flow in patients with LSCS. Study designThis was a retrospective longitudinal registry and magnetic resonance imaging study. Patient sampleThe subjects consisted of 23 patients who had LSCS associated with NIC (stenosis group). Ten asymptomatic volunteers who did not have NIC served as controls (control group). In the LSCS group, the cross-sectional area of the dural sac was < 75 mm2 at the site of most severe stenosis. These patients were further divided into single and double stenosis subgroups. Outcome measuresThe main measures we used were the signal intensity (S-I) ratio and the shape and size of the time intensity (T-I) curves. We compared these between the stenosis and control groups. MethodsAt first, plain T1-weighted MR images were obtained and the lumbar dural sac cross-sectional area was measured using a digitizer. For DCE-MRI, sagittal T1-weighted images of the same slice were acquired continuously for 10 minutes after administration of gadolinium as an intravenous bolus to observe the distribution of contrast medium (gadolinium) in the cauda equina. To objectively evaluate changes in contrast enhancement of the cauda equina at the site of canal stenosis, regions of interest were established. The signal intensity (SI) ratio was calculated to compare the signal intensities before and after contrast enhancement, and time-intensity curves were prepared to investigate changes over time. ResultsThe static imaging findings and the changes of gadolinium uptake showed striking differences between the study and control patients. In the stenosis group, abnormal intrathecal enhancement showed around the site of stenosis on enhanced MR imaging. The SI ratio at the site of canal stenosis had a slower increase in the arterial phase when compared with that in the control group and remained high in the venous phase for up to 10 minutes. Finally, abnormal intrathecal enhancement was visible around the site of stenosis on enhanced MR imaging in all patients. ConclusionsThese clinical data indicate that cauda equina nerve roots in the LSCS patients are pathologic even when symptoms are not elicited in the supine position, suggesting that intraradicular venous congestion and edema themselves do not influence the existence of radicular symptoms.

The Mechanism of Ligamentum Flavum Hypertrophy

Biochemical alterations associated with mechanical stress have been explored as an initiating step in the pathological progression of ligamentum flavum hypertrophy (LFH); however, this mechanism remains poorly understood. Recently, the inflammation induced after mechanical stress and the subsequent response of ligamentum flavum (LF) cells have been implicated in LFH pathology. To investigate the hypothesis that angiogenesis may be a critical link between hypertrophy and a series of stimulating events, including mechanical stress. LF from 20 lumbar spinal canal stenosis (LSCS) patients and 16 non-LSCS patients (control group) were collected during surgery. Patient demographic and radiographic data were obtained. The levels of angiogenic factors (vascular endothelial growth factor [VEGF], angiopoietin-1, vascular cell adhesion molecule, and basic fibroblast growth factor) in the LF were investigated by using an enzyme-linked immunosorbent assay. Angiogenesis was also quantified by immunohistochemical detection of CD34-positive capillaries. The correlations among clinical factors, including radiographic factors, angiogenic factors, and angiogenesis, were statistically analyzed. The LSCS group was older and exhibited a longer symptom duration, wider segmental motion, and thicker LF than the control group. The LSCS group showed significantly higher tissue concentrations of VEGF (P < .001) that positively correlated with LF thickness (r = 0.557, P < .001) and segmental motion (r = 0.586, P < .001). The LSCS group showed significantly more CD34-positive capillaries than the control group (P = .004). The LSCS group showed greater segmental motion, higher VEGF concentrations, and more CD34-positive capillaries than the control group. These data indicate that VEGF-mediated angiogenesis following mechanical stress may be a critical step within the series of pathological events in LFH.

Chondrogenic and Fibrotic Process in the Ligamentum Flavum of Patients With Lumbar Spinal Canal Stenosis

A histological, biological, and immunohisto-chemical study of human lumbar ligamentum flavum. To analyze changes in the hypertrophied ligamentum flavum and clarify their etiology. Hypertrophy of the ligamentum flavum has been considered a major contributor to the development of lumbar spinal canal stenosis (LSCS). Although previous studies have reported some factors related to ligamentum flavum hypertrophy, its etiology is still unclear. Ligamentum flavum samples were collected from 20 patients with LSCS (LSCS group) and 10 patients with lumbar disc herniation (LDH group) as a control. The thickness of the ligamentum flavum was measured histologically. The amounts of elastic fibers and proteoglycans were assessed by Elastica-Masson staining and alcian blue staining, respectively. Gene and protein expressions related to fibrosis, inflammation, and chondrogenesis were analyzed by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. The total genes of the 2 groups were compared by DNA microarray analysis. The ligamentum flavum was significantly thicker in the LSCS group, which had a smaller amount of elastic fibers and a larger amount of proteoglycans. The gene expression related to fibrosis was significantly higher in the LSCS group; however, the immunoreactivities of collagen types I and III were weaker on the dorsal side of the ligamentum flavum in the LSCS group. The gene expression related to chondrogenesis and proteoglycan synthesis was significantly higher in the LSCS group. There was no significant difference in the gene expression related to inflammation between the 2 groups. Synthesis of the collagenous fibers and degradation of the elastic and collagenous fibers are both accelerated in the ligamentum flavum of patient with LSCS, which may be the reason for hypertrophy of the tissue. In addition, chondrogenesis and proteoglycan synthesis may have critical roles in the pathogenesis of the ligamentum flavum hypertrophy. 5.

Characterization of symptomatic lumbar foraminal stenosis by conventional imaging.

The preoperative identification of lumbar foraminal stenosis (LSFS) is important because a lack of recognition of this clinical entity is often associated with failed back surgery syndrome. Although magnetic resonance imaging (MRI) is widely used, and is considered by many as an appropriate tool for studying spine pathologies, there is limited data to suggest that MRI examinations are sufficiently sensitive or specific for the diagnosis of LSFS. There is a paucity of literature on the diagnostic performance of the combination of conventional diagnostic imaging methods. The purpose of this study is to determine the characteristics of conventional diagnostic imaging for symptomatic lumbar foraminal stenosis. The characteristics of conventional diagnostic imaging of LSFS (X-ray, computed tomography (CT) and MRI) were assessed in 68 patients in whom the site of the stenosis was confirmed by means of selective decompression surgeries. Measurement of the foraminal width and height on CT imaging of the diseased side was significantly less than that on the intact side in the LSFS group. The grading scale for facet joint arthritis on the diseased side was significantly higher than that on the intact side in the LSFS group. The prevalence of the vacuum phenomenon and stage of intervertebral disk (IVD) pathology were higher in the L5-S1 spine of the LSFS group (95.2%) compared with the lumbar spinal canal stenosis (LCS) group (21.1%). MRI study revealed that the prevalence of Type 3 Modic changes was significantly higher in the LSFS group (39.3%) compared with the LCS group (7.7%). Our study demonstrates combination of conventional imaging techniques, to improve the detection of symptomatic foraminal stenosis.