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2.
Spine (Phila Pa 1976) ; 49(17): E284-E290, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39133228

RESUMEN

STUDY DESIGN: Experimental study. OBJECTIVE: We sought to elucidate the association between ligamentum flavum thickening and tissue buckling, and the clinical and imaging factors related to buckling by comparing the ligamentum flavum thickness on MRI images and within the actual tissue. SUMMARY OF BACKGROUND DATA: Ligamentum flavum thickening is a main contributor to lumbar spinal canal stenosis. Buckling of the tissue may contribute to ligamentum flavum thickening along with tissue hypertrophy; however, this association has not been established conclusively. MATERIALS AND METHODS: Ligamentum flavum samples (135 ligament samples) from 70 patients with lumbar spinal canal stenosis were evaluated. The ligamentum flavum thicknesses on magnetic resonance imaging (MRI) and in the tissue samples were compared to assess for the presence of buckling. The ligamentum flavum samples were divided into groups with or without buckling based on the difference between their thicknesses on MRI and in the tissues. The Pearson correlation coefficient test was used to assess the relationships between the LF thicknesses on MRI and in the tissues, MRI-tissue difference and LF thickness in the tissues, and MRI-tissue difference and LF thickness on MRI. Further, differences between the buckling+ and buckling- groups were compared using the unpaired t-test (LF thickness on MRI, LF thickness in the tissues, age, disc angle, and disc height) and χ2 (disc level, disc degeneration, and receival/nonreceival of dialysis) test. RESULTS: The ligamentum flavum thickness on MRI and in the tissues had a positive linear relationship, although the thickness was estimated to be significantly larger on MRI than in the tissues themselves. The ligamentum flavum with buckling had a larger thickness on MRI, less tissue hypertrophy, more severe disc degeneration, and was present in patients with a higher rate of dialysis. There were no differences in age and disc height, angle, or level between the two groups. CONCLUSIONS: Buckling of the ligamentum flavum coexists with tissue hypertrophy and contributes to perceived ligamentum thickening on imaging. Buckling of the ligamentum flavum tends to occur in less hypertrophied tissues and is associated with the grade of disc degeneration and the presence of other characteristics associated with spinal degeneration.


Asunto(s)
Ligamento Amarillo , Vértebras Lumbares , Imagen por Resonancia Magnética , Estenosis Espinal , Humanos , Ligamento Amarillo/patología , Ligamento Amarillo/diagnóstico por imagen , Estenosis Espinal/diagnóstico por imagen , Estenosis Espinal/patología , Masculino , Femenino , Anciano , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/patología , Persona de Mediana Edad , Adulto , Anciano de 80 o más Años , Canal Medular/diagnóstico por imagen , Canal Medular/patología , Hipertrofia
3.
Medicine (Baltimore) ; 103(27): e38782, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38968524

RESUMEN

Lumbar spinal stenosis (LSS) can cause a range of cauda equina symptoms, including lower back and leg pain, numbness, and intermittent claudication. This disease affects approximately 103 million people worldwide, particularly the elderly, and can seriously compromise their health and well-being. Ligamentum flavum hypertrophy (LFH) is one of the main contributing factors to this disease. Surgical treatment is currently recommended for LSS caused by LFH. For patients who do not meet the criteria for surgery, symptom relief can be achieved by using oral nonsteroidal anti-inflammatory drugs (NSAIDs) and epidural steroid injections. Exercise therapy and needle knife can also help to reduce the effects of mechanical stress. However, the effectiveness of these methods varies, and targeting the delay in LF hypertrophy is challenging. Therefore, further research and development of new drugs is necessary to address this issue. Several new drugs, including cyclopamine and N-acetyl-l-cysteine, are currently undergoing testing and may serve as new treatments for LSS caused by LFH.


Asunto(s)
Hipertrofia , Ligamento Amarillo , Vértebras Lumbares , Estenosis Espinal , Humanos , Ligamento Amarillo/patología , Estenosis Espinal/terapia , Estenosis Espinal/etiología , Hipertrofia/etiología , Antiinflamatorios no Esteroideos/uso terapéutico , Antiinflamatorios no Esteroideos/administración & dosificación , Terapia por Ejercicio/métodos , Tratamiento Conservador/métodos
4.
BMC Musculoskelet Disord ; 25(1): 513, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38961370

RESUMEN

BACKGROUND: Although posterior decompression with fusion (PDF) are effective for treating thoracic myelopathy, surgical treatment has a high risk of various complications. There is currently no information available on the perioperative complications in thoracic ossification of the longitudinal ligament (T-OPLL) and thoracic ossification of the ligamentum flavum (T-OLF). We evaluate the perioperative complication rate and cost between T-OPLL and T-OLF for patients underwent PDF. METHODS: Patients undergoing PDF for T-OPLL and T-OLF from 2012 to 2018 were detected in Japanese nationwide inpatient database. One-to-one propensity score matching between T-OPLL and T-OLF was performed based on patient characteristics and preoperative comorbidities. We examined systemic and local complication rate, reoperation rate, length of hospital stays, costs, discharge destination, and mortality after matching. RESULTS: In a total of 2,660 patients, 828 pairs of T-OPLL and T-OLF patients were included after matching. The incidence of systemic complications did not differ significantly between the T-OPLL and OLF groups. However, local complications were more frequently occurred in T-OPLL than in T-OLF groups (11.4% vs. 7.7% P = 0.012). Transfusion rates was also significantly higher in the T-OPLL group (14.1% vs. 9.4%, P = 0.003). T-OPLL group had longer hospital stay (42.2 days vs. 36.2 days, P = 0.004) and higher medical costs (USD 32,805 vs. USD 25,134, P < 0.001). In both T-OPLL and T-OLF, the occurrence of perioperative complications led to longer hospital stay and higher medical costs. While fewer patients in T-OPLL were discharged home (51.6% vs. 65.1%, P < 0.001), patients were transferred to other hospitals more frequently (47.5% vs. 33.5%, P = 0.001). CONCLUSION: This research identified the perioperative complications of T-OPLL and T-OLF in PDF using a large national database, which revealed that the incidence of local complications was higher in the T-OPLL patients. Perioperative complications resulted in longer hospital stays and higher medical costs.


Asunto(s)
Bases de Datos Factuales , Descompresión Quirúrgica , Ligamento Amarillo , Osificación del Ligamento Longitudinal Posterior , Complicaciones Posoperatorias , Fusión Vertebral , Vértebras Torácicas , Humanos , Masculino , Femenino , Vértebras Torácicas/cirugía , Ligamento Amarillo/cirugía , Fusión Vertebral/economía , Fusión Vertebral/efectos adversos , Fusión Vertebral/métodos , Persona de Mediana Edad , Descompresión Quirúrgica/economía , Descompresión Quirúrgica/efectos adversos , Descompresión Quirúrgica/métodos , Anciano , Osificación del Ligamento Longitudinal Posterior/cirugía , Osificación del Ligamento Longitudinal Posterior/economía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/economía , Japón/epidemiología , Osificación Heterotópica/cirugía , Osificación Heterotópica/economía , Osificación Heterotópica/epidemiología , Tiempo de Internación/economía , Reoperación/economía , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Pacientes Internos , Resultado del Tratamiento
5.
Pathol Int ; 74(8): 475-481, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38994749

RESUMEN

"Cysts of the ligamentum flavum (cysts-LF)" is the term for non-neoplastic cystic lesion involving LF. The aim of the present study was to elucidate the histopathological characteristics and pathogenesis of "cysts-LF". Herein, we defined cysts-LF as spinal cysts containing degenerative LF components. From archival cases, we investigated 18 symptomatic cysts-LF surgically removed from 18 patients (13 males and five females; median age 68.5 years [range, 42-86 years]). The elastic fibers of LF components in the wall were separated and/or torn, and cyst walls were accompanied by chondroid metaplasia (17 cases), myxoid changes (13 cases), ossification (11 cases), amyloid deposits (14 cases), hemosiderosis (six cases), granular/smudgy calcification (four cases), synovial cell linings (three cases), and severe inflammatory infiltrates (one case). These histologic features of our cysts-LF were shared by previously reported "cysts-LF." Fourteen cysts-LF demonstrated vascular stenosis/occlusion, and eight showed thick hyalinized vessels, suggesting local circulatory insufficiency. Eight cases (44%) exhibited lipomembranous fat necrosis, accompanied by hyalinized vascular changes (p = 0.003). Ischemic conditions were observed in nearly half of the present cysts-LF, and may be one of the main contributing factors for the formation of cysts-LF, via degeneration and cystic changes in the LF.


Asunto(s)
Quistes , Ligamento Amarillo , Humanos , Femenino , Masculino , Anciano , Ligamento Amarillo/patología , Persona de Mediana Edad , Adulto , Anciano de 80 o más Años , Quistes/patología , Isquemia/patología
6.
Neurosurg Rev ; 47(1): 345, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39037535

RESUMEN

In recent years, there has been growing interest in an alternative approach for treating TOLF, such as endoscopic decompression, which minimizes the disruption of surrounding tissues. It is important to understand the advantages, disadvantages, and potential differences in outcomes associated with each approach. This comparative study aims to evaluate and contrast the effectiveness, safety, and outcomes of these two surgical techniques, open laminectomy and endoscopic decompression, in the management of thoracic OLF. The literature review was conducted on Embase, PubMed, Scopus and Google Scholar databases. After a thorough screening of all search results, 14 studies were shortlisted, from which data was extracted, and statistical analysis was done. Pooled analysis was done to ascertain the intra-operative and post-operative outcomes after surgery for TOLF. Overall, 351 patients were included in the study for evaluation. 174 patients were operated on by open laminectomy, and 177 patients were seen in the endoscopy group. Decreased operative time was seen in the endoscopic subgroup. The mean length of hospital stay of 6.6 days. Both groups showed improvement in mJOA and VAS score. The recovery rate for the reported study cohort was 66.8%, with the Endoscopic surgical approach showing a positive correlation with the mean recovery rate. The dural tear was the most common complication, with a rate of 6.6%. The mean estimated infection rate was 2.7% and postoperative CSF leak was 3.7%, with a trend of significantly higher rates in the open subgroup. Both of the groups showed improvement in functional scores, VAS scores, and cross-sectional area. However, the Endoscopic decompression group experienced reduced hospital stays, operating times, and intraoperative blood loss. The most frequent side effects were CSF leak and dural tear. A few cases showed revision and infection. None of the problems differed between the groups.


Asunto(s)
Descompresión Quirúrgica , Laminectomía , Ligamento Amarillo , Vértebras Torácicas , Humanos , Descompresión Quirúrgica/métodos , Endoscopía/métodos , Laminectomía/métodos , Ligamento Amarillo/cirugía , Neuroendoscopía/métodos , Osificación Heterotópica/cirugía , Complicaciones Posoperatorias/epidemiología , Vértebras Torácicas/cirugía , Resultado del Tratamiento
7.
Eur Rev Med Pharmacol Sci ; 28(12): 3822-3827, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38946379

RESUMEN

OBJECTIVE: A condition known as ligamentum flavum (LF) hypertrophy occurs when the ligamentum flavum (LF) swells as a result of pressures applied to the spine. Among the elderly population, lumbar spinal stenosis is a major cause of pain and disabilities. Numerous studies indicate that lumbar spinal stenosis etiology involves the ligamentum flavum in a major way. This study looks into the relationship between low back pain and ligamentum flavum thickening. PATIENTS AND METHODS: The imaging tests and case histories of all patients with low back pain who had consecutive magnetic resonance imaging exams performed at the Prince Sattam University and King Khalid hospitals in Al Kharj City will serve as the basis for this retrospective observational study. A radiologist utilized the Pfirrmann grading system, which is based on spinal levels starting from the first lumbar to the first sacral vertebrae, to measure the thickness of the ligamentum flavum in all cases who underwent magnetic resonance imaging (MRI). A correlation between age, hypertrophy of LF, and low back pain was investigated. RESULTS: There were 79 participants in the study, ages ranging from 21 to 82, 49 of which were men. The patients' average age was 54 years, and 62% of them were men. We found no appreciable variations in LF thickness according to gender. At the L4-L5 and L5-S1 levels, the left LF was noticeably thicker than the right. Moreover, there was a significant difference (p < 0.05) in the bilateral LF thicknesses at L5-S1 compared to the comparable sides at L4-L5. CONCLUSIONS: By evaluating the thickness of LF on magnetic resonance images, we discovered that it may be closely associated with the etiology of pain processes in the spine.


Asunto(s)
Hipertrofia , Ligamento Amarillo , Dolor de la Región Lumbar , Imagen por Resonancia Magnética , Humanos , Ligamento Amarillo/patología , Ligamento Amarillo/diagnóstico por imagen , Dolor de la Región Lumbar/diagnóstico por imagen , Dolor de la Región Lumbar/patología , Dolor de la Región Lumbar/etiología , Masculino , Persona de Mediana Edad , Femenino , Anciano , Estudios Retrospectivos , Adulto , Anciano de 80 o más Años , Adulto Joven , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/patología , Estenosis Espinal/diagnóstico por imagen , Estenosis Espinal/patología
8.
Eur Spine J ; 33(8): 3161-3164, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38955867

RESUMEN

PURPOSE: Spinal tuberculosis, if not promptly treated, can lead to kyphotic deformity, causing persistent neurological abnormalities and discomfort. Spinal cord compression can occur due to ossification of the ligamentum flavum (OLF) at the apex of kyphosis. Traditional surgical interventions, including osteotomy and fixation, pose challenges and risks. We present a case of thoracic myelopathy in a patient with post-tuberculosis kyphosis, successfully treated with biportal endoscopic spinal surgery (BESS). METHOD: A 73-year-old female with a history of untreated kyphosis presented with walking difficulties and lower limb pain. Imaging revealed a kyphotic deformity of 120° and OLF-induced cord compression at T8-9. UBE was performed under spinal anesthesia. Using the BESS technique, OLF was successfully removed with minimal damage to the stabilizing structures. RESULTS: The patient exhibited neurological improvement after surgery, walking on the first day without gait instability. Follow-up at 1 year showed no kyphosis progression or recurrence of symptoms. BESS successfully resolved the cord compression lesion with minimal blood loss and damage. CONCLUSION: In spinal tuberculosis-related OLF, conventional open surgery poses challenges. BESS emerges as an excellent alternative, providing effective decompression with reduced instrumentation needs, minimal blood loss, and preservation of surrounding structures. Careful patient selection and surgical planning are crucial for optimal outcomes in endoscopic procedures.


Asunto(s)
Descompresión Quirúrgica , Endoscopía , Cifosis , Ligamento Amarillo , Osificación Heterotópica , Tuberculosis de la Columna Vertebral , Humanos , Anciano , Femenino , Cifosis/cirugía , Cifosis/etiología , Cifosis/diagnóstico por imagen , Ligamento Amarillo/cirugía , Ligamento Amarillo/diagnóstico por imagen , Descompresión Quirúrgica/métodos , Tuberculosis de la Columna Vertebral/cirugía , Tuberculosis de la Columna Vertebral/complicaciones , Tuberculosis de la Columna Vertebral/diagnóstico por imagen , Endoscopía/métodos , Osificación Heterotópica/cirugía , Osificación Heterotópica/complicaciones , Osificación Heterotópica/diagnóstico por imagen , Compresión de la Médula Espinal/cirugía , Compresión de la Médula Espinal/etiología , Compresión de la Médula Espinal/diagnóstico por imagen , Vértebras Torácicas/cirugía , Vértebras Torácicas/diagnóstico por imagen , Resultado del Tratamiento
9.
Bone ; 186: 117174, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38917962

RESUMEN

Spinal stenosis (SS) is frequently caused by spinal ligament abnormalities, such as ossification and hypertrophy, which narrow the spinal canal and compress the spinal cord or nerve roots, leading to myelopathy or sciatic symptoms; however, the underlying pathological mechanism is poorly understood, hampering the development of effective nonsurgical treatments. Our study aims to investigate the role of co-expression hub genes in patients with spinal ligament ossification and hypertrophy. To achieve this, we conducted an integrated analysis by combining RNA-seq data of ossification of the posterior longitudinal ligament (OPLL) and microarray profiles of hypertrophy of the ligamentum flavum (HLF), consistently pinpointing CTSD as an upregulated hub gene in both OPLL and HLF. Subsequent RT-qPCR and IHC assessments confirmed the heightened expression of CTSD in human OPLL, ossification of the ligamentum flavum (OLF), and HLF samples. We observed an increase in CTSD expression in human PLL and LF primary cells during osteogenic differentiation, as indicated by western blotting (WB). To assess CTSD's impact on osteogenic differentiation, we manipulated its expression levels in human PLL and LF primary cells using siRNAs and lentivirus, as demonstrated by WB, ALP staining, and ARS. Our findings showed that suppressing CTSD hindered the osteogenic differentiation potential of PLL and LF cells, while overexpressing CTSD activated osteogenic differentiation. These findings identify CTSD as a potential therapeutic target for treating spinal stenosis associated with spinal ligament abnormalities.


Asunto(s)
Ligamento Amarillo , Osificación del Ligamento Longitudinal Posterior , Estenosis Espinal , Regulación hacia Arriba , Humanos , Masculino , Diferenciación Celular/genética , Ligamento Amarillo/patología , Ligamento Amarillo/metabolismo , Ligamentos Longitudinales/patología , Ligamentos Longitudinales/metabolismo , Osificación del Ligamento Longitudinal Posterior/genética , Osificación del Ligamento Longitudinal Posterior/patología , Osificación del Ligamento Longitudinal Posterior/metabolismo , Osteogénesis/genética , Estenosis Espinal/patología , Estenosis Espinal/genética , Estenosis Espinal/metabolismo , Regulación hacia Arriba/genética
10.
Zhonghua Wai Ke Za Zhi ; 62(8): 793-797, 2024 Aug 01.
Artículo en Chino | MEDLINE | ID: mdl-38937131

RESUMEN

Thoracic ossification of the ligamentum flavum (TOLF) is a pathological heterotopic ossification disease in which the fibrous tissue of the ligamentum flavum of the thoracic spine converts into bony tissue, often leading to thoracic spinal stenosis and compression of the thoracic spinal cord nerve. When TOLF patients present with symptoms of spinal cord nerve compression, surgical treatment is usually required, and traditional open surgery is more invasive and carries a higher risk of spinal cord nerve injury. In recent years, domestic and foreign researchers have tried to apply spinal endoscopic techniques such as microendoscopy, percutaneous foraminoscopy, and unilateral biportal endoscopy for the treatment of TOLF, which can maximize the preservation of normal bone while achieving adequate decompression of the spinal cord nerve, with less damage to spinal stability, and have the advantages of less surgical trauma, less bleeding, and faster postoperative recovery. Due to the special anatomical structure of the thoracic vertebra, spinal endoscopic techniques should focus on safety and it is recommended that they are performed in experienced centers, and surgical indications should be strictly controlled.


Asunto(s)
Endoscopía , Ligamento Amarillo , Osificación Heterotópica , Vértebras Torácicas , Humanos , Ligamento Amarillo/cirugía , Osificación Heterotópica/cirugía , Vértebras Torácicas/cirugía , Endoscopía/métodos
11.
Pain Physician ; 27(4): 229-234, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38805529

RESUMEN

BACKGROUND: Transforaminal epidural steroid injection (TFESI) is commonly used for radicular pain, but can lead to an unintentional injection into the retrodural Space of Okada (RSO), an extradural space located dorsal to the ligamentum flavum, instead of the epidural space. OBJECTIVES: To determine the prevalence and describe the fluoroscopic imaging features of an unintentional injection into the RSO during a TFESI and to review the history of injections into the RSO. STUDY DESIGN: Observational study and original research. SETTING: This work was conducted at Jeju National University School of Medicine, Jeju, Republic of Korea. METHODS: A total of 5,429 lumbar TFESIs performed from the September 1, 2018 through October 31, 2021 were analyzed for unintentional RSO injections using fluoroscopic-guided contrast medium patterns. RESULTS: The rate of unintentional injection into the RSO was 0.20% (11 incidents). Contrast medium patterns in the RSO had a sigmoid or ovoid shape confined to the affected facet joint, or a butterfly-shaped pattern extending into the contralateral facet joint, but rarely extending beyond the upper or lower level. LIMITATION: The rarity of unintentional injection into the RSO prevented a randomized controlled study design. CONCLUSIONS: Careful fluoroscopic examination of contrast medium patterns during lumbar TFESI is crucial to identify needle placement in the RSO. If detected, the procedure can be corrected by slightly advancing the needle into the foramen.


Asunto(s)
Esteroides , Humanos , Inyecciones Epidurales/métodos , Inyecciones Epidurales/efectos adversos , Fluoroscopía , Esteroides/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Adulto , Ligamento Amarillo , Anciano , República de Corea , Vértebras Lumbares
12.
Cell Cycle ; 23(5): 555-572, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38695374

RESUMEN

The study investigates molecular changes in the lumbosacral (L/S) spine's yellow ligamentum flavum during degenerative stenosis, focusing on the role of transforming growth factor beta 1-3 (TGF-ß-1-3). Sixty patients with degenerative stenosis and sixty control participants underwent molecular analysis using real-time quantitative reverse transcription reaction technique (RTqPCR), enzyme-linked immunosorbent assay (ELISA), Western blot, and immunohistochemical analysis (IHC). At the mRNA level, study samples showed reduced expression of TGF-ß-1 and TGF-ß-3, while TGF-ß-2 increased by only 4%. Conversely, at the protein level, the study group exhibited significantly higher concentrations of TGF-ß-1, TGF-ß-2, and TGF-ß-3 compared to controls. On the other hand, at the protein level, a statistically significant higher concentration of TGF-ß-1 was observed (2139.33 pg/mL ± 2593.72 pg/mL vs. 252.45 pg/mL ± 83.89 pg/mL; p < 0.0001), TGF-ß-2 (3104.34 pg/mL ± 1192.74 pg/mL vs. 258.86 pg/mL ± 82.98 pg/mL; p < 0.0001), TGF-ß-3 (512.75 pg/mL ± 107.36 pg/mL vs. 55.06 pg/mL ± 9.83 pg/mL, p < 0.0001) in yellow ligaments obtained from patients of the study group compared to control samples. The study did not establish a significant correlation between TGF-ß-1-3 concentrations and pain severity. The findings suggest that molecular therapy aimed at restoring the normal expression pattern of TGF-ß-1-3 could be a promising strategy for treating degenerative stenosis of the L/S spine. The study underscores the potential therapeutic significance of addressing molecular changes at the TGF-ß isoforms level for better understanding and managing degenerative spinal conditions.


Asunto(s)
Isoformas de Proteínas , Estenosis Espinal , Humanos , Femenino , Masculino , Persona de Mediana Edad , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/genética , Estenosis Espinal/metabolismo , Estenosis Espinal/patología , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/genética , Anciano , Factor de Crecimiento Transformador beta2/metabolismo , Factor de Crecimiento Transformador beta2/genética , Ligamento Amarillo/metabolismo , Ligamento Amarillo/patología , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta/genética , ARN Mensajero/metabolismo , ARN Mensajero/genética , Factor de Crecimiento Transformador beta3/metabolismo , Factor de Crecimiento Transformador beta3/genética , Adulto , Vértebras Lumbares/metabolismo , Vértebras Lumbares/patología , Región Lumbosacra/patología , Estudios de Casos y Controles
13.
J Orthop Surg Res ; 19(1): 244, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38622696

RESUMEN

BACKGROUND: Ossification of ligamentum flavum (OLF) is a prevalent degenerative spinal disease, typically causing severe neurological dysfunction. Kruppel-like factor 5 (KLF5) plays an essential role in the regulation of skeletal development. However, the mechanism KLF5 plays in OLF remains unclear, necessitating further investigative studies. METHODS: qRT-PCR, immunofluorescent staining and western blot were used to measure the expression of KLF5. Alkaline Phosphatase (ALP) staining, Alizarin red staining (ARS), and the expression of Runt-related transcription factor 2 (RUNX2), osteopontin (OPN), and osteocalcin (OCN) were used to evaluate the osteogenic differentiation. Luciferase activity assay and ChIP-PCR were performed to investigate the molecular mechanisms. RESULTS: KLF5 was significantly upregulated in OLF fibroblasts in contrast to normal ligamentum flavum (LF) fibroblasts. Silencing KLF5 diminished osteogenic markers and mineralized nodules, while its overexpression had the opposite effect, confirming KLF5's role in promoting ossification. Moreover, KLF5 promotes the ossification of LF by activating the transcription of Connexin 43 (CX43), and overexpressing CX43 could reverse the suppressive impact of KLF5 knockdown on OLF fibroblasts' osteogenesis. CONCLUSION: KLF5 promotes the OLF by transcriptionally activating CX43. This finding contributes significantly to our understanding of OLF and may provide new therapeutic targets.


Asunto(s)
Ligamento Amarillo , Osificación Heterotópica , Humanos , Células Cultivadas , Conexina 43/genética , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Osificación Heterotópica/genética , Osificación Heterotópica/metabolismo , Osteogénesis/genética , Factores de Transcripción/metabolismo
14.
Acta Neurochir (Wien) ; 166(1): 185, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38639798

RESUMEN

Calcium pyrophosphate deposition disease (CPPD), known as pseudogout, is characterized by the accumulation of calcium pyrophosphate crystals in musculoskeletal structures, primarily joints. While CPPD commonly affects various joints, involvement in the cervical spine leading to myelopathy is rare. Surgical intervention becomes necessary when conservative measures fail, but reports on full endoscopic surgeries are extremely rare. We present two successful cases where full endoscopic systems were used for CPPD removal in the cervical spine. The surgical technique involved a full endoscopic approach, adapting the previously reported technique for unilateral laminotomy bilateral decompression. Full-endoscopic removal of cervical CPPD inducing myelopathy were successfully removed with good clinical and radiologic outcomes. The scarcity of endoscopic cases for cervical ligamentum flavum CPPD is attributed to the condition's rarity. However, our successful cases advocate for endoscopic surgery as a potential primary treatment option for CPPD-induced cervical myelopathy, especially in elderly patients or those with previous cervical operation histories. This experience encourages the consideration of endoscopic surgery for managing cervical ligamentum flavum CPPD as a viable alternative.


Asunto(s)
Condrocalcinosis , Ligamento Amarillo , Enfermedades de la Médula Espinal , Humanos , Anciano , Condrocalcinosis/diagnóstico por imagen , Condrocalcinosis/cirugía , Ligamento Amarillo/diagnóstico por imagen , Ligamento Amarillo/cirugía , Enfermedades de la Médula Espinal/diagnóstico por imagen , Enfermedades de la Médula Espinal/cirugía , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/cirugía , Cuello
15.
J Neurosurg Spine ; 41(1): 33-45, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38608299

RESUMEN

OBJECTIVE: Spinal stenosis is one of the most common spinal disorders in the elderly. Hypertrophy of the ligamentum flavum (HLF) can contribute to spinal stenosis. The current literature suggests that various biomarkers may play important roles in the pathogenesis of HLF. However, the connection between these biomarkers and the development of HLF is still not well understood. This systematic review aims to explore the current literature on biomarkers related to the development of HLF. METHODS: A literature search was conducted using PubMed, Embase, Web of Science, and Cochrane Library. The search strategy looked for the titles, abstracts, and keywords of studies that contained a combination of the following phrases: "ligamentum flavum OR yellow ligament," "biomarkers," and "hypertrophy." Recorded data included study design, demographic characteristics (number of patients of each gender and mean age), study period, country where the study was conducted, biomarkers, and diagnostic modalities used. Risk of bias was assessed using the Newcastle-Ottawa Scale for case-control studies. RESULTS: The authors identified 39 studies. After screening, 26 full-text original articles assessing one or more biomarkers related to HLF were included. The included studies were conducted over a 22-year period. The most popular biomarkers studied, in order of frequency reported, were collagen types I and III (n = 10), transforming growth factor ß (TGF-ß) (n = 8), and interleukin (IL)-6 (n = 6). The authors found that mechanical stretching forces, tissue inhibitor of metalloproteinases 2 (TIMP-2) induction, and TGF-ß were associated with increased amounts of collagen I and III. IL-6 expression was increased by microRNA-21, as well as by leptin, through the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. CONCLUSIONS: Biomarkers such as TGF-ß, IL-6, and collagen I and III have been consistently correlated with the development of HLF. However, the pathogenesis of HLF remains unclear due to the heterogeneity of the studies, patient populations, and research at the molecular level. Further studies are necessary to better characterize the pathogenesis of HLF and provide a more comprehensive understanding of how these biomarkers may aid in the diagnosis and treatment of HLF.


Asunto(s)
Biomarcadores , Hipertrofia , Ligamento Amarillo , Humanos , Ligamento Amarillo/patología , Ligamento Amarillo/metabolismo , Biomarcadores/metabolismo , Estenosis Espinal/metabolismo
16.
J Orthop Res ; 42(9): 2061-2071, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38546147

RESUMEN

The study aimed to examine matrix metalloproteinase-2 (MMP-2) expression in a rat ligamentum flavum (LF) hypertrophy model in vivo, and the effect of elastin-derived peptides (EDPs) on MMP-2 and tissue inhibitors of metalloproteinases (TIMPs) in rat LF cells in vitro. Surgical destabilization was performed at the rat spinal L3/4 level to induce increased mechanical stress. Rats were killed at 6- and 12-weeks postsurgery for histological staining, immunohistochemical staining, RT-qPCR and western blot. 100 µg/mL EDPs were applied to isolated normal rat LF cells, with or without pretreatment of elastin receptor complex (ERC) inhibitors, to assess the expression of MMP-2, TIMP-1, and TIMP-2. Spinal destabilization led to LF hypertrophy, observed through increased LF thickness and area, along with histological changes of chondrometaplasia and elastic fiber degradation. LF was also stained positively for Col I and Col II, where elastic fiber has broken down. MMP-2 expression was notably elevated in the hypertrophied LF, accompanied by increased TIMP-2 and TIMP-3 levels. EDPs were found to suppress MMP-2 expression and reduce TIMP-1 and TIMP-2 levels in rat LF cells. Interestingly, exposure to EDPs led to a significant rise in MMP-2/TIMP-1 and MMP-2/TIMP-2 ratios, dependent on the ERC. Collectively, the study suggests that increased MMP-2 activity contributes to elastic fiber degradation in hypertrophied LF, generating EDPs that further enhance the MMP-2/TIMPs ratio in LF cells in an ERC-dependent manner. Further research is essential to delve into the mechanisms of EDPs in LF hypertrophy.


Asunto(s)
Elastina , Hipertrofia , Ligamento Amarillo , Metaloproteinasa 2 de la Matriz , Ratas Sprague-Dawley , Inhibidor Tisular de Metaloproteinasa-2 , Animales , Metaloproteinasa 2 de la Matriz/metabolismo , Ligamento Amarillo/metabolismo , Ligamento Amarillo/patología , Elastina/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/metabolismo , Masculino , Ratas , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Péptidos/farmacología , Péptidos/metabolismo
17.
Tohoku J Exp Med ; 263(1): 43-50, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38355112

RESUMEN

Thickening of the ligamentum flavum is the main factor in the development of lumbar spinal canal stenosis (LSCS). Although previous studies have reported factors related to ligamentum flavum thickening, its etiology has not been clarified. Furthermore, it is often difficult to set proper controls to investigate the pathologies of thickening due to differences in patient characteristics, such as age, sex, obesity, and comorbidities. This study aimed to elucidate the pathologies of ligamentum flavum thickening by comparing the dural and dorsal sides of the thickened ligamentum flavum in patients with LSCS. Ligamentum flavum samples were collected from 19 patients with LSCS. The samples were divided into the dural and dorsal sides. The dural side was used as a control to assess the pathologies occurring on the dorsal side. Elastic Masson staining was used to assess the elastic fibres. Gene expression levels were comprehensively assessed using quantitative reverse transcription polymerase chain reaction and DNA microarray analyses. Gene ontology analysis was used to identify biological processes associated with differentially expressed genes. The elastic fibres were significantly decreased on the dorsal side of the thickened ligamentum flavum. Genes related to fibrosis, inflammation, tissue repair, remodeling, and chondrometaplasia, such as COL1A2, COL3A1, COL5A1, TGFB1, VEGFA, TNFA, MMP2, COL10A1, and ADAMTS4, were highly expressed on the dorsal side of the thickened ligamentum flavum. The biological processes occurring on the dorsal side of the thickened ligamentum flavum were extracellular matrix organization, cell adhesion, extracellular matrix disassembly, and proteolysis.These are considered important pathologies of ligamentum flavum thickening.


Asunto(s)
Duramadre , Perfilación de la Expresión Génica , Ligamento Amarillo , Vértebras Lumbares , Estenosis Espinal , Humanos , Ligamento Amarillo/patología , Ligamento Amarillo/metabolismo , Estenosis Espinal/genética , Estenosis Espinal/patología , Masculino , Femenino , Vértebras Lumbares/patología , Anciano , Duramadre/patología , Duramadre/metabolismo , Regulación de la Expresión Génica , Persona de Mediana Edad , Ontología de Genes , Análisis de Secuencia por Matrices de Oligonucleótidos
18.
Neurol Med Chir (Tokyo) ; 64(5): 184-191, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38403719

RESUMEN

Ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF) are related diseases associated with the ossification of spinal ligaments that can occasionally lead to thoracic myelopathy. We retrospectively analyzed the clinical data of 34 consecutive patients who underwent thoracic spinal surgeries for OPLL and/or OLF at our hospital between July 2010 and June 2022, and statistically compared data between patients with thoracic OPLL (TOPLL; n = 12) and those with thoracic OLF (TOLF; n = 22). The mean age of the TOPLL group was significantly lower than that of the TOLF group (53.7 vs. 68.4 years). The TOPLL group exhibited a greater female predominance than the TOLF group (58.3% vs. 18.2%). The median body mass index of the TOPLL group was significantly higher than that of the TOLF group (33.0 vs. 26.0 kg/m2). Patients with TOPLL significantly required instrumented fusion and repetitive surgical intervention more than those with TOLF (83.3% vs. 9.1%; 50.0% vs. 0.0%). Although neurological deterioration just after the intervention was more common in patients with TOPLL (41.7% vs. 4.6%), no difference was observed in thoracic Japanese Orthopaedic Association score and recovery rate in the chronic phase between TOPLL and TOLF. The TOPLL group had a younger onset, female dominance, and a greater degree of obesity when compared with the TOLF group. The surgery for TOPLL is challenging, considering that it requires long-range decompression and fusion, subsequent operations, careful management, and long-term follow-up, when compared to TOLF, which necessitates only simple decompression.


Asunto(s)
Ligamento Amarillo , Osificación del Ligamento Longitudinal Posterior , Osificación Heterotópica , Compresión de la Médula Espinal , Vértebras Torácicas , Humanos , Femenino , Osificación del Ligamento Longitudinal Posterior/cirugía , Osificación del Ligamento Longitudinal Posterior/complicaciones , Masculino , Persona de Mediana Edad , Ligamento Amarillo/cirugía , Ligamento Amarillo/patología , Anciano , Estudios Retrospectivos , Vértebras Torácicas/cirugía , Compresión de la Médula Espinal/cirugía , Compresión de la Médula Espinal/etiología , Osificación Heterotópica/cirugía , Adulto , Fusión Vertebral , Descompresión Quirúrgica
19.
Sci Rep ; 14(1): 4342, 2024 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-38383583

RESUMEN

Surgical intervention is typically recommended for thoracic ossification of the ligamentum flavum (TOLF). This study aimed to evaluate the efficacy and safety of a novel non-coaxial one-hole split endoscope (OSE) technique for treating TOLF. We performed OSE procedure on 13 patients with TOLF from June 2022 to July 2023. The mean operative time was 117.5 ± 15.4 min. VAS scores for lower limbs decreased from 6.5 ± 0.8 preoperative to 1.6 ± 0.4 at the last follow-up (P < 0.001). ODI scores improved from 62.4 ± 5.7 preoperative to 18.6 ± 2.2 at the last follow-up (P < 0.001), and mJOA scores increased from 5.1 ± 1.6 preoperative to 8.4 ± 1.5 at the latest follow-up (P < 0.001). All patients achieved ASIA scale grade D or E at the final follow-up, except for two patients remained residual limb numbness. None of the thirteen patients suffered from severe perioperative complications. The OSE technique proves to be a safe and effective procedure for treating TOLF or even with dura mater ossification, characterized by minimal surgical trauma, relatively smooth learning curve and flexible operation.


Asunto(s)
Ligamento Amarillo , Osificación Heterotópica , Humanos , Osteogénesis , Osificación Heterotópica/cirugía , Osificación Heterotópica/complicaciones , Ligamento Amarillo/cirugía , Vértebras Torácicas/cirugía , Endoscopios , Resultado del Tratamiento , Estudios Retrospectivos
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