中央型腰椎管狭窄症患者黄韧带组织生化成分变化的研究

目的:通过测定中央型腰椎管狭窄症患者腰椎黄韧带胶原蛋白和蛋白多糖含量变化,观察组织显微结构改变,探讨黄韧带组织生化成分改变与中央型腰椎管狭窄症发病的相关性方法:收集中央型腰椎管狭窄症患者的腰椎黄韧带65块作为退变组,正常腰椎黄韧带27块作为对照组,采用微量羟脯氨酸测定法和硫酸-咔唑法分别测定两组黄韧带中羟脯氨酸及糖醛酸吸光度,并计算胶原蛋白和蛋白多糖含量;游标卡尺测量黄韧带厚度;并行HE染色和Masson染色,显微镜下观察各组组织结构改变。结果:退变组黄韧带厚度、胶原蛋白及蛋白多糖含量均高于对照组,差异有显著性(P0.05);病理学观察退变黄韧带弹性纤维排列紊乱,数量减少,胶原纤维增生。结论:退变腰椎黄韧带中胶原蛋白和蛋白多糖含量增加,黄韧带生化成分改变可能引起黄韧带厚度增加,参与中央型腰椎管狭窄症的发生。     

Hypertrophied ligamentum flavum in lumbar spinal canal stenosis. Pathogenesis and morphologic and immunohistochemical observation.

To investigate the pathogenesis of hypertrophy of the ligamentum flavum, 45 cases of lumbar canal stenosis were evaluated by computed tomography scan and pathologic and immunohistochemical studies. The ligamentum flavum along with the medial one-third of the superior facet was obtained en bloc to include the enthesis. Statistically significant differences in transverse area and thickness of the ligamentum flavum were evident compared to the control group (P < 0.01). Pathogenesis of the hypertrophied ligamentum flavum was classified into three major groups: 1) fibrocartilage change due to proliferation of type II collagen, 2) ossification, and 3) calcium crystal deposition. It is stressed that marked proliferation of Type II collagen from the enthesis to the ligament side was revealed in the capsular portion of the hypertrophied ligament.     

Parathyroid hormone [PTH(1-34)] and parathyroid hormone-related protein [PTHrP(1-34)] promote reversion of hypertrophic chondrocytes to a prehypertrophic proliferating phenotype and prevent terminal differentiation of osteoblast-like cells.

The effects of parathyroid hormone/parathyroid hormone-related protein (PTH/PTHrP) on late events in chondrocyte differentiation were investigated by a dual in vitro model where conditions of suspension versus adhesion culturing are permissive either for apoptosis or for the further differentiation of hypertrophic chondrocytes to osteoblast- like cells. Chick embryo hypertrophic chondrocytes maintained in suspension synthesized type II and type X collagen and organized their extracellular matrix, forming a tissue highly reminiscent of true cartilage, which eventually mineralized. The formation of mineralized cartilage was associated with the expression of alkaline phosphatase (ALP), arrest of cell growth, and apoptosis, as observed in growth plates in vivo. In this system, PTH/PTHrP was found to repress type X collagen synthesis, ALP expression, and cartilage matrix mineralization. Cell proliferation was resumed, whereas apoptosis was blocked. Hypertrophic chondrocytes cultured in adherent conditions in the presence of retinoic acid underwent further differentiation to osteoblast-like cells (i.e., they resumed cell proliferation, switched to type I collagen synthesis, and produced a mineralizing bone-like matrix). In this system, PTH addition to culture completely inhibited the expression of ALP and matrix mineralization, whereas cell proliferation and expression of type I collagen were not affected. These data indicate that PTH/PTHrP inhibit both the mineralization of a cartilage-like matrix and apoptosis (mimicked in the suspension culture) and the production of a mineralizing bone-like matrix, characterizing further differentiation of hypertrophic chondrocytes to osteoblasts like cells (mimicked in adhesion culture). Treatment of chondrocyte cultures with PTH/PTHrP reverts cultured cells in states of differentiation earlier than hypertrophic chondrocytes (suspension), or earlier than mineralizing osteoblast-like cells (adhesion). However, withdrawal of hormonal stimulation redirects cells toward their distinct, microenvironment-dependent, terminal differentiation and fate.     

Mechanical stretching force promotes collagen synthesis by cultured cells from human ligamentum flavum via transforming growth factor-beta1.

Although mechanical stress as a result of spinal instability is known to cause hypertrophy of the ligamentum flavum resulting in degenerative spinal canal stenosis, the mechanism of the ligament hypertrophy is not well understood. In the present study, we investigated the effect of mechanical stretching force on collagen synthesis and transforming growth factor-beta1 (TGF-beta1) production using ligament cells isolated from human ligamentum flavum in vitro. Ligamentum flavum cells (LFCs) were isolated from human ligamentum flavum obtained from patients who underwent lumbar spine surgery. The LFCs were subjected to a mechanical stretching force using a commercially available stretching device that physically deformed the cells. Collagen synthesis and TGF-beta1 production levels in the LFCs were then examined. Notable increases were observed in the gene expressions of collagen types I, III, and V in LFCs subjected to mechanical stretching force. The increase in collagen gene expression of LFCs was inhibited in the presence of anti-TGF-beta1 antibodies. Production of TGF-beta1 by the LFCs also increased significantly by the mechanical stretching force. Exogenous application of TGF-beta1 was confirmed to increase collagen synthesis of the LFCs. This data indicated that mechanical stretching force can promote TGF-beta1 production by LFCs, resulting in hypertrophy of the ligament.     

退行性变黄韧带细胞的体外培养及初步鉴定

目的：探讨黄韧带退变的发生机理。方法：采用组织块培养法，体外培养正常黄韧带和退变性黄韧带细胞．并进行细胞化学、免疫细胞化学等方面研究。结果：黄韧带细胞可以在体外增殖和传代，退变性黄韧带细胞呈现出某些成骨细胞表型特征，而正常黄韧带细胞主要为成纤维细胞表型。结论：退变黄韧带中存在大量具备某些成骨细胞表型特征的细胞，其中包括软骨细胞，它们可能被骨形成蛋白等骨生长因子所调控。     

Rare ligamentum flavum cyst causing incapacitating lumbar spinal stenosis: Experience with 3 Chinese patients

Three Chinese patients suffered from severe lumbar spinal stenosis with debilitating symptoms due to a rare condition of ligamentum flavum cysts in the midline of the lumbar spine. This disease is distinct from synovial cyst of the facet joints or ganglion cysts, both intraoperatively and histopathologically. Magnetic Resonance imaging features of the ligamentum flavum cyst are also demonstrated. We share our surgical experiences of identification of the ligamentum flavum cysts, decompression and excision for two of the patients with demonstrably good recovery. This disease should be considered in the differential diagnosis of an extradural instraspinal mass in patients with lumbar spinal stenosis.     

Lumbar canal stenosis caused by amyloidosis of the yellow ligament]

Symptomatic lumbar canal stenosis without bony stenosis has previously been described. We describe the pathological modifications of ligamentum flavum among such operated patients. Ten patients were prospectively included in this study. Their mean age was 74, ranges: from 52-90. Clinical manifestation was a radicular claudication (sciatic or crural). Neuroradiology confirmed in all cases the ligamentum flavum thickness as the main cause of the symptomatology. This feature was also confirmed operatively and complete resection of the ligamentum flavum was performed. Resolution of the radicular pain was obtained in all cases at last follow-up. Pathological examination of the ligamentum flavum displayed characteristic features of degenerative modifications and elastic fibers fragmentation caused by numerous amorphous deposits. The deposits were studied using red Congo staining, polarized light and immunostaining methods. Such technique showed evidence of amyloid origin of the deposits. Immunodetection was positive for the P component in the amyloid deposits and for beta-2-microglobulin in one case (chronic renal failure and hemodialysis). The deposits did not express antitransthyretin antibodies. In parallel, control ligamentum flavum were obtained from 10 operated patients affected by bony lumbar stenosis. Moderate degenerative features were observed but small amounts of amyloid deposits were found in only 3 of those cases, without thickening of the ligamentous structure. This study correlates the presence of thickened ligamentum flavum caused by amyloid deposition, with symptomatic non-osseous lumbar canal stenosis. Association with degenerative modifications of the spine in the studied cases is suggestive of a microtraumatic origin.     

Two-level ligamentum flavum hematoma in the lumbar spine. Case report

Ligamentum flavum hematoma is a rare cause of spinal root or cord compression that usually occurs at a single level. No case of multiple-level ligamentum flavum hematoma has previously been reported. We report an extremely rare case of double, contiguous ligamentum flavum hematomas in the lumbar spine. A 71-year-old man with hypertension and degenerative lumbar scoliosis presented with pain and muscle weakness in the left lower extremity after physical exertion. Magnetic resonance imaging of the lumbar spine showed severe spinal stenosis caused by two-level ligamentum flavum hematoma (L3-L4 and L4-L5). Both hematomas were completely removed and the diagnosis was histologically confirmed. Symptoms completely resolved after surgery. Despite being extremely rare, ligamentum flavum hematoma with involvement of multiple levels may be observed.     

Quantitative analysis of transforming growth factor-beta 1 in ligamentum flavum of lumbar spinal stenosis and disc herniation.

STUDY DESIGN: The concentration of transforming growth factor-beta 1 (TGF-beta1) was examined in the ligamentum flavum of lumbar spinal stenosis and disc herniation. OBJECTIVE: To investigate the role of TGF-beta1 on hypertrophy of the ligamentum flavum in lumbar spinal stenosis compared with that of lumbar disc herniation. SUMMARY OF BACKGROUND DATA: The hypertrophy of the ligamentum flavum is known to be related to degenerative changes that are secondary to the aging process or mechanical instability. However, there has been no study to investigate the effect of biochemical factors, such as growth factors, associated with hypertrophy of the ligamentum flavum. METHODS: The concentrations of TGF-beta1 were analyzed in the surgically obtained ligamentum flavum specimens from lumbar spinal stenosis (n = 10; mean age 62.8 years) and disc herniation (n = 10; mean age 35.6 years) by enzyme-linked immunosorbent assay. The localization of TGF-beta1 within the ligamentum flavum was determined using immunohistochemical study. The thickness of the ligamentum flavum was measured with axial T1-weighted magnetic resonance imaging. The biochemical and radiologic results were compared for these two conditions. RESULTS: The mean concentration of TGF-beta1 was 123.78 pg/100 microg protein (range 11-374 pg/100 microg protein) in lumbar spinal stenosis and 38.56 pg/100 microg protein (range 0-155 pg/100 microg protein) in lumbar disc herniation; the difference between lumbar spinal stenosis and disc herniation was statistically significant (P = 0.029). The mean thickness of the ligamentum flavum was 4.44 mm (range 3.4-5.4 mm) in lumbar spinal stenosis and 2.44 mm (range 1.8-4.0 mm) in lumbar disc herniation; the difference between lumbar spinal stenosis and disc herniation was statistically significant (P = 0.001). On immunohistochemical study TGF-beta1 was positively stained on the fibroblasts within the ligamentum flavum specimens. CONCLUSION: The current results suggest that higher expression of TGF-beta1 by fibroblasts might be related to the development of hypertrophy of the ligamentum flavum in lumbar spinal stenosis.     

Cryomicrotomy of the lumbar spine

To investigate the pathogenesis of lumbar canal stenosis, a morphologic study was carried out by cryomicrotomy using 10 fresh lumbar spine specimens from the 3rd lumbar vertebra to the 1st sacral vertebra. The cryomicrotomy findings confirmed that anatomical relations were clearly demonstrated between dura, nerve root, osseous structure, disc and ligamentum flavum in frontal, sagittal, and transverse section. Furthermore, in sagittal section specimens, thickness of ligamentum flavum varies from extension to flexion. These conditions play a dynamic factor in the pathogenesis of spinal canal stenosis.     

The narrowing of the lumbar spinal canal during loaded MRI: the effects of the disc and ligamentum flavum

Load and activity changes of the spine typically cause symptoms of nerve root compression in subjects with spinal stenosis. Protrusion of the intervertebral disc has been regarded as the main cause of the compression. The objective was to determine the changes in the size of the lumbar spinal canal and especially those caused by the ligamentum flavum and the disc during loaded MRI. For this purpose an interventional clinical study on consecutive patients was made. The lumbar spines in 24 supine patients were examined with MRI: first without any external load and then with an axial load corresponding to half the body weight. The effect of the load was determined through the cross-sectional areas of the spinal canal and the ligamentum flavum, the thickness of ligamentum flavum, the posterior bulge of the disc and the intervertebral angle. External load decreased the size of the spinal canal. Bulging of the ligamentum flavum contributed to between 50 and 85% of the spinal canal narrowing. It was concluded that the ligamentum flavum, not the disc had a dominating role for the load induced narrowing of the lumbar spinal canal, a finding that can improve the understanding of the patho-physiology in spinal stenosis.     

单纯黄韧带肥厚致腰椎管狭窄及根性疼痛

目的：探讨单纯黄韧带肥厚致腰椎管狭窄及根性疼痛的临床表现。方法：回顾1997年－2001年腰腿痛的143例病例，其中例为单纯黄韧带肥厚所致，年龄65－78岁，均手术行单纯黄韧带切除，达到椎管减压，结果：此类患者均为老年，病程长，可有急性加重过程，疼痛可与椎间盘突出相似，但以下腰疼痛明显，而下肢放射痛相对较轻，临床及影像学均易误诊。结论：退变引起的黄韧带肥厚可造成椎管狭窄及根性疼痛，手术切除后症状明显缓解。长期随访，患者腰痛消失，可以长时间行走，明显提高了生活质量。     

胸椎黄韧带骨化与腰椎黄韧带退变的病理及基本代谢元素的比较研究

目的：探讨胸椎黄韧带骨化的病因。方法：对１４例胸椎黄韧带骨化（包括５例氟骨症）及１４例腰椎管狭窄症患者手术切除的黄韧带标本作病理研究；对患者血清及黄韧带采用雾化原子吸收法等方法测定钙、磷、镁、锌、铜、锰、钼、氟含量，取急性外伤性截瘫患者为对照。结果：（１）骨化黄韧带初期的病理改变与黄韧带退变性质类似；（２）除氟元素外，７种基本代谢元素在骨化与退变患者血清及黄韧带中含量均呈基本一致的变化规律；（３）非氟骨症骨化患者黄韧带中氟含量显著增高（Ｐ＜０．０１）。结论：本文证实胸椎黄韧带骨化发生于黄韧带退变的基础之上，但退变不直接导致骨化，元素氟是诱导退变黄韧带进一步骨化的重要诱因。     

胸椎黄韧带骨化的病理组织学研究

目的：探讨黄韧带骨化的病理变化特点和发生机理。方法：利用组织病理学、组织化学和影像学检查对比研究正常黄韧带和12例骨化黄韧带的病理形态学特点。结果：组织学上可见病变早期出现胶原纤维肿胀、融合,进一步发生软骨化生,最终出现钙化和骨化。在肿胀融合的胶原纤维和软同有化生处可见阿新蓝（pH2.5）阳性的粘液性物质,根据病理学检查特点,结合影像学表现可将黄韧带骨化分为结节型（增生性）、周围型和弥漫型3种类型。结论：韧带的退行性改变是黄韧带骨化的基本原因;胶原纤维的肿胀融合及其粘液样变性是黄韧带骨化的起始病变;黄韧带骨化的大体类型代表着同一病变发展的不同阶段。     

Hypertrophy of ligamentum flavum in lumbar spinal stenosis associated with increased proteinase inhibitor concentration

BACKGROUND: It is well known that age-related fibrosis, or decreases in the elastin-to-collagen ratio of the ligamentum flavum, along with hypertrophy of the ligamentum flavum, are associated with lumbar spinal stenosis. However, the molecular mechanism by which this fibrosis and hypertrophy develop is unknown. Tissue inhibitors of matrix metalloproteinase (TIMPs) are proteinase inhibitors that suppress extracellular matrix degradation. Elevated TIMP-1 and TIMP-2 expression has been implicated in various fibrotic diseases of the liver, kidney, lung, and heart. These TIMPs can also induce cellular proliferation and inhibit apoptosis in a wide range of cell types. These findings led us to postulate that TIMP-1 and TIMP-2 might also be associated with hypertrophy and fibrosis of the ligamentum flavum in lumbar spinal stenosis. METHODS: We quantified and localized TIMP expression in ligamentum flavum tissues that had been obtained during surgery from thirty patients with spinal stenosis and from thirty gender-matched control patients with disc herniation. The thickness of the ligamentum flavum at the level of the facet joint was measured on axial T1-weighted magnetic resonance images. In addition, we examined ligamentum flavum tissues for the expression of markers of cellular proliferation and apoptosis. RESULTS: The ligamentum flavum was significantly thicker in the patients with spinal stenosis (mean, 5.68 mm) than in the patients with disc herniation (mean, 2.70 mm) (p < 0.001). The concentration of TIMP-2 in the ligamentum flavum was significantly higher in the patients with spinal stenosis (mean, 12.62 ng/mL) than in those with disc herniation (mean, 8.85 ng/mL) (p = 0.028). TIMP-1 and TIMP-2 were detected in the cytoplasm of ligamentum flavum fibroblasts. TIMP-1 and TIMP-2 concentrations were associated with hypertrophy of the ligamentum flavum (p = 0.015 and p = 0.003, respectively). None of the samples from the patients with stenosis had evidence of proliferation of ligamentum flavum fibroblasts. The expression of markers for apoptosis was significantly higher in the patients with spinal stenosis (58.8%) than in those with disc herniation (26.6%) (p < 0.001). CONCLUSIONS: Increased TIMP expression has been implicated in fibrosis and hypertrophy of the extracellular matrix of several organs. Our results suggest that increased expression of TIMP-2 in ligamentum flavum fibroblasts is associated with fibrosis and hypertrophy of the ligamentum flavum in patients with spinal stenosis.     

Ligamentum flavum hematoma in the rigid thoracic spinal segments: case report

Ligamentum flavum hematoma, a rare cause of spinal nerve root and canal compression, typically occurs in the mobile lumbar spine segments. A thoracic ligamentum flavum hematoma is extremely rare--only one such case of a thoracolumbar (T11-12) lesion has been reported. The thoracolumbar region with its floating ribs, however, is structurally and biomechanically similar to the lumbar spine and its mobility is greater than the higher thoracic levels. To the best of their knowledge, the authors report the first case of a ligamentum flavum hematoma in the region of the rigid thoracic spinal segments with the contiguous rib cage. A symptomatic T9-10 ligamentum flavum hematoma is described in the case of a 66-year-old woman with compensatory thoracic lordosis secondary to the lumbar degenerative kyphosis. The hematoma was removed and the diagnosis was histologically confirmed. The authors speculate that thoracic lordosis might have contributed to the development of the hematoma because the ligamentum flavum and the facet joint were subjected to greater axial stress than in individuals with normal spinal alignment.     

全椎板截骨再植椎管扩大成形术治疗胸椎黄韧带骨化症

目的总结胸椎黄韧带骨化症导致胸椎椎管狭窄的影像学特点，探讨改良椎管减压术的临床疗效。方法胸椎黄韧带骨化症31例，男18例，女13例；年龄26—73岁，平均45．7岁。术前均行MR、CT检查以明确诊断。合并颈椎管狭窄3例、腰椎管狭窄5例，颈胸腰椎管狭窄同时存在者2例；合并胸椎后纵韧带骨化和椎间盘突出症9例。单节段3例，双节段12例，三节段11例，四节段以上5例。局限型6例，连续型17例，跳跃型8例。共94个病变节段，其中上胸段(T1～T4)23个节段、中胸段(T5～T8)19个节段、下胸段(T9-T12)52个节段。手术采用全椎板截骨原位再植椎管扩大成形术。对9例合并胸椎后纵韧带骨化和椎间盘突出者，在后方减压的同时，行切除椎管前方突出椎间盘的环脊髓减压及后路钉棒系统内固定。术后疗效评价参照Epstein标准。结果24例患者随访6—63个月，平均15个月。术后疗效优14例、良7例、可3例，优良率87．5％。1例因术后停用脱水药物过早引起下肢瘫痪症状加重；2例出现下肢静脉血栓；2例硬脊膜撕裂。结论MR结合CT检查是诊断胸椎黄韧带骨化症最有效的手段，全椎板截骨再植椎管扩大成形术安全可靠，疗效满意。     

Management of cervical and lumbar stenosis]

Spinal stenosis is most common in elderly patients and is defined as narrowing of the spinal canal and (or) lateral nerve root canals. The underlying processes leading to spinal stenosis are degenerative changes in facet joints and intervertebral discs and buckling of the ligamentum flavum. Spinal stenosis can occur in both the cervical and the lumbar spine. Cervical stenosis mayleat to the development of radiculopathy and (or) myelopathy. The majority of patients respond to nonoperative management. Degenerative lumbar spinal stenosis presents with back and (or) leg paints of valuing severity and duration. Nonoperative treatment associated with lumbar spinal stenosis consists of restituting and avoiding those maneuvers that reproduce pain. Surgical treatment of cervical and lumbar stenosis includes decompressive lamine ctomy, often fusion and instrumentation.     

Pseudocystic degeneration of the lumbar ligamentum flavum: a little known entity

OBJECTIVE: The objective of this work was to investigate the clinical and histologic features of patients with pseudocystic lesions of the ligamentum flavum in the lumbar region of the spinal canal and ascertain the existence of genuine ligamentum flavum pseudocysts. METHODS: Retrospective chart and histologic study of a patient cohort with lumbar radiculopathy due to a cystic intraspinal lesion and who had undergone decompressive surgery was conducted. Intraoperatively, the stenosing process had been found to be different from common etiologic entities and had been submitted for histologic examination. RESULTS: The 33 patients with symptoms and signs of lumbar radiculopathy were between 48 and 85 years of age (mean 63.5 years). Twenty (61%) of them were women. All patients showed degenerative changes of the bony structures of the spine by conventional radiography. Segmental instability due to degeneration of the lumbar spine was present in 45%. Computed tomography and/or magnetic resonance imaging showed a cystic lesion. Clinical and histologic examination confirmed their origin from within the severely degenerated ligamentum flavum. CONCLUSIONS: Radiologic, surgical, and histologic findings suggest that the pseudocystic degeneration of the ligamentum flavum represents a genuine entity that is associated with degenerative changes of the structures of the respective lumbar spine segment. These pseudocystic lesions may compress the adjacent nerve roots, provoking symptoms and signs of radiculopathy. The findings suggest that the surgical treatment not only must consist of removal of the pseudocyst but must also include a radical extirpation of the ligamentum flavum surrounding the pseudocyst to avoid recurrence of such a lesion.     

棘突截骨椎管成形术治疗腰椎黄韧带骨化症

目的 :观察棘突截骨椎管成形术治疗腰椎黄韧带骨化症的临床疗效和影像学。方法 :单侧椎板显露后行棘突基底截骨、中央椎管潜式扩大治疗 13例腰椎黄韧带骨化症患者 ,术前和术后进行腰椎功能Oswestry问卷调查和椎管直径测量。结果 :本组术后随访 2～ 4年 ,腰腿痛较术前平均改善 76 %～ 74% ,术后腰椎CT显示椎管中矢径平均增加2 1.6 % (P <0 .0 5 ) ,椎管横径平均增加 18.5 % (P <0 .0 5 )。结论 :棘突截骨椎管成形术治疗腰椎黄韧带骨化症 ,具有操作简单、椎管中央和侧方减压充分、对腰椎后方张力带结构影响小等优点 ,术后近期和中期临床疗效和影像学评估满意