Hypertrophy of the posterior longitudinal ligament is a prodromal condition to ossification: a cervical myelopathy case report

STUDY DESIGN: A histopathologic examination of a specimen that showed hypertrophy of the posterior longitudinal ligament of the cervical spine. OBJECTIVES: To illustrate the possibility of hypertrophy of the posterior longitudinal ligament as a prodromal condition to ossification of the posterior longitudinal ligament. SUMMARY OF BACKGROUND DATA: Despite much study, the pathology of ossification of the posterior longitudinal ligament still remains unclear. Hypertrophic change often is seen in the part of the ossified ligament; however, there have been few histopathologic reports on hypertrophy of the posterior longitudinal ligament. Some reports have suggested that hypertrophy of the posterior longitudinal ligament is a prodrome of ossification of the posterior longitudinal ligament. METHODS: A 64-year-old man was admitted to the hospital because of gait disturbance and developed oliguria. In a plain radiograph, segmental ossification of the posterior longitudinal ligament was found at C4, C5, and C6. Computed tomograph myelogram revealed a soft tissue shadow, maximum 3.8 mm in diameter, on the dorsal side of the ossification of the posterior longitudinal ligament at C5 and C6. Magnetic resonance T1-weighted image (T1WI) showed an equivalent signal with the intervertebral disc on the dorsal side of ossification of the posterior longitudinal ligament. This lesion was enhanced with Gd-DTPA and confirmed as hypertrophy of the posterior longitudinal ligament. Cervical anterior decompression and fusion were performed using Yamaura's technique. The ossified and thickened lesion was elevated and removed en bloc. Then, hematoxylin-eosin and toluidine blue staining was performed to detect metachromasia. RESULTS: Macroscopic examination of the specimen revealed that soft tissue formation was connected with the C4-C5 intervertebral space and extended downward to C6-C7. Histopatholgically, collagen fibers were proliferating in the long-axis direction on both ventral and dorsal sides. This was surrounded by extended nucleus pulposus-like chondrocyte tissue, where endplate cartilage was detected around the C4 pedicle. Roux staining was low, and partial vascular and cellular infiltration was observed, although it was not marked. CONCLUSION: The herniated nucleus pulposus involving endplate cartilage from C4-C5 was limited to the superficial layer, and proliferation of nucleus pulposus-like chondrocytes occurred in the herniated tissue, where they might undergo a change in cell phenotype. The results of the present study support the hypothesis that hypertrophy of the posterior longitudinal ligament is a prodromal condition to ossification of the posterior longitudinal ligament.     

椎间盘脱出伴后纵韧带破裂的磁共振表现

目的研究后纵韧带破裂与椎间盘脱出的磁共振表现。方法回顾性分析经临床手术和病理证实为椎间盘脱出并后纵韧带破裂的患者65例,与术前MRI结果做对比研究。结果 65例椎间盘脱出患者均经手术证实后纵韧带有不同程度的破裂,分析术前MRI,其中28例可直接显示后纵韧带低信号及其破损情况,37例间接判断后纵韧带损伤。后纵韧带断端连线为界,评估脱出椎间盘位于连线外的体积与脱出椎间盘总体积之比。结论 MRI可清楚地显示后纵韧带破损的直接或间接征象。     

An immunohistochemical evaluation of extracellular matrix components in the spinal posterior longitudinal ligament and intervertebral disc of the tiptoe walking mouse

Ossification of the posterior longitudinal ligament (OPLL) in the spine is caused by systemic and/or regional factors affecting the regulation of osteocartilaginous formation and maintenance. The aims of this study were to elucidate the relationship between the degeneration of the intervertebral discs and changes in the posterior longitudinal ligament (PLL) in the tiptoe walking (ttw) mouse, an animal model of OPLL, and to analyze the sequential changes of the cells producing extracellular matrix components using immunohistochemical methods. At 6 weeks of age, the discs degenerated and the chondrocytes in the nucleus pulposus were positive for chondroitin-6-sulfate in the ttw mice. The fibroblasts in the PLL at the disc level were positively stained with type II and XI collagens. At 14 weeks, the discs herniated into the thickened PLL, and chondrocyte-like cells appeared in the PLL at vertebral endplate level. At 18 and 22 weeks, the number of chondrocyte-like cells increased in the PLL and expressed type I collagen. A potent regional factor causing OPLL in the ttw mice appears to be the initial degeneration and subsequent herniation of the nucleus pulposus. These sequential changes in the ttw mice were accelerated by administration of etidronate. It was suggested that etidronate stimulated the cartilaginous hyperplasia in the PLL of the ttw mice. It appeared as if the PLL transformed itself into cartilaginous tissue to repair the degeneration of the intervertebral disc.     

Histological study on chemonucleolysis with special reference to the relationship between the dose of chymopapain and disc regeneration

The present study on chemonucleolysis was conducted to determine the influence of chymopapain dose level and patient age on the degree and mode of the response and regeneration of the intervertebral disc. Chymopapain at various doses was injected into the intervertebral discs of young (8-week-old) and mature (20-week-old) rabbits respectively for a histological study. In rabbits undergoing high dose injection, not only the nucleus pulposus but also the inner layer of the annulus fibrosus was digested. Regeneration hardly occurred, and only a slight amount of scar tissue appeared in many animals. At lower dose, the annulus fibrosus remained intact and the posterior inner layer of the annulus fibrosus mainly proliferated toward the anterior portion of the disc, filled the space of digested nucleus pulposus, and restored disc height. This regeneration process was not thought to be specific to the damages caused by chymopapain but rather a common response of injured intervertebral discs.     

益气逐瘀利水方治疗青少年腰椎间盘突出症的疗效观察

目的通过与成年患者的临床对照研究,观察益气逐瘀利水方对青少年腰椎间盘突出症的疗效及重吸收的影响。方法以苏州中医院骨伤科门诊的27例青少年腰椎间盘突出症患者和79例成年患者为研究对象,以益气逐瘀利水方为主要治疗手段,采用JOA评分,ODI指数,指地距以及直腿抬高度数观测进行疗效评估;通过MRI观察,对青少年腰椎间盘突出症患者突出类型与重吸收的关系进行相关析因分析。结果提高患者的JOA评分,降低ODI指数,提高直腿抬高度数,减少指地距对于青少年和成年患者的吸收率进行Mann-Whitney秩和检验,青少年吸收率与成年患者吸收率无统计学差异对于所有样本后纵韧带破裂型和后纵韧带非破裂型的吸收率进行fisher精确概率计算检验结果具有统计学意义（P=0.003）。结论益气逐瘀利水方对于青少年腰椎间盘突出症具有良好的疗效。青少年与成年患者在突出髓核的吸收机率方面无明显差异。腰椎间盘突出症患者,后纵韧带破裂型突出较易发生重吸收。     

Herniated and spondylotic intervertebral discs of the human cervical spine: histological and immunohistological findings in 500 en bloc surgical samples. Laboratory investigation

OBJECT: In this paper the authors' goal was to identify histological and immunohistochemical differences between cervical disc hemrniation and spondylosis. METHODS: A total of 500 cervical intervertebral discs were excised from 364 patients: 198 patients with disc herniation and 166 patients with spondylosis. We examined en bloc samples of endplate-ligament-disc complexes. Types of herniation and graded degrees of disc degeneration on MR images were examined histologically and immunohistochemically. RESULTS: The herniated discs showed granulation tissue, newly developed blood vessels, and massive infiltration of CD68-positive macrophages, which surrounded the herniated tissue mainly in the ruptured outer layer of the anulus fibrosus. The vascular invasion was most significant in uncontained (extruded)-type herniated discs. Chondrocytes positive for matrix metalloproteinase (MMP)-3, tumor necrosis factor (TNF)-alpha, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) were abundant in both herniated and spondylotic discs. Free nerve fibers, positive for nerve growth factor (NGF), neurofilament 68, growth-associated protein (GAP)-43, and substance P, were strongly apparent in and around the outer layer of uncontained (extruded)-type herniated discs, with enhanced expression of NGF. The authors observed that herniated discs showed more advanced degeneration in the outer layer of the anulus fibrosus around the granulation tissue than spondylotic discs. On the other hand, spondylotic discs showed more advanced degeneration in the cartilaginous endplate and inner layer of the anulus fibrosus than herniated discs. Spondylotic discs also had thicker bony endplates and expressed TNFalpha and MMP-3 more diffusely than herniated discs, especially in the inner layer of the anulus fibrosus. CONCLUSIONS: The authors' results indicate that herniated and spondylotic intervertebral discs undergo different degenerative processes. It is likely that TNFa, MMP-3, bFGF, and VEGF expression is upregulated via the herniated mass in the herniated intervertebral discs, but by nutritional impairment in the spondylotic discs. Macrophage accumulation around newly formed blood vessels in the herniated disc tissues seemed to be regulated by MMP-3 and TNFalpha expression, and both herniated and spondylotic discs exhibited marked neoangiogenesis associated with increased bFGF and VEGF expression. Nerve fibers were associated with NGF overexpression in the outer layer of the anulus fibrosus as well as in endothelial cells of the small blood vessels.     

Analysis of rabbit intervertebral disc physiology based on water metabolism. I. Factors influencing metabolism of the normal intervertebral discs

Basic factors influencing the metabolism of intervertebral discs of rabbits were quantitatively analyzed based on the water metabolism. The blood flow surrounding the intervertebral disc was calculated using pharmacokinetic concepts from the data obtained by time-related tritiated water distribution analyses. The blood flow was estimated as 0.056 (mg/min/mg tissue) in the anterior annulus, 0.106 in the posterior annulus, 0.120 in the lateral annulus, and 0.084 in the nucleus pulposus, respectively (Experiment 1). Water content and fixed charge density in the intervertebral disc fractions also were measured (Experiment 2). The cations and uncharged small solutes transported into the disc tissue ranged in descending order from nucleus pulposus, lateral annulus, posterior annulus, to anterior annulus. The authors also calculated theoretically the swelling pressure of the proteoglycan in the intervertebral disc fractions from the results of Experiment 2. It was concluded that swelling pressure was highest in the nucleus pulposus, and lowest in the anterior annulus. The water in the posterior annulus is less exchangeable than in the other disc tissue fractions.     

腰椎间盘突出症突出髓核中抗原抗体复合物测定的临床意义

目的：探讨抗原体复合物在突出髓核中的分布及临床意义。方法：应用免疫酶组织化学染色的方法，对31例腰椎间盘突出症患的突出髓核中抗原抗体复合物进行检测，与20例正常椎间盘作对照并结合临床资料分析其意义。结果：在突出髓核的标本中可在髓核细胞膜周围观察到显示阳性的棕色沉淀物存在，而在正常椎间盘对照组中却未见阳性显示。突出型及脱垂游离型髓核中68．42％显示为强阳性，31．58％显示为阳性，膨隆型髓核中58．33％显示为阳性，41．67％显示为阴性。两组之间P＜0．05，有统计差异。结论：在突出髓核组织普遍存在抗原体复合物，而健康椎间盘中却不含有此免疫复合物。抗原体复合物阳性与强阳性表达与髓核暴露于机体免疫系统的程度相关，临床疼痛症状的程度与自身免疫反应的程度相关。髓核突出后引起的自身免疫反应是导致神经根慢性炎症的重要原因。     

Metaplastic proliferative fibrocartilage as an alternative concept to herniated intervertebral disc

It is hypothesized on the basis of experimental intervertebral disc degeneration that herniated disc is actually newly synthesized proliferative metaplastic fibrocartilage and not herniation of pre-existing disc tissue, particularly that of the nucleus pulposus. Human material in selected surgical tissues was examined to test this concept. Histology revealed evidence for proliferative fronts of fibroblastic cells in herniated discs with hypocellular interiors. Hydroxypyridinium cross-link assay was used to determine the maturity of the collagen. Results indicated, with statistical significance, that herniated disc is a younger tissue than in situ annulus fibrosis, and that herniated disc is not from the nucleus pulposus, thus supporting the hypothesis.     

Hyperextension-dislocation of the cervical spine. Ligament injuries demonstrated by magnetic resonance imaging.

We reviewed the magnetic resonance (MR) images of eight adults with acute hyperextension-dislocation of the cervical spine. The images were obtained to evaluate damage to the spinal cord. All eight patients had disruption of the anterior longitudinal ligament and of the annulus of the intervertebral disc, and separation of the posterior longitudinal ligament from the subjacent vertebra. Some, but not all, showed widening of the disc space, posterior bulging or herniation of the nucleus pulposus, and disruption of the ligamentum flavum. The MR demonstration of these ligament injuries, taken with the clinical and radiographic findings, establishes the mechanism of hyperextension-dislocation, confirms the diagnosis, and is relevant to management.     

腰椎间盘MRI高信号区的组织病理学特点和临床意义

目的研究椎间盘源性下腰痛患者腰椎间盘纤维环后方MRI高信号区的组织病理学特征及其临床意义。方法对52例经保守治疗无效、CT片显示无腰椎间盘突出的下腰痛患者行腰椎MR检查及腰椎间盘造影术。男39例,女13例;平均年龄38.8岁。选择纤维环后方出现高信号区的部分病例行腰椎后路椎间盘切除、椎体间融合、椎弓根螺钉内固定术,术中收集包括高信号区部位的椎间盘。对标本行矢状面连续组织学切片,光镜下观察高信号区椎间盘组织的组织病理学结构,并分析其临床意义。结果在行腰椎间盘造影的52例142个椎间盘中,17例17个椎间盘显示高信号区,且在椎间盘造影过程中全部呈现2或3级的纤维环破裂和疼痛复制反应。敏感性和特异性均为100%。高信号区与纤维环破裂程度分级呈正相关,说明纤维环破裂程度分级越高,越易出现高信号区(R=0.462,P<0.01)。共收集11例患者11个椎间盘,组织学研究发现对应高信号区的椎间盘组织表现为沿纤维环裂隙形成的不同程度的血管化肉芽组织,有成熟的瘢痕化胶原组织。结论症状性下腰痛患者的腰椎MRI上有椎间盘高信号区,可以作为椎间盘源性下腰痛诊断的重要征象。     

Relationship between neovascularization and degenerative changes in herniated lumbar intervertebral discs

Purpose

Lumbar disc degeneration may be associated with intensity of neovascularization in disc herniations. Our study was designed to evaluate how much the severity of histodegeneration is related to the development of neovascularization and to the level of pleiotrophin in the herniated lumbar discs.

Methods

Surgically excised lumbar disc specimens were obtained from 29 patients with noncontained (i.e., extruding through the posterior longitudinal ligament) and 21 patients with contained disc herniations. The histodegeneration scores and levels of neovascularization were estimated according to semiquantitative analysis in lumbar disc and endplate samples. Immunohistochemical staining were performed to identify the newly formed blood vessels and to detect the presence of pleiotrophin in the specimens.

Results

Higher levels of disc and endplate neovascularity were registered in noncontained herniations. The level of neovascularization was significantly related to the score of histodegeneration in the herniated disc tissues but not in the endplate specimens. Both contained and noncontained herniations had the highest values of histodegeneration in conjunction with the highest level of neovascularization but the relations between neovascularity and degenerative changes remained to be significant only in the group of noncontained herniations. Registration or frequency of pleiotrophin positive cells did not correlate significantly with histodegeneration or level of neovascularization in the disc samples.

Conclusion

Severe histodegeneration of the lumbar disc herniations is associated with enhanced neovascularization and potentially also spontaneous regression of the herniated tissue.     

临床症状体征与影像学检查分离的腰椎间盘突出症的发生机制研究进展

临床会出现少数症状体征与影像学检查结果不相符的腰椎间盘突出症患者,而单纯用传统的突出髓核直接机械压迫刺激神经根的理论不能解释这种反常的腰椎间盘突出症。腰椎间盘髓核的突出与患者临床症状体征的出现受多因素、多环节的影响,脊神经根的间接性机械压迫与神经根牵张效应为主要因素,而反常症状体征的产生往往与突出的髓核自身位置的迁移、神经系统对信息的传递以及髓核与硬膜囊或神经根的相互作用密切相关。此外,突出的髓核组织所继发的局部微循环、炎症改变,相应节段的骨质增生退变和腰椎应力姿势改变诱发此类反常腰椎间盘突出症患者出现多样性的症状体征。同时,一些患者还存在神经或椎体的先天性发育异常,并可能出现影像学检查上的误诊或漏诊。突出髓核对硬膜囊以及周围神经根之间的确切相互作用机制及其继发的局部病理生理、生物力学改变,病变责任节段的确定以及如何克服影像学检查的局限性需进一步研究。     

Anaphylactoid reaction to chymopapain

Chymopapain is a proteolytic enzyme used in the chemonucleolysis of the herniated nucleus pulposus of lumbar intervertebral discs. It causes rapid hydrolysis of the noncollagenous polypeptides that maintain the tertiary structure of the chondromucoprotein of the nucleus pulposus. We report here an anaphylactoid reaction after the intervertebral injection of chymopapain.     

Three-dimensional evaluation of lumbar disc hernia and prediction of absorption by enhanced MRI

Both the spontaneous shrinkage and the disappearance of disc hernia have been confirmed through the use of computed tomography (CT) and magnetic resonance imaging (MRI). There is, however, no practical method to predict the likely absorption of the herniated mass. The objective of this study was to predict the spontaneous absorption of disc hernia by MRI, and to select the optimum treatment. The study involved 65 patients with lumbar disc hernias. Conservative treatment was carried out in 21 patients, while 44 patients underwent herniotomy. In the nonoperated patients, an MRI was taken both during the painful period, and shortly after pain remission. Hernial shrinkage was evaluated according to the decrease in the calculated volume, in addition to the decrease in hernial area, calculated by MRI. In the operated group, preoperative MRI enhancement, type of hernia, and invasion of granulation tissue in the histological specimens were studied. In the 21 nonoperated patients, the volume (mean ± SD) was 0.488 ± 208 cm³ (range, 0.197–0.931 cm³) in the painful period and 0.214 ± 0.181 cm³ (range, 0.0–0.744 cm³) in the remission period. This decrease in volume was statistically significant. There was also a greater decrease in hernias exhibiting positive enhancement by MRI. In the operated patients, hernias that penetrated the posterior longitudinal ligament (PLL) had high rates of preoperative enhancement, and these hernias showed invasion of granulation tissue with marked neovascularization. Positive enhancement by MRI confirms an ongoing absorption process. Enhanced MRI can be a good method for the prediction of spontaneous absorption of lumbar disc hernias. Received: September 20, 2000 / Accepted: July 17, 2001     

Nerve root compression by herniated intradiscal gas. Case report

Intervertebral disc degeneration of any etiology may be associated with the formation of spaces or clefts within the disc. Gas collects within these spaces and can be seen roentgenographically. A case is presented in which intradiscal gas herniated into a connective tissue capsule, displacing the left S-1 nerve root and producing symptoms and signs identical to those of a herniated nucleus pulposus. The pathophysiology of gas within a disc space and the possibility that it may herniate much like the nucleus pulposus is discussed.     

颈椎间盘与后纵韧带上交感神经的解剖学观察及在颈椎间盘源性疼痛中作用的探讨

目的观察颈椎间盘及后纵韧带上交感神经的分布特点并探讨其在颈椎间盘源性疼痛中的作用。方法分别切取8只兔子颈椎间盘及颈椎后纵韧带，用冰冻切片-乙醛酸（SPG）法对其交感神经纤维进行特异性染色，荧光显微镜观察并辅以图像分析软件（Image-pro plus5．0）观察其分布特点。结果颈椎间盘外环有少量交感神经节后纤维，颈椎后纵韧带椎间盘区有大量密集的交感神经节后纤维，它们互相交叉成网状或排列成丛状，且有着复杂的三维空间联系。分布于后纵韧带浅层的交感神经较深层密集（P〈0．05）。结论分布于颈椎间盘外环及后纵韧带上的交感神经纤维是感受颈椎间盘紊乱、病变刺激的生理基础，可能在颈椎间盘源性疼痛发病中起着重要作用。     

腰椎组织胶原酶活性测定及临床意义

目的研究腰椎黄韧带，正常和突出的椎间盘髓核胶原酶活性变化与组织退变的关系。方法 用＾３Ｈ－可溶性胶原底物标记法对１１例黄韧带，３４例正常椎间盘髓核和３５例椎间盘突出症髓核的胶原酶活性进行测定。结果 受测腰椎组织胶原酶活性为：黄韧带〈正常椎间盘髓核〈突出椎间盘髓核，３种组织之间测定值差异有显著性。     

Immunophenotypic analysis of the inflammatory infiltrates in herniated intervertebral discs

STUDY DESIGN: The herniated portion of the lumbar disc was analyzed immunohistochemically for inflammatory infiltrates to determine their immunophenotype. OBJECTIVE: To investigate the pathomechanism behind spontaneous regression of herniated discs. SUMMARY OF BACKGROUND DATA: Spontaneous regression of herniated intervertebral discs has been increasingly reported. The inflammatory response of the host has been suggested as a factor in this phenomenon. However, whether the inflammation is induced from direct chemical irritation of the nucleus pulposus material or whether it is secondary to an autoimmune response to the nucleus pulposus remains controversial. METHODS: The herniated portion of the disc was collected from 38 patients who underwent surgery for lumbar disc herniation. Thin cryostat sections were made, and the extent to which inflammatory cells had infiltrated the disc specimen was defined. Then the immunophenotype of cellular infiltrates in the herniated disc specimens was assessed by immunostaining using a series of antibodies for lymphocyte, monocyte, macrophage, and dendritic cell markers. RESULTS: The inflammatory infiltrates in 14 of the 38 herniated discs were subjected to immunohistochemical analysis. None of them expressed the immunophenotypic markers of the lymphocyte (CD20, CD45RO, CD4, CD8, TCRgammadelta), mature monocyte (CD33), or dendritic cell (CD1a, CD80, CD86, S100). Abundant infiltration of CD68-positive cells that lacked CD33 but had a variable amount of CD11b, CD11c, and CD40 likely represents a process of differentiation from monocytes to macrophages. CONCLUSIONS: These findings are consistent with an immunophenotype of inflammatory responses to tissue injury or chemical irritation rather than antigen-specific immune responses. Therefore, understanding the mechanism of tissue repair is fundamentally important in the management of patients with disc herniations.