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。     

Presence and distribution of antigen-antibody complexes in the herniated nucleus pulposus.

STUDY DESIGN: Herniated tissue was studied by immunohistochemistry in eight patients with lumbar disc herniation. The results were compared with those of control subjects. OBJECTIVE: To assess the presence and distribution of possible antigen-antibody complexes in herniated disc tissue. SUMMARY OF BACKGROUND DATA: It has been suggested that the nucleus pulposus may be recognized as a foreign-body by the immune system and that this will lead to secondary nerve root disturbance. Such immunologic events should be initiated by binding of antibodies to a specific antigen in the disc tissue. However, the presence of antigen-antibody complexes in the herniated disc tissue has not been assessed. METHODS: Amplification of the peroxidase reaction produced in avidin-biotin-peroxidase complex immunostaining by diaminobenzidine was used to visualize antigen-antibody complexes in the herniated tissue. The authors used herniated tissue from eight patients with lumbar disc herniation and nucleus pulposus from five control subjects with nonlumbar disc herniation. Thin paraffin sections, prefixed in 4% paraformaldehyde, were incubated with anti-human IgG antibody to allow visualization of antigen-antibody complexes in the specimens. RESULTS: A brown deposit, indicating antigen-antibody complexes, could be observed in the pericellular capsule in herniated disc tissue but not in control discs or in the residual discs of the herniation patients. CONCLUSION: Antigen-antibody complexes seem to be commonly present in herniated disc tissue, but not in healthy discs. However, the pathophysiologic and clinical significance of this observation has to be elucidated further.     

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.     

游离型腰椎间盘突出的组织学观察

目的 观察游离型腰椎间盘突出组织的病理学改变,并探讨影响其自然吸收的相关因素.方法 对经手术治疗的37例39个游离型腰椎间盘突出组织行HE染色及免疫组化研究.HE染色用于观察突出组织的病理来源;免疫组化研究包括CD68、CD34染色,分别用于观察突出组织巨噬细胞浸润程度及新生血管形成程度.按髓核组织含量将突出组织分为3组：髓核组、含髓核组及不含髓核组,分析巨噬细胞浸润程度、新生血管形成程度与年龄、病程、病理来源以及影像学各因素的相关性.所有资料采用单因素方差分析或直线相关分析.结果 游离型突出组织以髓核为主的占62%,92%的游离型突出组织周围有新生肉芽组织形成.在新生肉芽组织内可见新生血管周围大量巨噬细胞浸润.3组间新生血管形成程度、巨噬细胞浸润程度差异均有统计学意义（F=5.663,P=0.008;F=3.604,P=0.038）.突出组织的巨噬细胞浸润程度、新生血管形成程度与年龄、病程无显著相关,与突出组织大小呈显著正相关关系（r=0.342,P=0.033;r=0.440,P=0.005）;且当突出组织MRI相对信号强度为0.30～0.72时,其巨噬细胞浸润程度、新生血管形成程度最显著.结论 多数游离型腰椎间盘突出组织以髓核组织为主要来源,并呈现不同程度的自然吸收现象.突出组织的自然吸收程度与年龄、病程无关,与突出组织的病理来源显著相关;当突出组织越大、突出组织相对信号强度为0.30～0.72时,自然吸收程度越显著.     

Lumbar disc herniation regression after successful epidural steroid injection

In some lumbar disc herniation patients, noninvasive measures fail, necessitating more aggressive treatment, such as epidural steroid injections or surgery. This study sought to determine whether improvement in patients who receive epidural steroid injections is related to regression of herniated nucleus pulposus or whether such patients' symptoms decrease because of the steroid effect in the presence of continued herniated nucleus pulposus. Two nonoperatively treated patient cohorts were followed who had follow-up MRI. Specifically, 38 other patients who improved without invasive treatment within 6 weeks after the onset of their symptoms were compared with 20 patients who improved with epidural steroid injections. Results found that both groups had similar initial and follow-up herniated nucleus pulposus size and outcomes. The epidural steroid injection group had fewer sequestered or extruded herniations that resorbed, and most were of lower hydration. In conclusion, epidural steroid injections do not alter ultimate herniated nucleus pulposus regression. Patients in whom the disc herniation has less hydration may have prolonged symptoms, but many improve with epidural steroid injections.     

Neovascularization of the outermost area of herniated lumbar intervertebral discs

In 64 surgically treated herniated lumbar intervertebral discs, we performed histopathological studies of neovascularization in the outermost layer of the herniated mass in various types of hernia. We obtained specimens separately from the capsule tissue covering the herniated mass and the inner tip tissue of the herniated mass for comparison. Histologically, in most cases, the capsule tissue was the outermost layer of the annulus fibrosus or posterior longitudinal ligament, and the inner tip tissue was the nucleus pulposus. In the capsule tissue, newly formed small blood vessels were present in 73.4% of the total cases examined, regardless of the hernia type. However, the frequency and degree of such vessels in the tip tissue were significantly higher in hernias that perforated the posterior longitudinal ligament than in those that did not. When the intervertebral disc herniates, new blood vessels proliferate in the capsule of the hernial tissue. At the stage when the hernial capsule tissue is still present, these vessels were observed to have difficulty reaching the inner tip portion. These findings suggest that when the nucleus pulposus portion of the herniated mass perforates the posterior longitudinal ligament, it may be subject to a stronger neovascularization reaction. Received for publication on May 18, 1998; accepted on Jan. 19, 1999     

2000 Volvo Award winner in basic science studies: Exogenous tumor necrosis factor-alpha mimics nucleus pulposus-induced neuropathology. Molecular, histologic, and behavioral comparisons in rats

STUDY DESIGN: This study tested the hypothesis that the 17-kDa form of tumor necrosis factor-alpha is the pathophysiologic agent expressed by herniated nucleus pulposus in vivo that is primarily responsible for the histologic and behavioral manifestations of experimental sciatica associated with herniated lumbar discs. OBJECTIVE: The authors determined the molecular weight and concentration of active tumor necrosis factor-alpha in rat herniated disc and used exogenous tumor necrosis factor-alpha at the same molecular weight to study its neuropathologic effect on rat nerve root and dorsal root ganglion preparations in vivo. SUMMARY OF BACKGROUND DATA: Expressed by herniated nucleus pulposus in culture, tumor necrosis factor-alpha causes neuropathologic injury in nerve roots and neuropathic pain states in which mechanical allodynia is seen in response to peripheral stimuli. METHODS: Western blotting was used to identify the molecular weight of the operative tumor necrosis factor-alpha protein form, and measures of optical density were used for semiquantitative determination of concentration. Plastic-embedded nerve roots and dorsal root ganglion were used for neuropathologic evaluation, and von Frey stimulation was used to quantify mechanical allodynia. RESULTS: The 17-kDa form of tumor necrosis factor-alpha is expressed by herniated nucleus pulposus at a concentration of approximately 0.48 ng per herniated rat lumbar disc. Exogenous tumor necrosis factor-alpha applied in vivo to rat nerve roots produced neuropathologic changes and behavior deficits that mimicked experimental studies with herniated nucleus pulposus applied to nerve roots. CONCLUSIONS: The data reinforce other evidence that tumor necrosis factor-alpha is involved in mechanisms of neuropathic pain.     

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。     

Role of leukocytes in radicular pain secondary to herniated nucleus pulposus

Some studies have assessed inflammatory cells such as macrophages, lymphocytes, and neutrophils in herniated lumbar disc tissues using histologic analysis. However, there is no consensus regarding the relationships between clinical symptoms, including radicular pain and the presence of inflammatory cells. It has been shown that autologous nucleus pulposus relocated on the lumbar nerve root in rats produces time dependent and reversible mechanical hyperalgesia, which is thought to be a pain related behavior in peripheral neuropathic pain models. The purpose of this study was to determine whether leukocytes play a role in the mechanical hyperalgesia induced by the nucleus pulposus and to characterize the role of leukocytes in radicular pain attributable to lumbar disc herniation. Nitrogen mustard was used to induce and evaluate leukocytopenia in rats. Sensitivity to mechanical noxious stimuli was measured quantitatively, and inflammatory cells in granulation tissue around the nerve root were examined histologically. The nucleus pulposus produced neither mechanical hyperalgesia nor abundant inflammatory cells in rats with nitrogen mustard induced leukocytopenia. Neuropathic pain produced by the nucleus pulposus, when placed on the nerve root, may be related to inflammatory cell infiltration induced by relocation of the nucleus pulposus, rather than the nucleus pulposus itself.     

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.     

The alpha2 type IX collagen tryptophan polymorphism is associated with the severity of disc degeneration in younger patients with herniated nucleus pulposus of the lumbar spine

Tryptophan alleles in COL9A2 (Trp2) and COL9A3 (Trp3) have been linked to lumbar disc diseases in the Finnish population. Although such diseases consist of various pathogenetically different conditions, detailed analysis of each has not been well documented. The aim of this study was to clarify whether the collagen IX tryptophan alleles influence the symptomatic degeneration of the lumbar disc in Japanese patients with herniated nucleus pulposus. We performed a prospective study of 84 patients who underwent lumbar discectomy. The degree of disc degeneration was evaluated by magnetic resonance images in relation to the collagen IX genotype. Twenty patients (21.4%) had the Trp2 allele and no patients had the Trp3 allele. Patients under 40 years with the Trp2 allele showed more severe disc degeneration at the surgical level than did those without the Trp2 allele (odds ratio 6.00, P=0.043). In contrast, patients aged 40 years or over did not show significant association between disc degeneration and collagen IX genotype. Our results suggest that the Trp2 allele is an age-dependent risk factor for the severity of disc degeneration in younger patients with symptomatic herniated nucleus pulposus of the lumbar spine.     

前列腺素E2在突出腰椎间盘中的表达及其与坐骨神经痛的关系

目的探讨前列腺素(PG)E2在突出腰椎间盘组织中的表达及其在坐骨神经痛发病机制中的作用。方法 42个突出椎间盘标本取自42例腰椎间盘突出并有坐骨神经放射性疼痛症状的手术治疗患者,其中膨隆型12例,破裂型15例,游离型15例,取材部位为紧贴神经根突入椎管的椎间盘组织(A部位)和椎间隙内残存的椎间盘组织(B部位)。术前采用视觉模拟评分(VAS)对所有患者坐骨神经痛严重程度进行评分。应用酶联免疫吸附试验(ELISA)检测PGE2含量。结果 A部位PGE2含量自膨隆型、破裂型至游离型逐渐升高,差异有显著性(P<0.01);A部位PGE2含量高于B部位(P<0.01);PGE2含量与患者坐骨神经痛VAS评分存在明显相关性(r=0.848,P<0.01)。结论 PGE2参与了腰椎间盘退变、突出的发病机制,PGE2含量与坐骨神经痛程度呈正相关性。     

腰椎间盘突出症非对称性下肢放射痛的原因及治疗

目的：探讨腰椎间盘突出症导致非对称性下肢放射痛的原因及治疗。方法：回顾性分析了手术治疗的53例病人。其中全椎板切除39例，扩大半椎板切除14例。结果：对侧侧隐窝狭窄23例，游离髓核组织压迫对侧神经根24例，脊髓丘脑侧束内存在不交叉纤维6例。结论：对侧侧隐窝狭窄和游离髓核组织压迫对侧神经根是导致非对称性下肢放射痛的主要原因，手术日寸要注意对对侧侧隐窝减压，除游离的髓核组织。只有确定无导致对侧下肢放射痛的原因后。才能确定为脊髓丘脑侧束内存在不交叉纤维。     

Magnetic resonance imaging of adolescent disc herniation

Magnetic resonance imaging (MRI) was used to compare the appearance of the spine in 20 adolescents with proven symptomatic intervertebral disc herniations with that in 20 asymptomatic patients who acted as controls. Abnormality in the signal from the nucleus pulposus of one or more discs was present in all patients, while only four of the 20 controls had any abnormal signals. In all the patients the symptomatic disc produced an abnormal signal and in most a herniated fragment of the nucleus pulposus was identified. Fifteen of the 20 patients had multiple-disc abnormality: six had three abnormal discs and nine had two. This suggests there was an underlying diathesis in patients who later developed disc herniation.     

The effect of age on inflammatory responses and nerve root injuries after lumbar disc herniation: an experimental study in a canine model

STUDY DESIGN: An experimental investigation on the effect of age on pathologic events surrounding the herniated disc and at the adjacent nerve root. OBJECTIVES: To investigate the role of age on the inflammatory responses and nerve root damage surrounding a sequestered lumbar disc fragment using a dog model. SUMMARY OF BACKGROUND DATA: Lumbar disc herniation is manifested in patients by variable clinical findings, natural history, and resorption phenomena in which the variability is particularly noted among patients with different ages. There are no previous reports on the effect of age on pathologic events induced by the herniated disc. METHODS: Six beagle dogs, including two animals of each age group of 6, 12, and 24 months (human equivalent ages of 10, 15, and 24 years), were used in this study. The dogs underwent L4-L5, L5-L6, and L6-L7 laminotomy and discectomy under general anesthesia. An autologous intervertebral disc from the tail was divided into anulus fibrosus and nucleus pulposus fragments. The anulus fibrosus and nucleus pulposus fragments were placed in the anterolateral epidural space of L5-L6 and L6-L7, respectively. The L4-L5 discectomy site served as a control. Dogs were killed at 12 weeks after surgery. The lumbar spine was removed en bloc, and histologic sections were prepared consecutively and examined. RESULTS: In the nucleus pulposus group at L6-L7, neovascularity, and intensive infiltration of lymphocytes, macrophages, and fibroblasts were observed surrounding the nucleus pulposus fragment in the 24-month-old group only. Degenerative changes of the nerve root fibers were observed in the 24-month-old group only. In the control and anulus fibrosus groups at L4-L5 and L5-L6, there were no marked inflammatory reactions in all age groups. The nerve root fibers around the anulus fibrosus were normal in all age groups. CONCLUSIONS: There is an effect of age on the inflammatory response and nerve root injury caused by the herniated disc. The apparent neuroprotective mechanism in the young animal, and the apparent inflammatory and resorption changes of the nucleus pulposus fragment in the older animal are quite intriguing.     

Abnormalities in muscle function during gait in relation to the level of lumbar disc herniation

STUDY DESIGN: A comparison between gait in patients undergoing surgery for L4 and L5 lumbar disc herniations and that in an age- and weight-matched control group. OBJECTIVES: To study whether changes in the moments produced at the ankle and knee joints during walking reflect the neurologic level of a herniated nucleus pulposus. SUMMARY OF BACKGROUND DATA: Lumbar herniated discs often cause muscle weakness, reduced motor function, and change in walking capacity. The specific effects of a disc herniation on muscle function during gait is poorly documented. METHODS: Conventional physical examination and kinetic analysis of gait were performed on 16 patients who subsequently underwent surgery for herniated discs (eight with L4-L5 and eight with L5-S1 disc herniations) and 16 healthy control subjects. The three components of the external moment at the ankle and knee were computed. The peak magnitudes of specific components of the external moments were compared with those of the control group. RESULTS: Reduced external ankle plantar flexion moment, indicating a decreased function of the ankle dorsiflexors, was found in patients with herniated nucleus pulposus of both L4-L5 and L5-S1. Reduced external ankle dorsiflexion moment, indicating a decreased function of the ankle plantar flexors, was found only in patients with a lesion to the L5-S1 disc, but not in those with herniations at L4-L5. CONCLUSIONS: Preoperative gait analysis identified functional deficits of the muscles about the ankle and foot that relate to the level of the herniation. Kinetic measurements can assist in understanding the functional limitations associated with specific levels of a herniation.     

Epidural injection of cyclooxygenase-2 inhibitor attenuates pain-related behavior following application of nucleus pulposus to the nerve root in the rat.

Cyclooxygenase-2 (COX-2), the inducible isoform of COX, has been identified as the key enzyme to regulate prostaglandin E2 synthesis in inflammatory conditions. Although it has been reported that COX-2 is present in herniated disc samples obtained from patients, little is known concerning the relationships between COX-2 and painful radiculopathy. The purpose of this study was to evaluate whether epidural injection of COX-2 inhibitor abolishes hyperalgesia induced by nucleus pulposus, which is a pain-related behavior in the rat. Rats, in which nucleus pulposus was relocated on the nerve root, exhibited evidence of mechanical hyperalgesia. Epidural injection of COX-2 inhibitor resulted in decrease in mechanical hyperalgesia 1 h, 3 and 7 days after the epidural injection of COX-2 inhibitor (0.1 mg/kg SC-'236 dissolved in the vehicle). There were no significant differences in sensitivity to thermal noxious stimuli after either application of the nucleus pulposus or epidural injections. These results suggest that prostaglandins and thromboxane, which are produced by COX-2 in inflammatory cells, appear to be related to the inflammatory process produced by application of nucleus pulposus to the nerve root. It is possible that COX-2 plays a significant role in painful radiculopathy following herniated nucleus pulposus.     

临床症状与髓核突出左右不一致的腰椎间盘突出症的诊治

目的探讨腰椎间盘突出症导致非对称性下肢放射痛的可能原因及术式的选择。方法25例经SCT、MRI检查证实为突出侧与临床症状侧别左右不一致的腰椎间盘突出症患者，均行手术治疗，其中14例行双侧开窗减压探查髓核摘除术，11例仅行突出侧开窗术。结果影像学上髓核突出侧别与术中所见相吻合，但该侧神经根未见到明显压迫或炎性水肿等病理表现；而症状侧无髓核突出，5例神经根未发现异常表现，9例存在不同程度的炎性水肿，其中6例探查发现神经根与对侧髓核不同程度粘连。术后所有患者症状均得到缓解，经过1～5年（平均2．4年）的随访，均无复发。结论SCT结合MRI检查有助于此类腰椎间盘突出症的明确诊断。纤维环无破裂的突出型腰椎间盘突出症，单纯突出侧减压可以获得较好的治疗效果；纤维环破裂的游离型及脱出型腰椎间盘突出症，宜同时行对侧开窗探查。     

Clinical evaluation of lumbar CT assisted discography in comparison with human cadaver

In order to estimate the clinical value of lumbar CT assisted discography (CTD), results obtained by this method were compared with histological findings of the cross section of the spine in fresh human cadavera. Based on these findings, preoperative CTD of lumbar disc herniation was investigated. In the discs of human cadavera, the contrast medium mainly invaded the fissures of nucleus pulposus and the ruptures of annulus fibrosus and then diffused to the surrounding tissues. These ruptures were classified into two categories: radial and circumferential. This identification was possible only in CTD and was obscure in the usual discogram. Not all the ruptures could be dyed in a severe degenerative disc, and a rupture which was not communicated with nucleus pulposus was not dyed in a mild degenerative disc. In the preoperative CTD of lumbar disc herniation, the posterior radial ruptures representing the route of herniated nuclei were characteristic and the circumferential ruptures were found complicated.