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PubMed1986

Ultrastructural study of the short-term effects of chymopapain on the intervertebral disc.

The initial effects of chymopapain, a chemonucleolytic agent, on the intervertebral disc of dogs were studied by light and electron microscopic techniques. Fragments of nucleus pulposus and annulus fibrosis were incubated with chymopapain up to 24 h in vitro. Proteoglycans and matrix proteins were rapidly removed, while collagen fibers remained intact up to 24 h. For several hours, most cells remained normal in appearance with only slight swelling and an increased number of vacuoles. After exposure to the protease for 24 h cells in both the annulus and nucleus showed extensive membrane damage and some were necrotic, but many survived relatively intact. These results suggest that, similar to the results of the digestion of cartilage with other proteases, the cells of the disc can survive brief chymopapain exposure during chemonucleolysis procedures and could serve as a source for regenerating tissue. The nature of the regeneration may depend on the extracellular scaffold that remains and the nutrition available to tissue as well as the age and biomechanical state of the disc. As for clinical significance, chemonucleolysis is an important nonsurgical alternative for treating prolapsed disc. The cells of nucleus and annulus can survive short-term exposure to treatment, and thus be responsible for partial regeneration of the tissue. This regeneration may be important in preventing long-term degenerative disease in the facet joints caused by increased pressure due to decreased disc height.

Animals↗
PubMed2001

Magnetic resonance classification of lumbar intervertebral disc degeneration.

STUDY DESIGN: A reliability study was conducted. OBJECTIVES: To develop a classification system for lumbar disc degeneration based on routine magnetic resonance imaging, to investigate the applicability of a simple algorithm, and to assess the reliability of this classification system. SUMMARY OF BACKGROUND DATA: A standardized nomenclature in the assessment of disc abnormalities is a prerequisite for a comparison of data from different investigations. The reliability of the assessment has a crucial influence on the validity of the data. Grading systems of disc degeneration based on state of the art magnetic resonance imaging and corresponding reproducibility studies currently are sparse. METHODS: A grading system for lumbar disc degeneration was developed on the basis of the literature. An algorithm to assess the grading was developed and optimized by reviewing lumbar magnetic resonance examinations. The reliability of the algorithm in depicting intervertebral disc alterations was tested on the magnetic resonance images of 300 lumbar intervertebral discs in 60 patients (33 men and 27 women) with a mean age of 40 years (range, 10-83 years). All scans were analyzed independently by three observers. Intra- and interobserver reliabilities were assessed by calculating kappa statistics. RESULTS: There were 14 Grade I, 82 Grade II, 72 Grade III, 68 Grade IV, and 64 Grade V discs. The kappa coefficients for intra- and interobserver agreement were substantial to excellent: intraobserver (kappa range, 0.84-0.90) and interobserver (kappa range, 0.69-0.81). Complete agreement was obtained, on the average, in 83.8% of all the discs. A difference of one grade occurred in 15.9% and a difference of two or more grades in 1.3% of all the cases. CONCLUSION: Disc degeneration can be graded reliably on routine T2-weighted magnetic resonance images using the grading system and algorithm presented in this investigation.

Algorithms↗
PubMed1996

[The study of the morphology of ultramicrostructure in molecular level of nucleus herniation of lumbar intervertebral disc].

In order to investigate the morphology of ultramicrostructure in molecular level of nucleus herniations, the authors studied the ultramicrostructure of three cases of nucleus herniations of lumbar intervertebral disc which were proved by operations and one case of normal nucleus pulposus of fresh corpse by using of atomic force microscope. The results showed that the arrangement of collagen bundle, collagen fiber and procollagen fiber were different between the two conditions, and the morphology of molecular particles of proteoglycan in nucleus herniations was different from that in the normal condition. In the condition of nucleus herniations, the collagen fiber formed procollagen fiber reticular porous adhering to the molecules of protein and proteoglycan, and the DNA adhering to the monochain of RNA in fiberal cell nuclei, in the form of bichain and multichain three dimensions helix structures. The banded structure (64-78 mm) of the procollagen fiber, and the collagenation and calcification of the degenerated nuclens pulposuses, the quantity of which was significant greater than normal (P < 0.05) indicated that the chronic injury of lumbar intervertebral nucleus pulposuses gave rise to the injury and break of the collagen fiber which resulted in twist (tangle) phenomenon so that nucleus pulposuses lost their normal resistance strength.

Adult↗
PubMedDate not supplied

Sequestrated lumbar intervertebral disc in the posterior epidural space: a report on two cases and review of the literature.

BACKGROUND: Posterior epidural migration is an interesting but rare path taken by a prolapsed intervertebral disc fragment. There are only seven cases reported of a similar migration of the disc fragment in the lumbar spine. PURPOSE: To diagnose the unusual presentation and interpretation of the sequestrated disc in the posterior epidural space. STUDY DESIGN: Case report. METHODS: Two cases of migration of the sequestrated disc into the posterior epidural space are presented. In one patient there was weakness of the ankle dorsiflexors, foot invertors, and toe extensors of the left foot, with sensory loss over the back of the calf and over the lateral three toes. The left ankle jerk was also absent. However, in the other case, there was no objective evidence of neurological deficit distally. RESULTS: Gadolinium magnetic resonance imaging scans showed ring enhancement preoperatively. Biopsy of the specimen taken from surgery confirmed it to be sequestrated disc fragment. CONCLUSION: Diagnosis of posterior epidural migration of the sequestrated discs may be difficult. It may present with subtle clinical features even though the disc transgresses through numerous anatomic restraints including the nerve roots in such cases.

Adult↗
PubMed2004

Apparent diffusion coefficient of intervertebral discs related to matrix composition and integrity.

While tremendous work has been performed to characterize degenerative disc disease through gross morphologic, biochemical, and histologic grading schemes, the development of an accurate and noninvasive diagnostic tool is required to objectively detect changes in the matrix with aging and disc degeneration. In the present study, quantitative magnetic resonance was used to determine if the quality of the nutritional supply to the intervertebral disc at various ages and levels of degeneration could be assessed through measurement of the apparent diffusion coefficients (ADCs). Modifications of the nucleus pulposus matrix content, specifically of water and glycosaminoglycan contents, with age and disc degeneration, were reflected in correlating changes in the ADCs. From unforced stepwise linear regression analyses, relations were established showing that decreases in glycosaminoglycan or water contents in the nucleus pulposus resulted in direct decreases in the ADCs. Relations obtained for the ADCs of the nucleus pulposus were direction dependent, in conformity with the anisotropic diffusion in the intervertebral discs. Changes in matrix integrity, as evidenced by the percentage of denatured collagen, were also detected in the nucleus pulposus with a low positive correlation to the ADC along the height of the disc and an inverse statistically significant regression to the ADC along the anterior to posterior axis of the disc. Correlations between the matrix content and integrity of the annulus fibrosus and its ADCs were not as evident, with only the ADC in the lateral direction of the disc of the anterior annulus fibrosus able to reflect changes in matrix content. The information obtained by the ADCs, particularly of the nucleus pulposus, can potentially be used in combination with quantitative T1, T2, and MT parameters to noninvasively obtain a quantitative assessment of the disc matrix composition and structural integrity.

Adolescent↗
PubMed2006

Aggrecan turnover in human intervertebral disc as determined by the racemization of aspartic acid.

We have used the racemization of aspartic acid as a marker for the "molecular age" of aggrecan components of the human intervertebral disc matrix (aggregating and non-aggregating proteoglycans as well as the different buoyant density fractions of aggrecan). By measuring the D/L(Asp) ratio of the various aggrecan species as a function of age and using the values of the racemization constant, k(i), found earlier for aggrecan in articular cartilage, we were able to establish directly the relative residence time of these molecules in human intervertebral disc matrix. For A1 preparations taken from normal tissue, turnover rates of 0.059 +/- 0.01 and 0.063 +/- 0.01/year correspond to half-life values of 12 +/- 2.0 and 11.23 +/- 1.9 years for nucleus pulposus and annulus fibrosus, respectively; the turnover rates of 0.084 +/- 0.022 and 0.092 +/- 0.034/year for degenerate tissue correspond to half-life values of 8.77 +/- 2.2 and 8.41 +/- 2.8 years, suggesting increased rate of removal of small aggrecan fragments. For the large monomer, fraction A1D1, turnover is 0.13 +/- 0.04/year, corresponding to a half-life of 5.56 +/- 1.58 years, similar to 3.4 years in human articular cartilage. For the binding region (A1D6), turnover is 0.033 +/- 0.0012/year, corresponding to a half-life of 21.53 +/- 0.6 years, similar to 23.5 years in articular cartilage. A1 preparations from nucleus pulposus contain a lower proportion of aggregating proteoglycans as compared with annulus fibrosus, suggesting increased proteolytic modification in the nucleus pulposus. D/L(Asp) values in aggregating and non-aggregating proteoglycans of a 24-year-old individual show similar results, suggesting that the non-aggregating molecules are synthesized initially as aggregating proteoglycans, which thereafter undergo cleavage and detachment from hyaluronan.

Adolescent↗
PubMedDate not supplied

The effect of uniform heating on the biomechanical properties of the intervertebral disc in a porcine model.

BACKGROUND CONTEXT: The use of minimally invasive lumbar intradiscal heating techniques, including intradiscal electro-thermal therapy (IDET), endoscopic radio-frequency annuloplasty, nucleoplasty and laser discectomy, for chronic lumbar discogenic pain and contained disc herniation has recently gained popularity. The purported therapeutic mechanisms of these interventions include subtotal nuclectomy, annular nociceptor ablation, and stabilization of the annular fibers. Basic science data elucidating the biomechanical and histomorphologic alterations of heat treatments on disc remain sparse. PURPOSE: The purpose of this study is to examine the effects of uniform heating on biomechanical properties and histomorphology of intervertebral disc tissues using a porcine model. STUDY DESIGN/SETTING: In a laboratory setting, porcine functional spinal units consisting of vertebra-nucleus pulposus-vertebra core and porcine hamstring tendons were harvested. Studies were performed on these tissue samples by uniformly heating the specimens in a constant temperature water bath. Ten porcine lumbar disc core and twenty-five porcine hamstring tendons were utilized as the subjects for this study. The effects of uniform heat treatments on disc core and hamstring tendon were measured for shrinkage, stiffness, and load to failure strength. Histomorphological study was also carried on the same specimen. METHODS: The porcine vertebra-nucleus pulposus-vertebra segments were cored to a uniform 1-cm diameter. The hamstring tendons were cut to uniform 1.2-inch lengths. The tendon specimens were divided into groups of five each and heated in constant temperature water baths of 60 degrees C, 65 degrees C, 70 degrees C, or 75 degrees C for 10 min. Unheated specimens served as controls. The disc core specimens were divided in two group of five each, and tested at room temperature or after immersion in a 70 degrees C bath. The shrinkage was monitored during immersion in the water bath. Biomechanical testing to failure was carried out using mechanical loading on an MTS servohydraulic testing machine operating under stroke control. Strength and stiffness of the tissue was determined. Histomorphology was studied by staining the specimen with hematoxylin and eosin (H&E), and examined under 200 times magnification. Non-heated controls were used for comparisons. RESULTS: The porcine hamstring tendons had no measurable shrinkage in specimens heated up to 65 degrees C. At temperatures above 65 degrees C, the shrinkage was concluded within 2 min of immersion and 70 degrees C appeared to be the optimal temperature, as temperatures higher than this did not demonstrate incremental effects. The disc core samples were heated to 70 degrees C (optimum temperature), and there appeared to be gross contraction of the disc core circumference to visual inspection, but no measurable lengthwise shrinkage could be appreciated. Histologically, the specimens demonstrated progressive loss of individual collagen fiber outline as the temperature increased. In the tendons, at 75 degrees C all of the fibers appear to be fused together, and the voids between individual collagen fibers were no longer present. Biomechanical testing revealed that the tendons undergo a substantial reduction in stiffness after heating. The mean tendon stiffness for the unheated specimens was 19,356 psi, while the corresponding value for the heated tendons was 1023 psi. These were significantly different using the paired t-test at p=0.0043. For the disc core samples, there was no significant difference in either stiffness (p=0.182) or failure strength (p=0.998) after heating. All failures occurred in mid-substance of the specimen. CONCLUSIONS: The application of uniform heating to nucleus pulposus disc core caused visible contraction of its circumference but not lengthwise shrinkage. The same heating shrinks the hamstring tendon and reduces its stiffness. Ultimate failure strength of the disc core specimen remains unchanged. The failure data was not obtainable for the tendon due to premature slippage from the fixation apparatus before failure. The results of this study fail to support a biomechanical justification for the application of uniform heat treatment to the whole intervertebral disc. Heating annulus fibrosus and nucleus pulposus separately to specific temperatures may have potential clinical benefits.

Animals↗
PubMed2006

Vertebral height growth predominates over intervertebral disc height growth in adolescents with scoliosis.

STUDY DESIGN: A cross-sectional study of spinal stereoradiographs of adolescents with scoliosis to measure growth. OBJECTIVE: To determine the relative contributions of the vertebral bodies and intervertebral discs to the increase in spinal length between T5 and L5, over the age range of 7.5-20 years. SUMMARY OF BACKGROUND DATA: The progression of spinal deformity (scoliosis) is associated with skeletal growth, but the relative roles of asymmetrical growth and remodeling of the vertebrae and discs during adolescent growth are unclear. METHODS: An existing database of 406 spinal stereoradiographic studies of 188 adolescents with idiopathic scoliosis, aged between 7.5 and 20 years, was used to measure the heights of vertebral bodies and intervertebral discs, and the summation of both (spinal length). RESULTS: Spinal length was observed to increase from about 250 to 350 mm over this range of ages. Spinal growth was associated with an increase in vertebral height after age 10 years, with minimal if any increase in disc height. The contribution of vertebral and discal height was estimated to be about 17 and 8 mm per year, respectively, at age 7.5 years, but discal height growth was estimated to be effectively zero after age 12 years. CONCLUSION: Spinal growth of patients with scoliosis aged between 10 and 20 years occurs almost exclusively by height increases in the vertebrae, not the discs.

Adolescent↗
PubMed1993

Age-related changes in glycosaminoglycans of human intervertebral discs.

The age-related changes in glycosaminoglycan composition of human intervertebral discs were studied. Large number of tissue samples taken from 301 individuals at autopsy or at operation of prolapsed discs was investigated. It was found that the ageing process is accompanied by a progressive decrease in GAG content, both in annulus fibrosus and in nucleus pulposus. The GAG: collagen ratio significantly decreases. The KS and Ch-6-S were found to be the most abundant GAGs in both parts of the disc and their amounts decrease during the ageing. A distinct, age-related increase in KS:Ch-S and Ch-6-S:Ch-4-S ratios was observed. Significant quantitative differences between the GAG contents in normal and prolapsed discs were found. The nuclei pulposi of prolapsed discs contained less GAGs, especially KS and Ch-6-S in comparison to normal tissue of the same age. Furthermore, the age-related decline of GAGs:collagen ratio was more distinct in the prolapsed discs. It seems that these differences in GAG composition may be important in the mechanism of predisposition to discs prolapse.

Adolescent↗
PubMed1971

Diagnosis and treatment of thoracic intervertebral disc protrusions.

A series of 14 patients with a protruded thoracic intervertebral disc is reported. We believe that the true incidence may be as high as one patient per million population per annum. Trauma, sometimes mild, seems to have played a significant role in this series. This fact coupled with pronounced numbness and disagreeable paraesthesiae should suggest the diagnosis with thoracic spinal lesions. Armed with clinical suspicion, radiological verification of the lesion can be expected using a thorough myelographic technique supported if necessary by tomography. A posterolateral approach which combines laminectomy, complete excision of the ligamentum flavum, and the extradural removal of protruded disc is described. The technique is safe and effective.

Adult↗
PubMed2006

A preliminary in vitro study into the use of IL-1Ra gene therapy for the inhibition of intervertebral disc degeneration.

Conventional therapies for low back pain (LBP) are purely symptomatic and do not target the cause of LBP, which in approximately 40% of cases is caused by degeneration of the intervertebral disc (DIVD). Targeting therapies to inhibit the process of degeneration would be a potentially valuable treatment for LBP. There is increasing evidence for a role for IL-1 in DIVD. A natural inhibitor of IL-1 exists, IL-1Ra, which would be an ideal molecular target for inhibiting IL-1-mediated effects involved in DIVD and LBP. In this study, the feasibility of ex vivo gene transfer of IL-1Ra to the IVD was investigated. Monolayer and alginate cultures of normal and degenerate human intervertebral disc (IVD) cells were infected with an adenoviral vector carrying the IL-1Ra gene (Ad-IL-1Ra) and protein production measured using an enzyme-linked immunosorbent assay. The ability of these infected cells to inhibit the effects of IL-1 was also investigated. In addition, normal and degenerate IVD cells infected with Ad-IL-1Ra were injected into degenerate disc tissue explants and IL-1Ra production in these discs was assessed. This demonstrated that both nucleus pulposus and annulus fibrosus cells infected with Ad-IL-1Ra produced elevated levels of IL-1Ra for prolonged time periods, and these infected cells were resistant to IL-1. When the infected cells were injected into disc explants, IL-1Ra protein expression was increased which was maintained for 2 weeks of investigation. This in vitro study has shown that the use of ex vivo gene transfer to degenerate disc tissue is a feasible therapy for the inhibition of IL-1-mediated events during disc degeneration.

Adenoviridae↗
PubMed1976

Effects of collagenase upon the intervertebral disc in monkeys.

The authors studied 5 rhesus monkeys for the effects of annulotomy, with or without the addition of a bacterially-derived collagenase into the nuclear-evacuated centrum of lumbar intervertebral discs. The animals were sacrificed from 3 weeks to 21 months after the single or staged double procedures. The earliest radiographic changes were loss of height of the interspace at 7 days, erosion of the vertebral body margins at 3 weeks, malalignment at 6 weeks, osteophytic formation at 3 1/2 months, sclerosis of vertebral body surfaces at 9 1/2 months, and fusion of adjacent vertebral bodies at 13 1/2 months. Pathological changes included early loss of disc convexity, focal new home formation, osteophytic new growth, through-and-through bone formation, irregular cystification, and disc replacement by hyaline fibrous tissue. Changes were reminiscent of those seen in humans with naturally acquired disc disease or aging of the disc. Injuries were produced in a tissue that probably has a limited scope of variation in reaction to insult.

Animals↗
PubMed2005

Narrowing of lumbar spinal canal predicts chronic low back pain more accurately than intervertebral disc degeneration: a magnetic resonance imaging study in young Finnish male conscripts.

The objective of this magnetic resonance imaging study was to evaluate the role of degenerative changes, developmental spinal stenosis, and compression of spinal nerve roots in chronic low back (CLBP) and radicular pain in Finnish conscripts. The degree of degeneration, protrusion, and herniation of the intervertebral discs and stenosis of the nerve root canals was evaluated, and the midsagittal diameter and cross-sectional area of the lumbar vertebrae canal were measured in 108 conscripts with CLBP and 90 asymptomatic controls. The midsagittal diameters at L1-L4 levels were significantly smaller in the patients with CLBP than in the controls. Moreover, degeneration of the L4/5 disc and protrusion or herniation of the L5/S1 disc and stenosis of the nerve root canals at level L5/S1 were more frequent among the CLBP patients. Multifactorial analysis of the magnetic resonance imaging findings provided a total explanatory rate of only 33%. Narrowing of the vertebral canal in the anteroposterior direction was more likely to produce CLBP and radiating pain than intervertebral disc degeneration or narrowing of the intervertebral nerve root canals.

Adolescent↗
PubMed1998

[Gaseous degeneration of the intervertebral disc within the lumbar spine].

The finding of gas within the vertebral disc space (vacuum phenomenon) is relatively common. This disorder often presents major diagnostic and therapeutic challenges, especially in the presence of multiple degenerative changes and chronic back pain in elderly patients. The author describes pathophysiology and diagnostics of gaseous degeneration associated with the herniated disc. Degenerative spine disease, gaseous degeneration of the intervertebral disc and epidural gas can be disclosed by imaging studies. The presence of epidural gas is attributed to gaseous disc degeneration. This pathology may cause radicular pain similar to sciatic pain produced by disc herniation. Surgery might be indicated in these cases.

Back Pain↗
PubMed2004

The functional significance of cell clusters in the notochordal nucleus pulposus: survival and signaling in the canine intervertebral disc.

STUDY DESIGN: Cell viability was assessed in relation to cell clustering, and mechanisms of cell-cell signaling in the clusters were investigated. OBJECTIVES: To explore the functional role of cell clustering in the notochordal nucleus pulposus. SUMMARY OF BACKGROUND DATA: The intervertebral disc of some species contains residual cells from the embryonic notochord. These cells form large three-dimensional clusters in the young, healthy disc but are replaced by chondrocyte-like cells during aging and degeneration. METHODS: Forty nucleus pulposi of adult dog lumbar intervertebral discs were isolated, and were left untreated, mechanically disrupted through a syringe, or enzymatically digested. The presence of functional gap junctions was determined by the fluorescence recovery after photobleaching method. Cell viability was also assessed over 20 days in vitro. RESULTS: The cell clusters were interconnected via functional gap junctions. Mechanical disruption of the tissue had little effect on long-term cell viability, but enzymatic disruption of the tissue had a substantial negative impact on cell survival. CONCLUSIONS: These results demonstrate that the notochordal cells in adult dog nucleus pulposi are able to communicate via cytoplasmic signals and that such communications may influence the functionality of these cells in the young disc.

Animals↗