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Amyloid in intervertebral discs: a histopathological investigation of surgical material from 100 consecutive operations on herniated discs.

Material from 100 consecutive operations on herniated discs has been investigated for amyloid. Various degrees of amyloid degeneration were found in disc tissue from 41 patients. Material from patients over 50 years old showed significantly more amyloid than that from younger patients; there was no sex difference. Eighteen patients had previously been operated on for herniated discs; seven of these (39%) had pyrophosphate deposits in their disc tissue, often in close topographical relation to amyloid. 26% of the patients had calcium phosphate deposits and 29% had slight inflammation--both without relation to amyloid. No pathogenetic correlation between amyloid degeneration and herniation of intervertebral disc tissue could be shown.

Adult↗

Nucleus pulposus notochord cells secrete connective tissue growth factor and up-regulate proteoglycan expression by intervertebral disc chondrocytes.

OBJECTIVE: To identify the components of conditioned medium obtained from intervertebral disc nucleus pulposus-derived canine notochord cells, and to evaluate the capacity of such factors to affect disc-derived chondrocyte gene expression of aggrecan, versican, and hyaluronic acid synthase 2 (HAS-2) as a function of culture conditions. METHODS: Canine notochord cells obtained from nonchondrodystrophic dogs were cultured within alginate beads under conditions of serum deficiency (Dulbecco's modified Eagle's medium [DMEM]) to produce notochord cell-conditioned medium (NCCM). NCCM was evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and liquid chromatography-tandem mass spectroscopy. Bovine disc-derived chondrocytes were cultured with serum-deficient medium (DMEM) and NCCM and assayed for the effect of tissue culture conditions on aggrecan, versican, and HAS-2 gene expression. Next, chondrocyte gene expression for aggrecan was evaluated using DMEM containing recombinant connective tissue growth factor (rCTGF), and the results compared with those obtained using NCCM and DMEM. RESULTS: NCCM contained aggrecan, Cu/Zn superoxide dismutase, fibronectin, and CTGF precursor. Culture with NCCM caused an up-regulation of aggrecan, versican, and HAS-2 gene expression. NCCM induced aggrecan gene expression in chondrocytes at a level similar to that induced by 100-200 ng/ml rCTGF. Nonchondrodystrophic and chondrodystrophic canine notochord cells exhibited similar levels of CTGF gene expression. CONCLUSION: Nucleus pulposus-derived notochord cells secrete CTGF (CCN2), a recently discovered multifunctional growth factor. There is no difference between CTGF gene expression in nonchondrodystrophic and chondrodystrophic canine notochord cells, suggesting a possible role of CTGF as an anabolic factor within the disc nucleus that is, to at least some degree, dependent on the population of notochord cells within the disc nucleus.

Aggrecans↗

On the mechanical behaviour of intervertebral discs.

The response to compression, shear, bending, and axial rotation of an intervertebral disc is studied by using a theoretical disc model. The annulus fibrosus is modelled by ten fibre layers with alternating fibre inclination. The nucleus pulposus as well as the substance filing the space between the fibre layers is assumed to consist of an incompressible fluid. The end-plates are assumed to bulge at action of the pressure in the fluid phase. Geometry of fibre layers and end-plates are chosen to agree as closely as possible with what is representative for lumbar discs. The results show considerable increase of the different stiffnesses at increasing levels of the axial load. They also show quite large fibre strains, well over 10% at motions within normal physiological limits.

Biomechanical Phenomena↗

The effects of an interspinous implant on intervertebral disc pressures.

STUDY DESIGN: Measurement of intradiscal pressure was performed after placement of an interspinous implant in a cadaver model. OBJECTIVE: To understand the likelihood of accelerated adjacent-level disc degeneration as a result of the implant. SUMMARY OF BACKGROUND DATA: An interspinous implant has been developed to treat lumbar neurogenic claudication secondary to spinal stenosis that places the stenotic segment in slight flexion and prevents extension. Previous biomechanical studies demonstrated that fusing one level may significantly increase the intradiscal pressures at adjacent levels. Moreover, clinical studies have reported an increased incidence of adjacent-level degeneration after lumbar spinal fusion. METHODS: Eight cadaver lumbar specimens (L2-L5) were loaded in flexion, neutral, and extension. A pressure transducer measured intradiscal pressure and annular stresses during each of the three positions at each of the three disc levels. An appropriately sized implant was placed at L3-L4, and the pressure measurements were repeated. RESULTS: The pressures at the adjacent discs were not significantly affected by the interspinous implant insertion. There was a significant decrease in intradiscal pressure at the L3-L4 disc in the posterior annulus and nucleus in the neutral and extended positions. CONCLUSIONS: The implant does not significantly change the intradiscal pressures at the adjacent levels, yet it significantly unloads the intervertebral disc at the instrumented level in the neutral and extended positions. On the basis of the current findings, it does not appear that the implant causes accelerated disc degeneration at the adjacent levels.

Aged↗

Localized stresses in the intervertebral disc resulting from a loose fragment. A theory for fissure and fragment.

STUDY DESIGN: A theoretical analysis of estimate the stresses generated in the anulus fibrosus by a loose fragment. OBJECTIVES: To test the hypothesis that a fragment can generate stress concentrations in an intervertebral disc that could lead to the progression of a fissure, and to provide a theoretical foundation for the laboratory model of lumbar disc protrusion, which proposes that a fragment is formed first and that prolapse is the final event of a chronic process. SUMMARY OF BACKGROUND DATA: A laboratory model was developed by Brinckmann and Porter in 1994, which indicated that introducing a fragment into an otherwise intact disc resulted in rapid failure of the disc under physiologic loads and flexion. Identical in vitro surgery with no reintroduction of fragments did not result in failure. METHODS: A theoretical model was developed in which a spherical fragment was impressed against a plane surface, representing the inner surface of the anulus. The stiffness of the sphere and that of the surface were varied, and the stresses generated in the anulus were calculated as a function of applied load. RESULTS: The contact stress and the shear stress increased as the stiffness of the fragment approached and exceeded that of the matrix. Increases in stiffness to more than four times that of the matrix resulted in little further increase in stress. Peak shear stresses are developed in the bulk matrix beyond the point of contact between the fragment and the anulus. For relatively small forces on the fragment, these stresses were comparable with those found in diarthrodial joints. CONCLUSIONS: It is shown that a fragment in an intervertebral disc produces localized areas of increased stress. Fatigue over long periods at these stresses could result in fissuring and premature failure of the tissue.

Humans↗

Interobserver reliability of detecting lumbar intervertebral disc high-intensity zone on magnetic resonance imaging and association of high-intensity zone with pain and anular disruption.

STUDY DESIGN: Retrospective analysis of a spine imaging center's records of patients with chronic low back pain referred by tertiary care facilities. OBJECTIVES: 1) To assess the interobserver reliability of detecting lumbar intervertebral disc high-intensity zone on T2-weighted magnetic resonance imaging, and 2) to assess the relation between high-intensity zone and discography or post-computed tomography in symptomatic patients with low back pain. SUMMARY OF BACKGROUND DATA: Two of the three previous studies on this subject found an association between high-intensity zone and the presence of Grade 4 anular disruption with discographic reproduction of patients' exact low back pain. METHODS: Records of patients with low back pain who had undergone lumbar spine discography injection and post-computed tomography from June 1995 to August 1996 were reviewed. Two independent observers were asked to identify the presence of an high-intensity zone from the T12-L1 disc to L5-S1 on T2-weighted magnetic resonance images. With this data, interobserver reliability was assessed with the kappa statistic. Concordant high-intensity zone results were then compared with the Dallas Discogram rating for anular disruption and to patients' subjective pain response to discography injection. With this data, the sensitivity, specificity, and predictive values of high-intensity zone for detecting disc disruption and pain response were calculated. RESULTS: The interobserver reliability for detecting a high-intensity zone in a given disc was fair to good (kappa = 0.57; 95% confidence interval = 0.44, 0.70). The sensitivity of high-intensity zone for detecting Grade 4 anular disruption and exact pain was poor (31%) but its specificity was relatively high (90%). The positive predictive value of a high-intensity zone was low (40%) for a severely disrupted and exactly painful disc. CONCLUSIONS: The interobserver reliability of detecting a high-intensity zone and the positive predictive value of the presence of a high-intensity zone for detecting a severely disrupted and exactly painful disc were much lower than previous studies have shown. The relatively low positive predictive value may be attributable to differences in sample characteristics or procedural variations, or suggest that a high-intensity zone is not indicative of exactly painful internal intervertebral disc disruption.

Adult↗

Detection and distribution of the carbohydrate binding protein galectin-3 in human notochord, intervertebral disc and chordoma.

Galectin-3 is an endogenous carbohydrate-binding protein which plays a role in cell differentiation, morphogenesis and cancer biology. We investigated the occurrence and distribution of galectin-3 in the embryonic and fetal human notochord, the developing human vertebral column, adult intervertebral discs and in six chordomas, which are tumors thought to originate from notochordal remnants. By means of Western blots, the expression of galectin-3 was confirmed in tissue probes from the vertebral column region beginning with the 8th gestational week. These results were supported by immunohistochemical data which revealed the presence of galectin-3 in the cytoplasm of cells of the notochord also from the 8th gestational week onwards. Notochordal immunostaining became stronger with increasing gestational age. A persisting notochordal remnant in an adult intervertebral disc and various cells of the nucleus pulposus also contained galectin-3. All chordomas showed moderate or strong immunoreactivity irrespective of their cellular composition. Subcellularly, galectin-3 was localized mostly in the cytoplasm, while a subset of tumor cells also showed nuclear distribution. Differences in staining patterns of chordoma cells could not, in general, be correlated to any histological features of these tumors.

Adolescent↗

The origin and fate of herniated lumbar intervertebral disc tissue.

STUDY DESIGN: In a clinicopathologic study, disc tissue collected from surgery and from cadaveric spines was examined to test an hypothesis about the pathogenesis of herniation. OBJECTIVES: To determine the origin and fate of herniated lumbar intervertebral disc tissue. SUMMARY OF BACKGROUND DATA: Previous studies have ascribed herniated disc tissue to the nucleus, anulus, or endplate, or combinations of the three. One study describes it as newly synthesized fibrocartilage. Regardless of its origin, peripheral neovascularization of disc fragments has been described and may be related to pain symptoms. METHODS: Disc tissue was collected after extrusion and was examined histologically to determine its origin and fate. To test the hypothesis that sequestration results from migration of isolated, degenerate fragments of nucleus pulposus through preexisting tears in the anulus fibrosus, cadaveric lumbar disc were examined in detail. RESULTS: Ninety-eight percent of sequestrations contained some nuclear material indicating that nucleus pulposus is the principal substance extruded from the disc. None contained anulus alone. Although vascular repair was present in 89% of specimens, it did not correlate with several clinical parameters. CONCLUSIONS: The autopsy study confirmed the model of nuclear fragmentation, migration, and extrusion along radiating anular clefts. Neovascularization of extruded fragments bore no relationship with duration of sciatic pain symptoms or clinical outcome.

Adolescent↗

Calcification of intervertebral discs in the dachshund: a radiographic study of 21 stud-dogs.

The vertebral columns of 21 clinically normal, 4.9 to 13.2 year old dachshunds were x-rayed. This sample represented 55.3% of all male dachshunds with 20 or more offspring registered with the Norwegian Kennel Club in the period 1985-1989. Calcified intervertebral discs were identified in 9 (42.9%) of the stud-dogs, and the number of calcified discs in each individual varied from 2 to 5 with a mean of 3.7. The frequency of stud-dogs with 1 or more calcified discs was compared with the corresponding frequency in a material of 327 one-year-old dachshunds. In this comparison, the relative risk was estimated with 95% confidence bounds. When the different composition of size and coat varieties in the 2 materials was not considered, the relative risk of calcified discs was found to be 1.77 (0.99-3.2) times higher in stud-dogs than in young dogs. When the different composition of varieties in the 2 materials was considered, the relative risk was found to be 1.9 (1.1-3.4) times higher in stud-dogs than in young dogs. The results of the present study strongly suggest that an increase in the frequency of dachshunds with 1 or more calcified intervertebral discs occurs after 1 year of age.

Animals↗

Benign notochordal cell tumors: A comparative histological study of benign notochordal cell tumors, classic chordomas, and notochordal vestiges of fetal intervertebral discs.

Intraosseous benign notochordal cell tumors are recently recognized conditions that may undergo malignant transformation to classic chordomas. This study attempts to define the morphologic and immunohistochemical characteristics of 34 benign notochordal cell tumors by contrasting them with classic chordomas and the notochordal vestiges in fetal intervertebral discs. Benign notochordal cell tumors were characterized by well-demarcated though unencapsulated sheets of adipocyte-like vacuolated and less vacuolated eosinophilic cells within axial bones. The round nuclei were mildly polymorphic but bland. The tumor cells often contained cytoplasmic eosinophilic hyaline globules and lack any intercellular myxoid matrix or necrosis. The involved bone trabeculae were often sclerotic without evidence of bone destruction. The histologic features were different from those of both notochordal vestiges in fetal intervertebral discs and classic chordomas. There was overlap in immunohistochemical reactivity of benign notochordal cell tumors and chordomas, but notochordal vestiges failed to demonstrate cytokeratin 18 positivity. A more appropriate term for the lesions is "benign notochordal cell tumor" rather than "notochordal rest" or "notochordal hamartoma" as they are not rests and do not fulfill the definition of hamartoma. Benign notochordal cell tumors do not need any surgical procedure and must be adequately recognized to prevent unnecessary operations.

Adult↗

Wear studies for development of an intervertebral disc prosthesis.

Two long-term wear behavior studies used in part of the process of selecting the best materials for a new all-metal orthopaedic spinal implant are presented. The relative and absolute wear volume rates of candidate metals were investigated through simulation of two bearing regions of an intervertebral disc prosthesis. It was determined gravimetrically that hot isostatically pressed Co-Cr-Mo alloy provided the lowest Co-Cr-Mo alloy wear debris generation. It had an average wear volume rate of 0.093 mm3/million cycles from a spring-in-pocket simulation and 0.126 mm3/million cycles from a hinge (pin-in-slot) simulation. The estimated total wear volume of a hot isostatically pressed intervertebral disc prosthesis with titanium-6%Al-4%V alloy springs was 2.9 mm3/million cycles.

Humans↗

A historical review and current perspective on the intervertebral disc prosthesis.

Spinal fusion for degenerative disc disease has been associated with a variety of side effects, including increased morbidity, infection, failed back syndrome, pseudoarthrosis, and acceleration of degenerative changes in adjacent intervertebral discs and facet joints. Based on the experience of arthroplasty of hip and other joints, there has been an escalating in research emphasizing the design and development of an artificial disc prosthesis. However, these artificial discs have not been very successful when compared with hip or knee replacements. Based on clinical and anatomical data, multiple authors have postulated that the degenerative process of intervertebral disc evolves through three stages; dysfunction, instability and stabilization, with relatively distinct clinical and radiological findings. Even though magnetic resonance imaging is considered as the primary diagnostic tool for degenerative disease, it is unable to reliably ascertain which disc level is responsible for generating axial pain symptoms. Consequently, discography is the most precise test to localize the level of pathology. Multiple design criteria have been proposed for an ideal intervertebral prosthesis which included endurance, materials behavior, geometry, kinematics, dynamics, motion constraints, fixation to bones and safety. The development of artificial disc technology has culminated into two types of disc replacements, namely total disc replacement and a nucleus pulposus replacement. In addition, four prosthetic models have been proposed which include hydraulic, elastic, composite, and mechanical. Clinical outcomes of total disc replacement and nucleus replacement have been variable. This review describes natural history of disc disease and the diagnostic process, anatomical and biomechanical considerations, design criteria for an ideal intervertebral prosthesis, evolution of artificial disc prosthesis, clinical outcomes of the total disc and nucleus replacement, and prospects and meridians for future research.

Journal Article↗

The composition and protein metabolism in the immature rabbit intervertebral disc.

The nucleus pulposus (NP) and annulus fibrosus (AF) of immature rabbit intervertebral discs (IVD) have been subjected to the dissociative extraction procedure of Sajdera and Hascall (1969). The soluble, insoluble and unextracted fractions so obtained were analysed for total nitrogen, collagen, tyrosine, uronic acid, hexosamine and sialic acid content. A high proportion of non-collagenous protein, hexose and sialic acid in the NP insoluble fraction suggests the presence of glycopeptides associated with collagen and/or proteoglycans. The levels of proteoglycan in the soluble NP and AF fraction are similar. Immature (soluble) collagen, however, resides largely in the AF region. The metabolism of rabbit IVD protein components was also investigated both chemically and by autoradiography. L-Tyrosine-3,5-H3 was administered intraperitoneally (3 mc/kg) to 4 week-old rabbits. Animals were sacrificed at various time intervals and the harvested tissues extracted as before and lumbar discs collected. The levels of L-Tyrosine-3,5-H3 in the NP and AF insoluble and soluble fractions were determined using a tritium scintillation counting procedure and localisation by autoradiography. Pronounced extracellular activity of proteoglycan and glycoprotein is not evident before 24 hours. Soluble collagen, however, is synthesized and dispersed within 4 hours of isotope administration.

Animals↗