A case report; herniated intervertebral disc.
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Anthropometric measurements were studied for their prediction of herniated lumbar intervertebral disc in 332 men and women who had been discharged from hospital with this diagnosis during an 11-year follow-up. The patients were compared with 1,205 controls matched individually for sex, age, and place of residence. Men with a height of 180 cm or more showed a relative risk of 2.3 (95% confidence limits, 1.4-3.9) and women with a height of 170 cm or more 3.7 (1.6-8.6), compared with those who were more than 10 cm shorter (1.0). In men, but not in women, increased body mass index proved to be an independent risk factor for herniated lumbar disc, whereas the thickness of triceps skinfold had no predictive significance. Height and heavy body mass may be important contributors to the herniation of lumbar intervertebral disc.
The authors attempted to investigate the effect of vibration on the physiologic behavior of the intervertebral disc from rheologic and biological responses. Using fresh disc-cartilaginous end plate complexes of porcine coccygeal vertebrae, the frequency characteristics of dynamic compressive elastic modulus and dissipated energy were monitored by means of a biomechanical spectrometer. The effect of vibration on proteoglycan synthetic rates and solute transport in the intervertebral disc were analyzed using a radioisotope. When the disc-cartilaginous plate complexes were subjected to sinusoidal vibration with a static load of 5 N and a vibratory load of 3 N, the elastic modulus decreased at 11 Hz compared with 3.5 Hz. After this, it increased again at 35 Hz. The dissipated energy increased rapidly with an increase in frequency. Proteoglycan synthetic rates did not change appreciably down to the inner and outer layers of the anulus fibrosus, but the rate in the nucleus pulposus alone decreased remarkably at 10 Hz and 35 Hz. Solute transport increased as a response to vibration, particularly in the nucleus pulposus. When the intervertebral disc is exposed to vibration for a long period of time, therefore, the proteoglycan content in the nucleus pulposus may be decreased, eventually resulting in disruption of matrix integrity.
STUDY DESIGN: In vivo studies using a rat model were performed to determine the feasibility of microbubble-enhanced ultrasound gene transfer technique to the intervertebral disc. OBJECTIVES: 1) To establish this microbubble-enhanced ultrasound gene therapy technique for intervertebral disc cells in vivo without using viral vectors and 2) to estimate the duration of transgene expression in vivo. SUMMARY OF BACKGROUND DATA: Intervertebral disc degeneration and associated spinal disorders remain a formidable problem. Although gene therapy approaches have been reported as having promising therapeutic potential to regenerate the disc, concerns over safety issues using recombinant viral vectors limits its application. Successful gene transfer using ultrasound has been reported in muscle and cardiovascular systems in vivo. MATERIALS AND METHODS: Two different reporter plasmid DNA encoding green fluorescent protein (GFP) and firefly luciferase were used. Plasmid DNA was mixed with ultrasonography contrast agent (microbubbles) and injected into coccygeal intervertebral discs of Sprague-Dawley rats. The therapeutic ultrasound was irradiated on the surface of injected discs. Rats were killed 1, 3, 6, 12, and 24 weeks after gene transduction. Harvested nucleus pulposus tissues were used for evaluation of transgene expression. The intact discs were used as a control. RESULTS: Seven days after gene transfection, considerable numbers of GFP-positive cells were observed in nucleus pulposus from the GFP-transfected group. Luciferase assay revealed that the ultrasound group demonstrated approximately an 11-fold increase in luciferase activity over the plasmid DNA-only group. Furthermore, transgene expression mediated by this method was observed, at least up to 24 weeks. CONCLUSIONS: Our study indicated that ultrasound transfection method with microbubbles significantly enhanced transfection efficiency of plasmid DNA into the nucleus pulposus cells in vivo. Furthermore, the sustained transgene expression in vivo was possible up to 24 weeks. The long-term gene expression mediated by simple and safe procedure has important clinical applications, including the treatment of chronic types of disease such as degenerative disc diseases.
Since relaxation times are influenced by the hydration of the tissue and the chemical environment of the water molecules, T1 and T2 measurements (quantitative MRI) could be used as an indicator for the water content and the biochemical composition of lumbar intervertebral discs. The discriminating power of quantitative MRI for tissue characterization in individuals (for clinical diagnosis) and in cohorts (e.g. for investigations on disc physiology or composition) relies on the reproducibility in relation to the expected tissue differences. We therefore investigated the reproducibility in vitro (lumbar spine phantom) and in vivo (10 volunteers). To estimate the differences between normal and pathologic tissues in vivo, 100 normal and 20 herniated intervertebral discs were examined by quantitative MRI in a first application of our method. The relaxation times were calculated from a set of 20 images obtained with five single-slice/multi-echo sequences at different TR values on a commercial whole-body system (1.5 T). We have found a satisfactory reproducibility in vitro (T1: 1.9%; T2: 6.2%), while the reproducibility was less satisfactory in vivo (T1: 16.4%; T2: 13.4%). Calculated from theses values, differences in relaxation times of various tissues must exceed 486 ms for T1 and 24 ms for T2 (tolerance limits) to allow discrimination with a 95% confidence in individuals. We observed statistically significant (p = 0.001) mean differences between normal (n = 100) and herniated (n = 20) intervertebral discs (delta T1: 196 ms; delta T2: 15 ms). Although statistical significant in cohorts, a discrimination of normal and herniated intervertebral discs is limited by quantitative MRI in individuals, since the differences are smaller than the tolerance limits necessary for a reliable clinical diagnosis. However, our results indicate that variations in the disc hydration and/or composition can be noninvasively detected by quantitative MRI in studies of cohorts with sufficient accuracy.
Quantification of changes in intervertebral disc height is critical for studying intervertebral disc degeneration. Reliability of disc height measurement is therefore especially important for in vivo studies using animal models of disc degeneration. In this study, the effects of image intensity and percentage of disc width used for disc height measurement from radiographic images were evaluated in a rat-tail model. Radiographs were taken for 10 Sprague-Dawley rats using a standardized protocol. Average disc heights of the caudal 8-9 discs were determined using original and intensity adjusted images with different percentages of disc width. The average disc height was found to be significantly affected by both the image intensity and the percentage of disc width measured. A higher reliability was found in the measurement for image with adjusted intensity and using smaller disc width. Image intensity is suggested to be controlled and the disc width should be taken into account in quantifying the disc height.
Autogenous implantation of nucleus pulposus or nucleus pulposus cells that were activated by coculture retards intervertebral disc degeneration, but harvesting such grafts causes disc degeneration at the donor site. This study examined whether nucleus pulposus allografts similarly retard disc degeneration and whether such allografting induces immunologic rejection. Japanese White rabbits served as donors and recipients for allografts. Lumbar disc degeneration was induced by aspirating the nucleus pulposus. Two weeks later, intact nucleus pulposus or nucleus pulposus cells were injected and compared with a sham procedure and normal control. The recipients' discs were examined histologically and immunologically at intervals for 16 weeks. Discs receiving an intact nucleus pulposus showed the least degeneration, followed by discs receiving nucleus pulposus cells, both of which were better than no treatment. These findings correlated directly with the intensity of immunochemical staining for Type II collagen. Allogeneic grafts did not induce any appreciable host-versus-graft response. Injection of nucleus pulposus and nucleus pulposus cells retards intervertebral disc degeneration. However, injection of intact nucleus pulposus is more effective than injection of nucleus pulposus cells alone. The intercellular matrix plays an important, but poorly understood, role in preserving intervertebral discs.
BACKGROUND CONTEXT: While the biomechanical properties of the isolated intervertebral disc have been well studied in the three principal anatomic directions of flexion/extension, axial rotation, and lateral bending, there is little data on the properties in the more functional directions that are combinations of these principal anatomic directions. PURPOSE: To determine the bending flexibility, range of motion (ROM), and neutral zone (NZ) of the human lumbar disc in multiple directions and to determine if the values about the combined moment axes can be predicted from the values about principal moment axes. STUDY DESIGN/SETTING: Three-dimensional biomechanical analysis of the elastic bending properties of human lumbar discs about principal and combined moment axes. METHODS: Pure, unconstrained moments were applied about multiple axes. The bending properties (flexibility, ROM, and NZ) of isolated lumbar discs (n=4 for L2/L3 and n=3 for L4/L5) were determined in the six principal directions and in 20 combined directions. The experimental values were compared with those predicted from the linear combination of the six principal moment axes. RESULTS: The maximum and minimum values of the biomechanical properties were found at the principal moment axes. Among combined moment axes, ROM and NZ (but not flexibility) values were predicted from the principal moment axis values. CONCLUSIONS: The principal moment axes coincide with the primary mechanical axes of the intervertebral disc and demonstrate significant differences in direction for values of flexibility, ROM, and NZ. Not all combined moment axis values can be predicted from principal moment axis values.
Eleven cervical intervertebral space calcifications were studied in ten children (5 boys, 5 girls), with mean age of 9.4 years. The aetiology, symptoms, roentgenographic clinic features were analyzied. All ten patients showed evidence of calcification of the cervical intervertebral disc. One had calcification in two disc spaces of the cervical spine and associated with subluxation of C1,2. Two patients had calcification protruded into the spinal canal without symptoms of spinal cord compression. One had symptom of nerve root irritation. Eight of ten patients had symptoms which disappeared in two weeks after treatment. Eight patients had been followed over one year. The calcification disappeared from 2 to 8 months. The diagnostic criteria for the syndrome of this study are: (1) pediatric age group only; (2) local or referred pain; (3) limited cervical spine motiion; (4) evidence of inflammation; (5) visible calcification of the cervercal intervertebral disc on roentgenogram; (6) self-limited course; (7) good result after conservative treatment and good prognosis.
Experimental chemonucleolysis of the canine intervertebral disc with chondroitinase ABC and chymopapain was compared during a 52-week period. Roentgenograms and magnetic resonance imaging were used to examine changes in disc space and water content, respectively. Disc space narrowing and reductions in disc water content after chondroitinase ABC treatment were less than that after chymopapain. High-performance liquid chromatography was performed to measure changes in proteoglycans. Similarly to chymopapain, chondroitinase ABC degrades proteoglycans in the nucleus pulposus and decreases their quantity. However, large differences in the molecular weight and acidity of the resynthesized proteoglycans and in the chain length of the resynthesized glycosaminoglycans were observed between the two enzymes. The difference in disc space narrowing and the changes in disc water content between the two enzymes might result from differences in the characteristics of the resynthesized proteoglycans.
Physiologic loading of the intervertebral disc may lead to changes in the osmotic pressure experienced by the resident cells. In this study, changes in gene expression levels for extracellular matrix and cytoskeletal proteins were quantified in disc cells subjected to hypo-osmotic (255 mOsm) or hyper-osmotic conditions (450 mOsm), relative to iso-osmotic conditions (293 mOsm). Important differences were observed in osmolarity and between cells of different regions, corresponding to the transition zone and nucleus pulposus. Under hypo-osmotic conditions, gene expressions for aggrecan and type II collagen were up-regulated in the transition zone, but not in the nucleus pulposus cells. Genes for the small proteoglycans, biglycan, and decorin, but not lumican, were up-regulated in transition zone cells following incubation in either hypo- or hyper-osmotic media. The same genes were down-regulated in nucleus pulposus cells under either hypo- or hyper-osmotic conditions. Differences in the response to altered osmolarity between cells of the intervertebral disc may relate to their different cytoskeletal structures or embryological origins.
Polarization-sensitive optical coherence tomography (PS-OCT) is used to measure the birefringence properties of bovine intervertebral disc and equine flexor tendon. For equine tendon the birefringence delta n is (6.0 +/- 0.2) x 10(-3) at a wavelength of 1.3 microm. This is somewhat larger than the values reported for bovine tendon. The surface region of the annulus fibrosus of a freshly excised intact bovine intervertebral disc displays an identical value of birefringence, delta n = (6.0 +/- 0.6) x 10(-3) at 1.3 microm. The nucleus pulposus does not display birefringence, the measured apparent value of delta n = (0.39 +/- 0.01) x 10(-3) being indistinguishable from the effects of depolarization due to multiple scattering. A clear difference is found between the depth-resolved retardance of equine tendon and that of bovine intervertebral disc. This apparently relates to the lamellar structure of the latter tissue, in which the collagen fibre orientation alternates between successive lamellae. A semi-empirical model based on Jones calculus shows that the measurements are in reasonable agreement with previous optical and x-ray data. These results imply that PS-OCT could be a useful tool to study collagen organization within the intervertebral disc in vitro and possibly in vivo and its variation with applied load and disease.
STUDY DESIGN: This article is based on a comprehensive review of the literature related to intervertebral disc prostheses. OBJECTIVE: To compile an overview of the results and complications related to various types of lumbar and cervical disc replacements. SUMMARY OF BACKGROUND DATA: A functional disc prosthesis has been sought since the 1950s. Although there were a few early attempts, disc replacement did not become a viable therapy until the late 1980s. Devices that were used in Europe at that time are now being evaluated in the United States in clinical trials. Cervical disc replacements are currently in the early stages of development and evaluation. METHODS: A thorough literature search was conducted to identify articles published on intervertebral disc prostheses. Proceedings from conferences were reviewed as well. Articles were classified by topics, including lumbar total disc replacement, disc nucleus replacement, and cervical disc replacement. RESULTS: Results of total disc replacement are favorable, with 63-85% of patients having a good outcome. As with any procedure, issues related to patient selection, operative technique, and device size selection were learned from the early experiences with these devices. There has been only one disc nucleus replacement used in an appreciable number of patients. This has yielded good results, but there have been problems related to device displacement. There are increasing reports on the use of cervical disc replacements, but they are still in the early evaluation phases. However, as with the lumbar counterparts, new designs are being evaluated. DISCUSSION: Although still in the early phases of development, functional disc replacement will become a part of the spine surgeon's armamentarium for the treatment of patients with disc-related pain unresponsive to nonoperative care. The future in this area is exciting and bright with the introduction of new materials and new designs for implants. However, as with any new technology, there must be careful consideration of the safety of the devices, and their effectiveness will only be determined in long-term follow-up studies.
STUDY DESIGN: An immunohistochemical study on human autopsy lumbar intervertebral discs and surgical specimens was conducted. OBJECTIVE: To investigate the presence of phagocytic cells within herniated and nonherniated disc tissue and its correlation with disc calcification and degeneration. SUMMARY OF BACKGROUND DATA: Increasing knowledge is gathered on the molecular mechanisms of extracellular matrix degradation during the process of disc degeneration. However, the data available on the cells involved in this process are sparse. METHODS: Three different study populations were investigated: 1) 31 midsagittal tissue slices (age range, 0-86 years) encompassing the complete motion segment were decalcified and stained with a monoclonal antibody against the lysosomal CD68 antigen; 2) 12 additional midsagittal (undecalcified) tissue slices from normal fresh cadavers were resin-embedded and used for colocalization of calcifications (Kossa staining) and CD68-positive cells; and 3) in 53 surgical disc specimens from 32 individuals undergoing lumbar surgical interventions, the abundance of CD68-positive cells was correlated with diagnostic groups and magnetic resonance image findings. RESULTS: In the discs of fetuses, infants, and adolescents, no labeled cells were seen. However, CD68-positive cells were detected in the nucleus pulposus of all individuals with histomorphologic signs of disc degeneration, predominantly in discs adjacent to cleft formations. Morphologically, CD68-positive cells did not differ from nuclear chondrocytes. In the anulus fibrosus, CD68-positive cells were seen less frequently. In the resin-embedded specimens, CD68-positive cells were not associated with tissue calcifications. In most of the surgical specimens, positive cells in cluster-like arrangements were seen frequently, particularly in areas of vascular ingrowth. CONCLUSIONS: This is the first study describing the abundant presence of CD68-positive cells in human nonherniated disc nucleus pulposus. The findings additionally suggests that these cells are not invaded monocytes or macrophages, but rather, transformed resident cells. It is assumed that these cells are involved in the phagocytosis of extracellular matrix, and that discal cells therefore promote disc degradation, ultimately leading to a loss of biomechanical properties.
STUDY DESIGN: Six cases are reported in which the clinical presentation of a prolapsed intervertebral disc was found to be caused by a localized venous plexus. OBJECTIVES: To emphasize the fact that the clinical presentation of a localized plexus of epidural veins in the lumbar spine can resemble that of an acute disc prolapse. SUMMARY OF BACKGROUND DATA: The finding of enlarged epidural veins during lumbar disc decompression is relatively common, but it is only recently that they have been implicated as the cause of the presenting symptoms. METHODS AND RESULTS: Six individuals presented with severe pain in the lower back accompanied by sciatica, which had begun acutely. Physical examination in most of these patients showed the presence of neurologic signs in the affected leg. The initial clinical assessment was that of an acute prolapse of a lumbar disc. This diagnosis appeared to be borne out by the MRI scans, which demonstrated a "prolapsed disc" at the relevant level of the spine. However, at surgery, the intervertebral disc appeared to be relatively normal, but at the spine was found a large, localized plexus of epidural veins whose configuration matched the MRI image. The symptoms were relieved by decompression of the spine and ablation of the veins. CONCLUSIONS: Any pathologic process in the lumbar spine compressing a nerve root can cause localized pain in the back accompanied by sciatica. Most of these conditions can be differentiated by means of an MRI scan. The MRI image of a localized plexus of epidural veins, however, closely resembles that of a prolapsed intervertebral disc, which may be diagnostically misleading.
Type X collagen expression in intervertebral disc of young adult beagle dogs (n = 10) was studied. Type X collagen was immunostained mainly pericellularly in the central area of the vertebral endplate, but interterritorial staining there was also present. Annulus fibrosus and nucleus pulposus did not usually stain for type X collagen. However, immunostaining of nucleus pulposus for type X collagen with a simultaneous expression of collagen alpha1(X) mRNA was observed in one dog. A weak staining was observed in two other animals with a weak collagen alpha1(X) mRNA signal. In annulus fibrosus, lamellar staining was observed in two dogs. In three animals, type X collagen mRNAs were observed in the outer edge of the annulus fibrosus, but immunohistochemical staining did not always correlate with in situ hybridization signals. In conclusion, intervertebral disc type X collagen was mainly expressed in the cartilaginous endplate. In some apparently healthy animals there was type X collagen expression in the nucleus pulposus and also in the annulus fibrosus.