RESUMEN

The complex structure of the intervertebral disc within the spine is well suited to its mechanical function. However, it is also prone to degeneration, which is associated with various clinical symptoms and conditions, ranging from disc herniation to back pain to spinal stenosis. Most patients' conditions are managed conservatively but a small proportion progress to having surgery. This may be decompression (to remove tissue such as the disc, bone, or hypertrophic ligaments impinging on nerves) or fusion of the normally mobile intervertebral joint to immobilize it and so reduce pain. These used to involve fairly major surgical procedures, but in the past decade there has been much progress to make the surgery more refined and less invasive, for example using endoscopic approaches. Simultaneously, the research world has been studying and developing tissue engineering and cellular techniques for attempting to regenerate the intervertebral disc, whether simply the central nucleus pulposus or a complete intricate assembly to replicate the native structure of this and the surrounding annulus fibrosus, cartilage endplate, and bone. To date, none of the complex entities have been trialed, while cellular approaches are easier to utilize, have progressed to clinical trials, and may offer a better solution.

Asunto(s)

RESUMEN

PURPOSE: The objective of this study was to establish the prevalence and significance of ossicles of lumbar articular facets (OLAF) in young athletes with backache diagnosed by multi-detector computed tomography (MDCT). MATERIALS AND METHODS: The MDCT examinations of the lumbar spine carried out for suspected spondylolysis on 46 consecutive symptomatic young athletes presenting to a sports injury clinic over a 1-year period were retrospectively reviewed. OLAF study included detailed correlation with the structural and morphological stress features of the posterior neural arches. This was then compared with a control group composed of 39 patients. RESULTS: Twenty-three OLAF were identified in 15 patients. Eleven of the 15 patients with ossicles had posterior element stress changes (PEST)/pars defects. In the control group, two OLAF were identified in two patients, one demonstrating PEST changes. CONCLUSION: The high prevalence of OLAF in young symptomatic athletes compared with the asymptomatic control group is indicative of stress fractures. The non-united articular process fractures should be regarded as part of the spectrum of stress-induced changes in the posterior neural arch in the same way as spondylolysis. MDCT with volumetric acquisition and multi-planar reformation is the most reliable investigation in the diagnosis of OLAF. KEY POINTS: 1) This CT study supports a traumatic aetiology for lumbar articular facets ossicles. 2) OLAF represent part of a spectrum of stress-induced changes in the posterior neural arch. 3) OLAF are associated with typical spondylolysis. 4) OLAF can be overlooked on reverse gantry angle computed tomography (RG-CT). 5) OLAF may account for some of the discrepancy between radionuclide and RG-CT studies.

Asunto(s)

RESUMEN

PURPOSE: Proteoglycans are important to the functioning of the intervertebral disc. In addition to aggrecan there are the small leucine-rich proteoglycans (SLRPs). These are less common but in other locations their functions include collagen organisation, sequestering growth factors and stimulating inflammation. We have performed a comparative analysis of the SLRP core protein species present in intervertebral discs with various pathologies. METHODS: Eighteen intervertebral discs from patients with scoliosis (n = 7, 19-53 years), degenerative disc disease (n = 6, 35-51 years) and herniations (n = 5, 33-58 years) were used in this study. Proteoglycans were dissociatively extracted from disc tissues and the SLRPs (biglycan, decorin, fibromodulin, keratocan and lumican) assessed by Western blotting following deglycosylation with chondroitinase ABC and keratanase. RESULTS: Intact SLRP core proteins and a number of core protein fragments were identified in most of the discs examined. Biglycan and fibromodulin were the most extensively fragmented. Keratocan generally occurred as two bands, one representing the intact core protein, the other a smaller fragment. The intact core protein of lumican was detected in all samples with fragmentation evident in only one of the older scoliotic discs. Decorin was less obvious in the disc samples and showed little fragmentation. CONCLUSION: In this cohort of pathological intervertebral discs, fragmentation of certain SLRP core proteins was common, indicating that some SLRPs are extensively processed during the pathological process. Identification of specific SLRP fragments which correlate with disc pathology may not only help understand their aetiopathogeneses, but also provide biomarkers which can be used to monitor disease progression or to identify particular disc disorders.

Asunto(s)

RESUMEN

Intervertebral disc (IVD) degeneration is an often investigated pathophysiological condition because of its implication in causing low back pain. As human material for such studies is difficult to obtain because of ethical and government regulatory restriction, animal tissue, organs and in vivo models have often been used for this purpose. However, there are many differences in cell population, tissue composition, disc and spine anatomy, development, physiology and mechanical properties, between animal species and human. Both naturally occurring and induced degenerative changes may differ significantly from those seen in humans. This paper reviews the many animal models developed for the study of IVD degeneration aetiopathogenesis and treatments thereof. In particular, the limitations and relevance of these models to the human condition are examined, and some general consensus guidelines are presented. Although animal models are invaluable to increase our understanding of disc biology, because of the differences between species, care must be taken when used to study human disc degeneration and much more effort is needed to facilitate research on human disc material.

Asunto(s)

RESUMEN

STUDY DESIGN: Case report and literature review. OBJECTIVES AND METHODS: We report a case of subaxial cervical spondylolysis and review 142 reports of this anomaly in the English language literature to determine the cause, the distribution, the stability, and the prognosis of cervical spondylolysis. RESULTS: Cervical spondylolysis may affect any level of the lower cervical spine with the C6 isthmus being the most commonly affected region (48%). In 40% of cases, there were radiologic features consistent with congenital cervical spondylolysis and in 74% of cases there was a history of acute trauma. The radiographic features of congenital cervical spondylolysis are quite specific and can exclude trauma as a cause for the spondylolysis. Although instability was not commonly assessed, 30% of cases assessed with flexion-extension views were found to be unstable. These included 27 cases of myelopathy of which 26 were attributable to instability. Many treatment modalities have been employed to treat ranging from early mobilization to decompression and fusion. Three patients with radiologic signs of instability and no neurologic deficit were treated conservatively, whereas 1 patient with no neurologic deficit or instability was treated with spinal fusion. CONCLUSIONS: We found a direct relationship between spinal instability and the presence of neurologic deficit (P < 0.001). On the basis of this systematic review of case reports of lower cervical spondylolysis, we can recommend that spondylolysis of the lower cervical spine can be treated nonoperatively except in those with radiologically documented cervical instability.

Asunto(s)

RESUMEN

STUDY DESIGN: An immunohistological study of surgical specimens of human intervertebral disc. OBJECTIVE: To examine the presence of pleiotrophin in diseased or damaged intervertebral disc tissue and the association between its presence and the extent of tissue vascularization and innervation. SUMMARY OF BACKGROUND DATA: Increased levels of pleiotrophin, a growth and differentiation factor that is active in various pathophysiologic processes, including angiogenesis, has been associated with osteoarthritic changes of human articular cartilage. The association between pleiotrophin expression and pathologic conditions of the human intervertebral disc is unknown. METHODS: Specimens of human lumbar intervertebral discs, obtained following surgical discectomy, were divided into 3 groups: non-degenerated discs (n = 7), degenerated discs (n = 6), and prolapsed discs (n = 11). Serial tissue sections of each specimen were immunostained to determine the presence of pleiotrophin, blood vessels (CD34-positive endothelial cells), and nerves (neurofilament 200 kDa [NF200]-positive nerve fibers). RESULTS: Pleiotrophin immunoreactivity was seen in disc cells, endothelial cells, and in the extracellular matrix in most specimens of intervertebral disc but was most prevalent in vascularized tissue in prolapsed discs. There was a significant correlation between the presence of pleiotrophin-positive disc cells and that of CD34-positive blood vessels. NF200-positive nerves were seen in vascularized areas of more degenerated discs, but nerves did not appear to codistribute with blood vessels or pleiotrophin positivity in prolapsed discs. CONCLUSIONS: Pleiotrophin is present in pathologic human intervertebral discs, and its prevalence and distribution suggest that it may play a role in neovascularization of diseased or damaged disc tissue.

Asunto(s)

RESUMEN

STUDY DESIGN: Review of clinical file information and postoperative imaging, collected prospectively over a period of 14 years, in anticipation of study. OBJECTIVES: 1) Assessment of technical success in achieving anterior cervical fusion without internal fixation; 2) assessment of postoperative neck pain relevant to technical success or failure of fusion; and 3) assessment of morbidity arising from iliac crest bone graft donor site. SUMMARY OF BACKGROUND DATA: After anterior cervical discectomy and bone grafting for cervical radiculopathy or the intractable pain of cervical spondylosis, common clinical practice varies widely between the extremes of internal fixation in all cases, and never applying fixation. The clinical information and relevant imaging of 97 consecutive patients, 46 male, was reviewed at 12 months after surgery. METHODS: All surgery was performed at no more than 2 contiguous levels, by one surgeon (S.M.E.). After anterior discectomy alone, or combined with posterior vertebral body margin osteophytectomy, anterior bone grafting (Smith-Robinson) was performed at each level using a tricortical autogenous iliac crest bone block inserted under compression. In the interests of maximizing resource allocation and minimizing potential complications, all surgery was completed without internal fixation. A postoperative semirigid cervical collar was prescribed for 2 months. RESULTS: In 54 patients having 1-level fusion, there were 6 pseudarthroses (11%). In 43 patients having 2-level fusion, 12 patients demonstrated pseudarthroses (28% of patients) at a total of 18 levels (21% of levels). Only 2 of the 97 patients had pain related to the donor site. CONCLUSIONS: These results tend to confirm published reports of high pseudarthrosis rates in anterior cervical fusions carried out at 2 or more levels without fixation, as against improved fusion rates when internal fixation is applied. The authors are inclined to change their practice to include internal fixation in the form of anterior plating for fusions carried out at more than one level. Patients with technically successful fusions were less likely to have postoperative neck pain. Donor site pain was not a significant postoperative complication.

Asunto(s)

RESUMEN

The anulus fibrosus (AF) of the intervertebral disc consists of concentric sheets of collagenous matrix that is synthesised during embryogenesis by aligned disc cells. This highly organised structure may be severely disrupted during disc degeneration and/or herniation. Cell scaffolds that incorporate topographical cues as contact guidance have been used successfully to promote the healing of injured tendons. Therefore, we have investigated the effects of topography on disc cell growth. We show that disc cells from the AF and nucleus pulposus (NP) behaved differently in monolayer culture on micro-grooved membranes of polycaprolactone (PCL). Both cell types aligned to and migrated along the membrane's micro-grooves and ridges, but AF cells were smaller (or less spread), more bipolar and better aligned to the micro-grooves than NP cells. In addition, AF cells were markedly more immunopositive for type I collagen, but less immunopositive for chondroitin-6-sulphated proteoglycans than NP cells. There was no evidence of extracellular matrix (ECM) deposition. Disc cells cultured on non-grooved PCL did not show any preferential alignment at sub-confluence and did not differ in their pattern of immunopositivity to those on grooved PCL. We conclude that substratum topography is effective in aligning disc cell growth and may be useful in tissue engineering for the AF. However, there is a need to optimise cell sources and/or environmental conditions (e.g. mechanical influences) to promote the synthesis of an aligned ECM.

Asunto(s)

RESUMEN

STUDY DESIGN: Coculture assays of the migration and interaction of human intervertebral disc cells and chick sensory nerves on alternate substrata of collagen and aggrecan. OBJECTIVE: To examine the effects of aggrecan on disc cell migration, how disc cells and sensory nerves interact, and whether disc cells affect previously reported inhibitory effects of aggrecan on sensory nerve growth. SUMMARY OF BACKGROUND DATA: Human intervertebral disc aggrecan is inhibitory to sensory nerve growth in vitro, suggesting that a loss of aggrecan from the disc may have a role in the increased innervation seen in disc degeneration. Endothelial cells that appear to co-migrate with nerves into degenerated intervertebral disc express neurotrophic factors, but the effects of disc cells on nerve growth are not known. METHODS: Human disc cells were seeded onto tissue culture plates that had been coated with type I collagen and human intervertebral disc aggrecan. Explants of chick dorsal root ganglions (DRGs) were subsequently added to the plates and sensory neurite outgrowth stimulated by the addition of nerve growth factor. Time-lapse video and fluorescence microscopy were used to examine the migration and interaction of the disc cells and sensory neurites, in the context of the different matrix substrata. The effects of disc cell conditioned medium on nerve growth were also examined. RESULTS: Disc cells spread and migrated on collagen until they encountered the aggrecan substrata, where some cells, but not all, were repelled. In coculture, DRG neurites extended onto the collagen/disc cells until they encountered the aggrecan, where, like the disc cells, many were repelled. However, in the presence of disc cells, some neurites were able to cross onto this normally inhibitory substratum. The number of neurite crossings onto aggrecan correlated significantly with the number of disc cells present on the aggrecan. In control experiments using DRG alone, all extending neurites were repelled at the collagen/aggrecan border. Conditioned medium from disc cell cultures stimulated DRG neurite outgrowth on collagen but did not increase neurite crossing onto aggrecan substrata. CONCLUSIONS: Human disc cells migrate across aggrecan substrata that are repellent to sensory DRG neurites. Disc cells synthesize neurotrophic factors in vitro that promote neurite outgrowth. Furthermore, the presence of disc cells in coculture with DRG partially abrogates the inhibitory effects of aggrecan on nerve growth. These findings have important implications for the regulation of nerve growth into the intervertebral disc, but whether disc cells promote nerve growth in vivo remains to be determined.

Asunto(s)

RESUMEN

STUDY DESIGN: The effect of human intervertebral disc aggrecan on endothelial cell growth was examined using cell culture assays. OBJECTIVE: To determine the response of endothelial cells to human intervertebral disc aggrecan, and whether the amount and type of aggrecan present in the intervertebral disc may be implicated in disc vascularization. SUMMARY OF BACKGROUND DATA: Intervertebral disc degeneration has been associated with a loss of proteoglycan, and the ingrowth of blood vessels and nerves. Neovascularization is a common feature also of disc herniation. Intervertebral disc aggrecan is inhibitory to sensory nerve growth, but the effects of disc aggrecan on endothelial cell growth are not known. METHODS: Aggrecan monomers were isolated separately from the anulus fibrosus and nucleus pulposus of human lumbar intervertebral discs, and characterized to determine the amount and type of sulfated glycosaminoglycan side chains present. The effects of these aggrecan isolates on the cellular adhesion and migration of the human endothelial cell lines, HMEC-1 and EAhy-926, were examined in vitro. RESULTS: Homogenous substrata of disc aggrecan inhibited endothelial cell adhesion and cell spreading in a concentration dependent manner. In substrata choice assays, endothelial cells seeded onto collagen type I migrated over the collagen until they encountered substrata of disc aggrecan, where they either stopped migrating, retreated onto the collagen, or, more commonly, changed direction to align along the collagen-aggrecan border. The inhibitory effect of aggrecan on endothelial cell migration was concentration dependent, and reduced by enzymatic treatment of the aggrecan monomers with a combination of chondroitinase ABC and keratinase/keratinase II. Anulus fibrosus aggrecan was more inhibitory to endothelial cell adhesion than nucleus pulposus aggrecan. However, this difference did not relate to the extent to which the different aggrecan isolates were charged, as determined by colorimetric assay with 1,9-dimethylmethylene blue, or to marked differences in the distribution of chondroitin sulfated and keratan sulfated side chains. CONCLUSIONS: Human intervertebral disc aggrecan is inhibitory to endothelial cell migration, and this inhibitory effect appears to depend, in part, on the presence of glycosaminoglycan side chains on the aggrecan monomer.

Asunto(s)

Asunto(s)

RESUMEN

OBJECTIVE: To assess the effects of human intervertebral disc aggrecan on nerve growth and guidance, using in vitro techniques. METHODS: Aggrecan extracted from human lumbar intervertebral discs was incorporated into tissue culture substrata for the culture of the human neuronal cell line, SH-SY5Y, or explants of chick dorsal root ganglia. The effects on nerve growth of different concentrations of aggrecan extracted from the anulus fibrosus and nucleus pulposus, and of these aggrecan preparations following enzymic deglycosylation, were compared. RESULTS: Disc aggrecan inhibited the growth of neurites from SH-SY5Y cells and induced growth cone turning of chick sensory neurites in a concentration-dependent manner. Aggrecan isolated from the anulus fibrosus was more inhibitory than that isolated from the nucleus pulposus, but enzymic pretreatments to reduce the glycosylation of both types of disc aggrecan partially abrogated their inhibitory effects. CONCLUSION: Nerve growth into degenerate intervertebral discs has been linked with the development of low back pain, but little is known about factors affecting disc innervation. The finding that disc aggrecan inhibits nerve growth in vitro, and that this inhibitory activity depends on aggrecan glycosylation, has important implications for our understanding of mechanisms that may regulate disc innervation in health and disease.

Asunto(s)

RESUMEN

STUDY DESIGN: This retrospective study evaluates two groups of patients with scoliosis and Duchenne muscular dystrophy, treated with two different surgical stabilization methods. OBJECTIVE: To determine whether fixation to the sacropelvis is always necessary for adequate stabilization of scoliosis in Duchenne muscular dystrophy. SUMMARY OF BACKGROUND DATA: Pelvic fixation is generally recommended for scoliosis in Duchenne muscular dystrophy. Recent studies describe a more selective approach toward lumbar or pelvic fixation. Pelvic fixation is reserved for larger curves and established pelvic tilt. METHODS: Fifty cases of Duchenne muscular dystrophy, operated in two different centers and followed up for a minimum of 3 years, were reviewed. In the first group (Oswestry), 31 patients had fixation to the pelvis, using standard Luque instrumentation and pelvic fixation. The Galveston technique was used in 9 cases and L-rod configuration in 22 cases. In the second group (Nottingham), 19 cases had fixation to L5 using pedicle screws in the lumbar spine and sublaminar wires in the thoracic spine. These cases were operated on early, usually shortly after becoming wheelchair dependent. RESULTS: In the pelvic fixation group, the mean age at the time of surgery was 14 years, and forced vital capacity was 44%. The mean Cobb angle and pelvic obliquity were 48 degrees and 19.8 degrees at the time of surgery, 16.7 degrees and 7.2 degrees immediately after surgery, and 22 degrees and 11.6 degrees at the final follow-up (mean 4.6 years), respectively. The mean blood loss was 4.1 L, and the average hospital stay was 17 days. There were five major complications, including a deep wound infection in one case, revision of instrumentation prominence at the proximal end in two cases, and loosening of pelvic fixation in two cases. In the lumbar fixation group, the mean age at the time of surgery was 11.7 years, and forced vital capacity was 58%. The mean Cobb angle and pelvic obliquity were 19.8 degrees and 9 degrees at the time of surgery, 3.2 degrees and 2.2 degrees immediately after surgery, and 5.2 degrees and 2.9 degrees at the final follow-up (mean 3.5 years), respectively. The mean estimated blood loss (3.3 L) and mean hospital stay (7.7 days) were much less compared with the pelvic fixation group. Pelvic obliquity was corrected and maintained below 10 degrees in all but two cases, who had an initial pelvic obliquity exceeding 20 degrees. One patient had instrumentation failure at the proximal end, and one had a deep wound infection. CONCLUSION: Lumbar fixation to L5 is adequate if the surgery is performed early, soon after becoming wheelchair bound, and with smaller curves and minimal pelvic obliquity. Use of pedicle screws in lumbar spine provides a solid foundation to maintain the correction over the period of relatively short life expectancy of these children. Pelvic fixation may be necessary in older children, who have larger curves and established pelvic obliquity. In the presence of deteriorating lung function, this is associated with a greater morbidity and higher complication rate.

Asunto(s)