Claus Carstens

Effects of controlled dynamic disc distraction on degenerated intervertebral discs: An in vivo study on the rabbit lumbar spine model

Study Design. An in vivo study on the rabbit lumbar spine model. Objectives. Effects of temporary dynamic distraction on intervertebral discs were studied on the lumbar spine rabbit model to characterize the changes associated with disc distraction and to evaluate feasibility of temporary disc distraction to previously compressed discs in order to stimulate disc regeneration. Summary of Background Data. Studies have shown that accelerated degeneration of the intervertebral disc results from altered mechanical loading conditions. The development of methods for the prevention of disc degeneration and the restoration of disc tissue that has already degenerated are needed. Methods. New Zealand white rabbits (n = 32) were used for this study. The rabbits were randomly assigned to one of five groups. In 12 animals, the discs were first loaded for 28 days using a custom-made external loading device to stimulate disc degeneration. After 28 days loading time, the discs in six animals were distracted for 7 days and in six animals for 28 days using the same external device, however, modified as dynamic distraction device. In six animals, the discs were distracted for 28 days without previous loading; and in six animals, the discs were loaded for 28 days and afterwards the loading device removed for 28 days for recovery without distraction. Six animals were sham operated. The external device was situated; however, the discs remained undistracted and they also served as controls. After 28 to 56 days loading and distraction time, the animals were killed and the lumbar spine was harvested for examination. Disc height, disc morphology, cell viability, relative neutral zone, and tangent modulus were measured. Results. After 28 days of loading, the discs demonstrated a significant decrease in disc space. Histologically, disorganization of the architecture of the anulus occurred. The number of dead cells increased significantly in the anulus and cartilage endplate. These changes were re-versible after 28 days of distraction. The disc thickness increased significantly as compared with the specimens from the 28 days loading group without distraction. Histologically, the discs showed signs of tissue regeneration after 28 days of distraction. The number of dead cells decreased significantly in comparison with the loaded discs without distraction. The flexibility of compressed discs was higher than of compressed/distracted discs. Conclusions. The results of this study suggest that disc regeneration can be induced by axial dynamic distraction in the rabbit intervertebral disc. The decompressed rabbit intervertebral discs showed signs of tissue recovery on a biologic, cellular, and a biomechanical level after 28 days of distraction.

Complications of scoliosis surgery in children with myelomeningocele

Abstract The purpose of the present study was to evaluate whether the high incidence of complications in scoliosis surgery in myelomeningocele (MMC) could be attributed to the surgical technique and whether improvements were possible. Between 1984 and 1996, 77 patients with MMC and scoliosis were treated surgically. The clinical and radiological follow-up ranged from 1 to 10 years with a mean follow-up of 3.6 years. The mean age at time of surgery was 12 years 8 months. The average preoperative scoliosis measured 90.20° and was corrected by 47%. The first four patients were stabilized with Harrington rods after anterior correction with a Zielke device (group 1). Twenty-five patients were operated only from posterior, using Cotrel-Dubousset (CD) instrumentation (group 2). In 13 patients an anterior release and discectomy was performed prior to CD posterior instrumentation (group 3). In 26 patients (group 4) this was combined with an anterior instrumentation. The 9 patients of group 5 had congenital vertebral malformations which made a special treatment necessary. Complications could be divided into hardware problems, such as implant failure, dislocation or pseudarthrosis, infections, anesthetic, and neurologic complications. Hardware problems were seen in 29% of all patients. More hardware problems were seen with the Harrington rod (75%) and after solitary posterior instrumentation (30%). The occurrence of pseudarthrosis was dependent on the surgical technique, the extent of posterior spondylodesis, and lumbosacral fusion. Patients with hardware problems had a mean loss of correction of 49% compared to 13% in the other patients. Depending on the different surgical techniques a loss of more than 30% was seen in 12–75% of the cases. Early postoperative shunt failure occurred in four cases; delayed failure – after more than 1 year – in three cases. One patient died within 1 day due to an acute hydrocephalus, another died after 21/2 years because of chronic shunt insufficiency with herniation. Wound problems were not dependent on the surgical technique, but on the extent of posterior spondylodesis and the lumbosacral fusion. Based on this analysis we believe our current practice of instrumented anterior and posterior fusion is justified. Further, we are very careful to check shunt function prior to acute correction of spinal deformity.

Stimulation of gene expression and loss of anular architecture caused by experimental disc degeneration--an in vivo animal study.

Study Design. An external compression model was used to evaluate gene and protein expression in intervertebral discs with moderate disc degeneration. Objective. To determine messenger ribonucleic acid and protein expression levels of relevant disc components. Summary of Background Data. An animal model of mechanically induced disc degeneration was developed and characterized histologically. However, little is known at the molecular level in moderate disc degeneration. Methods. There were 8 New Zealand white rabbits subjected to monosegmental posterior compression to induce moderate disc degeneration. Twelve animals served as controls or sham controls. Discs were analyzed using immunohistochemistry for collagen type 1 (COL1), COL2, aggrecan, and bone morphogenetic protein-2/4 (BMP-2/4). For gene analysis, conventional and quantitative polymerase chain reactions were used for COL1A2, COL2A1, aggrecan, BMP-2, biglycan, decorin, osteonectin, fibromodulin, fibronectin, matrix metalloproteinase-13 (MMP-13), and tissue inhibitor of MMP-1. Gene expression for nontreated, sham-treated, and compressed discs was quantified in relation to the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase. Results. Immunohistochemistry of compressed discs showed a loss of anular architecture, and a significant reduction of BMP-2/4 and COL2 positive cells. Gene expression analysis showed a significant up-regulation of COL1A2, osteonectin, decorin, fibronectin, tissue inhibitor of MMP-1, BMP-2, and MMP-13 in compressed discs. Conclusions. Experimental moderate disc degeneration is characterized by a loss of BMP-2/4 and COL2 positive cells, although gene expression of disc constituents, catabolic enzymes, and growth factors is stimulated to reestablish disc integrity.

Occurrence and regional distribution of apoptosis in scoliotic discs.

Study Design. Seventy surgically obtained intervertebral discs from 9 patients with idiopathic and 7 patients with neuromuscular scoliosis were analyzed for the regional distribution of apoptosis. Objectives. To investigate the role of apoptotic mechanisms in scoliotic discs. Summary of Background Data. The reasons for the development of scoliosis are complex and yet not completely understood. In herniated lumbar disc tissue, increased apoptosis and a high expression of Fas and Fas ligand and caspase-3 activity have already been reported, suggesting a pivotal role of apoptotic mechanisms in intervertebral disc degeneration. In scoliotic discs, cell death was correlated with disc deformity and changes in nutrient supply and metabolic levels. The role of apoptosis in scoliotic discs, however, is still unclear. Methods. Apoptosis was determined by terminal deoxyribonucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay and poly(ADP-ribose) polymerase (PARP) p85 immunohistochemistry. Expression of Fas and Fas-ligand was analyzed by immunohistochemistry and reverse transcription polymerase chain reaction analysis. Results. In all samples analyzed, apoptotic cells could be detected in the nucleus, anulus, and endplate. The number of apoptotic cells was significantly higher in the nucleus compared to the other areas and in the apex versus the nonapex discs. There was no difference between the discs of idiopathic and neuromuscular scoliosis and between the 2 age groups studied (10–17 years and 17–48 years, respectively). A strong expression of Fas and Fas-ligand could be detected in all samples. Conclusion. Increased numbers of apoptotic cells in the nucleus of scoliotic discs and the apex disc suppose a pivotal role of programmed cell death for the progression of this common disorder. The simultaneous increase of Fas and Fas-ligand expression in areas with increased cell death point to an activation of the apoptotic process via the Fas/Fas-L system.

Disc distraction shows evidence of regenerative potential in degenerated intervertebral discs as evaluated by protein expression, magnetic resonance imaging, and messenger ribonucleic acid expression analysis.

Study Design. An animal model of degeneration was used to determine the effects of disc distraction, and was evaluated with magnetic resonance imaging (MRI) as well as gene and protein expression levels. Objective. To investigate gene expression and MRI effects of distraction. Summary of Background Data. Disc degeneration can result from hyper-physiologic loading. Distracted discs with degeneration showed histologic signs of tissue recovery. Methods. There were 18 rabbits that underwent 28 days of compression (200 N) to induce moderate disc degeneration followed by 28 days of distraction (120 N; attached and loaded distraction device) or sham distraction (attached but unloaded distraction device). Comparison was performed with 56 days of compressed discs without distraction. Quantitative outcome measures were MRI signal intensity and gene expression analysis to determine: messenger ribonucleic acid levels for extracellular matrix genes, including collagen 1, collagen 2, biglycan, decorin, aggrecan, fibromodulin, and osteonectin; and matrix-regulative genes, including matrix metalloproteinase-13, tissue-inhibitor of matrix metalloproteinase-1, and bone morphogenetic protein (BMP)-2. Immunohistology was performed for collagen 2 and BMP-2 to label cells semiquantitatively by staining of the cell-surrounding matrix. Results. A total of 28 days of compression decreased signal intensity. Distraction over the same period reestablished physiologic signal intensity, however, a persistent reduction was found in sham distraction. Distraction resulted in gene expression up-regulation of collagen 1 (5.4-fold), collagen 2 (5.5-fold), biglycan (7.7-fold), and decorin (3.4-fold), while expression of fibromodulin (0.16-fold), tissue-inhibitor of matrix metalloproteinase-1 (0.05-fold), and BMP-2 (0.15-fold) was decreased, as compared with 56 days compression. Distracted discs showed more BMP-2 (19.67 vs. 3.67 in 56 days compression) and collagen 2 (18.67 vs. 11.33 in 56 days compression) positive cells per field. Conclusions. Distraction results in disc rehydration, stimulated extracellular matrix gene expression, and increased numbers of protein-expressing cells.

A new porcine in vivo animal model of disc degeneration: response of anulus fibrosus cells, chondrocyte-like nucleus pulposus cells, and notochordal nucleus pulposus cells to partial nucleotomy.

Study Design. In vivo animal study. Objectives. To describe a new porcine disc degeneration model, and to analyze disc remodeling and degeneration after nucleotomy with special view to the different nucleus pulposus (NP) cell types. Summary of Background Data. Thus far, predominantly smaller animals were used for disc degeneration models; however, such small discs were inappropriate to investigate cell implementation therapies. Though notochordal cells (NCs) are important for disc formation and maintenance, differences in the amount of NCs between human and animal discs have often been neglected. Methods. Twenty-four Goettingen minipigs underwent partial nucleotomy with a 16G biopsy cannula, to remove ∼10% of total NP volume. Animals were followed up for 3, or 24 weeks and analyzed by radiographs, MRIs, (immuno)histology, gene expression analysis, and biomechanical testing. Results. Three weeks after nucleotomy disc height was reduced by 26%, and magnetic resonance imaging signal intensity by 40%. At 24 weeks disc height was decreased by 32%. Increased degenerative changes were found in a histodegeneration score 3 and 24 weeks after nucleotomy, as well as considerable NP scarification after 3 weeks. In controls, cytokeratin-8 immunohistochemistry identified NCs in proximity to chondrocyte-like NP cells at approximately equal ratio. After nucleotomy, NCs were considerably reduced to <10% of total NP cells. Matrix genes were upregulated, except for aggrecan that decreased to 35% of initial values 3 weeks after nucleotomy. Matrix degrading factors (matrix metalloproteinases 13 and 3) were continuously upregulated, whereas transcripts of their inhibitors (tissue inhibitors of matrix metalloproteinase 2 and 3) were downregulated. No significant changes in segmental spinal flexibility or bone density were found after nucleotomy. Conclusion. We introduced a new disc degeneration model with relatively large discs that could be used for cell therapeutic approaches. The study gives further information about disc remodeling after nucleotomy and indicates the relevance of an altered cellular composition for the development of disc degeneration.

Sports activity of patients with idiopathic scoliosis at long-term follow-up.

ObjectiveThe aim of the study was to assess long-term the sports activities of operatively and nonoperatively treated patients with idiopathic scoliosis and compare these activities with those of controls. Study DesignCross-sectional case-control study, performed at The Orthopaedic University Hospital Heidelberg. Patients and MethodsThe study enrolled 59 patients (53 female, 6 male; mean age 43 years) with idiopathic scoliosis and a minimum follow-up of 5 years (mean 22 years) since treatment (28 nonoperative, 31 operative). Mean Cobb angle at the time of the study was 54°. An age-adjusted control group (n = 33) with no history of spinal disorder was evaluated at the same time. All participants in the study (n = 92) completed a questionnaire assessing spinal function (Spine Score) and sporting activity (Sport Score). In addition, the scoliosis patients underwent radiographic evaluation of their spine. The groups were compared by analysis of variance. In order to assess the relationship between two variables, Spearmans correlation coefficient was calculated. ResultsBoth groups of scoliosis patients attained a lower Sport Score than the controls (p < 0.015 and p < 0.006, respectively). There was no difference between the two scoliosis groups. Reduced spinal function correlated with reduced sports activity (p < 0.001). In both scoliosis groups, the subscales “back pain” and “physical activity” correlated with sporting activity (p < 0.03 and p < 0.02, respectively). In the surgically treated patients, Cobb angle correlated with reduced sports activity (p < 0.03). The extent of the spinal arthrodesis (number of segments) in surgically treated patients had no effect on their sports activity. ConclusionsOver the long term, patients with idiopathic scoliosis suffer impairment of their sports activities compared with age-matched controls. The main reasons for this are functional impairment and the frequency of back pain. Sports activity is not more restricted after extended spinal fusion than it is after nonoperative treatment.

Kyphectomy in children with myelodysplasia : Results 1994-2004

Study Design. We retrospectively studied 24 consecutive pediatric patients with lumbar kyphosis due to myelodysplasia who had received corrective surgical treatment with the Warner and Fackler technique from 1994 to 2004. Objectives. The purpose of the study was to evaluate the technical problems and outcome and to identify complications of this treatment modality, especially regarding the biomechanics. Summary of Background Data. The management of lumbar kyphosis (8%–20%) in conjunction with myelodysplasia is difficult. In 1993, Warner and Fackler presented an elegant surgical technique, which was used here. Methods. Corrective surgery was performed in 24 patients with an average preoperative lumbar kyphosis of 124°. The correction was achieved by kyphectomy combined with stabilization using rods and wires as described by Warner and Fackler. Outcome was rated and complications were identified using data from the clinical records. For biomechanical analysis of the surgical construct, a force model was developed. Results. The mean extent of lumbar kyphosis could be corrected from 124° before surgery to 43° after surgery. Biomechanical analysis showed that inadequate correction results in implant failure. Conclusion. Surgery should always be performed with the intention to reestablish the sagittal profile inasfar as possible so as to reduce the risk of implant failure.

Surgical management of paralytic scoliosis in myelomeningocele.

A retrospective analysis of 54 patients with paralytic scoliosis due to myelomeningocele, who underwent surgical treatment, was performed. The aim of this study was to compare different surgical techniques and to identify clinical parameters influencing primary and midterm results. Three surgical techniques were used: 1) group I, posterior fusion/instrumentation; 2) group II, anterior fusion/no instrumentation combined with posterior fusion/instrumentation; and 3) group III, anterior and posterior fusion/instrumentation. Average age at surgery was 13.1 years. A preoperative scoliosis angle of 90 degrees [interquartile range (25th-75th percentile) (IQR), 76-106 degrees] was primarily reduced to 38 degrees (IQR, 30-50 degrees). At final follow-up (mean, 3.3 years), correction deteriorated to 44 degrees (IQR, 38-65 degrees). The group III procedure resulted in a better midterm correction of scoliosis compared with group I (P = 0.02). The extension of anterior fusion correlated with primary and midterm correction of scoliosis (P < 0.03). Patients with a thoracic level of paralysis had a higher relative loss of correction compared with patients with a lumbar level (P < 0.06). This finding can be attributed mostly to group I patients (P = 0.011). Hardware complications occurred in 16 patients (30%). Relative loss of correction among these patients was high (P < 0.01) and relative midterm correction low (P = 0.001). We recommend anterior and posterior fusion, each with instrumentation for the treatment of paralytic scoliosis in myelomeningocele. In patients with a thoracic level of paralysis, the two-stage procedure is mandatory to reduce the risk of hardware complications and subsequent major loss of correction.

Results of kyphectomy with the technique of Warner and Fackler in children with myelodysplasia.

&NA; Pathological lumbar kyphosis occurs in approximately 8% to 20% of patients with myelomeningocele. During the past 4 years, nine patients with an average preoperative kyphosis of 152° were surgically corrected. They had a short fusion and a long stabilization with Luque rod instrumentation using a technique described by Warner and Fackler (1993). The average degree of correction was 104° and, on average, 2.5 vertebrae were resected. The average surgical time was 225 minutes, and blood loss averaged 635 ml. We saw two complications: one penetration of the distal part of the rod through the sacrum after 32 months, and a dislocation of the rods out of the first sacral foramen after 33 months. From our experience, this procedure is highly demanding, but effective. It should be limited to patients below the weight of 30 kg.