An organ culture system to model early degenerative changes of the intervertebral disc

ABSTRACT: INTRODUCTION: Back pain, a significant source of morbidity in our society, is related to the degenerative changes of the intervertebral disc. At present, the treatment of disc disease consists of therapies that are aimed at symptomatic relief. This shortcoming stems in large part from our lack of understanding of the biochemical and molecular events that drive the disease process. The goal of this study is to develop a model of early disc degeneration using an organ culture. This approach is based on our previous studies that indicate that organ culture closely models molecular events that occur in vivo in an ex vivo setting. METHODS: To mimic a degenerative insult, discs were cultured under low oxygen tension in the presence of TNF-α, IL-1β and serum limiting conditions. RESULTS: Treatment resulted in compromised cell survival and changes in cellular morphology reminiscent of degeneration. There was strong suppression in the expression of matrix proteins including collagen types 1, 2, 6 and 9, proteoglycans, aggrecan and fibromodulin. Moreover, a strong induction in expression of catabolic matrix metalloproteinases (MMP) 3, 9 and 13 with a concomitant increase in aggrecan degradation was seen. An inductive effect on NGF expression was also noticed. Although similar, nucleus pulposus and annulus fibrosus tissues showed some differences in their response to the treatment. CONCLUSIONS: Results of this study show that perturbations in microenvironmental factors result in anatomical and gene expression change within the intervertebral disc that may ultimately compromise cell function and induce pathological deficits. This system would be a valuable screening tool to investigate interventional strategies aimed at restoring disc cell function

The incidence of C5 palsy after multilevel cervical decompression procedures: a review of 750 consecutive cases

STUDY DESIGN: Retrospective review of 750 consecutive multilevel cervical spine decompression surgeries performed by a single spine surgeon. OBJECTIVE: To determine the incidence of C5 palsy in a large consecutive series of multilevel cervical spine decompression procedures. SUMMARY OF BACKGROUND DATA: Palsy of the C5 nerve is a well-known potential complication of cervical spine surgery with reported rates ranging from 0% to 30%. The etiology remains uncertain but has been attributed to iatrogenic injury during surgery, tethering from shifting of the spinal cord, spinal cord ischemia, and reperfusion injury of the spinal cord. METHODS: We included patients undergoing multilevel cervical corpectomy, corpectomy with posterior fusion, posterior laminectomy and fusion, and laminoplasty. Exclusion criteria included lack of follow-up data, spinal cord injury preventing preoperative or postoperative motor testing, or surgery not involving the C5 level. Incidence of C5 palsy was determined and compared to determine whether significant differences existed among the various procedures, patient age, sex, revision surgery, preoperative weakness, diabetes, smoking, number of levels decompressed, and history of previous upper extremity surgery. RESULTS: Of the 750 patients, 120 were eliminated on the basis of the exclusion criteria. The 630 patients included in the analysis consisted of 292 females and 338 males. The mean age was 58 years (range, 19-87). The incidence of C5 nerve palsy for the entire group was 42 of 630 (6.7%). The incidence was highest for the laminectomy and fusion group (9.5%), followed by the corpectomy with posterior fusion group (8.4%), the corpectomy group (5.1%), and finally the laminoplasty group (4.8%), although these differences did not reach statistical significance. There was a significantly higher incidence in males (8.6% vs. 4.5%, P = 0.05). CONCLUSION: Incidence of C5 nerve palsy after cervical spine decompression was 6.7%. This is consistent with previously published studies and represents the largest series of North American patients to date. There is no statistically significant difference in incidence of C5 palsy based on surgical procedure, although there was a trend toward higher rates with laminectomy and fusion