5:58 138. The role of activation inducible tumor necrosis factor receptor and ligand in lumbar disc herniation

5:58 138. The role of activation inducible tumor necrosis factor receptor and ligand in lumbar disc herniation

Proceedings of the NASS 20th Annual Meeting / The Spine Journal 5 (2005) 1S–189S DISCLOSURES: No disclosures. CONFLICT OF INTEREST: No conflicts. doi:...

55KB Sizes 0 Downloads 9 Views

Proceedings of the NASS 20th Annual Meeting / The Spine Journal 5 (2005) 1S–189S DISCLOSURES: No disclosures. CONFLICT OF INTEREST: No conflicts. doi: 10.1016/j.spinee.2005.05.137

5:46 136. Disc regeneration after posterior lumbar dynamic stabilization Antonio Ribas, I, MD; Clinica Santa Lucia, Rio de Janeiro, RJ, Brazil BACKGROUND CONTEXT: Spine surgery currently consists of two basic treatment options: decompression and fusion. Some new spinal implant systems are designed to restore ligamentous function and they have the same goal: maintemance of motion. The Dynafix, a new dynamic interspinous distraction system for lumbar stabilization offers an important alternative for arthrodesis. Perhaps the most fascinating aspect of the Dynafix System has been the observation that not only do Modic‘s changes reverse after implantation of the device but that some patients also developed MR imaging-documented rehydratation and regeneration of their discs. PURPOSE: This study was designed to determine the safety and efficacy of this new device for pain resolution, which also provides stability of motion; and to demonstrate the disc rehydration and regeneration. STUDY DESIGN/SETTING: This study was designed to demonstrate the disc regeneration after the implant of a new interspinous device for posterior arthroplasty. PATIENT SAMPLE: 212 protheses were implanted in 153 patients: 87 men and 66 women. Mean age 52.26. OUTCOME MEASURES: Resolution of pain and of neurological disorders proved excellent (88.32%). All the patients experinced leg pain relief. METHODS: The main criterion for patients selection was the occurrence of intractable leg pain, with or without low back pain. The Dynafix implant was a complementary procedure related to the following disorders, for which the current standart treatment consists of decompression and fusion: herniated disc with severe shortening of the disc space; reccurrent herniated disc; degenerative spondylolisthesis and lumbar stenosis. The implant technique is quick, safe and easy to perform. Using a median approach, the supraspinous ligament is reflected and the interspinous ligament removed. If necessary, the endocanal step is performed. Following this, the Dynafix is inserted and fixated. Follow-up ranged from one to 19 months. RESULTS: In 80% of the patients was observed disc rehydration / regeneration after 3 to 6 months after surgery. Serial MR was performed. 88.32% of the patients experienced excellent clinical results. CONCLUSIONS: The device and method described are viable for selected patients. The disc regeneration was observed in 80%–even in patients which the microsurgical discectomy was performed. The Dynafix System offers an important alternative for arthrodesis, with the advantages of minimally invasive techniques and fast recovery time, being a highly cost-effective procedure. Further analyses and long-term outcome is recommended. DISCLOSURES: FDA device/drug: Dynafix System. Status: Investigational/not approved. CONFLICT OF INTEREST: No conflicts. doi: 10.1016/j.spinee.2005.05.138

5:52 137. Mitochondrial involvement in Fas-mediated apoptosis of human lumbar disc cells Jong-Beom Park, MD, PhD1, Sung-Jin Park, MD1, K. Daniel Riew, MD2; 1The Catholic University of Korea School of Medicine, Uijongbu-si, South Korea; 2Washington University in St. Louis, St. Louis, MO, USA BACKGROUND CONTEXT: Two main pathways of Fas-mediated apoptosis have been identified: Type I (Death-inducing signaling complex– DISC) and Type II (mitochondrial). While apoptotic cell death has been implicated in lumbar degenerative disc disease, to date there is no human data concerning on which of the two pathways disc cells succumb.

71S

PURPOSE: As an initial step to developing therapeutic modalities to inhibit inappropriate or premature apoptotic cell death in disc cells, our objective is to first determine which pathway is involved in the apoptotic cell death of human disc cells. STUDY DESIGN/SETTING: Immunohistochemical staining, Western blot analysis, and TUNEL were done on surgically obtained herniated lumbar disc tissues. PATIENT SAMPLE: Thirty-two samples of herniated lumbar disc tissues were obtained from 32 patients who had undergone posterior open discectomy for persistent radiculopathy. The average age of the patients at the time of surgery was 34.7 years (range, 21 to 49 years), and the average duration of radiculopathy between symptom onset and the operation was 6.4 weeks (range, 1 to 19 weeks). Six were sequestrated discs, 11 transligamentous extruded, 10 subligamentous extruded, and 5 were protruded discs on the operative findings. According to Thompson’s grading system, mean grade of disc degeneration of 32 herniated disc specimens was 4.01⫾0.64 grades. Those patients with concomitant spinal stenosis or recurrent disc herniation were originally excluded from this study OUTCOME MEASURES: The expression of proteins related to Fas Type I and II pathways and presence of TUNEL-positive disc cells were identified in herniated lumbar disc tissues. METHODS: We performed immunohistochemistry and Western blot analysis to determine which proteins were present: those associated with Type I pathway (caspase-8), Type II (Bid, cytochrome-c, and caspase-9), and executioner of apoptosis (caspase-3). TUNEL assay was examined to confirm the occurrence of apoptosis in disc cells. RESULTS: The proteins associated with the Type II pathway (Bid, cytochrome-c, caspase-9) were positively stained in all samples. Whereas the Type I pathway protein, caspase-8, was not detected by immunohistochemistry, a small amount of caspase-8 was detected by Western blot analysis. However, the expression of Type II proteins (bid, cytochrome-c, and caspase-9) was still higher than the expression of caspase-8 by Western blot analysis. The expression of caspase-3 was identified in all samples by immunohistochemisty and Western blot analysis. TUNEL-positive disc cells were identified in all samples. CONCLUSIONS: The current findings imply that human disc cells are Type II cells, which undergo apoptotic cell death via mitochondrial involvement. Future therapeutic modalities to inhibit inappropriate or premature apoptotic cell death in degenerating disc cells should be directed to the mitochondrial pathway. DISCLOSURES: No disclosures. CONFLICT OF INTEREST: No conflicts. doi: 10.1016/j.spinee.2005.05.139 5:58 138. The role of activation inducible tumor necrosis factor receptor and ligand in lumbar disc herniation Moon-Soo Park, MD1, Hwan-Mo Lee, MD2, Soo-Bong Hahn, MD2, Seong-Hwan Moon, MD2, Yung-Tae Kim, MD3, Choon-Sung Lee, MD3, Hyo-Won Jung, PhD4, Byoung-Se Kwon, PhD4; 1Ulsan University Hospital, Ulsan University College of Medicine, Ulsan, South Korea; 2 Yonsei University College of Medicine, Seoul, South Korea; 3Asan Medical Center, Ulsan University College of Medicine, Seoul, South Korea; 4Ulsan University, Ulsan, South Korea BACKGROUND CONTEXT: In lumbar disc herniation the herniated nucleus pulposus may be recognized as a foreign body by the immune system, and this will lead to autoimmune reaction. Pathogenic autoreactive T cells play a role in the pathogenesis of autoimmune reaction. A distinct lineage of CD4⫹CD25⫹ regulatory T cells has been identified to suppress pathogenic autoreactive T cells and plays an essential role to prevent autoimmunity. The GITR (murine, glucocorticoid-induced tumor necrosis factor receptor) is a new costimulatory molecule expressed at high levels on CD4⫹CD25⫹ regulatory T cells, and regulates their suppressive phenotype. The human AITR (human, activation-inducible tumor necrosis factor receptor) shares a homology of 55% in the cytoplasmic domain with the

72S

Proceedings of the NASS 20th Annual Meeting / The Spine Journal 5 (2005) 1S–189S

murine GITR and is expressed in lymph node and peripheral blood leukocytes. The ligand for AITR (AITRL) is a member of the TNF family, which is expressed in endothelial cells. It was demonstrated that antagonistic monoclonal antibodies specific for costimulatory molecules could be used as novel therapeutic agents to delete autoreactive lymphocytes and block autoimmune disease progression. The agonistic anti-GITR monoclonal antibody suppressing CD4⫹CD25⫹ regulatory T cells results in the activation of pathogenic autoreactive T cells, leading to autoimmune reaction in animal models. The AITRL was found overexpressed on the fibroblast-like synoviocyte of the patients with rheumatoid arthritis, one of the autoimmune diseases (unpublished data). PURPOSE: Although AITR and AITRL might be considered to play an important role in the pathogenesis of autoimmune diseases such as rheumatoid arthritis, their examination in lumbar disc herniation remains unexplored. The purpose is to investigate whether AITR and AITRL might be overexpressed in lumbar disc herniation. STUDY DESIGN/SETTING: It is a prospective study. PATIENT SAMPLE: The study population consisted of 20 patients suffering from lumbar disc herniation. Five macroscopically normal discs were obtained from patients with spinal fracture managed with anterior discectomy as a control group of healthy individuals. OUTCOME MEASURES: The disc tissues and peripheral blood samples from the patients and healthy individuals were collected during the same period of this study. The expression levels of AITR and AITRL were investigated in the professional antigen presenting cells such as macrophages, non-professional antigen presenting cells such as fibroblasts from disc tissues and peripheral blood mononuclear cells (PBMC) by means of flow cytometric analysis (FCA), confocal laser scanning microscopy, immunohistochemistry and reverse transcriptase–polymerase chain reaction (RT-PCR). Serum levels of soluble AITR and AITRL were measured by an enzyme-linked immunosorbent assay. METHODS: Statistical analysis was performed. P value less than 0.05 was considered significant. RESULTS: In FCA of AITR and AITRL, the patients with lumbar disc herniation had significantly higher levels than did normal controls expressed as percentages of cells from disc tissues and PBMC. We found AITRL expression in the immunohistochemistry and RT-PCR from the patients with lumbar disc herniation. Serum levels of soluble AITR and AITRL were elevated in the patients with lumbar disc herniations. CONCLUSIONS: AITR and AITRL increased in the herniated disc tissue and peripheral blood of the patients with lumbar disc herniation, but decreased in healthy discs. They could be considered to play a special role in the pathogenesis of lumbar disc herniation. DISCLOSURES: No disclosures. CONFLICT OF INTEREST: No conflicts. doi: 10.1016/j.spinee.2005.05.140

Thursday, September 29, 2005 5:40–6:40 PM SIPP 8: Tumors and Reconstruction 5:40 139. Hemangioblastomas of the spinal cord Dwarakanath Srinivas1*, Ashish Suri2, Bhavanishanker Sharma2, Veersingh Mehta2; 1Manipal Institute of Neurological Disorders, Manipal Hospital, Bangalore, Bangalore, India; 2All India Institute of Medical Sciences, New Delhi, India BACKGROUND CONTEXT: Hemangioblastomas are histologically benign vascular tumors which can occur throughout the neural axis. They represent 1.5–2.5% of all spinal cord neoplasms. Early diagnosis is essential because several associated conditions such as retinal hemangioblastomas and renal carcinoma are treated more effectively if detected

early. Also, the treatment is more likely to be successful and without complications when tumor or associated cyst is small. PURPOSE: The purpose of this retrospective study was to analyze the clinical features, treatment outcomes, and long-term results of patients with spinal hemangioblastomas. STUDY DESIGN/SETTING: Retrospective study. PATIENT SAMPLE: All patients with spinal hemangioblastomas treated in the department of Neurosurgery, All India Institute of Medical Sciences, over a period of 11 years from January1992 through December 2003. OUTCOME MEASURES: Preoperative and regular postoperative clinical and radiological assessment. METHODS: Clinical and radiological assessment. RESULTS: Among the 84 patients with central nervous system (CNS) hemangioblastomas, 15 had spinal hemangioblastomas. Of these, 9 were males and 6 were females in the ratio 1.5:1 with the average age being 35.9 years. Only one patient had Von-Hippel Lindau (VHL) disease. All the patients presented with features suggestive of progressive compressive myelopathy, while 4 patients (27%) had features of bladder/bowel involvement. Pain as one of the presenting symptoms was seen in 6 patients (40%). No patients presented with acute onset of symptoms. Hemangioblastomas were located in the cervical region in 9 (60%), dorsal region in 5 (33%), and the cervicodorsal region in 1 patient. An associated syrinx was present in 13 patients (87%). In 10 of these patients the syrinx extended for a length greater than 5 vertebral segments. 12 of the patients had a posterior or a laterally located tumor while 3 had an anteriorly located tumor. All underwent surgery and excision of the tumor. Five patients had deterioration in power immediately following surgery. Of these, 3 improved gradually whereas 2 remained paraplegic. Two among the 12 posterior/lateral located tumors developed postoperative deficits, whereas 1 of the anterior located tumors developed paraplegia. One patient developed a CSF leak which was managed successfully with CSF diversion and resuturing. There was no mortality. The follow-up period ranged between 2 weeks to 3.5 years. One patient had a recurrence after 18 months for which she was reoperated successfully. CONCLUSIONS: Spinal hemangioblastomas are a rare group of tumors amenable to complete cure. Surgical excision is the treatment of choice and results in complete cure. There was no relation of the length of the syrinx either to the location or to the outcome of the patient. DISCLOSURES: No disclosures. CONFLICT OF INTEREST: No conflicts. doi: 10.1016/j.spinee.2005.05.141

5:46 140. Minimally invasive surgery for ablation of osteoid osteoma of the spine Alexander Hadjipavlou, MD1, Michael Tzermiadianos2, Pavlos Katonis1, Ioannis Gaitanis, MD1, George Kontakis3; 1University Hospital Of Crete, Heraklion, Crete, Greece; 2University of Crete, Heraklion, Greece; 3Orthopeadic Department University Hospital of Crete, Rethymno, Crete, Greece BACKGROUND CONTEXT: The successful treatment of osteoid osteoma of the appendicular skeleton by percutaneous radiofrequency ablation, gives a paradigm to the management of spinal involvement by this lesion. Only a few cases utilizing this method to treat spinal lesions have been reported. The high success rate of percutaneous transpedicle vertebral biopsy and discectomy led us to believe this technique can also be applicable for the treatment of osteoid osteoma of the spine. PURPOSE: To determine the effectiveness of two minimally invasive methods for the ablation of osteoid osteoma of the spine. STUDY DESIGN/SETTING: Retrospective study of patients treated with two different minimally invasive surgical procedures under local or general anesthesia. PATIENT SAMPLE: Five patients with symptomatic osteoid osteoma of the spine were treated. In two patients the lesion was localized in the apex