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Daniel Haschtmann, Stephen J. Ferguson and Jivko V. Stoyanov

Object

The object of this study was to characterize the biological response of isolated intervertebral disc fragments to in vitro culture conditions with respect to cell death and inflammatory and catabolic changes. The acquired data could help to gain a better understanding of the biological reaction of disc tissue when exposed to environmental changes along with altered nutritional and osmotic conditions, as are encountered in different in vitro disc models or disc diseases in vivo.

Methods

Intervertebral disc anulus fragments were isolated from Burgundy rabbits and cultured in standard media for 3 days. The disc fragments were analyzed for their swelling properties, proteoglycan loss on histological studies, lactate dehydrogenase activity, apoptosis, gene expression of collagenases and gelatinases, and for proinflammatory (MCP-1, IL-8, and IL-6) and apoptosis-associated (TNF-α, Fas-L, and caspase 3) genes.

Results

The results demonstrate that disc specimens were swelling, and a loss of proteoglycans with disarrangement of anulus architecture was observed. The disc cells underwent rapid apoptosis with upregulation of various proinflammatory genes. Both collagenases, matrix metalloproteinase (MMP)–1 and MMP-13, were increasingly transcribed, whereas the gelatinases MMP-2 and MMP-9 did not respond or were downregulated.

Conclusions

Cultured disc fragments swell and undergo necrotic and apoptotic cell death combined with a catabolic gene response and gene expression of proinflammatory and chemoattractant proteins. Some of these findings have been demonstrated before in various spinal disorders. In addition, disc fragments are not suitable for long-term culture if a stable disc metabolism is desired, and the described changes have to be considered when using isolated disc material for in vitro cultures.

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Stephen I. Ryu, Daniel H. Kim and Steven D. Chang

Object

The optimal treatment for intramedullary spinal tumors is controversial, because both resection and conventional radiation therapy are associated with potential morbidity. Stereotactic radiosurgery can theoretically deliver highly conformal, high-dose radiation to surgically untreatable lesions while simultaneously mitigating radiation exposure to large portions of the spinal cord. The purpose of this study was to evaluate the authors' initial experience with frameless stereotactic radiosurgery for intramedullary spinal tumors.

Methods

Between 1998 and 2003, 10 intramedullary spinal tumors were treated with stereotactic radiosurgery at the authors' institution. Seven hemangioblastomas and three ependymomas were treated in four men and three women. These patients either had recurrent tumors, had undergone several previous surgeries, had medical contraindications to surgery, or had declined open resection. Conformal treatment planning delivered a prescribed dose of 1800 to 2500 cGy (mean 2100 cGy) to the lesions in one to three stages. No significant treatment-related complications have been recorded. The mean radiographic and clinical follow-up duration was 12 months (range 1–24 months). One ependymoma and two hemangioblastomas were smaller on follow-up neuroimaging. The remaining tumors were stable at the time of follow-up imaging.

Conclusions

Stereotactic radiosurgery for intramedullary spinal tumors is feasible and safe in selected cases and may prove to be another therapeutic option for these challenging lesions.

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Daniel M. May, Stephen J. Jones and H. Alan Crockard

✓ Cortical and subcortical somatosensory evoked potentials (SSEPs) were noninvasively monitored in 191 surgical procedures involving the cervical spine. In nine patients in the poorest neurological condition, SSEPs could not be monitored. Lower limb SSEPs were often too degraded to be useful.

Upper limb responses were reliably recorded in 182 procedures, with a sensitivity of 99% and a specificity of 27% in 10 patients who developed neurological signs postsurgery. The aim of monitoring was to detect changes in spinal cord function at a time when neurological deterioration could be prevented or reversed, and these studies alerted the authors to certain clinical and SSEP risk factors associated with deterioration. Clinical and operative risk factors were: 1) poor preoperative neurological function (one-third of Ranawat Class IIIb patients deteriorated); 2) use of instrumentation (the risk doubled in preoperatively unimpaired patients); 3) upper cervical and clival surgery (the risk tripled); and 4) and multi-segmental surgery (increased risk with each additional level).

There were SSEP changes in 33 patients. Fifty percent of patients with a complete loss had neurological damage, unlike those who had incomplete loss or whose electrical changes had recovered by the end of surgery. In the authors' view these “false positives” may represent real physiological changes, the effects of which might have been minimized by an alteration in the surgeon's response as a result of the warning. Although these initial studies have made this surgical team more alert to potential problems, the role of intraoperative SSEP monitoring is still being debated.

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Daniel G. Nehls, Stephen R. Marano and Robert F. Spetzler

✓ Recent experience with an intraventricular arteriovenous malformation (AVM) demonstrated the usefulness of a transcallosal approach to the contralateral ventricle. Although this technique provides excellent exposure, its application has not been stressed in the literature. A brief description of the technique and its value is presented.

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Daniel G. Nehls, Stephen R. Marano and Robert F. Spetzler

✓ A case of angiographically verified positional occlusion of the internal carotid artery is presented. A small web-like atherosclerotic plaque was found to be responsible for producing the intermittent occlusion. Endarterectomy was curative. The clinical implications of the case are discussed.

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Kent Sauter, Howard H. Kaufman, Stephen M. Bloomfield, Sandi Cline and Daniel Banks

✓ The case is reported of a 45-year-old woman who was being treated for chronic back and right leg pain with intrathecal morphine administered via a subcutaneous continuous-infusion device. She received an accidental 450-mg bolus injection of morphine intrathecally and developed hypertension, status epilepticus, intracerebral hemorrhage, and respiratory failure. Treatment with continuous intravenous naloxone infusion, lumbar catheter drainage of cerebrospinal fluid, and control of hypertension and status epilepticus resulted in an excellent outcome with return to neurological baseline. Care providers who refill pump reservoirs with morphine must be knowledgeable about these devices and the life-threatening consequences associated with errors in refilling them. This case describes the complications and successful treatment of high-dose intrathecal morphine overdose.

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Thomas J. Wilson, Daniel A. Orringer, Stephen E. Sullivan and Parag G. Patil

Thoracic vertebral compression fractures are a known complication of generalized tetanus. The authors report the first known case of an L-2 burst fracture leading to cauda equina syndrome, as a result of generalized tetanus.

This 51-year-old man had generalized tetanus with a constellation of symptoms including compartment syndrome requiring fasciotomies, severe axial spasms and spasms of the extremities, autonomic dysreflexia, hypercarbic respiratory failure, and rhabdomyolysis. During the course of his illness, areflexic paraparesis developed in his lower extremities. He was found to have an L-2 burst fracture with retropulsion of a bone fragment resulting in cauda equina syndrome. Operative intervention was undertaken to decompress the cauda equina and stabilize the spine.

The natural progression of tetanus can be complex, with a mixed picture ranging from spasms plus increased tone and reflexes to reduced tone and reflexes as presynaptic nerve terminals become damaged. The authors suggest that all sudden changes in the neurological examination should prompt consideration of diagnostic imaging before attributing such changes to natural progression of the disease.

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Howard P. Charman, Daniel H. Lowenstein, Kyung G. Cho, Stephen J. DeArmond and Charles B. Wilson

✓ A 65-year-old man with a history of exposure to industrial solvents developed a primary cerebral angiosarcoma in the left posterior parieto-occipital lobe. The tumor had features typical of angiosarcoma on light and electron microscopy, immunohistochemical evidence of factor VIII-related antigen produced in tumor cells, and a high labeling index with bromodeoxyuridine. The relationship of angiosarcoma to toxins and viruses is discussed.

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Stephen C. Saris, Paul Spiess, Daniel M. Lieberman, Shan Lin, Stuart Walbridge and Edward H. Oldfield

✓ Methods have recently been described for the isolation and expansion of lymphocytes that have trafficked into animal and human tumors. These CD8-positive tumor-infiltrating lymphocytes (TIL's) have exceptional trafficking ability to, and efficacy against, tumor targets in extracranial sites. Prior to Phase I clinical trials for patients with gliomas, adoptive immunotherapy with TIL's was studied in a mouse model of primary brain tumors to determine if intracerebral tumors have a similar response.

Glioma 261 (GL261) tumors were grown in the subcutaneous space of C57BL/6 mice. After enzymatic digestion, the cells were incubated in vitro with interleukin-2 (IL-2) until a confluent population of T lymphocytes was present. The in vitro efficacy of these TIL's was tested against fresh GL261 targets with a chromium release assay; the in vivo efficacy was tested against GL261 tumors in the liver and against irradiated and nonirradiated GL261 tumors in the brain. Mice received one of the following: intraperitoneal saline; intraperitoneal IL-2 (7500 to 50,000 U three times daily for 5 days); IL-2 plus intravenous TIL's (1 to 3 × 107 cells); 10 Gy cranial irradiation; irradiation plus IL-2; or irradiation plus IL-2 plus TIL's.

The TIL preparation killed 77% of tumor targets in 4 hours at an effector:target ratio of 100:1. In animals with GL261 tumors in the liver, at 2 weeks there were 93 ± 37, 128 ± 45, and 21 ± 14 liver metastases in the control, IL-2, and IL-2 plus TIL groups, respectively. However, in animals with GL261 tumors in the brain, no treatment group had an increased survival rate compared to the control group.

It is concluded that, although TIL and IL-2 immunotherapy can be used effectively to treat brain tumors in vitro and at sites outside the central nervous system, it is ineffective against the same type of tumor in the brain. Different methods of delivery or different combinations of these immunomodulators may be more effective; however, based on these findings, treatment of patients with IL-2 and TIL cannot be recommended until efficacy has been demonstrated in an animal model.

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William J. Triffo, J. Daniel Bourland, Daniel E. Couture, Kevin P. McMullen, Stephen B. Tatter and Padraig P. Morris

Vein of Galen aneurysmal malformations (VGAMs) are uncommon congenital malformations arising from fistulous communication with the median vein of the prosencephalon, a primitive precursor of midline cerebral venous structures. Angiographic embolization is the primary modality for treatment given historically poor microsurgical outcomes. Only a few reports of treatment by Gamma Knife radiosurgery (GKRS) exist in the literature, and the results are variable. The authors present 2 cases of VGAM in which GKRS provided definitive treatment with good outcome: one case involving antenatal presentation of a high-output, mural-type VGAM with complex clinical course refractory to multiple embolic procedures, and the other a choroidal-type VGAM presenting with hemorrhage in an adult and without a feasible embolic approach. With discussion of these cases and review of the literature, the authors advocate inclusion of GKRS as a therapeutic option for treatment of these complex lesions.