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Lynn S. Ashby and Timothy C. Ryken

✓Despite recent successes in the treatment of cancer with multidisciplinary multimodal treatment approaches, the duration of survival for patients with malignant glioma remains limited. Malignant gliomas represent a class of infiltrative, aggressive neoplasms that are generally resistant to combination therapies. The basic approach to treatment has involved a combination of surgery and radiotherapy. The use of chemotherapy has been met with skepticism because of its limited efficacy and the significant side effects demonstrated in clinical trials. Nevertheless, based on findings in randomized trials of new agents, it has been suggested that further evaluation of the role of chemotherapy is warranted. Temozolomide and Gliadel (carmustine wafers) are generally well tolerated due to their limited systemic toxicity. These agents appear particularly well suited for incorporation into multimodal treatment strategies. Proposed investigations and ongoing clinical trials will be conducted to assess the use of these agents in novel combination therapies. Future treatment strategies may include a wide variety of biological response modifiers, but will need to continue to address local control with surgery, radiation, and adjuvant chemotherapy.

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Timothy Ryken and Arnold Menezes

Rheumatological complications have been described in up to 30% of patients being followed for inflammatory bowel disease. The majority of these complications occur as spondylitic changes in the lumbar spine. Erosive arthritic disease associated with inflammatory bowel disease occurs less frequently, but it can result in ligamentous laxity and joint instability. To highlight the potential significance of the process at the craniocervical junction, the authors describe the long-term follow-up care of a complicated case. A 56-year-old woman, with a long history of ulcerative colitis, presented with atlantoaxial instability and underwent a C1-3 fusion; however, the presence of significant occipitoatlantal instability was not recognized. This resulted in high cervicomedullary quadriplegia, requiring traction reduction and a combined anterior transoral decompressive-posterior occipitocervical fusion. The patient's neurological deficit completely resolved postoperatively.

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Timothy C. Ryken and Arnold H. Menezes

✓ Six patients with achondroplasia and symptoms suggestive of cervicomedullary junction compression are reviewed; these included three females and three males, with an average age of 8 years (range 7 months to 30 years). The mean duration of symptoms prior to intervention was 1.9 years. Symptoms included occipitocervical pain, ataxia, incontinence, apnea, and respiratory arrest. Radiological investigations consisted of plain films with flexion and extension views, pluridirectional tomography, thin-section computerized tomography, and magnetic resonance imaging. Typical findings included marked foramen magnum stenosis, ventrolateral cervicomedullary junction compression secondary to central and paramesial basilar invagination, and dorsal cervicomedullary junction compression secondary to ligamentous hypertrophy and invagination of the posterior atlantal arch. All patients underwent posterior fossa decompression and atlantal laminectomy. Surgery consistently revealed marked dorsal and paramesial overgrowth of the rim of the foramen magnum, with thickening and invagination of the atlantal posterior arch and a dense fibrotic epidural band resulting in dorsal cervicomedullary compression. Intraoperative ultrasonography was used to determine the extent of decompression required.

Three patients required duraplasty. Three patients had concurrent hydrocephalus, two of whom had undergone ventriculoperitoneal shunting prior to surgical decompression of the posterior fossa. One patient developed a pseudomeningocele postoperatively, requiring serial lumbar punctures before it resolved. No patient developed craniovertebral instability following decompression. Improvement or resolution of symptoms was noted in all patients, with an average follow-up period of 4.8 years. Thus, cervicomedullary compression in patients with achondroplasia can be successfully treated with dorsal decompression of the craniovertebral junction. Dense epidural fibrotic bands are frequently noted in these cases and must be aggressively released to ensure satisfactory decompression.

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Kurt M. Eichholz and Timothy C. Ryken

Surgical treatment for symptomatic cervical and lumbar spondylosis has become prevalent in recent years. With this increased intervention, increasing numbers of patients experience persistent symptoms and require revision spinal surgery. Although many aspects of the workup and operation are similar for both primary and revision surgery, there are special considerations that must be examined when determining if a patient is a candidate for revision surgery.

Preoperative workup should include evaluation for spinal instability. Intraoperatively, scar tissue may complicate the procedure, and care must be taken to avoid incidental durotomy. The prognosis for a revision surgery can be predicted best by the patient's outcome after the primary surgery. As with any surgical procedure, patient selection is imperative for successful outcome.

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Clifford B. Soults, Greg S. Canute and Timothy C. Ryken

Using an evidence-based approach to available clinical studies, the authors examined the role of reoperation in the management of malignant glioma. A review of 1270 Medline-referenced articles spanning the period from 1966 through March 1998 was undertaken using the key words “glioblastoma” and “astrocytoma.” Using an evidence-based four-tiered grading system, the authors found only 14 articles that met their inclusion criteria. Of these, 11 were graded as Class III (retrospective case series) and three as Class II (prospective nonrandomized studies). There were no Class I reports (randomized clinical trials), and all Class IV reports (opinion reports) were excluded. The authors of 10 Class III and one Class II articles supported the role of reoperation in increasing survival time or quality of life in selected patients; however, the results of multivariate analysis in two Class II and one Class III article did not support prolonged survival. The authors conclude that there was insufficient evidence to support either a standard or a guideline for reoperation in malignant glioma given the current status of the literature. Selection bias was a major factor in these studies. With continued interest in clinical trials for recurrent malignant glioma, the role of reoperation needs to be addressed in case-controlled or randomized fashion to establish either standards or guidelines on this commonly debated issue.

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Timothy C. Ryken, Vincent C. Traynelis and Ramon Lim

✓ The mitogenic and morphological effects of acidic fibroblast growth factor (aFGF) and transforming growth factor-β (TGF-β) were assessed on cultured fetal rat astrocytes and C6 rat glioma cells in the presence and absence of serum. Astrocytes incubated with aFGF exhibited an increase in mitotic activity and characteristic morphological changes involving extensive process formation and rounding of cell bodies. Astrocytes incubated with TGF-β underwent a slight decrease in mitotic activity and remained morphologically unchanged. Cells exposed to a combination of aFGF and TGF-β demonstrated an attenuation of both the mitogenic and morphological changes observed in the presence of aFGF alone. The C6 glioma cells cultured in the presence of aFGF underwent a characteristic morphological change from a rounded piling cell mass to a more spindle-shaped bipolar cell layer, accompanied by an increase in mitotic activity. In contrast to the astrocyte cultures, increased growth and similar morphological effects were produced by TGF-β. The combination of aFGF and TGF-β did not result in attenuation of the mitogenic and morphological changes (as seen in astrocytic cells). These results suggest that, in normal fetal rat astrocytes, TGF-β is capable of attenuating the mitogenic and morphological changes induced by aFGF in vitro. In the transformed C6 glioma cell line, aFGF and TGF-β elicit similar mitogenic and morphological changes, without evidence of an antagonistic interaction as seen in normal astrocytes.

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Derek A. Taggard, Arnold H. Menezes and Timothy C. Ryken

Object. Operative intervention for craniovertebral junction (CVJ) instability in patients with Down syndrome has become controversial, with reports of a low incidence of associated neurological dysfunction and high surgical morbidity rates. The authors analyzed their experience in light of these poor results and attempted to evaluate differences in management.

Methods. Medical and radiographic records of 36 consecutive patients with Down syndrome and CVJ abnormalities were reviewed. The most common clinical complaints included neck pain (15 patients) and torticollis (12 patients). Cervicomedullary compression was associated with ataxia and progressive weakness. Hyperreflexia was documented in a majority of patients (24 cases), and 13 patients suffered from varying degrees of quadriparesis. Upper respiratory tract infection precipitated the presentation in five patients. Four patients suffered acute neurological insults after a minor fall and two after receiving a general anesthetic agent.

Atlantoaxial instability was the most common radiographically observed abnormality (23 patients), with a rotary component present in 14 patients. Occipitoatlantal instability was also frequently observed (16 patients) and was coexistent with atlantoaxial dislocation in 15 patients. Twenty individuals had bone anomalies, the most frequent of which was os odontoideum (12 patients) followed by atlantal arch hypoplasia and bifid anterior or posterior arches (eight patients).

Twenty-seven patients underwent surgical procedures without subsequent neurological deterioration, and a 96% fusion rate was observed. In five of 11 patients basilar invagination was irreducible and required transoral decompression. Overall, 24 patients enjoyed good or excellent outcomes.

Conclusions. The results of this series highlight the clinicopathological characteristics of CVJ instability in patients with Down syndrome and suggest that satisfactory outcomes can be achieved with low surgical morbidity rates.

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Derek A. Taggard, Arnold H. Menezes and Timothy C. Ryken

Operative intervention for the treatment of instability at the craniovertebral junction in patients with Down's syndrome has become somewhat controversial because some authors have reported high surgery-related complication rates and suggested that the incidence of neurological abnormality associated with this abnormal motion may be low. In this report, the authors describe the clinical and radiographic findings in 33 patients treated at their institution. Common presenting symptoms included neck pain (14 patients), torticollis (12 patients), and myelopathy manifested as hyperreflexia (21 patients), or varying degrees of quadriparesis (11 patients). Four patients suffered acute neurological insults, two after receiving routine general anesthetics for minor surgical procedures and two other patients following minor falls. Atlantoaxial instability was the most common abnormality documented on radiography (22 patients). Atlantooccipital instability (15 patients) was also frequently observed and was coexistent with the presence of atlantoaxial luxations in 14 patients. A rotary component of the atlantoaxial luxation was present in 13 cases. In 17 patients bony anomalies were present, the most frequent of which was os odontoideum (10 patients). Twenty-four patients underwent operative intervention, and successful fusion was achieved in 23. In six of nine patients with basilar invagination, reduction was achieved with preoperative traction and thus avoided the need for ventral decompressive procedures. There were no cases of postoperative deterioration, and 22 patients made excellent or good recoveries. The results of this series highlight the clinicopathological phenomena of craniovertebral instability in patients with Down's syndrome and suggest that satisfactory outcomes can be achieved with a low rate of surgical morbidity.

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Daniel K. Resnick, David G. Malone and Timothy C. Ryken

Object

Discography has been used as a diagnostic test in the evaluation of patients with recalcitrant low-back pain. Recently, its usefulness has been questioned because of the occurrence of false-positive results as well as the influence of psychological factors on test results. The purpose of this review is to establish the literature support for and against the use of discography.

A search of the English-language literature published between 1966 and 2001 was performed. Papers were selected based on inclusion criteria described in the text, and the quality of information was graded using previously described methods.

Conclusions

The authors propose a set of practice parameters based on the literature. Although the data were not judged adequate for the determination of a treatment standard, parameters for the use of discography are provided at a guideline and option level.

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Timothy Ryken, Bruce Frankel, Sharon Longo and Zita Sibenaller

Object

An experimental model of the fas and fas ligand (fasL) interaction in malignant glioma was developed.

Methods

Using plasmid-based delivery, 36B10 rat glioma cells were modified to express fas (36B10-fas), and a delivery fibroblast cell line was modified to produce fasL, resulting in the FR-fasL cell line. Evaluation of fas expression was performed with flow cytometry and expression of fasL confirmed by Western blot analysis. Once the cell lines were created and partially characterized, fas-induced cytotoxicity was evaluated using an antibody-mediated assay for 36B10-fas that demonstrated significant toxicity at 24 and 48 hours. To evaluate the potential for activating the fas molecule by using cell-mediated delivery, coculture cytotoxicity studies were performed with a target cell line (36B10-fas) and effector cell line (FR-fasL). Using a series of culture ratios, increasing cytotoxicity was noted, suggesting that activation of the transfected fas receptor by fasL expression on the carrier cell was occurring.

Conclusion

Based on their experiments, the authors describe a model for evaluating the interaction of fas and fasL in a cellular model of malignant glioma.