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Michael J. Harrison, Blake G. Welling and Jeffrey J. Dubois

✓ This technical note describes a simple percutaneous mechanism for placement of the atrial end of ventriculoatrial shunts. The method is fast, efficient, and involves no neck dissection. No special equipment is required. Placement involves the technique of central line insertion familiar to all surgeons. This new method has been used successfully in one adult and one pediatric patient.

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Christine Wild-Bode, Michael Weller and Wolfgang Wick

Object. Migration and invasion are important prerequisites for the infiltrative and destructive growth patterns of malignant gliomas. Infiltrative growth prevents complete tumor resection and causes significant neurological morbidity and mortality.

Methods. The authors assessed the expression of matrix metalloproteinases (MMPs) at messenger RNA and protein levels, MMP-2 and MMP-9 activities, and expression levels of a panel of anti- and proapoptotic proteins of the BCL-2 family. They then correlated their findings with αVβ3 integrin expression and the migratory and invasive potentials in 12 human malignant glioma cell lines.

Multiple MMPs were expressed by most cell lines. The levels of MMP-2 and MMP-3 and the activities of MMP-2 and MMP-9 correlated with tumor cell invasion. Migration and invasion were also correlated. Although the expression levels of αVβ3 integrin did not predict migration or invasion, a neutralizing αVβ3 integrin antibody inhibited migration and invasion selectively in cell lines that contained a high level of αVβ3 integrin expression, thus indicating the important role of αVβ3 integrin for migration and invasion in this subset of cell lines. An expression pattern of BCL-2 family proteins that favor resistance to apoptosis was associated with enhanced migration, invasion, and MMP activity. Wild-type p53 cell lines migrated farther than mutant p53 cell lines.

Conclusions. Activities of MMP-2 and MMP-9 are the best predictors of glioma cell invasion. The αVβ3 integrin mediates migration and invasion in a subset of glioma cell lines, but these processes do not depend on αVβ3 integrin expression. Antiapoptotic BCL-2 family protein expression is a predictor of efficient migration and invasion.

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M. Peter Heilbrun, Theodore S. Roberts, Michael L. J. Apuzzo, Trent H. Wells Jr. and James K. Sabshin

✓ The production model of the Brown-Roberts-Wells (BRW) computerized tomography (CT) stereotaxic guidance system is described. Hardware and software modifications to the original prototype now allow the system to be used independently of the CT scanner after an initial scan with the localizing components fixed to the skull. The system is simple and efficient, can be used universally with all CT scanners, and includes a phantom simulator system for target verification. Preliminary experience with 74 patients at two institutions is described. It is concluded that CT stereotaxic guidance systems will become important tools in the neurosurgical armamentarium, as they allow accurate approach to any target identifiable on the CT scan.

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Samuel L. Barnett, Michael J. Wells, Bruce Mickey and Kimmo J. Hatanpaa

The authors present a case illustrating the importance of obtaining a biopsy of any facial skin lesions in a patient presenting with an intracranial tumor involving the facial or trigeminal nerve. Conventional malignant melanoma metastasizes to the brain frequently and does not usually pose diagnostic difficulties. Direct intracranial spread of cutaneous melanoma is rare. In our patient, desmoplastic melanoma with perineural spread to the Meckel cave mimicked a malignant peripheral nerve sheath tumor clinically, radiographically, and histologically.

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Wells I. Mangrum, John Huston III, Michael J. Link, David O. Wiebers, Robyn L. McClelland, Teresa J. H. Christianson and Kelly D. Flemming

Object. Vertebrobasilar nonsaccular intracranial aneurysms (NIAs) are characterized by elongation, dilation, and tortuosity of the vertebrobasilar arteries. The goal of this study was to define the frequency, predictors, and clinical outcome of the enlargement of vertebrobasilar NIAs.

Methods. Patients with vertebrobasilar fusiform or dolichoectatic aneurysms demonstrated on imaging studies between 1989 and 2001 were identified. In particular, patients who had undergone serial imaging were included in this study and their medical records were retrospectively reviewed. Prospective information was collected from medical records or death certificates when available. Both initial and serial imaging studies were reviewed. The authors defined NIA enlargement as a change in lesion diameter greater than 2 mm or noted on the neuroradiologist's report. A Cox proportional hazards regression was used to model time from diagnosis of the vertebrobasilar NIA to the first documented enlargement as a function of various predictors. The Kaplan-Meier method was used to study patient death as a function of aneurysm growth.

Of the 159 patients with a diagnosis of vertebrobasilar NIA, 52 had undergone serial imaging studies including 25 patients with aneurysm enlargement. Lesion growth significantly correlated with symptomatic compression at the initial diagnosis (p = 0.0028), lesion type (p < 0.001), and the initial maximal lesion diameter (median 15 mm in patients whose aneurysm enlarged compared with median 8 mm in patients whose aneurysm did not enlarge; p < 0.001). The mortality rate was 5.7 times higher in patients with aneurysm growth than in those with no enlargement after adjustment for patient age (p = 0.002).

Conclusions. Forty-eight percent of vertebrobasilar NIAs demonstrated on serial imaging enlarged, and this growth was associated with significant morbidity and death. Significant risk factors for aneurysm enlargement included symptomatic compression at the initial diagnosis, transitional or fusiform vertebrobasilar NIAs, and initial lesion diameter. Further studies are necessary to determine appropriate treatments of this disease entity once enlargement has been predicted or occurs.

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Michael D. Jenkinson, Damien C. Weber, Brian J. Haylock, Frances C. Sherratt, Bridget Young, Michael Weller, Helen Bulbeck, Giovanna Culeddu, Dyfrig A. Hughes, Alice Brain, Kumar Das, Matthias Preusser, Priya Francis and Carrol Gamble

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Michael D. Jenkinson, Damien C. Weber, Brian J. Haylock, Frances C. Sherratt, Bridget Young, Michael Weller, Helen Bulbeck, Giovanna Culeddu, Dyfrig A. Hughes, Alice Brain, Kumar Das, Matthias Preusser, Priya Francis and Carrol Gamble

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James Miller, Guenter Eisele, Ghazaleh Tabatabai, Steffen Aulwurm, Gabriele von Kürthy, Lothar Stitz, Patrick Roth and Michael Weller

Object

Given the overall poor outcome with current treatment strategies in malignant gliomas, immunotherapy has been considered a promising experimental approach to glioblastoma for more than 2 decades. A cell surface molecule, CD70, may induce potent antitumor immune responses via activation of the costimulatory receptor CD27 expressed on immune effector cells. There is evidence that a soluble form of CD70 (sCD70) may exhibit biological activity, too. A soluble costimulatory ligand is attractive because it may facilitate immune activation and may achieve a superior tissue distribution.

Methods

To test the antiglioma effect of sCD70, the authors genetically modified SMA-560 mouse glioma cells to secrete the extracellular domain of CD70. They assessed the immunogenicity of the transfected cells in cocultures with immune effector cells by the determination of immune cell proliferation and the release of interferon-γ. Syngeneic VM/Dk mice were implanted orthotopically with control or sCD70-releasing glioma cells to determine a survival benefit mediated by sCD70. Depletion studies were performed to identify the cellular mediators of prolonged survival of sCD70-releasing glioma-bearing mice.

Results

The authors found that ectopic expression of sCD70 enhanced the proliferation and interferon-γ release of syngeneic splenocytes in vitro. More importantly, sCD70 prolonged the survival of syngeneic VM/Dk mice bearing intracranial SMA-560 gliomas. The survival rate at 60 days increased from 5 to 45%. Antibody-mediated depletion of CD8-positive T cells abrogates the survival advantage conferred by sCD70.

Conclusions

These data suggest that sCD70 is a potent stimulator of antiglioma immune responses that depend critically on CD8-positive T cells. Soluble CD70 could be a powerful adjuvant for future immunotherapy trials for glioblastoma.

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James S. Waldron, Steven W. Hetts, Jennifer Armstrong-Wells, Christopher F. Dowd, Heather J. Fullerton, Nalin Gupta and Michael T. Lawton

Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is a rare genetic syndrome characterized by extremely small stature and microcephaly, and is associated in 25% of patients with intracranial aneurysms and moyamoya disease. Although aneurysmal subarachnoid hemorrhage and stroke are leading causes of morbidity and death in these patients, MOPD II is rarely examined in the neurosurgical literature. The authors report their experience with 3 patients who presented with MOPD II, which includes a patient with 8 aneurysms (the most aneurysms reported in the literature), and the first report of a patient with both moyamoya disease and multiple aneurysms. The poor natural history of these lesions indicates aggressive microsurgical and/or endovascular therapy. Microsurgery, whether for aneurysm clip placement or extracranial-intracranial bypass, is challenging due to tight surgical corridors and diminutive arteries in these patients, but is technically feasible and strongly indicated when multiple aneurysms must be treated or cerebral revascularization is needed.