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Behnam Badie, J. Keith Preston, and Gregory K. Hartig

✓ The authors evaluated the role of titanium mesh used in combination with vascularized pericranium to provide rigid support during reconstruction of anterior skull base defects.

Thirteen patients with large anterior skull base defects caused by tumor invasion or traumatic injury involving the cribriform plate, orbital roof, and planum sphenoidale were included in the study. The reconstruction technique involved placement of titanium mesh between two layers of continuous vascularized pericranium. Surgical glue and routine lumbar cerebrospinal fluid (CSF) drainage were not used in any patient.

At a mean postoperative follow-up time of 22 months (range 8–39 months), none of the patients had developed infection or meningocele. Postoperative CSF rhinorrhea occurred in two patients with extensive dural defects, which resolved with temporary lumbar drainage.

Use of titanium mesh and a two-layer vascularized pericranial graft is a safe, reproducible, and feasible method for reconstructing the anterior skull base. Patients with large dural defects may need temporary CSF diversion to avoid postoperative fistula formation.

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Anne E. Chauvet, Prabhakar P. Kesava, Chern Sing Goh, and Behnam Badie

Object

The goal of this study was to evaluate gene delivery to a benign brain tumor.

Methods

A recombinant adenovirus vector bearing the Escherichia coli ß-galactosidase reporter gene was selectively injected into the vascular supply of a spontaneously occurring canine olfactory groove meningioma. The tumor and a small amount of peritumoral brain tissue were removed 5 days after viral injection and stained with X-Gal to assess gene delivery. The authors noted significant ß-galactosidase gene expression by the tumor, but not by surrounding brain tissue. No obvious viral-related cytotoxicity was noted.

Conclusions

The authors found that meningiomas can be successfully transduced by adenovirus vectors by using endovascular techniques.

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Anne E. Chauvet, Prabhakar P. Kesava, Chern Sing Goh, and Behnam Badie

Object. The goal of this study was to evaluate gene delivery to a benign brain tumor.

Methods. A recombinant adenovirus vector bearing the Escherichia coli β-galactosidase reporter gene was selectively injected into the vascular supply of a spontaneously occurring canine olfactory groove meningioma. The tumor and a small amount of peritumoral brain tissue were removed 5 days after viral injection and stained with X-Gal to assess gene delivery. The authors noted significant β-galactosidase gene expression by the tumor, but not by surrounding brain tissue. No obvious viral-related cytotoxicity was noted.

Conclusions. The authors found that meningiomas can be successfully transduced by adenovirus vectors by using endovascular techniques.

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Behnam Badie, Jill M. Schartner, Jasmeet Paul, Becky A. Bartley, Jessica Vorpahl, and J. Keith Preston

Object. Commonly used for management of cerebral edema in patients with brain tumors, steroid medications also have immunosuppressive functions. To characterize the effects of steroids on the central nervous system's response to tumors more clearly, flow cytometry was used to quantify the extent of inflammatory cell infiltration in an immunogenic rat glioma model.

Methods. Freshly prepared 11-day-old intracranial C6 tumors that had been excised from dexamethasone-treated and untreated rats were labeled ex vivo with monoclonal antibodies against CD11b/c, CD45, and CD8a antigens. The extent of microglia (CD11b/c—highly positive, CD45—slightly positive cell), macrophage (CD11b/c—highly positive, CD45—highly positive cell), lymphocyte (CD11b/c-negative, CD45—highly positive cell), and cytotoxic T-cell (CD8a-positive cell) infiltration into each rat's tumor, tumor periphery, and contralateral tumor-free hemisphere was analyzed using flow cytometry.

Microglia and lymphocytes constituted a significant component of infiltrating cells in this model, comprising 23 ± 3% and 33 ± 5% of viable cells, respectively. Macrophages, on the other hand, accounted for only 9 ± 1% of infiltrating cells. Treatment of rats with a 7-day course of low-dose dexamethasone (0.1 mg/kg/day) resulted in a greater than 50% inhibition of microglia (p = 0.03) and lymphocyte (p = 0.001) infiltration into tumors. Increasing the dexamethasone dose to 1 mg/kg/day further abolished lymphocyte infiltration (89% inhibition, p = 0.001) but had no additional inhibitory effect on microglia invasion. Macrophage infiltration of tumors was not inhibited at the dexamethasone doses used in this study (p = 0.42).

Conclusions. Flow cytometry is a valuable technique for characterizing tumor-associated inflammatory cells in gliomas. Even at low doses, dexamethasone was found to inhibit significantly the infiltration of brain tumors by lymphocytes and microglia. These findings should be considered when experimental immunotherapeutic strategies are evaluated for clinical application.

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Samir B. Lapsiwala, G. Mark Pyle, Ann W. Kaemmerle, Frank J. Sasse, and Behnam Badie

Object. Hearing loss is the most common presenting symptom in patients who harbor a vestibular schwannoma (VS). Although mechanical injury to the cochlear nerve and vascular compromise of the auditory apparatus have been proposed, the exact mechanism of this hearing loss remains unclear. To test whether pressure on the cochlear nerve from tumor growth in the internal auditory canal (IAC) is responsible for this clinical finding, the authors prospectively evaluated intracanalicular pressure (ICaP) in patients with VS and correlated this with preoperative brainstem response.

Methods. In 40 consecutive patients undergoing a retrosigmoid—transmeatal approach for tumor excision, ICaP was measured by inserting a pressure microsensor into the IAC before any tumor manipulation. Pressure recordings were correlated with tumor size and preoperative auditory evoked potential (AEP) recordings.

The ICaP, which varied widely among patients (range 0–45 mm Hg), was significantly elevated in most patients (median 16 mm Hg). Although these pressure measurements directly correlated to the extension of tumor into the IAC (p = 0.001), they did not correlate to total tumor size (p = 0.2). In 20 patients in whom baseline AEP recordings were available, the ICaP directly correlated to wave V latency (p = 0.0001), suggesting that pressure from tumor growth in the IAC may be responsible for hearing loss in these patients.

Conclusions. Tumor growth into the IAC results in elevation of ICaP and may play a role in hearing loss in patients with VS. The relevance of these findings to the surgical treatment of these tumors is discussed.

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Lindsey Nelson, Samir Lapsiwala, Victor M. Haughton, Jane Noyes, Amir H. Sadrzadeh, Chad H. Moritz, M. Elizabeth Meyerand, and Behnam Badie

Object. Injury to the supplementary motor area (SMA) is thought to be responsible for transient motor and speech deficits following resection of tumors involving the medial frontal lobe. Because direct intraoperative localization of SMA is difficult, the authors hypothesized that functional magnetic resonance (fMR) imaging might be useful in predicting the risk of postoperative deficits in patients who undergo resection of tumors in this region.

Methods. Twelve patients who had undergone fMR imaging mapping while performing speech and motor tasks prior to excision of their tumor, that is, based on anatomical landmarks involving the SMA, were included in this study. The distance between the edge of the tumor and the center of SMA activation was measured and was correlated with the risk of incurring postoperative neurological deficits.

In every patient, SMA activation was noted in the superior frontal gyrus on preoperative fMR imaging. Two speech and two motor deficits typical of SMA injury were observed in three of the 12 patients. The two speech deficits occurred in patients with tumors involving the dominant hemisphere, whereas one of the motor deficits occurred in a patient with a tumor in the nondominant hemisphere. The risk of developing a postoperative speech or motor deficit was 100% when the distance between the SMA and the tumor was 5 mm or less. When the distance between SMA activation and the lesion was greater than 5 mm, the risk of developing a motor or a speech deficit was 0% (p = 0.0007).

Conclusions. Early data from this study indicated that fMR imaging might be useful in localizing the SMA and in determining the risk of postoperative deficits in patients who undergo resection of tumors located in the medial frontal lobe.

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Brian P. Witwer, Roham Moftakhar, Khader M. Hasan, Praveen Deshmukh, Victor Haughton, Aaron Field, Konstantinos Arfanakis, Jane Noyes, Chad H. Moritz, M. Elizabeth Meyerand, Howard A. Rowley, Andrew L. Alexander, and Behnam Badie

Object. Preserving vital cerebral function while maximizing tumor resection is a principal goal in surgical neurooncology. Although functional magnetic resonance imaging has been useful in the localization of eloquent cerebral cortex, this method does not provide information about the white matter tracts that may be involved in invasive, intrinsic brain tumors. Recently, diffusion-tensor (DT) imaging techniques have been used to map white matter tracts in the normal brain. The aim of this study was to demonstrate the role of DT imaging in preoperative mapping of white matter tracts in relation to cerebral neoplasms.

Methods. Nine patients with brain malignancies (one pilocytic astrocytoma, five oligodendrogliomas, one low-grade oligoastrocytoma, one Grade 4 astrocytoma, and one metastatic adenocarcinoma) underwent DT imaging examinations prior to tumor excision. Anatomical information about white matter tract location, orientation, and projections was obtained in every patient. Depending on the tumor type and location, evidence of white matter tract edema (two patients), infiltration (two patients), displacement (five patients), and disruption (two patients) could be assessed with the aid of DT imaging in each case.

Conclusions. Diffusion-tensor imaging allowed for visualization of white matter tracts and was found to be beneficial in the surgical planning for patients with intrinsic brain tumors. The authors' experience with DT imaging indicates that anatomically intact fibers may be present in abnormal-appearing areas of the brain. Whether resection of these involved fibers results in subtle postoperative neurological deficits requires further systematic study.