Faculty Bibliography

OBJECTIVE AND IMPORTANCE: In rare cases, posterior fossa meningiomas can involve the endolymphatic sac. Such involvement can result in endolymphatic hydrops and a constellation of symptoms suggestive of Meniere's disease. The diagnosis and management of patients with these tumors is discussed. CLINICAL PRESENTATION: Three patients, each of whom presented with symptoms consistent with Meniere's disease, were found to have posterior fossa meningiomas limited to the dura overlying the endolymphatic sac. INTERVENTION: All 3 patients were diagnosed by magnetic resonance imaging and underwent complete surgical resection. In all cases, the symptoms resolved after tumor removal. CONCLUSION: Clinicians should have a degree of suspicion of posterior fossa meningioma when patients present with symptoms suggestive of Meniere's disease. Failure to do so may result in delayed diagnosis or worse outcomes for an otherwise treatable tumor

INTRODUCTION: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), has shown promise in the treatment of patients with recurrent high-grade glioma. The purpose of this study is to test the feasibility of using bevacizumab with chemoradiation in the primary management of high-grade glioma. METHODS AND MATERIALS: Fifteen patients with high-grade glioma were treated with involved field radiation therapy to a dose of 59.4 Gy at 1.8 Gy/fraction with bevacizumab 10 mg/kg on Days 14 and 28 and temozolomide 75 mg/m(2). Subsequently, bevacizumab 10 mg/kg was continued every 2 weeks with temozolomide 150 mg/m(2) for 12 months. Changes in relative cerebral blood volume, perfusion-permeability index, and tumor volume measurement were measured to assess the therapeutic response. Immunohistochemistry for phosphorylated VEGF receptor 2 (pVEGFR2) was performed. RESULTS: Thirteen patients (86.6%) completed the planned bevacizumab and chemoradiation therapy. Four Grade III/IV nonhematologic toxicities were seen. Radiographic responses were noted in 13 of 14 assessable patients (92.8%). The pVEGFR2 staining was seen in 7 of 8 patients (87.5%) at the time of initial diagnosis. Six patients have experienced relapse, 3 at the primary site and 3 as diffuse disease. One patient showed loss of pVEGFR2 expression at relapse. One-year progression-free survival and overall survival rates were 59.3% and 86.7%, respectively. CONCLUSION: Use of antiangiogenic therapy with radiation and temozolomide in the primary management of high-grade glioma is feasible. Perfusion imaging with relative cerebral blood volume, perfusion-permeability index, and pVEGFR2 expression may be used as a potential predictor of therapeutic response. Toxicities and patterns of relapse need to be monitored closely

BACKGROUND: The perioperative course of patients undergoing intracranial surgery is frequently complicated by hypertensive episodes. Dexmedetomidine (DEX), an alpha-2 adrenoreceptor agonist, is gaining popularity in neuroanesthesia, because its sympatholytic and antinociceptive properties may improve hemodynamic stability at critical moments of surgery. We designed this study to assess the efficacy of DEX in controlling hypertensive responses in patients undergoing intracranial surgery. METHODS: Patients scheduled for elective craniotomy were randomly assigned to receive either sevoflurane-opioid or sevoflurane-opioid-DEX anesthesia. Bispectral index was used to maintain a similar level of hypnosis in both groups (40-50). Opioids, sevoflurane, and vasoactive medications were titrated in a routine manner, at the discretion of the blinded anesthesiologist managing the case, to maintain systolic blood pressure (SBP) targeted within 90-130 mm Hg and heart rate (HR) between 50 and 90 bpm. Hemodynamic variables were continuously recorded and stored on a computer for analysis. Efficacy of the anesthetic technique in controlling SBP or HR is inversely proportional to the area under the curve (AUC) outside the targeted range. Areas under the curves above and below targeted ranges for SBP-time (AUCsbp mm Hg*min/h) and HR-time (bpm*min/h) were compared. Coefficient of variation was used to assess hemodynamic stability. RESULTS: Seventy-two patients were recruited for the study. Computerized records of 56 patients only were analyzed because of technical problems with data collection in 14 cases. AUCsbp for above the targeted range was significantly lower for patients in the DEX group (P=0.044). The coefficient of variation for SBP or HR did not differ between groups. A significantly smaller proportion of patients in the DEX group required treatment with antihypertensive medications (12 of 28, 42% vs 24 of 28, 86%, P=0.0008). The DEX group required fewer opioids in the intraoperative period, but there were no differences in the use of sevoflurane. In the postanesthesia care unit, patients in the DEX group had fewer hypertensive episodes (1.25+/-1.55 vs 2.50+/-2.00, P=0.0114) and were discharged earlier (91+/-17 vs 130+/-27 min, P<0.0001). There were no differences in the requirement for postoperative opioids or antiemetics. CONCLUSIONS: By using indices, which assess a global hemodynamic stability of the anesthetic, we determined that intraoperative DEX infusion was effective for blunting the increases in SBP perioperatively. The use of DEX did not increase the incidence of hypotension or bradycardia, common side effects of the drug

We evaluate the effects of adjuvant treatment with the angiogenesis inhibitor Avastin (bevacizumab) on pathological tissue specimens of high-grade glioma. Tissue from five patients before and after treatment with Avastin was subjected to histological evaluation and compared to four control cases of glioma before and after similar treatment protocols not including bevacizumab. Clinical and radiographic data were reviewed. Histological analysis focused on microvessel density and vascular morphology, and expression patterns of vascular endothelial growth factor-A (VEGF-A) and the hematopoietic stem cell, mesenchymal, and cell motility markers CD34, smooth muscle actin, D2-40, and fascin. All patients with a decrease in microvessel density had a radiographic response, whereas no response was seen in the patients with increased microvessel density. Vascular morphology showed apparent 'normalization' after Avastin treatment in two cases, with thin-walled and evenly distributed vessels. VEGF-A expression in tumor cells was increased in two cases and decreased in three and did not correlate with treatment response. There was a trend toward a relative increase of CD34, smooth muscle actin, D2-40, and fascin immunostaining following treatment with Avastin. Specimens from four patients with recurrent malignant gliomas before and after adjuvant treatment (not including bevacizumab) had features dissimilar from our study cases. We conclude that a change in vascular morphology can be observed following antiangiogenic treatment. There seems to be no correlation between VEGF-A expression and clinical parameters. While the phenomena we describe may not be specific to Avastin, they demonstrate the potential of tissue-based analysis for the discovery of clinically relevant treatment response biomarkers

PURPOSE: To retrospectively determine whether relative cerebral blood volume (CBV) measurements can be used to predict clinical outcome in patients with high-grade gliomas (HGGs) and low-grade gliomas (LGGs) and specifically whether patients who have gliomas with a high initial relative CBV have more rapid progression than those who have gliomas with a low relative CBV. MATERIALS AND METHODS: Approval for this retrospective HIPAA-compliant study was obtained from the Institutional Board of Research Associates, with waiver of informed consent. One hundred eighty-nine patients (122 male and 67 female patients; median age, 43 years; range, 4-80 years) were examined with dynamic susceptibility-weighted contrast material-enhanced perfusion magnetic resonance (MR) imaging and were followed up clinically with MR imaging (median follow-up, 334 days). Log-rank tests were used to evaluate the association between relative CBV and time to progression by using Kaplan-Meier curves. Binary logistic regression was used to determine whether age, sex, and relative CBV were associated with an adverse event (progressive disease or death). RESULTS: Values for the mean relative CBV for patients according to each clinical response were as follows: 1.41 +/- 0.13 (standard deviation) for complete response (n = 4), 2.36 +/- 1.78 for stable disease (n = 41), 4.84 +/- 3.32 for progressive disease (n = 130), and 3.82 +/- 1.93 for death (n = 14). Kaplan-Meier estimates of median time to progression in days indicated that patients with a relative CBV of less than 1.75 had a median time to progression of 3585 days, whereas patients with a relative CBV of more than 1.75 had a time to progression of 265 days. Age and relative CBV were also independent predictors for clinical outcome. CONCLUSION: Dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging can be used to predict median time to progression in patients with gliomas, independent of pathologic findings. Patients who have HGGs and LGGs with a high relative CBV (>1.75) have a significantly more rapid time to progression than do patients who have gliomas with a low relative CBV