Brain Edema In Meningiomas Research Articles

Peritumoral Brain Edema in Meningiomas May Be Related to Glymphatic Dysfunction.

The pathogenesis of peritumoral brain edema (PTBE) in meningiomas remains unclear. The glymphatic system is recently recognized as a pathway for waste clearance and maintaining fluid balance in the brain parenchymal interstitium. We aimed to investigate if the PTBE volume of meningiomas correlates with their glymphatic function. A total of 80 meningioma patients (mean age, 58.8 years; 37 men) and 44 normal subjects (mean age 53.3 years; 23 men) who had preoperative diffusion-tensor imaging for calculation of the analysis along the perivascular space (ALPS) index were retrospectively included. Information collected from each patient included sex, age, tumor grade, Ki-67 index, tumor location, tumor volume, PTBE volume and ALPS index. Comparisons of ALPS index among meningiomas without PTBE, meningiomas with PTBE, and normal subjects were performed using analysis of covariance with Bonferroni correction and adjustments for age and sex. Pearson correlation coefficient and multivariable linear regression analyses were performed to identify factors associated with PTBE volume. Group comparisons revealed that the ALPS index was significantly higher (P < 0.05) in meningiomas without PTBE vs. meningiomas with PTBE and normal subjects. On the other hand, ALPS index was not different between meningiomas with PTBE and normal subjects. On Pearson correlation and multivariable linear regression analyses, the ALPS index was the only factor significantly (P < 0.05) associated with PTBE volume. In conclusion, PTBE volume inversely correlated with ALPS index in meningiomas. PTBE formation in meningiomas may be related to glymphatic dysfunction.

Ki67 Proliferative Index and Peritumoral Brain Edema in Meningiomas: Do They Correlate? A Clinical Study on 56 Patients

Introduction: Meningiomas are the most common type of extra-axial neoplasm. Peritumoral brain edema (PTBE) can be seen around meningiomas while it may be absent in others. Despite that Ki67 proliferative index has been previously correlated with meningioma grades, no definite relationship has been established in relation to PTBE in meningioma patients. Objective: Correlate the peritumoral brain edema with the Ki67 proliferative index of meningiomas. Patients & Methods: Aclinical prospective study was conducted on 56 patients (47 women, 9 men; mean age 50.89 ± 12.55 years) diagnosed with meningiomas. All patients were evaluated regarding the presence of brain edema surrounding the lesion in pre-operative neuroimaging using T2W and FLAIR MR images. Immunohistochemical staining of Ki67 index (representing proliferative activity) was done. Correlation between presence of PTBE and Ki67 index values was evaluated. Results: PTBE was found in nearly half of the patients (48.2%), while the remaining (51.8%) of patients did not exhibit PTBE in their pre-operative neuroimaging. The mean value of Ki67 index in meningioma patients with PTBE was 4.83% compared to a value of 1.83% in patients without PTBE, P value = 0.014. Conclusion: High Ki67 indices are evident in meningiomas with surrounding peritumoral brain edema (PTBE).

P.035 Peritumoral brain edema in meningiomas: correlation with surgical findings and prognosis

Background: Peritumoral brain edema(PTBE) in meningiomas had been a subject of interest; its occurrence in an extra-axial tumor was the reason of many studies and published data.Our study was made to evaluate the exact implication of Peritumoral brain edema in meningiomas in intraoperative and short postoperative prognosis. Methods: During 2006 to 2011,45 patients with supratentorial meningiomas were studied.Intraoperatively,certain findings were reported including: easy or difficult resection,Simpson’s grade of removal,brain tumor interface,plane of cleavage, pial vascularization of the tumor and arachnoid disruption.Morbidity and mortality were recorded;also postoperative CT and/or MRI were obtained within the first 3 months. Results: There were 26 meningiomas (57.7%) with peritumoral edema and 19 meningiomas without (42.3%).Pial vascularization of the tumor was defined in 24 patients (53.3%),four patients(21%) had a pial blood supply in edema negative group compared to 20 patients (76.9%) in edema positive group. In this study, there was one case mortality (2.2%) in edema positive group.As regard morbidity, eight (30.6%) patients in edema positive group suffered an early postoperative morbidity this is in comparison to four patients(21%) in the edema negative group. Conclusions: Our study shows that PTBE in meningiomas affects the surgical prognosis and confers a higher risk of morbidity and postoperative complications.Preoperative management of PTBE and immediate post-operative monitoring are important.

Rapid and Accurate MRI Segmentation of Peritumoral Brain Edema in Meningiomas.

The extent of peritumoral brain edema (PTBE) in meningiomas commonly affects the clinical outcome. Despite its importance, edema volume is usually highly inaccurately approximated to a spheroid shape. We tested the accuracy and the reproducibility of semiautomatic lesion management software for the analysis of PTBE in a homogeneous case series of surgically confirmed intracranial meningiomas. PTBE volume was calculated on magnetic resonance images in 50 patients with intracranial meningiomas using commercial lesion management software (Vue PACS Livewire, Carestream, Rochester, NY, USA). Inter and intraobserver agreement evaluation and a comparison between manual volume calculation, the semiautomatic software and spheroid approximation were performed in 22 randomly selected patients. The calculation of edema volume was possible in all cases irrespective of the extent of the signal changes. The median time for each calculation was 3min. Interobserver and intraobserver agreement confirmed the reproducibility of the method. Comparison with standard (fully manual) calculation confirmed the accuracy of this software. Our study showed a high level of reproducibility of this semiautomatic computational method for peritumoral brain edema. It is rapid and easy to use after relatively short training and is suitable for implementation in clinical practice.

Expressions of Aquaporin4, VEGFR1 and the pattern of genetic aberrations in meningiomas have no influence on the peritumoral edema

Objective: Despite the frequently reported assumption that VEGFR and Aquaporin4 (AQP4) expression seem to correlate with peritumoral brain edema formation in meningiomas, the molecular pathogenesis of edema formation is still elusive. Therefore, the authors analyzed meningioma edema formation in correlation to typical chromosomal deletions and the expression of VEGFR and Aquaporin4. Methods: Tissue specimens of 69 meningiomas were obtained from surgery between 2008 and 2010. Locus specific FISH analysis detecting the chromosomes 1, 9, 14, 18 and 22 were performed. Moreover, immunoblotting was performed to detect the expression of VEGFR1 and VEGFR2. Aquaporin4 expression was investigated by ELISA. The results were correlated with the peritumoral brain edema in the preoperative MRI. Statistical analysis including Pearson correlation and multivariate statistical analysis was performed. Results: In contrast to previous reports, a significant correlation to the brain edema in meningiomas could be identified only for VEGFR2 ( p <.01). Progression associated aberrations of chromosomes 1, 9, 14, 18 and 22 showed no correlation with the expression of VEGFR1, VEGFR2 and AQP4. AQP4 had nosignificant impact on brain edema formation as well. Conclusions: The current data confirm a strong correlation of VEGFR expression with formation of peritumoral brain edema only for VEGFR2. Moreover, neither the expression of VEGFR1, nor the expression of VEGFR2 nor the expression of AQP4 did correlate with any specific chromosomal aberrations. The molecular actors which can induce a peritumoral brain edema in meningiomas remain widely unclear.

Peritumoral Brain Edema in Meningiomas : Correlation of Radiologic and Pathologic Features

The primary objective of this study was to perform a retrospective evaluation of the radiological and pathological features influencing the formation of peritumoral brain edema (PTBE) in meningiomas. The magnetic resonance imaging (MRI) and pathology data for 86 patients with meningiomas, who underwent surgery at our institution between September 2003 and March 2009, were examined. We evaluated predictive factors related to peritumoral edema including gender, tumor volume, shape of tumor margin, presence of arachnoid plane, the signal intensity (SI) of the tumor in T2-weighted image (T2WI), the WHO histological classification (GI, GII/GIII) and the Ki-67 antigen labeling index (LI). The edema-tumor volume ratio was calculated as the edema index (EI) and was used to evaluate peritumoral edema. Gender (p=0.809) and pathological finding (p=0.084) were not statistically significantly associated with peritumoral edema by univariate analysis. Tumor volume was not correlated with the volume of peritumoral edema. By univariate analysis, three radiological features, and one pathological finding, were associated with PTBE of statistical significance: shape of tumor margin (p=0.001), presence of arachnoid plane (p=0.001), high SI of tumor in T2WI (p=0.001), and Ki-67 antigen LI (p=0.049). These results suggest that irregular tumor margins, hyperintensity in T2WI, absence of arachnoid plane on the MRI, and high Ki-67 LI can be important predictive factors that influence the formation of peritumoral edema in meningiomas. By multivariate analysis, only SI of the tumor in T2WI was statistically significantly associated with peritumoral edema. Results of this study indicate that irregular tumor margin, hyperintensity in T2WI, absence of arachnoid plane on the MRI, and high Ki-67 LI may be important predictive factors influencing the formation of peritumoral edema in meningiomas.

Influence of interleukin-6 on the development of peritumoral brain edema in meningiomas

Peritumoral brain edema (PTBE) is associated with perioperative neurological deficits in patients with meningiomas. However, the pathogenesis of meningioma-associated edema remains unclear. In the present study, the authors investigated the expression of interleukin-6 (IL-6) and its relationship with PTBE in resected meningiomas. Thirty-six benign meningiomas obtained in 36 patients were studied retrospectively. Edema volume was assessed on MR images, and an edema index (EI) was calculated. Interleukin-6 mRNA and protein expression were examined by real-time reverse transcriptase polymerase chain reaction and immunohistochemical staining. Peritumoral brain edema was found in 16 patients (44%). Neither age, sex, histological subtype, nor tumor location were related to PTBE. The level of IL-6 mRNA was 7.72 times greater in the edema group (EI > 0.2) than in the nonedema group (EI < 0.2; p = 0.011). On immunohistochemical analysis, IL-6 protein was found localized in the cytoplasm of the tumor cells, and was detected in 12 (75%) of 16 cases of edematous meningiomas, but in only 6 (30%) of 20 nonedematous cases. There was a significant correlation between the severity of PTBE and IL-6 expression (p = 0.004). The authors' results in this study indicate that IL-6 expression may contribute to the development of brain edema associated with meningiomas.

Peritumoral brain edema in meningiomas: correlations between magnetic resonance imaging, angiography, and pathology

Background The purpose of this study was to evaluate the radiologic characteristics and pathology related to the formation of peritumoral edema in meningiomas. Methods Seventy-nine patients with meningioma were examined by MRI and cerebral angiography. The predictive factors possibly related to peritumoral edema, such as patient age, sex, tumor location, tumor size, peritumoral rim (CSF cleft), shape of tumor margin, signal intensity of tumor in T2WI, pial blood supply, and pathology, were evaluated. We defined the edema–tumor volume ratio as EI and used this index to evaluate peritumoral edema. Results Male sex ( P = .009), tumor size ( P = .026), signal intensity of tumor in T2WI ( P = .016), atypical and malignant tumor ( P = .004), and pial blood supply ( P = .001) correlated with peritumoral edema on univariate analyses. However, in multivariate analyses, pial blood supply was statistically significant as a factor for peritumoral edema in meningioma ( P = .029). Male sex ( P = .067, P < .1) and hyperintensity in T2WI ( P = .075, P < .1) might have statistical probability in peritumoral edema. Conclusions In our results, male sex, hyperintensity on T2WI, and pial blood supply were associated with peritumoral edema in meningioma that influence the clinical prognosis of patients.

Alterations in diffusion and perfusion in the pathogenesis of peritumoral brain edema in meningiomas.

Magnetic resonance perfusion and diffusion studies were undertaken to clarify the significance of ischemia in the pathogenesis of peritumoral brain edema in patients with meningiomas. Included in this study were 26 patients with 27 meningiomas and 5 gliomas. Perfusion-weighted imaging (PWI) was performed using a gradient-echo, echo-planar-imaging (EPI) sequence for calculation of the relative regional cerebral blood volume (rrCBV) and the relative regional cerebral blood flow index (rrCBFi). Furthermore, multi-slice spin-echo EPI sequences were applied in order to obtain anisotropic and isotropic diffusion-weighted imaging (DWI). Apparent diffusion coefficient (ADC) values were then calculated for peritumoral brain parenchyma from tumors, with and without edema, using various diffusion sensitivities. Meningiomas without edema demonstrated a minimal increase of perfusion parameters in the peritumoral brain tissue. In contrast, cases with brain edema had highly significant ( p<0.0005) lower rrCBV and rrCBFi. The edema index (EI) correlated strongly with the rrCBV. A fitting procedure resulted into the following mathematical relation: EI=0.1/rrCBV(2). The DWI showed a significantly larger ADC value within areas of brain edema, compared with the normal white matter (0.74 x 10(-3) vs 1.55 x 10(-3) mm(2)/s; p<0.0001). Increases in EI correlated with increases in ADC values. In 31% of the meningiomas associated with edema, areas with increased signal, probable ischemia, demonstrated significantly lower ADC values, in comparison with the rest of the edematous areas. These areas were confined to tissue immediately adjacent to the tumor. In general, the decrease in rrCBV in brain edema represents a consequence from, rather than a cause of, vasogenic edema. Ischemic alterations can be regarded as secondary, facultative phenomena in the pathogenesis of meningioma-related brain edema.

Role of hydrodynamic processes in the pathogenesis of peritumoral brain edema in meningiomas.

In a prospective study, 28 patients with 32 intracranial meningiomas were examined to determine the role of hydrodynamic interaction between tumor and surrounding brain tissue in the pathogenesis of peritumoral brain edema. Gadolinium-diethylenetriamine pentaacetic acid (Gd-DPTA), an extracellular contrast agent used for routine clinical imaging, remains strictly extracellular without crossing an intact blood-brain barrier. Therefore, it is well suited for investigations of hydrodynamic extracellular mechanisms in the development of brain edema. Spin-echo T1-weighted magnetic resonance images were acquired before and after intravenous administration of 0.2 mmol/kg Gd-DPTA. Additional T1-weighted imaging was performed 0.6, 3.5, and 6.5 hours later. No significant Gd-DPTA diffused from tumor into peritumoral brain tissue in 12 meningiomas without surrounding brain edema. In contrast, in 17 of 20 meningiomas with surrounding edema, contrast agent in peritumoral brain tissue was detectable after 3.5 hours and 6.5 hours. In three of 20 meningiomas with minimum surrounding edema (<5 cm3), contrast agent effusion was absent. After 3.5 hours and 6.5 hours strong correlations of edema volume and the maximum distance of contrast spread from the tumor margin into adjacent brain parenchyma (r = 0.84 and r = 0.87, respectively, p < 0.0001) indicated faster effusion in larger areas of edema. The results of this study show that significant contrast agent effusion from the extracellular space of the tumor into the interstitium of the peritumoral brain tissue is only found in meningiomas with surrounding edema. This supports the hypothesis that hydrodynamic processes play an essential role in the pathogenesis of peritumoral brain edema in meningiomas.

Zur Pathogenese des peritumoralen Ödems bei Meningeomen

In order to study the role of ischemia for induction of peritumoral brain edema in meningiomas, we examined postoperative MR images to evaluate reversible and persisting changes of peritumoral brain tissue after meningioma extirpation.We examined 14 patients with 17 meningiomas pre- and postoperatively by MRI. The postoperative examinations were performed half a year or more after surgery. Patients with postoperative complications (bleeding, ischemia, etc.) were excluded. Postoperative MRI was mainly based on a inversion-recovery-sequence. We considered persisting hyperintense white matter changes (HMV) and complete parenchyma defects (PD) isointense to CSF.Persisting HMVs showed a close spatial correlation with preoperative peritumoral edema, while PD's were found mainly in the preoperative tumor region. We found a significant correlation between the size of preoperative peritumoral edema and postoperative HMV (p≤0.02) and between preoperative tumor size and postoperative PD (p≤0..0001).Our results suggest that ischemic processes may occur in peritumoral edema of meningiomas, but are rather secondary and may lead to postischemic gliosis. Complete tissue necrosis, however, seems to be caused rather by direct tumor compression than by edema.

Die Bedeutung von morphologischen Veränderungen der Hirn-Tumor-Grenze für die Pathogenese des Hirnödems bei Meningeomen: Magnetresonanztomographie und intraoperative Untersuchungen

The aim of the study was to verify a possible correlation between macroscopic changes of the brain-tumor interface (BTI) and the development of a peritumoral brain edema in meningiomas. 27 meningiomas were investigated in this prospective study using an optimized inversion-recovery (IR) sequence. After i.v. administration of 0.2 mmol Gd-DTPA/kg axial and coronary images were acquired (slice thickness = 2 mm). The distances of signal altered cortex and obliterations of the subarachnoid space (SAS) were measured at the BTI and related to the pial tumor circumference (cortical-index and SAS-index). Intraoperatively the BTI was divided into the following categories: 0: SAS not obliterated, 1: SAS partially obliterated, 2: direct contact between tumor and white matter, 3: tumor infiltration into brain. Edema-associated meningiomas showed a significantly (p = 0.0001) increased SAS-index (0.47 vs. 0.07) and cortical index (0.45 vs. 0.0) compared to cases without edema. Intraoperatively 95% of meningiomas with brain edema showed SAS-obliterations, compared to 50% of cases without an edema. Arachnoid adhesions at the BTI with obliteration of the SAS seem to play an essential role in the induction of brain edema in meningiomas.

Tumor-related Venous Obstruction and Development of Peritumoral Brain Edema in Meningiomas

The exact pathogenesis of peritumoral brain edema (PTBE) in meningiomas is still unknown. A number of different pathophysiological hypotheses have been considered. A detrimental effect of tumor-related venous obstruction has been suggested as one pathogenetic mechanism. We sought to characterize the significance of venous stasis in the development of PTBE in meningiomas. Angiograms for 134 patients with 136 intracranial meningiomas were analyzed. Pathological changes affecting cortical veins, sylvian veins, bridging veins, deep veins, transmedullary veins, and dural sinuses were evaluated. From preoperative computed tomographic scans, the total tumor volume, the tumor/PTBE volume ratio (edema index [EI]), and the location of the edema were determined. For statistical evaluation, meningiomas associated with pathological venous drainage were compared with size-matched controls. The edema incidence and the mean EI were not different for meningiomas with unselected signs of obstructed venous drainage, compared with controls. In particular, lesions with involvement of cortical veins, bridging veins, and dural sinuses showed no higher edema incidence. However, meningiomas associated with venous changes in sylvian veins (EI = 4.9 versus EI = 2.7; P < 0.004) and with dysplastic transmedullary veins (EI = 3.3 versus EI = 1.7; P < 0.04) showed significantly higher mean EI values, compared with meningiomas without involvement of these vessels. Our data suggest that tumor-related venous obstruction does not play an essential role in the development of PTBE for the majority of meningiomas. For a small subgroup of meningiomas with involvement of sylvian veins or development of dysplastic transmedullary veins, changes in venous drainage may aggravate preexisting PTBE.

Tumor-related Venous Obstruction and Development of Peritumoral Brain Edema in Meningiomas

Tumor-related Venous Obstruction and Development of Peritumoral Brain Edema in Meningiomas

Tumor-related Venous Obstruction and Development of Peritumoral Brain Edema in Meningiomas

Tumor-related Venous Obstruction and Development of Peritumoral Brain Edema in Meningiomas

Tumor-related Venous Obstruction and Development of Peritumoral Brain Edema in Meningiomas

Tumor-related Venous Obstruction and Development of Peritumoral Brain Edema in Meningiomas

Tumor-related Venous Obstruction and Development of Peritumoral Brain Edema in Meningiomas

Tumor-related Venous Obstruction and Development of Peritumoral Brain Edema in Meningiomas

The importance of pial blood supply to the development of peritumoral brain edema in meningiomas.

In a retrospective analysis, the authors studied the pial and dural blood supplies in 74 intracranial meningiomas and quantified their associated peritumoral brain edema (PTBE). The extent and localization of pial blush in relation to the total tumor volume were determined angiographically. The amount of edema and tumor size were calculated using computerized tomography. The edema-tumor volume ratio was defined as Edema Index (EI). There were 49 meningiomas with PTBE; of those tumors, 46 were supplied by pial vessels, and three were supplied exclusively by dural vessels. Tumors without PTBE showed no pial blush. The mean EI in meningiomas with pial blush was significantly larger (EI = 3) than in meningiomas without pial supply (EI = 1.1; p < 0.0001). Meningiomas with a smaller pial supply than dural supply had a significantly smaller mean EI than tumors with a pial supply equal to or greater than the dural supply (EI = 2.9 vs. EI = 3.7; p < 0.015). In 69.9% of cases with pial blood supply, major portions of the edema were located adjacent to the tumor region supplied by pial vessels. Edema index differences among tumors of different subgroups, as defined by size or histology, were significantly related to the pial supply in each subset. Thus, pial blood supply may be associated with the development of PTBE in meningiomas.

Brain Edema in Meningiomas Is Associated with Increased Vascular Endothelial Growth Factor Expression

Brain Edema in Meningiomas Is Associated with Increased Vascular Endothelial Growth Factor Expression

Brain edema in meningiomas is associated with increased vascular endothelial growth factor expression.

Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF), an endothelial cell-specific cytokine, induces proliferation of endothelial cells and increases vascular permeability dramatically. All gliomas secrete significant amounts of VEGF, whereas meningiomas are variable in expression. Thus, we sought to determine whether the extent of VPF/VEGF expression in meningiomas correlated with differences in brain edema associated with these tumors. Meningioma tissue samples from 37 patients (15 men, average age 65 +/- 13 yr; 22 women, average age 60 +/- 10 yr) who underwent surgery at or were referred to the University of Alabama Hospital were examined retrospectively for the extent of expression of immunoreactive VPF/VEGF. Additionally, peritumoral edema was assessed on a blinded basis radiographically from preoperative magnetic resonance imaging scans. Selected specimens were examined by in situ hybridization to document the source of VPF/VEGF. The predominant meningioma subclassifications were transitional (57%) or meningothelial (27%) subtypes. VPF/VEGF immunoreactivity ranged from 0 to 3.5, with a median value of 2 on a subjective 5-point scale; magnetic resonance imaging-assessed edema ranged in extent from 0 to 4 (subjective 5-point scale), with a median value of 2.5. The correlation of determination (R2) of magnetic resonance imaging-assessed tumor edema rating and VPF/VEGF staining intensity rating was 0.6087 (r = 0.78; P = 0.0001). In situ hybridization localized VPF/VEGF messenger ribonucleic acid in meningioma cells and not in normal parenchymal brain cells. These data suggest that meningioma-associated edema may be a result of the capacity of meningioma cells to produce VPF/VEGF locally, leading to increased tumor neovascularization and enhanced vascular permeability.