The Role of Pre-operative MRI For Prediction of High-Grade Intracranial Meningioma: A Retrospective Study

Introduction: High histological grade (WHO grade II and III) intracranial meningiomas have been linked to greater risk for tumor recurrence and worse clinical outcomes compared to low-grade (WHO grade I) tumors. Preoperative magnetic resonance imaging (MRI) plays a crucial role tumor evaluation prior to decisions regarding management and allows for a better understanding of the tumor grading, which could potentially alter clinical outcomes. The present study sought to determine whether preoperative MRI features of intracranial meningiomas can serve as predictors of high-grade tumors.Methods: This study retrospectively reviewed 327 confirmed cases of intracranial meningiomas, among whom 210 (64.2%) had available preoperative MRI studies. Thereafter, data were analyzed using univariate and multivariate analyses.Results: Accordingly, multivariate analysis found that peritumoral brain edema and the presence of necrosis or hemorrhage were predictors of high-grade tumors, whereas hyperostosis was a predictor of low-grade tumors.Conclusions: Our study suggested that preoperative MRI features could potentially assist in decision-making regarding the appropriate management and surgical approach in order to achieve the desired clinical outcomes.

The Most Significant Surgical Risk Factors of Giant Intracranial Meningiomas: Localization Matters Much More than Grading and Volume of Peritumoral Brain Edema. A Retrospective Clinical Neuroradiological and Immunohistochemical Study

Background: Giant intracranial meningiomas (GIMs) are extremely rare and are usually considered arduous to resect totally with poorer prognosis. The real mechanisms by which a meningioma can grow to be defined as "giant" are unknown, as well as the real biological , radiological profile and the different outcomes.Methods: We performed a retrospective review of a consecutive series of surgically-treated patients suffering from intracranial Meningioma. All the patients were assigned on the ground of the preoperative imaging to the Giant and Medium/Large Meningiomas. We investigated whether the presence large diameter on radiological diagnosis is indicative for different mortality rate, grading, characteristic and clinical/neurological outcome.Results: The study shows that surgically treated giant meningiomas have a higher risk of developing complications in the postoperative phase (Chi square= 11.121, dF=1, p=0.001). The direct proportional relationship between peritumoral brain edema (PBE) volume and tumor volume was present only in the medium/large group and was not present in the giant meningioma group. When comparing the degree of performance there is a statistically significant difference between localization and KPS immediately postoperatively (p=0.04) particularly for sphenopetroclival meningiomas (p=0.071), and partially with GIM of the olfactory groove with arterial encasement. The most frequently encountered complications include the occurrence of ischemia (p=0.049), infection (p=0.03), and the occurrence of postoperative seizures.Conclusions: We identified that the major surgical risk factor for GIMs is location, where the petro-clival region and, to a lesser extent the anterior basicranium offer a greater risk of neurovascular involvement and arterial encasement. On other hand, the risk correlated with PBE is poorer in GIM although there is a well-noted correlation between the Edema volume and outcome in meningiomas.

Peritumoral Brain Edema in Metastases May Be Related to Glymphatic Dysfunction

ObjectivesThe proliferation of microvessels with increased permeability is thought to be the cause of peritumoral brain edema (PTBE) in metastases. The contribution of the glymphatic system to the formation of PTBE in brain metastases remains unexplored. We aimed to investigate if the PTBE volume of brain metastases is related to glymphatic dysfunction.Materials and MethodsA total of 56 patients with brain metastases who had preoperative dynamic susceptibility contrast-enhanced perfusion-weighted imaging for calculation of tumor cerebral blood volume (CBV) and diffusion tensor imaging for calculations of tumor apparent diffusion coefficient (ADC), tumor fractional anisotropy (FA), and analysis along perivascular space (ALPS) index were analyzed. The volumes of PTBE, whole tumor, enhancing tumor, and necrotic and hemorrhagic portions were manually measured. Additional information collected for each patient included age, sex, primary cancer, metastasis location and number, and the presence of concurrent infratentorial tumors. Linear regression analyses were performed to identify factors associated with PTBE volume.ResultsAmong 56 patients, 45 had solitary metastasis, 24 had right cerebral metastasis, 21 had left cerebral metastasis, 11 had bilateral cerebral metastases, and 11 had concurrent infratentorial metastases. On univariable linear regression analysis, PTBE volume correlated with whole tumor volume (β = -0.348, P = 0.009), hemorrhagic portion volume (β = -0.327, P = 0.014), tumor ADC (β = 0.530, P <.001), and ALPS index (β = -0.750, P <.001). The associations of PTBE volume with age, sex, tumor location, number of tumors, concurrent infratentorial tumor, enhancing tumor volume, necrotic portion volume, tumor FA, and tumor CBV were not significant. On multivariable linear regression analysis, tumor ADC (β = 0.303; P = 0.004) and ALPS index (β = -0.624; P < 0.001) were the two independent factors associated with PTBE volume.ConclusionMetastases with higher tumor ADC and lower ALPS index were associated with larger peritumoral brain edema volumes. The higher tumor ADC may be related to increased periarterial water influx into the tumor interstitium, while the lower ALPS index may indicate insufficient fluid clearance. The changes in both tumor ADC and ALPS index may imply glymphatic dysfunction, which is, at least, partially responsible for peritumoral brain edema formation.

Factors Associated With Dysfunction of Glymphatic System in Patients With Glioma

ObjectivesRodent experiments have provided some insights into the changes of glymphatic function associated with glioma growth. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) method offers an opportunity for the noninvasive investigation of the glymphatic system in patients with glioma. We aimed to investigate the factors associated with glymphatic function changes in patients with glioma.Materials and MethodsA total of 201 glioma patients (mean age = 47.4 years, 116 men; 86 grade II, 52 grade III, and 63 grade IV) who had preoperative diffusion tensor imaging for calculation of the ALPS index were retrospectively included. Information collected from each patient included sex, age, tumor grade, isocitrate dehydrogenase 1 (IDH1) mutation status, peritumoral brain edema volume, tumor volume, and ALPS index. Group differences in the ALPS index according to sex, tumor grade, and IDH1 mutation status were assessed using analysis of covariance with age adjustment. Linear regression analyses were performed to identify the factors associated with the ALPS index.ResultsGroup comparisons revealed that the ALPS index of grade II/III gliomas was significantly higher than that of grade IV gliomas (p < 0.001). The ALPS index of IDH1 mutant gliomas was significantly higher than that of IDH1 wild-type gliomas (p < 0.001). On multivariable linear regression analysis, IDH1 mutation (β = 0.308, p < 0.001) and peritumoral brain edema volume (β = −0.353, p < 0.001) were the two independent factors associated with the ALPS index.ConclusionIDH1 wild-type gliomas and gliomas with larger peritumoral brain edema volumes were associated with a lower ALPS index, which may reflect impaired glymphatic function.

Investigation of the Relationship Between the Degree of Peritumoral Brain Edema and Pathological Features of Glioma Before Surgery

Background: Gliomas are the most common malignant tumors of the central nervous system (CNS). Preoperative prediction of the malignancy grade of gliomas are of particular importance. These tumors are often accompanied by peritumoral brain edema (PTBE). Previous studies have suggested that the degree of PTBE is an independent indicator of the prognosis of gliomas. Objectives: This study aimed to investigate the relationships between the degree of PTBE and the grade of glioma, isocitrate dehydrogenase 1 (IDH1) mutation status, and Ki-67 expression level in gliomas. Patients and Methods: In this retrospective cross-sectional study, a total of 82 patients were enrolled, according to the 2016 World Health Organization (WHO) classification of CNS tumors. Overall, 29 tumors were pathologically confirmed as low-grade gliomas (LGGs , grade I-II), whereas the remaining 53 tumors were classified as high-grade gliomas (HGGs, grade III-IV). The IDH1 mutations, Ki-67 expression, and magnetic resonance imaging (MRI) findings were retrospectively analyzed. The tumor and tumor + PTBE volumes were also measured, and the tumor edema index (EI) was calculated for each patient. Edema was then graded and correlated with the pathological parameters. Results: The degree of EI was higher in the HGG group compared to the LGG group, and the difference was statistically significant (z = -7.018, P < 0.05). Besides, the degree of EI was higher in the IDH1 wild-type compared with mutant groups (z = -4.116, P < 0.05). The degree of EI significantly associated with Ki-67 expression and patient’s age (P < 0.05), whereas there was no significant association between the degree of EI and gender (z = -0.497, P = 0.619). The Spearman’s correlation test revealed that the EI degree was positively correlated with the Ki-67 expression level and age, with correlation coefficients of 0.740 and 0.466, respectively. Moreover, the multivariate logistic regression analysis indicated that EI and IDH1 had significant effects on differentiating LGGs from HGGs (P < 0.05 for both). The receiver operating characteristic (ROC) curve analysis showed that EI was an optimal index for differentiating LGGs from HGGs, with an area under curve (AUC) of 0.822 (cutoff value: 1.722, sensitivity: 95.8%, specificity: 70.0%, 95% CI: 0.718 - 0.899). Conclusion: The degree of PTBE was found to be a valuable index for the differential diagnosis of LGGs from HGGs. It has a significant difference between IDH1 wild and mutation status, furthermore, it was positively correlated with the age and Ki-67 level.

Effect of osteoporotic conditions on the development of peritumoral brain edema after LINAC-based radiation treatment in patients with intracranial meningioma

Purpose Disruption of the tumor-brain barrier in meningioma is a crucial factor in peritumoral brain edema (PTBE). We previously reported the possible effect of osteoporosis on the integrity of the arachnoid trabeculae because both the bone and the arachnoid trabeculae are composed of type 1 collagen. We hypothesized that osteoporotic conditions may be associated with PTBE occurrence after radiation treatment in patients with meningioma. Methods A receiver operating characteristic curve analysis was used to identify the optimal cut-off values of mean skull Hounsfield unit for predicting osteopenia and osteoporosis in patients from our registry. Multivariate Cox regression analysis was used to determine whether possible osteoporosis independently predicted PTBE development in patients with meningioma after radiation. Results A total of 106 intracranial meningiomas were included for the study. All patients received linear accelerator-based radiation therapy in our hospital over an approximate 6-year period. Multivariate Cox regression analysis identified that hypothetical osteoporosis was an independent predictive factor for the development of PTBE in patients with meningioma after linear accelerator-based radiation treatment (hazard ratio 5.20; 95% confidence interval 1.11–24.46; p = 0.037). Conclusions Our study suggests that possible osteoporotic conditions may affect PTBE development after linear accelerator-based radiation treatment for intracranial meningioma. However, due to the study’s small number of patients, these findings need to be validated in future studies with larger cohorts, before firm recommendations can be made. Graphic abstract

Role of Bevacizumab in High-grade Meningiomas

Background: To explore the role of bevacizumab (BV) in High-grade Meningiomas (HGMs) undergoing surgical treatment.Methods: Review the clinical data of 139 patients with HGMs and divide them into BV group and non- BV group according to whether they receive BV treatment. Then we compared the progression-free survival (PFS) and overall survival (OS) of the two groups.Results: The Chi-square test showed significant differences between the BV group and the non-BV group in terms of 12-month PFS (PFS-12), 36-month PFS (PFS-36), median PFS (M-PFS), 12-month OS (OS-12), 36-month OS (OS-36), and median OS (M-OS). However, there was no statistical difference between the BV group and the non-BV group in terms of 6-month PFS (PFS-6), 60-month PFS (PFS-60), and 60-month OS (OS-60). The log-rank test indicated significant differences in PFS and OS between the BV group and the non-BV group.Conclusion: The role of BV in patients with HGMs is to relieve the symptoms of peritumoral brain edema (PTBE) and prolong PFS and OS. However, whether increasing the dose of BV after surgery can improve the long-term PFS and OS of patients with HGMs needs further research.

The Relationship Between Peritumoral Brain Edema and the Expression of Vascular Endothelial Growth Factor in Vestibular Schwannoma

Objective: This study aimed to explore the potential mechanism of peritumoral brain edema (PTBE) formation in vestibular schwannoma (VS) by detecting intra-tumoral vascular endothelial growth factor (VEGF) expression.Methods: Between January 2018 and May 2021, 15 patients with PTBE and 25 patients without PTBE were included in the analysis. All patients enrolled in our study underwent surgery in our institution. Expression level of VEGF and microvessel density (MVD) between the two groups were analyzed. Edema index (EI) of each patient with PTBE was calculated.Results: In the PTBE group, the average of EI was 1.53 ± 0.22. VEGF expression levels were significantly enhanced in the PTBE group compared with the non-PTBE group (p &lt; 0.001). The expression level of VEGF in the PTBE group and non-PTBE group was 1.14 ± 0.21 and 0.52 ± 0.09, respectively. Similarly, there were significantly different amounts of MVD in the two groups (p &lt; 0.001). The amount of MVD in the PTBE group and non-PTBE group was 11.33 ± 1.59 and 6.28 ± 1.77, respectively. Correlation analysis showed a highly significant positive correlation between VEGF and MVD (r = 0.883, p &lt; 0.001) and VEGF and EI (r = 0.876, p &lt; 0.001).Conclusion: Our study confirmed the close relationship among VEGF expression, tumor angiogenesis, and formation of PTBE in VS patients. It may be possible to develop new effective therapies to attenuate PTBE in VS for alleviation of symptoms and reduction of postoperative complication.

The positive effects of surgery on symptomatic stereotactic radiation-induced peritumoral brain edema: A report of three cases

Background: Peritumoral brain edema is an uncommon but life-threatening side effect of brain tumors radiosurgery. Medical therapy usually alleviates symptoms until edema spontaneously disappears. However, when peritumoral brain edema endangers the patient’s life or medical therapy fails to guarantee an acceptable quality of life, surgery might be considered. Case Description: Our report focuses on three patients who developed extensive peritumoral brain edema after radiosurgery. Two were affected by vestibular schwannomas and one by a skull-base meningioma. Peritumoral brain edema worsened despite maximal medical therapy in all cases; therefore, surgical removal of the radiated lesion was carried out. In the first patient, surgery was overdue and resulted in a fatal outcome. On the other hand, in the latter two cases surgery was quickly effective. In all three cases, an unmanageable brain swelling was not found at surgery. Conclusion: Surgical removal of brain tumors previously treated with radiosurgery was safe and effective in resolving shortly peritumoral brain edema. This solution should be considered in patients who do not respond to medical therapy and before worsening of clinical conditions. Interestingly, the expected brain swelling was not confirmed intraoperatively. In our experience, this magnetic resonance finding should not be considered a criterion to delay surgery.

Meningiomas with Hemorrhagic Onset: A New Bleeding Classification and its Clinical Significance

Meningiomas are the commonest benign intracranial tumors and frequently present with a gradual onset of neurological deficits; however, their acute presentation with hemorrhagic onset appears to be a rare event. Nonetheless, because the mainstay of treatment is early surgical evacuation, prompt diagnosis of this rare category of intracranial hemorrhage is imperative. The purpose of this single-center study was to investigate the radiological characteristics and proposed a new bleeding classification for guiding diagnosis and treatment. A total of 19 consecutive patients diagnosed with hemorrhagic meningioma were enrolled in this retrospective study. Intracranial extra-axial mass, tumor-associated hemorrhage, and peritumoral brain edema were the three main radiological features. The site of tumor-associated hemorrhage included peritumoral space, subarachnoid space, subdural space, brain parenchyma, and/or intratumor. Based on the anatomical relationship between meningioma and hematoma, the spontaneous hemorrhage stemming from meningiomas were further summarized into three bleeding patterns involving purely intratumoral hemorrhage (type I), purely extratumoral hemorrhage (type II), and combined intra/extratumoral hemorrhage (type III); moreover, the type III hemorrhage usually came from the type I bleeding that extended into the surrounding regions. The symptoms in type I patients were generally mild, and early surgery was performed following adequate preoperative evaluations; the symptoms in type II patients were sometimes mild and may be sometimes moderate to severe, so early or emergency surgery was chosen according to the patients’ clinical statuses; almost all type III patients had moderate to severe symptoms, and these patients usually needed emergency surgery. In addition, the patients with different bleeding types may have different pathological mechanisms underlying the bleeding. Apart from being convenient for diagnosis, this concise and practical bleeding classification could offer some implications for the treatment strategy and facilitate understanding of the associated mechanisms.