Supracerebellar "Flyover" Approach to Dumbbell Falcotentorial Meningioma Encasing the Galenic Venous System.

Falcotentorial meningiomas involve the tentorial apex and straight sinus, posing challenges when encasing the galenic venous system.1 Microneurosurgery is considered the best treatment option for large falcotentorial meningiomas because it provides a definitive cure.2 In contrast, Gamma Knife surgery mainly allows the control of smaller or residual tumors after microsurgical resection.3 Approach selection between interhemispheric supratentorial versa supracerebellar transtentorial is dictated by the displacement of the Galen vein.1,4-8Video 1 describes the critical surgical steps of the supracerebellar "flyover" approach for a Bassiouni type II dumbbell falcotentorial meningiomas encasing the galenic venous system. Preoperative embolization was ruled out due to potential additional morbidity and mortality risks.9,10 A perimedian supracerebellar infratentorial transtentorial approach was performed with the patient in ¾ prone Concorde position. After early devascularization and division of the tentorium, the meningioma was internally debulked while preserving the arachnoid plane. The posterior choroidal arteries, internal cerebral veins, basal veins of Rosenthal, and vein of Galen were carefully dissected, and the tumor was completely resected. The patient was discharged on postoperative day 3 with no deficits. Postoperative magnetic resonance imaging confirmed a Simpson grade 1 resection. Pathology revealed a grade 2 meningioma. The patient remained asymptomatic with no recurrence at a 10-year follow-up. The reported case demonstrates that the most critical factor in the choice of approach to midline dumbbell falcotentorial meningiomas is the relationship of the tumor to the galenic venous system and its tributaries.

Relationship between Shear Stiffness Measured by MR Elastography and Perfusion Metrics Measured by Perfusion CT of Meningiomas.

BACKGROUND AND PURPOSE: When managing meningiomas, intraoperative tumor consistency and histologic subtype are indispensable factors influencing operative strategy. The purposes of this study were the following: 1) to investigate the correlation between stiffness assessed with MR elastography and perfusion metrics from perfusion CT, 2) to evaluate whether MR elastography and perfusion CT could predict intraoperative tumor consistency, and 3) to explore the predictive value of stiffness and perfusion metrics in distinguishing among histologic subtypes of meningioma. MATERIALS AND METHODS: Mean tumor stiffness and relative perfusion metrics (blood flow, blood volume, and MTT) were calculated (relative to normal brain tissue) for 14 patients with meningiomas who underwent MR elastography and perfusion CT before surgery (cohort 1). Intraoperative tumor consistency was graded by a neurosurgeon in 18 patients (cohort 2, comprising the 14 patients from cohort 1 plus 4 additional patients). The correlation between tumor stiffness and perfusion metrics was evaluated in cohort 1, as was the ability of perfusion metrics to predict intraoperative tumor consistency and discriminate histologic subtypes. Cohort 2 was analyzed for the ability of stiffness to determine intraoperative tumor consistency and histologic subtypes. RESULTS: The relative MTT was inversely correlated with stiffness (P = .006). Tumor stiffness was positively correlated with intraoperative tumor consistency (P = .01), while perfusion metrics were not. Relative MTT significantly discriminated transitional meningioma from meningothelial meningioma (P = .04), while stiffness did not significantly differentiate any histologic subtypes. CONCLUSIONS: In meningioma, tumor stiffness may be useful to predict intraoperative tumor consistency, while relative MTT may potentially correlate with tumor stiffness and differentiate transitional meningioma from meningothelial meningioma.

Classification of Peritumoral Veins in Convexity and Parasagittal Meningiomas and Its Significance in Preventing Cerebral Venous Infarction.

OBJECTIVE: The medium (2-4 cm) convexity located closer to the sinus and parasagittal meningiomas (Sindou type I-Ⅲ) without obvious invasion of the superior sagittal sinus are considered simple to operate on. However, the tumors are often accompanied by the cortical bridging vein. Because of lack of collateral vein circulation in cortical areas, the damage of peritumoral veins will subsequently lead to venous infarction. To avoid the serious complications caused by intraoperative injury of peritumoral veins, it is necessary to define the classification of the progression of peritumoral veins and tumors to guide surgical safety. METHODS: The clinical information of 57 patients with convexity and parasagittal meningiomas was collected and retrospectively analyzed. All patients underwent preoperative magnetic resonance imaging and magnetic resonance venography scanning to observe the imaging characteristics of peritumoral veins and preoperative evaluation. The actual relationship between the tumor and peritumoral vein was observed intraoperatively. Postoperative computed tomography and magnetic resonance imaging were used to determine tumor resection and the presence of venous infarction. RESULTS: According to preoperative magnetic resonance venography and intraoperative findings, we divided the peritumoral veins into 3 types: type A (n = 33, 57.9%), the vein surrounds the tumor; type B (n = 15, 26.3%), the vein is located on the ventral side of the tumor; and type C (n = 9, 15.8%), the vein is located on the dorsal side of the tumor. Peritumoral vein injury occurred in 6 cases followed by serious complications. Treatments were as follows: 4 cases underwent decompression and 2 cases were treated conservatively. The prognosis Glasgow Outcome Scale (GOS) scores were as follows: 3 cases were score 5 for injury of posterior frontal vein or middle frontal vein, 2 cases were score 3 for injury of the central vein, 1 case was score 1 for death due to injury of the central vein. All cases were followed up for 6 months. CONCLUSIONS: Attention should be paid to the peritumoral vein of special meningiomas. Injured vein in the medial third of superior sagittal sinus carries a high rate of postoperative morbidity. Understanding the type of peritumoral veins preoperatively can be used as a guide in determining the corresponding protective strategy during surgery, which can significantly decrease postoperative disability and improve quality of life.

Posterior Petrous Meningioma Fed by a Branch of the Persistent Trigeminal Artery Terminating in the Anterior Inferior Cerebellar Artery.

Persistent trigeminal artery (PTA) is the most common persistent carotid-basilar fetal anastomosis and terminates extremely rarely directly in the dominant hemispheric branch of the anterior inferior cerebellar artery (AICA). We present a case of a branch of this PTA variant (Saltzman type 3b) demonstrated as the feeding artery of a large posterior petrous meningioma, which was confirmed under direct vision during surgery through the extended retrosigmoid approach. Meticulous dissection from the tumor surface provided early identification of the feeding branch from the PTA and its bifurcation at the attachment of the posterior petrous surface adjacent to the jugular foramen enabled preservation of the terminal cortical branch of the cerebellar hemisphere. Meningioma in the posterior cranial fossa may recruit substantial supply from branches of the PTA terminating in the AICA. This PTA variant should be recognized during surgical resection of posterior fossa neoplasms to prevent ischemic complication of the AICA territory.

Effect of Tumor Perfusion and Receptor Density on Tumor Control Probability in 177Lu-DOTATATE Therapy: An In Silico Analysis for Standard and Optimized Treatment.

The aim of this work was to determine a minimal tumor perfusion and receptor density for 177Lu-DOTATATE therapy using physiologically based pharmacokinetic (PBPK) modeling considering, first, a desired tumor control probability (TCP) of 99% and, second, a maximal tolerated biologically effective dose (BEDmax) for organs at risk (OARs) in the treatment of neuroendocrine tumors and meningioma. Methods: A recently developed PBPK model was used. Nine virtual patients (i.e., individualized PBPK models) were used to perform simulations of pharmacokinetics for different combinations of perfusion (0.001-0.1 mL/g/min) and receptor density (1-100 nmol/L). The TCP for each combination was determined for 3 different treatment strategies: a standard treatment (4 cycles of 7.4 GBq and 105 nmol), a treatment maximizing the number of cycles based on BEDmax for red marrow and kidneys, and a treatment having 4 cycles with optimized ligand amount and activity. The red marrow and the kidneys (BEDmax of 2 Gy15 and 40 Gy2.5, respectively) were assumed to be OARs. Additionally, the influence of varying glomerular filtration rates, kidney somatostatin receptor densities, tumor volumes, and release rates was investigated. Results: To achieve a TCP of at least 99% in the standard treatment, a minimal tumor perfusion of 0.036 ± 0.023 mL/g/min and receptor density of 34 ± 20 nmol/L were determined for the 9 virtual patients. With optimization of the number of cycles, the minimum values for perfusion and receptor density were considerably lower, at 0.022 ± 0.012 mL/g/min and 21 ± 11 nmol/L, respectively. However, even better results (perfusion, 0.018 ± 0.009 mL/g/min; receptor density, 18 ± 10 nmol/L) were obtained for strategy 3. The release rate of 177Lu (or labeled metabolites) from tumor cells had the strongest effect on the minimal perfusion and receptor density for standard and optimized treatments. Conclusion: PBPK modeling and simulations represent an elegant approach to individually determine the minimal tumor perfusion and minimal receptor density required to achieve an adequate TCP. This computational method can be used in the radiopharmaceutical development process for ligand and target selection for specific types of tumors. In addition, this method could be used to optimize clinical trials.

Detailed Arterial Anatomy and Its Anastomoses of the Sphenoid Ridge and Olfactory Groove Meningiomas with Special Reference to the Recurrent Branches from the Ophthalmic Artery.

BACKGROUND AND PURPOSE: Detailed arterial anatomy of the sphenoid ridge and olfactory groove meningiomas is complicated due to the fine angioarchitecture and anastomoses between each feeder. Herein, we present details of the arterial anatomy and the relationships of feeders in these lesions. MATERIALS AND METHODS: This study included 20 patients admitted to our department between April 2015 and March 2020. Conditions of subjects consisted of 16 sphenoid ridge meningiomas and 4 olfactory groove meningiomas. We mainly analyzed arterial anatomy using 3D rotational angiography and slab MIP images of these lesions. We also analyzed the anastomoses of each feeder. RESULTS: We found that 19 (95%), 15 (75%), and 15 (75%) lesions had feeders from the ophthalmic, internal carotid, and external carotid arteries, respectively. As feeders from the ophthalmic artery, recurrent meningeal arteries were involved in 18 lesions (90%). Fifteen lesions (75%) had anastomoses between each feeder. CONCLUSIONS: Most of the meningiomas in the sphenoid ridge and olfactory groove had feeders from the ophthalmic and internal carotid arteries. There were various anastomoses between each feeder. This is the first report to demonstrate the detailed arterial anatomy and frequency of recurrent branches from the ophthalmic artery and their anastomoses using detailed imaging techniques.

Leptomeningeal malignancy of childhood: sharing learning between childhood leukaemia and brain tumour trials.

Leptomeningeal malignancy complicates childhood cancers, including leukaemias, brain tumours, and solid tumours. In leukaemia, such malignancy is thought to invade leptomeninges via the vascular route. In brain tumours, dissemination from the primary tumour, before or after surgery, via CSF pathways is assumed; however, evidence exists to support the vascular route of dissemination. Success in treating leptomeningeal malignancy represents a rate-limiting step to cure, which has been successfully overcome in leukaemia with intensified systemic therapy combined with intra-CSF therapy, which replaced cranial radiotherapy for many patients. This de-escalated CNS-directed therapy is still associated with some neurotoxicity. The balanced benefit justifies exploration of ways to further de-escalate CNS-directed therapy. For primary brain tumours, standard therapy is craniospinal radiotherapy, but attendant risk of acute and delayed brain injury and endocrine deficiencies compounds post-radiation impairment of spinal growth. Alternative ways of treating leptomeninges by intensifying drug therapy delivered to CSF are being investigated-preliminary evidence suggests improved outcomes. This Review seeks to describe methods of intra-CSF drug delivery and drugs in use, and consider how the technique could be modified and additional drugs might be selected for this route of administration.

Postembolization Change in Magnetic Resonance Imaging Contrast Enhancement of Meningiomas Is a Better Predictor of Intraoperative Blood Loss Than Angiography.

BACKGROUND: Preoperative embolization of meningiomas to reduce tumor vascularity and intraoperative blood loss remains controversial. Incomplete devascularization on angiography is not significantly correlated with intraoperative estimated blood loss (EBL). Magnetic resonance imaging (MRI) may provide a better assessment of devascularization and prediction of EBL. METHODS: We retrospectively analyzed patients undergoing preoperative embolization for intracranial meningiomas. Cohorts based on postembolization devascularization (>50% vs. ≤50%) were compared. RESULTS: Of 84 patients with meningioma undergoing preoperative embolization, 35 (42%) had a postembolization MRI before resection and met study inclusion criteria. The mean tumor diameter was 4.9 ± 1.3 cm, and mean intraoperative EBL was 576 ± 341 mL. Compared with MRI, angiography overestimated devascularization in 22 patients (63%). Using pre- versus postembolization MRIs, 17 (49%) patients had a >50% decrease in enhancement, which was associated with lower mean intraoperative blood loss (444 ± 255 mL) compared with 17 patients with ≤50% devascularization (700 ± 374 mL) (P = 0.03). On angiography, the 22 (63%) patients who demonstrated >50% devascularization during embolization did not statistically differ in intraoperative EBL when compared with 13 (37%) patients with <50% angiographic devascularization. Patients with a ≤50% decrease in contrast enhancement on postembolization MRI were 9 times more likely to lose >500 mL blood intraoperatively during resection (95% confidence interval 1.6-54, P = 0.01). CONCLUSIONS: Postembolization contrast-enhanced MRI is a better predictor of intraoperative blood loss during meningioma resection than postembolization angiography, which overestimates the degree of embolic devascularization. Postembolization preoperative MRI is warranted for optimal patient management.

Utility of dual-energy CT for predicting the vascularity of meningiomas.

PURPOSE: Dual-energy computed tomography (DECT) can provide iodine, electron density (ED), and effective atomic number Z (Zeff) maps, facilitating the identification of tissue types. We investigated whether DECT parameters can predict the vascularity of meningiomas. METHOD: We acquired DECT and perfusion CT (PCT) images in 24 patients with histologically diagnosed meningioma. Regions of interest (ROIs) were placed at the tumor in iodine, ED, and Zeff maps derived from DECT and in a blood volume (BV) map derived from PCT. To normalize these parameters' values, we divided them by the values of contralateral normal-appearing white matter, i.e., the relative (r)ED, rZeff, and rBV. The vascular density of the tumor specimens was immunohistochemically analyzed by calculating the von Willebrand factor-positive vessel wall. We calculated Pearson's correlation coefficients to determine the correlation with PCT/DECT parameters and an immunohistopathological index. RESULTS: Contrast rZeff (r = 0.7020, p = 0.0001) and iodine (r = 0.5814, p = 0.0029) both had positive correlations with rBV derived from PCT. The rED values were negatively correlated with the rBV values (r = -0.4735, p = 0.0194), and the vascular density results confirmed positive correlations with rBV (r = 0.6909, p = 0.0002) and contrast rZeff (r = 0.4982, p = 0.0132) and a negative correlation with rED (r = -0.4265, p = 0.0377). Regarding the radiation exposure, the mean estimated volume CT dose index (CTDIvol) of DECT was 33.1 ± 1.72 mGy, much lower than that of PCT (103.3 ± 4.65 mGy). CONCLUSIONS: DECT predicted vascular density with lower radiation exposure compared to PCT. DECT could potentially replace PCT for evaluating the vascularity of meningiomas.

Non-invasive qualitative and semiquantitative presurgical investigation of the feeding vasculature to intracranial meningiomas using superselective arterial spin labeling.

BACKGROUND: Intracranial meningiomas may be amenable to presurgical embolization to reduce bleeding complications. Detailed information usually obtained by digital subtraction angiography (DSA) on the contribution of blood supply from internal and external carotid artery branches is required to prevent non-target embolization and is helpful for pre-surgical planning. PURPOSE: To investigate the contribution of the feeding vasculature to intracranial meningiomas with superselective arterial spin labelling (sASL) as an alternative to DSA. MATERIAL AND METHODS: Consecutive patients presenting for meningioma resection were prospectively included. sASL perfusion images acquired on a clinical 3T MRI scanner were independently rated by two readers. Contribution of the external carotid artery (ECA), internal carotid artery (ICA) and vertebral/basilar artery (VA/BA) was rated as none, <50% or >50%. Correlation of sASL was performed in two patients undergoing DSA. RESULTS: 32 patients (61 ± 13 years) harboring 42 meningiomas could be included. sASL was technically successful in all patients. 19 meningiomas had ICA dominant supply, 19 had ECA dominant supply. One meningioma had mixed supply and in three meningiomas a perfusion signal could not be detected. While exclusive unilateral ECA supply was common (n = 14) and exclusive unilateral ICA was rare (n = 4), mixed supply from multiple vessels (n = 20) was a frequent finding. Interrater agreement was substantial (κ = 0.73). Agreement with DSA was perfect within our predefined categories. CONCLUSION: sASL is able to identify the presence and extent of the feeding vasculature in intracranial meningiomas.

The Effects of Silencing the Her2 Gene on Proliferation and Angiogenesis of Meningioma Cells in vivo and in vitro.

Despite the molecular mechanisms of meningioma having been elucidated, the curative effects of current treatments for invasive and malignant meningiomas have been unsatisfactory. Our previous study found that HER2 protein was overexpressed in human meningiomas. However, only a few studies regarding the correlation between meningiomas and HER2 have been reported. The present study aimed to investigate the influence of silencing the Her2 gene on the proliferation and angiogenesis of human malignant meningioma cells. Human malignant meningioma cells were transfected successfully by special shRNA. After lentivirus infection, mRNA and protein levels of Her2 in the shRNA group were significantly reduced. Cell viability began to decrease at 72 h and was most strongly inhibited at 96 h, as measured by CCK-8 assay. Protein levels of Ki-67 and VEGF in the Her2-sh group were significantly lower than in the control and mock groups. After injecting tumor cells into nude mice, the tumor volume was significantly lower in the Her2-sh group, and protein levels of Ki-67, VEGF and CD34 were significantly lower in Her2-sh group than in the control and mock groups. The results demonstrated that silencing Her2 may inhibit the proliferation and angiogenesis of human meningioma cells.

The Effect of Preoperative Direct Ligation of Ethmoidal Arteries on the Perioperative Outcomes of Large Anterior Skull Base Meningiomas Surgery: A Clinical Study.

BACKGROUND: Anterior skull base meningiomas often grow to a large size (≥4 cm) before detection. Their blood supply is mostly provided by the anterior and posterior ethmoidal arteries. Because of their vascularity, intraoperative bleeding can be a challenging prospect that increases the risk of perioperative complications. Preoperative ethmoidal arteries ligation has been used to aid in limiting blood loss. Our objective was to assess the effect of preoperative arterial ligation on the perioperative course of large (≥4 cm) to giant (≥6 cm) anterior skull base meningiomas. METHODS: We retrospectively searched our database for large anterior skull base meningiomas (≥4 cm). We analyzed differences in intraoperative blood loss, operative time, intraoperative transfusion, and hematologic parameters between patients who did not undergo preoperative ethmoidal arteries ligation (Group 1) and those who did (Group 2). RESULTS: Average estimated blood loss (EBL) was 825 mL (Group 1) versus 350 mL (Group 2) (P = 0.42), decrease in hemoglobin was 4 g/dL versus 3.2 g/dL (P = 0.53), decrease in hematocrit was 12.4% versus 9.6% (P = 0.64), and average operative time was 656 minutes versus 598 minutes (P = 0.58). EBL per volume yielded a ratio of 10.6 mL/cm3 versus 4.1 mL/cm3 (P = 0.06). CONCLUSIONS: Ethmoidal arteries ligation may have a benefit in large-to-giant anterior skull base meningiomas surgery. Our results showed a decrease in EBL and lesser decrease in pre- and postoperative hemoglobin and hematocrit levels as compared with cases in which no vascular ligation was performed when corrected for tumor volume.

Longitudinal Imaging of Tumor Volume, Diffusivity, and Perfusion After Preoperative Endovascular Embolization in Supratentorial Hemispheric Meningiomas.

OBJECTIVE: To describe longitudinal image changes in supratentorial hemispheric meningiomas based on magnetic resonance imaging after preoperative embolization using calibrated microspheres. METHODS: A total of 14 patients with symptomatic supratentorial meningiomas were included in a prospective, mono-centric, mono-arm study. Magnetic resonance imaging changes on diffusion-weighted imaging, dynamic contrast susceptibility-perfusion-weighted imaging, susceptibility-weighted imaging, and magnetization-prepared rapid acquisition gradient-echo sequence T1-weighted postcontrast sequences 6 and 48 hours after embolization were evaluated and correlated with angiographic and clinical data. RESULTS: The mean age of the patients was 63 ± 12.7 years with an equal female/male ratio. Twelve meningiomas were World Health Organization grade I and II tumors. After embolization, baseline apparent diffusion coefficient (901 ± 166 mm2/s) decreased significantly within 6 hours (696 ± 115 mm2/s, P = 0.0008) as well within 48 hours (752 ± 134 mm2/s; P = 0.0147). Baseline mean ratio of relative cerebral blood volume (rCBV)tumor/rCBVwhite matter (3.67 ± 1.83) and relative cerebral blood flow (rCBF)tumor/rCBFwhite matter (2.89 ± 1.57) significantly decreased after embolization within 6 hours (rCBVtumor/rCBVwhite matter of 1.45 ± 0.9; P = 0.0007, rCBF of 1.16 ± 0.68; P = 0.0029) and 48 hours (rCBV of 1.50 ± 1.07; P = 0.0009, rCBFtumor/rCBFwhite matter of 1.19 ± 0.8; P = 0.003). The viable enhanced baseline mean tumor volume (54.3 ± 34.9 mm3) was sustainably and significantly diminished within 6 hours (26.6 ± 20.8 mm3; P = 0.02) and 48 hours (29.7 ± 22.5 mm3; P = 0.035) after embolization. There was a good correlation between angiographic devascularization rate and the embolized tumor volume at 6 hours (r = 0.7; P = 0.03) and 48 hours (r = 0.78; P = 0.041). CONCLUSIONS: Preoperative meningioma embolization with calibrated microspheres is safe and effectively induces a significant and sustainable tissue transformation over 48 hours.

Arteries Paving the Way for Centrifugal Excision of Anterior Clinoidal Meningioma.

The anterior clinoidal meningiomas often engulf/encase or compress the internal carotid artery (ICA) and its branches, the optic nerve (ON), and structures passing through the superior orbital fissure (SOF). The transsylvian route of excising a tumor poses difficulty in exposing and safeguarding encased vessels. In addition, it may jeopardize the bulging brain and stretched veins, especially in large tumors. The objective is to present an operative video to demonstrate the technique of "centrifugal opening" and removal of anterior clinoidal meningiomas. The ICA, ON, and SOF are exposed after extradural anterior clinoidectomy. The dural base is devascularized and incised radially. Cuts start proximally from these neurovascular structures. The tumor is then debulked and removed by tracing these structures from proximal to distal. The arachnoid and veins are preserved. Early identification of the ICA, ON, and SOF provides better control and allows preservation of these structures despite their engulfment, encasement, or compression. The perforators and arteries are skeletonized in a stepwise manner to achieve maximal safe resection. Even with brain edema, the arachnoid and adjacent veins can be preserved. The technique was used by the authors in >15 cases with good outcome. Thus the discussed technique imparts better control of neurovascular structures with minimal handling of adjacent brain and veins, thereby allowing a more aggressive resection.

Classification and Protection of Peritumoral Draining Veins of Parasagittal and Falcine Meningiomas.

OBJECTIVE: To investigate the importance and types of peritumoral draining veins in parasagittal and falcine meningiomas and administer corresponding protective strategies during surgery according to these different types to improve tumor resection rate and maximize the protection of neurologic functions. METHODS: The clinical information of 156 patients with parasagittal and falcine meningiomas who were admitted at the Neurosurgery Department of our hospital was collected and retrospectively analyzed. All patients underwent pathologic classification, magnetic resonance imaging scanning and enhancement, and magnetic resonance venography examinations. RESULTS: Among these patients, 113 (72.4%) had Simpson grade I and II resection, whereas 43 patients (27.6%) had Simpson grade III and IV resection and underwent postoperative adjuvant gamma knife surgery. Karnofsky Performance Status evaluation was carried out at 1 week after surgery. In total, 69 patients (44.3%) improved, 66 patients (42.3%) had no changes, and 21 patients (13.4%) had worsened conditions (7 patients had hemiplegia, 5 patients had aphasia, 4 patients had decreased vision, and 5 patients had ataxia). There were no deaths. According to the 2016 World Health Organization pathologic grading, 131 patients (84%) were grade I, 22 patients (14%) were grade II, and 3 patients were grade III (2%). Furthermore, 105 patients were followed up for 1-4 years. There were 11 cases of recurrence. CONCLUSIONS: The classification and evaluation of peritumoral draining veins through preoperative-combined magnetic resonance venography can be used as a guide in determining the corresponding protective strategy during surgery. This can significantly improve the tumor resection rate and decrease the postoperative disability rate.

A Hematogenous Route for Medulloblastoma Leptomeningeal Metastases.

While the preponderance of morbidity and mortality in medulloblastoma patients are due to metastatic disease, most research focuses on the primary tumor due to a dearth of metastatic tissue samples and model systems. Medulloblastoma metastases are found almost exclusively on the leptomeningeal surface of the brain and spinal cord; dissemination is therefore thought to occur through shedding of primary tumor cells into the cerebrospinal fluid followed by distal re-implantation on the leptomeninges. We present evidence for medulloblastoma circulating tumor cells (CTCs) in therapy-naive patients and demonstrate in vivo, through flank xenografting and parabiosis, that medulloblastoma CTCs can spread through the blood to the leptomeningeal space to form leptomeningeal metastases. Medulloblastoma leptomeningeal metastases express high levels of the chemokine CCL2, and expression of CCL2 in medulloblastoma in vivo is sufficient to drive leptomeningeal dissemination. Hematogenous dissemination of medulloblastoma offers a new opportunity to diagnose and treat lethal disseminated medulloblastoma.

Meningioma assessment: Kinetic parameters in dynamic contrast-enhanced MRI appear independent from microvascular anatomy and VEGF expression.

BACKGROUND AND PURPOSE: Kinetic parameters of T1-weighted dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) are considered to be influenced by microvessel environment. This study was performed to explore the extent of this association for meningiomas. MATERIALS AND METHODS: DCE-MRI kinetic parameters (contrast agent transfer constants Ktrans and kep, volume fractions vp and ve) were determined in pre-operative 3T MRI of meningioma patients for later biopsy sites (19 patients; 15 WHO Io, no previous radiation, and 4 WHO IIIo pre-radiated recurrent tumors). Sixty-three navigated biopsies were consecutively retrieved. Biopsies were immunohistochemically investigated with endothelial marker CD34 and VEGF antibodies, stratified in a total of 4383 analysis units and computationally assessed for VEGF expression and vascular parameters (vessel density, vessel quantity, vascular fraction within tissue [vascular area ratio], vessel wall thickness). Derivability of kinetic parameters from VEGF expression or microvascularization was determined by mixed linear regression analysis. Tissue kinetic and microvascular parameters were tested for their capacity to identify the radiation status in a subanalysis. RESULTS: Kinetic parameters were neither significantly related to the corresponding microvascular parameters nor to tissue VEGF expression. There was no significant association between microvessel density and its presumed correlate vp (P=0.07). The subgroup analysis of high-grade radiated meningiomas showed a significantly reduced microvascular density (AUC 0.91; P<0.0001) and smaller total vascular fraction (AUC 0.73; P=0.01). CONCLUSIONS: In meningioma, DCE-MRI kinetic parameters neither allow for a reliable prediction of tumor microvascularization, nor for a prediction of VEGF expression. Kinetic parameters seem to be determined from different independent factors.

Microvascularization of Grade I meningiomas: effect on tumor volume, blood loss, and patient outcome.

OBJECTIVE Quantitative assessment of tumor microvascularity has the potential to improve prognostication, advance understanding of tumor biology, and help narrow potential molecular therapies. While the role of tumor microvascularity has been widely studied in meningiomas, this study examines both the role of automated measurements and the impact on surgical outcome. METHODS Two hundred seven patients with Grade I meningiomas underwent surgery between 1996 and 2011. Tissue samples from each patient were retrospectively evaluated for histopathological measures of microvascularity, including staining for von Willebrand factor (vWF), CD31, CD105, hypoxia-inducible factor 1 (HIF-1), vascular endothelial growth factor, glucose transporter 1, and carbonic anhydrase IX. Manual methods of assessing microvascularity were supplemented by a computational analysis of the microvascular patterns by means of fractal analysis. MIB-1 proliferation staining was also performed on the same tumors. These measures were compared with various patient characteristics, tumor volume, estimated blood loss (EBL) during surgery, progression-free survival (PFS), and overall survival (OS). RESULTS The mean patient age was 55.4 ± 14.8 years, and 63 (30.4%) patients were male. Patients harboring tumors ≥ 3 cm were significantly older (56.9 ± 15.2 years vs 53.1 ± 13.6 years; p = 0.07), more frequently male (40.8% vs 14.6%; p = 0.0001), and had greater EBL (446.5 ± 532.2 ml vs 185.4 ± 197.2 ml; p = 0.0001), greater tumor volume (33.9 ± 38.1 ml vs 29.4 ± 23.5 ml; p = 0.0001), higher MIB-1 index values (3.0% ± 5.4% vs 1.7% ± 1.7%; p = 0.03), higher vWF levels (85.6% ± 76.9% vs 54.1% ± 52.4%; p = 0.001), lower HIF-1 expression (1.4 ± 1.3 vs 2.2 ± 1.4; p = 0.004), and worse OS (199.9 ± 7.6 months vs 180.8 ± 8.1 months; p = 0.05) than patients with tumors < 3 cm. In the multivariate logistic regression, MIB-1 (OR 1.14; p = 0.05), vWF (OR 1.01; p = 0.01), and HIF-1 (OR 1.54; p = 0.0001) significantly predicted tumor size. Although multiple factors were predictive of EBL in the univariate linear regression, only vWF remained significant in the multivariate analysis (ß = 0.39; p = 0.004). Lastly, MIB-1 was useful via Kaplan-Meier survival analysis for predicting patients with disease progression, whereby an MIB-1 cutoff value of ≥ 3% conferred a 36% sensitivity and 82.5% specificity in predicting disease progression; an MIB-1 value ≥ 3% showed significantly shorter mean PFS (140.1 ± 11.7 months vs 179.5 ± 7.0 months; log-rank test, p = 0.05). The Cox proportional hazards model showed a trend for MIB-1 in predicting disease progression in a hazards model (OR 1.08; 95% CI 0.99-1.19; p = 0.08). CONCLUSIONS These results support the importance of various microvascularity measures in predicting preoperative (e.g., tumor size), intraoperative (e.g., EBL), and postoperative (e.g., PFS and OS) outcomes in patients with Grade I meningiomas. An MIB-1 cutoff value of 3% showed good specificity for predicting tumor progression. The predictive ability of various measures to detect aberrant tumor microvasculature differed, possibly reflecting the heterogeneous underlying biology of meningiomas. It may be necessary to combine assays to understand angiogenesis in meningiomas.

The McConnell's Capsular Arteries and Their Relevance in Endoscopic Endonasal Approach to the Sellar Region.

BACKGROUND: The McConnell's capsular arteries (MCCA) were first described in 1953. They consist of medial branches of the cavernous internal carotid artery (ICA) and are divided in anterior and inferior capsular arteries. OBJECTIVE: To highlight the anatomy of the MCCA and its importance in the surgical treatment of tuberculum sellae and planum sphenoidale tumors through an endoscopic endonasal approach. METHODS: Ten cadaveric specimens fixed in formalin and perfused with colored silicone were dissected. Standard endoscopic endonasal transsphenoidal approach to the sellar region was performed. The MCCA were identified and still images were captured for further analysis. We report 1 case to illustrate the importance of the MCCA. RESULTS: The anterior capsular artery, which originates from the anteromedial aspect of the anterior loop of the cavernous ICA and reaches the suprasellar space, was present in 70% of the specimens with no difference between the right and left sides. The anterior capsular artery plays an important role in the vascularization of tuberculum sellae meningiomas. The inferior capsular artery originates from the inferomedial aspect of the cavernous ICA, at its horizontal portion, and reaches the floor and anterior wall of the sella where it anastomoses to branches of the inferior hypophyseal artery. CONCLUSION: The MCCA are key structures when performing an endoscopic endonasal approach for tumors of the sellar and suprasellar regions.

Evaluation of Venous Drainage Patterns for Skull Base Meningioma Surgery.

The evaluation of venous drainage patterns prior to surgery for skull base meningioma is important owing to their deep location and the vulnerability of surrounding vascular structures. In recent years, the microsurgical skull base approach has matured as a surgical technique, making it an important option for reducing complications related to skull base meningioma surgery. In addition, knowledge of the venous anatomy can prevent venous drainage route disturbance and potentially life-threatening complications. Hence, this topic review aimed to provide an overview of normal venous anatomy as it relates to the microsurgical skull base approach, discuss known changes in venous drainage routes that are associated with the progression of skull base meningioma and the selection of an appropriate operative approach with the highest likelihood of preserving venous drainage structures.