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Jörg Schüller

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Long history of seizures and insular location were independent predictors of uncontrolled seizures at diagnosis, while history of seizures at diagnosis, tumor parietal and insular locations were independent predictors of uncontrolled seizures after oncological treatment.

Subtotal and total surgical resections were independent predictors of seizure control after oncological treatment. History of seizures at diagnosis was associated with longer survival without malignant transformation and with longer overall survival.

Introduction: The molecular mechanisms underlying the stem cell nature of glioblastoma are poorly understood.

Aberrant overexpression of EZH2, a histone methyltransferase normally required to maintain stem cell populations in other tissues, likely contributes to this oncogenic transformation.

Understanding EZH2 genomic targets in subventricular zone neural stem cells SVZ NSCs , where many brain tumors potentially arise, would advance our understanding of oncogenesis and identify novel therapeutic targets.

Neurosphere formation assays, chromatin immunoprecipitation ChIP , reverse transcriptase quantitative PCR, immunocytochemistry, and immunohistochemistry IHC were used to identify molecular targets of Ezh2.

Results: Ezh2 deletion in vitro greatly impairs both proliferation and neurogenesis. Co deleted cells had increased expression of basic helix loop helix transcription factor, OLIG2.

Transient overexpression of Olig2 profoundly inhibited neurogenesis and intriguingly, knockdown of Olig2 enhanced neurogenesis in Ezh2 deleted but not WT NSCs.

However, Ezh2 mediated repression of Olig2, commonly expressed in gliomas, is required for neuronal progression.

Rather than solely maintaining self renewal and anaplasticity, Ezh2 has a dual role in epigenetically regulating both self renewal and progressive lineage restriction in SVZ NSCs.

A Multicentre Study of Cases. Conclusions: Epileptic seizures occurrence depends on specific tumor characteristics and independently affect glioma prognosis.

Patients with a history of seizures and those with a complete surgical resection have better outcomes. Thus, in addition to the oncological benefit, early and maximal surgical resection could help in achieving seizure control of patients harboring a diffuse low grade glioma.

Here we analyzed the expression of CD in meningioma, a common intracranial tumor, and its molecular mechanism in association with meningioma progression.

Methods: First, we performed immunohistochemical analysis using 50 human meningioma specimens. Next, we established CD overexpressing human meningioma cell lines and investigated its roles on tumor progression in vitro and in vivo.

Results: Immunohistochemically, 26 out of 50 human meningioma specimens Furthermore, CD expression was correlated with histological atypical parameters which directly predict the prognosis of meningioma patients.

CD overexpressing meningioma cells showed significant suppression of apoptosis and accelerated tumor growth in nude mice. In addition, unexpected splenomegaly affiliated with the xenograft predicted to us the tumor derived 20 Conclusions: To our knowledge, this is the first report which demonstrates CD expression in meningioma not only by immunohistochemistry but also by RT PCR using primary culture cells, and provides the novel molecular function of CD to prevent apoptosis through the production of G CSF in meningioma.

Introduction: Meningiomas are among the most common primary adult brain tumors. The key molecular pathways involved in malignant transformation of meningiomas remain to be determined.

Results: At the genomic level, malignant and atypical meningiomas had more chromosomal losses average length in malignant: Mb, atypical: Mb, benign: 34Mb than their benign counterparts.

Monosomic loss of chromosome 22 was identified as one of the primary chromosomal level abnormalities in all subsets of meningiomas, particularly in malignant samples.

At the transcriptomic level, a weighted gene co expression network was constructed, 23 co expression modules were identified. Gene functional enrichment analysis identified a module with genes that was highly related to tumorigenesis.

A meningioma related gene MN1 , which is also associated with leukemia, was also identified in this module and shown to demonstrate differential expression between malignant and benign meningiomas.

Conclusions: DNA copy number variation analysis confirmed the high frequency of chromosome 22 monosomy and the association between WHO grade and chromosomal abnormalities.

Transcriptome analysis identified several genes with highly differential expression between the benign and malignant groups, including a meningioma candidate gene, MN1.

Genomic and transcriptomic analysis of surgical meningioma samples provides novel insight into the malignant transformation of meningiomas, with implications regarding molecular heterogeneity.

Grade II meningiomas have an aggressive clinical course with increased risk of post treatment recurrence. Distinguishing Grade II meningiomas from Grade I meningiomas preoperatively could affect surgical planning and improve treatment outcomes for patients.

Introduction: Glioblastoma multiforme GBM is the most common malignant brain tumor and contributes disproportionately to mortality.

Previous studies demonstrate that maximal extent of resection EOR is associated with increased survival. This prospective study assesses survival advantages of EOR in light of advancements in postoperative therapy.

Methods: Clinical data and MRI imaging from patients with Grade I or II meningiomas was retrospectively evaluated and correlated with histological grade to determine which features were predictive of more aggressive meningiomas.

Imaging factors analyzed included peritumoral edema, presence of a draining vein, tumor necrosis, and tumor location.

Results: The meningioma patients studied included 94 females and 34 males. Mean age at the time of meningioma diagnosis was Neither male sex nor patient age were significant.

Median preoperative tumor volume was Mean EOR was MS was KPS, age, eloquent location, and postoperative concomitant chemoradiation were significant predictors of survival.

Conclusions: Grade II meningiomas, are highly aggressive tumors that generally require early surgical resection and consideration of adjuvant radiation.

Observation of these cases, may lead to the development of neurologic symptoms and may complicate future resections.

We have identified three factors that are associated with increased risk of higher grade: convexity location, peritumoral edema, and presence of tumor necrosis.

Future studies including larger numbers of patients may allow us to build a useful multivariate model that clinicians can use to predict meningioma grade accurately prior to treatment.

Methods: Ninety consecutive patients underwent retrosigmoid unilateral AN surgery, and postoperative hearing and facial nerve function were evaluated.

A novel application of continuous direct brainstem evoked potentials CDBEPs that visualized and tracked these neural functions was used to analyze the factors affecting same grade functional preservation: auditory evoked dorsal cochlear nucleus action potentials AEDNAPs for cochlear nerve CN and continuous facial nerve root evoked muscle action potentials FREMAPs for facial nerve FN.

Patients in the IERT strategy group had a significantly better functional preservation rate than those in the monitoring alone group the adjusted hazard ratio for cochlear nerve same grade preservation in IERT strategy group relative to monitoring alone group, 0.

Methods: Adult patients with suspected intracranial meningiomas and without prior radiotherapy were included. Histopathological analysis included SRII expression.

Results: 12 patients 8x de novo and 4x recurrent meningiomas; median age 49 years were included. Overall, 59 specimens were collected.

SRII expression was exclusively found in tumor specimens. Results did not significantly differ between primary and recurrent tumors.

We aimed to broaden the receptor recognition by immunotoxins IT to a wider range of GBM by incorporating two totally unrelated ligands uPA and EGF that recognize common GBM and neovascular antigens and determinate whether this immunotoxin could inhibit the growth of aggressive human GBM in our mouse intracranial model via convection enhanced delivery CED.

We established aggressive brain tumors intracranially IC in nude mice with U87 Luc and LN Luc glioma cells genetically marked with a firefly luciferase reporter gene.

Results: DTATEGF was highly potent and selective in killing malignant glioblastoma cells lines, which is receptor specific since cytotoxicity could be blocked with antibodies and accompanied by increased apoptotic population.

Conclusions: A new co targeting agent that simultaneously recognizes EGFR and uPAR is more effective for anti glioblastoma therapy due to simultaneously targeting glioblastoma cells and the neovasculature.

We investigated morbidity of repeat transsphenoidal surgery in consecutive patients. Methods: Five year retrospective review of the first patients treated at our center since being named a pituitary center of expertise.

Three category analysis comparing first, second, and third fifth operations revealed increased meningitis 1.

Morbidity for reoperation was comparable amongst pathologies. No carotid artery injuries occurred. Conclusions: The benign nature of pituitary disease meant that reoperations were rarely needed in these patients undergoing operations.

However, when needed, repeat transsphenoidal had more frequent postoperative DI and meningitis and greater length of stay, with morbidity increasing with each subsequent operation.

Our findings underscore the importance of repeat transsphenoidal surgery being performed by experienced neruosurgeons working with endocrinologists to reduce morbidity.

We have applied delayed contrast extravasation MRI for calculating high resolution maps clearly differentiating tumor from non tumoral tissues.

Here we demonstrate the feasibility of applying these maps for improved targeting of stereotactic biopsies. High resolution maps were calculated and used for planning stereotactic biopsies.

Histological assessment was then compared with the pre surgical maps. Results: The maps showed two primary enhancement populations: the slow population where contrast clearance from the tissue was slower than contrast accumulation and the fast population where clearance was faster than accumulation.

In all cases, biopsies obtained from regions of the fast population consisted of morphologically active tumor while biopsies obtained from regions of the slow population consisted of non tumoral tissues.

According to our maps, in this cohort of patients The excellent correlation between our pre surgical maps and histology suggests that the maps may be applied for planning of diagnostic stereotactic biopsies thus improving targeting to regions of morphologically active tumor and for improved resection planning especially in the case of close proximity to functionally eloquent brain regions.

Methods: Standard molecular biology methods were used. GBM lines that stably overexpressed miR two fold 24 Furthermore, miR overexpressing cells was associated with significantly smaller xenografts than injection of sibling control GBM cells.

Clark C. As such, there is a critical need to develop predictive biomarkers to identify this patient subset. Patients unlikely to benefit from TMZ should be enrolled in novel therapeutic trials.

The observation that the transcription of MGMT is suppressed by methylation of its promoter has led one set of predictive biomarkers.

However, these biomarkers fail to assess the effect of post transcriptional regulation by micro RNAs. Conclusions: These studies establish the tumor suppressor activity of miR in GBM, which may lead to further development of miR related cell mechanisms as novel GBM therapies.

Imaging Genomics, a newly emerged field, links gene expression profiles with MRI phenotypes Zinn et al, , Methods: Laboratory study.

Top candidates were confirmed using multiple adherent and neurosphere glioblastoma lines. Conclusions: In this study, we validated a novel noninvasive diagnostic method to screen for functional networks of cellular invasion.

Furthermore, targeted individualized molecular therapies can be based on diagnostic imaging genomics and can be monitored through out the treatment period.

Since few experimental therapies are available for this subset of patients, we explored a cellular immunotherapeutic approach for the treatment of recurrent atypical meningiomas.

We measured alloCTL viability, growth and anti meningioma cytotoxicity and evaluated to what degree this antitumor activity was HLA specific. They displayed cytotoxic function toward the meningioma cells in 4 hr calcein AM cytotoxicity assays, i.

Conclusions: These preclinical data were used to support the inclusion of patients with recurrent meningiomas to our Phase I dose escalation clinical study www.

Multiple intratumoral adoptive transfers of alloCTL will be performed after they are made by one way mixed lymphocyte reaction, where only patient lymphocytes are needed to accomplish alloCTL generation.

Thus, a personalized immunotherapeutic approach is approved and open to enrollment for patients with recurrent meningioma. Introduction: Currently, contrast enhancing tumor volume is used to delineate tumor burden in patients with glioblastoma GBM.

However, the enhancing tumor volume may underestimate the full extent of tumor burden, as tumor infiltration into normal brain has been observed in non enhancing areas, which are characteristically hyperintense on T2 weighted sequences.

Results: One hundred twenty eight patients met study entry criteria. Median age was 60 years range, , with a median KPS score of 90 range, at diagnosis.

Median overall survival was Their varying growth rates and resistance to conventional therapies render them challenging to treat. This has led to dispute over the role of radiation in treatment.

Methods: We retrospectively reviewed the medical records of 78 surgically treated AM at our institution from to Overall survival OS and time to progression TTP were analyzed using univariate and multivariate Cox regression analyses.

Average follow up was 58 months range 12 Nineteen patients Seventeen patients Conclusions: This series describes outcomes of CNS hemangiopericytomas from a nationwide patient population.

In this study, overall survival benefit is only found when gross total resection can be accomplished, and it is combined with radiation therapy.

Here, we identify predictors of functional outcome following microsurgical resection. Conclusions: A subset of AM in our analysis were prone to progression irrespective of initial treatment.

As radiation introduces risk to patients without benefit, it should not be used as a first line treatment. Given the uniquely aggressive nature of a fraction of AM, further research should be aimed at identifying factors that render those tumors more prone to growth.

Methods: We identified patients with newly diagnosed grade II posterior fossa ependymomas surgically treated at the Barrow Neurological Institute between and Pediatric patients were excluded.

Routine clinical and radiographic variables were retrospectively collected, including volumetric extent of resection, cystic changes, peritumoral T2 signal changes, progression free survival, and overall survival.

Median progression free survival and overall survival were 5. Greater extent of resection and the adjuvant radiotherapy were both associated with improved survival.

Specifically, patients with cystic changes and increased peritumoral T2 signal recovered their baseline KPS by 1 year, while those without these features improved by 6 weeks.

Most of the literature on this disease consists of single institution case series collected over long periods of time, and thus may reflect selection bias and might not be representative of the outcomes of current treatment paradigms.

Methods: We queried the Surveillance Epidemiology and End Results SEER database to investigate the clinical behavior and prognostic factors for hemangiopericytomas originating within the CNS during the years Results: We identified patients with a diagnosis of CNS hemangiopericytoma.

Age, radiation therapy, and gross total resection plus adjuvant radiation were significantly associated with survival on univariate analysis.

On the multivariable model, age, location and adjuvant radiation therapy were significantly associated with prolonged overall survival.

Older patients had a hazard ratio of 1. Patients with supratentorial lesions were found to have prolonged survival, with infratentorial tumors associated with a hazard ratio of 2.

The only treatment paradigm to confer a survival advantage was gross total resection plus radiation therapy. Patients undergoing this combination therapy were found to have significantly better survival, with a hazard ratio of 0.

Conclusions: Following microsurgical resection of posterior fossa ependymomas, cystic changes and increased peritumoral T2 signal are independent predictors of the rate of neurological recovery.

Further study should examine the biological correlates underlying these radiographic features of adult posterior fossa ependymomas.

However, delineating tumor infiltrated tissue from normal brain remains a challenge. Here we describe the use of Coherent Raman scattering CRS microscopy for differentiating healthy brain from tumor infiltrated brain based on histologic and biochemical differences.

Unlike traditional histopathology, CRS is a label free technique that can be rapidly performed in situ. Methods: All experiments were performed using an established system for CRS microscopy.

To demonstrate the ability of CRS to detect tumor infiltration in unprocessed tissue specimens we imaged fresh 2mm thick tissue sections from normal and tumor bearing mice.

Frozen and fresh tissue CRS imaging demonstrated both normal brain structures and and tumor infiltrated brain with excellent clarity and accuracy.

We also demonstrated, that tumor detection with CRS is possible in vivo, revealing tumor margins that are invisible under the standard operative conditions.

Selective targeting of brain tumor cells by SapC DOPS was observed in astrocyte Gli36 co cultures, a model that better resembles the in vivo tumor environment.

Synergistic anticancer effects were observed after co treatment of glioma cell lines with SapC DOPS and chemotherapeutic drugs that promote PS externalization.

Conclusions: By providing the surgeons with rapid histologic assessment of the operative field, CRS microscopy may ultimately improve the safety and accuracy of tumor surgeries where tumor boundaries are visually indistinct.

CRS microscopy demonstrates a clear distinction between tumor infiltrated areas T and non infiltrated brain N a. Brightfield microscopy demonstrates no gross differences within the same FOV b.

In the multivariate analysis adjusting for age, sex, race, tumor grade, medical Introduction: Though research into the pathogenesis of primary and metastatic brain tumors has advanced, current therapies still show limited efficacy.

Saposin C dioleoylphosphatidylserine SapC DOPS nanovesicles are a novel antitumor agent that selectively target exposed phosphatidylserine PS on brain tumor cell membrane surface and induces cell death.

The authors present analysis of these procedures between to evaluate how procedural volume impacts complication rates.

Methods: The authors performed a retrospective cohort study using data from the Nationwide Inpatient Sample NIS for 62, admissions for biopsy or resection of supratentorial primary brain tumors from to The presence of one or more complications was significantly correlated with increased mortality OR 6.

The mutational profile of a meningioma can largely be predicted based on its anatomical position, serving as the basis for targeted therapeutics.

Conclusions: Consistent with the previous decade, the number of high volume hospitals and surgeons performing craniotomies and needle biopsies for primary brain tumor increased over the study period.

Analysis of outcomes demonstrate that high surgeon and hospital volumes correlate with decreased risk of adverse outcome and support a shift towards regionalization of care.

Introduction: Studies have suggested better outcome after complex surgery at hospitals with larger treatment volume, including meningioma craniotomy.

We investigated whether previously reported US national trends toward neurosurgical centralization, as for intracranial aneurysm treatment, affected meningioma craniotomy practice patterns from We aimed to comprehensively characterize the genomics of meningiomas.

Methods: We performed genome wide genotyping, exome sequencing, ChIP seq and gene expression analyses of 50 tumors, followed by targeted resequencing of an independent cohort of meningiomas.

We correlated the genomic analyses with clinical findings. Among the novel neoplasia genes, TRAF7, a pro apoptotic E3 ubiquitin ligase, is mutated in one fourth of all meningiomas.

These non NF2 meningiomas are nearly always benign, show chromosomal stability, include secretory and meningothelial histology, and mostly originate from the anterior and medial skull base with SMO mutants localizing to midline.

In contrast, the vast majority of NF2 mutant tumors show genomic instability, localize to the cerebral and cerebellar hemispheres and are more likely to be malignant.

In hospital mortality was 1. The number of US hospitals performing meningioma craniotomies remained largely stable: hospitals , After multivariate adjustment age, sex, race, payer, surgery year and admission type , larger hospital volume significantly predicted lower mortality both in OR 0.

Conclusions: Higher hospital volume continues to predict lower mortality after meningioma craniotomy.

An increasing proportion of meningioma craniotomies in the US are being performed at high volume centers. Conclusions: Our results clearly identify clinically relevant meningioma subgroups, distinguishing them based on their mutually exclusive distribution of mutations, distinct potential for 29 It has been proposed that the vascular nature of these tumors is the product of reactive angiogenesis.

Recent studies have shown that the characteristic islands of erythrocytes in VHL associated CNS hemangioblastomas develop from tumor cells.

We hypothesized that a subset of vascular structures within VHL associated lesions are a result of tumor derived vasculogenesis.

Methods: Tumor endothelial markers within CNS hemangioblastomas were visualized by immunofluorescence and three dimensional immunohistochemistry. Additionally, identified vascular elements from human vHL deficient murine xenografts were micro dissected and analyzed for loss of heterozygosity, as well as visualization by co localization immunofluorescence and fluorescence in situ hybridization FISH.

Three dimensional immunohistochemistry identified isolated islands of CD31 expressing structures. Micro dissected vascular structures demonstrated marked allelic imbalance after amplification with VHL gene flanking primers, indicating a loss of VHL and a somatic second hit deletion of the wild type allele.

Co localization by immunofluorescence for HLA and CD31 further confirmed the presence of tumor derived vascular tissue. Conclusions: The hemangioblast cell was identified as the embryologic progenitor cell for both endothelial cells and erythrocytes.

We established that some VHL associated tumor cells differentiate into endothelial cells, confirming that developmentally arrested vHL deficient hemangioblast cells are responsible for VHL associated tumorogenesis, and maintain the potential to develop into endothelial cells.

Introduction: While immunotherapy has demonstrated promise in clinical studies, overcoming immunosuppression within the tumor microenvironment remains a challenge.

Naturally occurring ribonucleoproteins known as vault nanoparticles have been found capable of enclosing, protecting and delivering various antigens and drugs.

In this study, we assay a bioengineered PVI Z vault containing CCL21, a potent lymphocyte chemoattractant, inducing antitumor immunity in glioblastoma in vivo.

Mice were euthanized if tumors were ulcerating or larger than 15mm in diameter. Survival and tumor growth rate were analyzed and compared.

Results: GBM was successfully injected into our animal model. For the other cohort, tumor size decreased on average by day 25, and stabilized until the conclusion of the study on day Conclusions: PVI Z CCL21 vault nanoparticles can be bioengineered efficiently, and treatment with recombinant vaults demonstrated the potential for tumor control.

This study demonstrates the in vivo efficacy of CCL21 vault nanoparticles, and its potential to be used as a potential novel therapy for high grade gliomas.

Because the mTORC1 mammalian target of rapamycin complex 1 pathway is activated in many tumors, we explored the usefulness of mTORC1 inhibition as therapeutic strategy in meningioma cell lines and mouse models.

Introduction: MicroRNAs miRs have been shown to modulate critical gene transcripts involved in tumorigenesis, but their role in tumor mediated immune suppression is largely unknown.

Methods: On the basis of miRNA gene expression in gliomas using tissue microarrays, in situ hybridization, and molecular modeling, miR was identified as the lead candidate for modulating signal transducer and activator of transcription 3 STAT3 signaling, a key pathway mediating immune suppression of the tumor microenvironment.

Results: MiR is down regulated in all grades and pathological types of gliomas. Both systemic administration of miR or adoptive miR transfected T cell transfers exerted potent anti glioma therapeutic effects in clonotypic and genetically engineered murine models of glioblastoma and enhanced effector responses in the local tumor microenvironment.

A significant dosage dependent growth inhibition by temsirolimus was observed in all cell lines which was also affected by NF2 status.

Conclusions: Our findings highlight the potential application of miR as a novel immunotherapeutic agent for neoplasms and serve as a model for identifying miRNAs that can be exploited as immune therapeutics.

We present a case report of a patient who had combination chemotherapy without histological diagnosis and had complete tumour regression.

Methods: The patient's case folder was retrieved and information relating to presentation, the working diagnosis and supporting investigations were sought.

She had pre chemotherapy ventriculo peritoneal shunt insertion for obstructive hydrocephalus. After due consultation with the Radio oncolgist, she had cyclical combination chemotherapy with cisplatin, etoposide and bleomycin.

Results: The patient's clinical condition improved following the ventriculo peritoneal shunt insertion. Post chemotherapy Brain CT scan showed complete tumor regression.

Conclusions: Tissue diagnosis may allow for precise, targeted management of pineal region tumours, however, in the absence of facilities which enable safe neurosurgery, resorting to the traditional chemo radiation is still a viable alternative.

There are several therapeutic options, but selection of the optimal treatment for individual patients remains controversial.

Classification schemes such as recursive partitioning analysis RPA , and diagnosis specific graded prognostic assessment DS GPA have been validated, but these provide group, rather than individualized estimates of outcome.

The purpose of this study was to develop and validate a nomogram for individualized patient prognosis which could be used for counseling patients.

Methods: De identified data from 7 randomized controlled trials of brain metastasis in patients was obtained from the RTOG database.

Overall survival was estimated using the Cox proportional hazards regression, RPA, and random survival forests RSF methods, and a nomogram was built using a concordance index to identify the best approach for each variable.

Results: The Cox analysis outperformed other methods thus the nomogram was built to estimate survival probabilities and median survival based on the Cox model.

This predictor of outcome could be readily applicable to clinical practice in enabling patients and their physicians to make informed decisions regarding treatment options and will be provided as free software application.

Future directions include external validation in a prospective dataset. The most biologically aggressive subtype is the glioblastoma multiforme GBM , a tumor associated with dismal prognosis.

The current standard of care for GBM patients; surgical resection followed by adjuvant radiation therapy and chemotherapy with the oral alkylating agent temozolomide; produces a median survival of only 15 months.

Even with the addition of the last generation of imaging studies, clinical assessment of tumor progression versus pseudo progression remains difficult.

This, combined with the high cost of these imaging modalities, can pose serious delays in treatment decisions and result in harm to the patient.

Hence, there is urgent need for a sensitive, specific, noninvasive and low cost biomarker which could be used routinely to monitor disease status in patients on treatment.

Methods: It is now well established that circulating mutant DNA cmDNA that originates in the tumor can be detected in the peripheral blood. We used next generation, paired end sequencing to analyze several GBM genomes and their isogenic controls and identified tumor specific mutations.

These mutations were detected by polymerase chain reaction PCR in the patients; plasma and were used to follow disease progression over time.

Conclusions: Mutation associated biomarkers offer a reliable measure that would be useful for monitoring tumor response to specific therapies, detecting residual disease after surgery, and for long term clinical management.

The endoribonuclease Dicer is crucial for microRNA biogenesis. Low expression of Dicer has been associated with cancer, even though there are no studies in meningiomas.

Methods: We used tissue microarray TMA slides containing 59 samples of meningiomas from patients that underwent surgical resection.

Clinical correlation was made between WHO grade classification, tumor recurrence, post operative radiation therapy, cavernous sinus invasion, Mib1 index and Dicerexpression.

Results: From the total of 59 patients studied, 42 In the high Dicer group, the WHO grade distribution was: 34 The low Dicer group revealed: 7 In addition, the low Dicer group had higher percentage of tumor recurrence Withdrawn The clinical signs and symptoms of spinal meningiomas are typical of slow growing space occupying lesions of the spinal canal.

Clinical symptoms are normally indolent, gradual in presentation, and dependent on the tumor level and breadth. These lesions have the potential to rapidly expand and cause acute neurological decline, often requiring emergent surgical intervention.

There is ample literature on the more common causes of epidural bleeds, but sparse data describing spinal epidural hematomas presenting secondary to cervical meningiomas.

This study describes a patient lacking the common risk factors for a spinal epidural hemorrhage, who presented clinically with acute paraparesis from a spontaneous cervical spinal hemorrhage.

Methods: The patient physical examination was most notable for dense paraparesis. Clinical workup was unremarkable for any typical causes of an acute epidural hematoma.

A cervical spine MRI revealed a meningioma at the C1 2 level, at the proximal portion of the epidural hematoma. We hypothesized the pathogenesis of the meningioma as the causative agent of the acute epidural hematoma.

Conclusions: This case provides evidence that, though not previously considered, spinal meningiomas should be included in the differential diagnosis of spinal hematomas.

This is especially the case when long term indolent pain is followed by acute symptoms without the commonly reported risk factors.

Conclusions: Therefore, low Dicer expression in meningiomas can be related to tumor aggressiveness and a worse clinical course.

Prognosis of affected patients is dependent on age, staging, and the pathology of the neoplasms, and this in turn affects treatment. A review of the literature reveals a constant debate between surgical or non surgical management of these types of neoplasms.

However, the literature unanimously reveals a poor prognosis in patients with severe acute progressive neurological deficits, regardless of treatment type.

The novel case herein reports a 3 month old patient with full resolution of a 4 day history of complete lower extremity paralysis status post neurosurgical intervention.

Methods: Magnetic resonance imaging showed complete spinal cord compression by a thoracolumbar intracanal extradural mass that was contiguous with a paraspinal mass.

Further pathological and radiological analysis, including MIBG and bone scintigraphy, showed that the mass was consistent with a non metastatic neuroblastoma.

The patient subsequently underwent a multilevel laminectomy that allowed for resection of the intraspinal mass and decompression of the spinal cord.

This was followed by adjuvant therapy on a delayed basis. Results: Fortunately, despite their prolonged lower extremity paralysis the patient regained full neurological function with resolution of spinal cord compression on radiographic imaging at 6 months follow up.

Conclusions: Currently, research states that patients with prolonged severe neurological deficits secondary to an intraspinal neuroblastoma have a very slim chance in regaining neurological function, irrespective of surgical or non surgical management.

This novel case seems to suggest that prompt surgical intervention followed by adjuvant therapy is the best treatment for these patients, given the potential benefit of rapid recovery of neurological function.

Meningiomas are benign brain tumors that are also associated with an increased VTE risk. Whether the presence or resection of meningiomas leads to systemic coagulation activation has not been clarified.

Methods: We hypothesize that patients with glioblastoma multiforme GBM demonstrate increased systemic coagulation activation compared to healthy individuals.

We further hypothesize that meningiomas are not associated with a significant increase in systemic coagulation activation and that this may account for the difference in VTE risk.

We will test this hypothesis by measuring surrogate markers of systemic coagulation activation in patients with GBM and meningiomas before and after treatment and in age and sex matched healthy control blood donors.

Markers of coagulation activation assayed for this study will include plasma D dimers, P selectin, tissue factor pathway inhibitor TFPI , thrombin generation via calibrated automated thrombography and tumor tissue factor and TFPI expression by immunohistochemistry.

Results: We are currently actively recruiting to this study and expect to complete arcual by the end of Conclusions: We expect this work to lead to clarification of coagulation abnormalities in patients with primary brain tumors and may result in identification of novel markers of VTE risk in these patients.

This however does not exclude the immunocompromising effect,which includes risks of lymphomatous disease. He was commenced on Stupp prorocal with concurrent Temozolomide.

His treatment completed 2 months after his initial presentation and a month later, he proceeded with first cycle of adjuvant chemotherapy.

This was complicated with large pulmonary embolism and left lower limb deep vein thrombosis. Follow up MRI Brain revealed a recurrence of his tumour.

There was also a new enhancing lesion in the left frontal lobe, measuring 1. He subsequenly underwent further debulking of his original tumour and stereotactic biopsy of the contralateral lesion.

He deteriorated during chemotherapy and died 10 months after his original presentation. Results: We describe herein an interesting case of primary GBM with concurrent primary CNS lymphoma diagnosed 2 months after completion of Temozolomide treatment.

To best of our knowledge, this is the first case reported in literature. This was observed on his surveillance MRI Brain 2 months after completion of treatment, therefore, the suspicion exists that the lesion may have developed while he was on treatment.

Excitatory glutamatergic mechanism are shown to be involved in the generation of epileptic activities in the cortex surrounding gliomas.

However, the contribution of defective Chloride homeostasis and paradoxical excitatory GABAergic mechanisms, crucial in other epilepsies, is unknown.

They can occur anywhere in the cranium and the spine and have varied pathology. Removal of meningiomas in certain locations can be challenging, we explored the use of ALA induced fluorescence to guide intracranial meningiomas; resection and its corrolation to histopathology.

Methods: We studied in neocortical slices from the security margin resected around human brain gliomas, the occurrence, networks, cells, signaling and origin of epileptic activities.

These events were synchronized in superficial layers of cortical columns in the neocortex surrounding glioma areas that presented a tumor infiltration and had a high frequency oscillation signature.

Interictal like events depended on glutamatergic transmission but also on depolarizing GABAergic signaling. This effect was related to perturbations in Chloride homeostasis, due to an abnormal load by the co transporter NKCC1.

Ictal like activities could be exclusively generated in these epileptogenic areas. Methods: Twenty nine consecutive lesions with MRI differential of meningiomas were included in this analysis, including 17 supratentorial, 10 infratentorial and one thoracic.

Twenty three were females, the mean age was All these patients received 1. Surgical resection was aided by using the blue light of the microscope Pentero, Zeiss, Germany.

The fluorescence was graded into strong very red fluorescent , faint pink and moderate in between red and pink. Results: Fluorescence was detected in 22 Faint signal was observed in six Total excision Simpson grade 1 was achieved in all meningiomas.

There was no correlation between histological type, ALA dose, or time to fluorescence and the intensity of fluorescence. Only two patients developed significant drop in their blood pressure 7.

ALA induced fluorescence is safe and helpful in intracranial meningioma surgical resection, but there was no correlation to histology.

On postoperative day 22 the EVD was clamped, and the patient remained asymptomatic the following day. A new brain MRI showed significantly decreased size of the germinoma along with flow artifact across the floor of the third ventricle, and his EVD was removed.

The patient's hydrocephalus did not recur over the following month. We undertook a multidisciplinary study among brain tumor experts to test this hypothesis.

Methods: The expert group included 2 CNS radiation oncologists, 3 tumor neurosurgeons, and 2 neuro radiologists. CERR Matlab tool was used to compare volumes.

CCC measured inter observer reproducibility. Conclusions: In this pilot substantial inter observer variability exists in meningioma target definition.

Over contouring increases normal tissue exposure. Under contouring increases recurrence risk. Our findings suggest lack of physician consensus regarding target volume.

We suggest a large scale study to confirm these findings and consideration of a multidisciplinary consortium to standardize target volumes.

Gump, MD; Ian Mutchnick, MD Louisville, KY Introduction: Endoscopic third ventriculostomy E3V is an established option for treatment of obstructive hydrocephalus and is often performed concurrently with biopsy of an obstructing mass lesion.

Delayed failure is a known complication. We report the case of a patient whose E3V became functionally patent in a delayed fashion, three weeks postoperatively, when mass effect on the brainstem had been adequately relieved.

Methods: A 13 year old boy presented to the emergency department with symptomatic obstructive hydrocephalus from a pineal region tumor.

Results: Pathology was consistent with pure germinoma. The patient returned to surgery four days later for a secondary E3V. He remained drain dependent, and initiated radiation therapy on postoperative day 7.

Therefore, advancements in research tools, including cell culture and animal models represent a challenge for basic research and are necessary for the development of more effective treatments.

Methods: We are developing the 3 Dimensional cell culture model in which primary Glioblastoma cells are forced to form multi cellular Glio Spheres.

This approach allows cells to grow for several months without losing their glial phenotype, the main problem with Glioblastoma culture. We use Seahorse Analyzer to characterize metabolic properties of Glio Spheres by measuring Extracellular acidification and Oxygen consumption rates; We also evaluate mitochondrial membrane potential, cell survival and response to a common lipid lowering drug, fenofibrate.

Conclusions: Here, we demonstrate a new approach to develop 3 dimentional cell culture system for primary Glioblastoma Glio Spheres and present their metabolic profiles.

We also include studies on fenofibrate, which has strong anti tumoral effect with low systemic toxicity, and could be introduced as a supportive regimen to the conventional therapies.

The Glio Spheres can be also implanted into the brains of immunodeficient mice, providing a clinically relevant model for testing anti tumoral regiments against Glioblastoma.

The tumor suppressor NF2 is disrupted in approximately half of meningiomas, but the complete spectrum of genetic changes remains undefined.

Introduction: Microcystic meningioma is a variant of meningioma with a multicystic appearance that can mimic intrinsic primary brain tumors, hemangioblastomas, and other non meningiomatous tumor types.

Methods: We performed whole genome or whole exome sequencing of 17 Grade I meningiomas and focused sequencing of an additional 48 tumors to comprehensively identify mutations, insertion deletions, copy number alterations, and genetic rearrangements contributing to oncogenesis.

A mutational significance algorithm was used to distinguish driver and passenger events. Methods: 18 subjects with histopathological diagnosis of microcystic meningioma and a cohort of 12 subjects with grade I meningioma and 54 subjects with grade IV primary glioma were considered.

Clinical variables including patient sex, age, extent of resection, surgical blood loss and need for adjunctive therapy were considered.

DSC images were acquired at a temporal resolution of either ms 3T or ms 1. Results: Overall, the tumors showed few somatic genetic events, consistent with their benign clinical status, but underscoring the potential importance of each individual event.

Several tumors harbored more complex patterns of copy number changes and rearrangements including one tumor with chromothripsis.

As expected, the NF2 gene was identified as the most frequently altered, with over half of tumors harboring NF2 disruptions. One sample had a novel translocation affecting the NF2 gene and a nearby region of chr Preoperative DCE analysis demonstrated kTrans values of 0.

Conclusions: This study begins to define the spectrum of genetic alterations in meningiomas. The discovery of novel drivers of meningiomagenesis with existing targeted therapeutics has the potential to rapidly transform the clinical management of meningiomas.

Higher nCBV values are associated with a trend to increased intraoperative blood loss. Introduction: Increasing use of endoscopic approaches for the treatment of various intracranial pathology has necessitated neurosurgeons have a thorough understanding of the anatomy from an endoscopic endonasal perspective.

We present a cadaveric anatomic study of the clinoidal and ophthalmic ICA from an endonasal endoscopic perspective. Methods: Testing of all basal hormone values and magnetic resonance imaging MRI were performed preoperatively and postoperatively in consecutive patients who underwent PEETS in the period between and The series consisted of 37 somatotroph adenomas, 4 prolactinomas, and 8 corticotroph and 72 nonfunctioning adenomas.

Remission was defined as hormonal excess normalization on the third postoperative day in functioning adenomas and as normal MRI findings approximately four months postoperatively in nonfunctioning adenomas.

Hypocortisolism was assessed through necessity for replacement therapy within 3 months postoperatively. Methods: Embalmed heads underwent thin cut CT scans for the purpose of neuronavigation.

The heads were registered with our neuronavigation system. An endonasal endoscopic transsphenoidal exposure was performed. Various measurements were taken some of which include: the inter carotid distance at the level of the distal dural rings DDR , the distance between the ICA at the distal dural ring and the optic chiasm and the distance between the ICA and the pituitary stalk.

The ratio of inter carotid distance to distance between the OCRs was also calculated. Results: A total of 10 cadaver heads were studied.

Neuronavigation was used achieving excellent accuracy in all cases. The average distance between the carotids at the distal dural rings was The average distance between the ICA at the distal dural ring and the optic chiasm is 9.

Endocrinological complications occurred in Seventy five percent of preoperatively present hormonal deficiencies improved after the surgery. Between tumor types there were no significant differences in remission, complications, and normal pituitary function recovery.

Conclusions: Expansion of endonasal endoscopic techniques for treatment of various intracranial pathology necessitates improved understanding of the clinoidal and proximal intradural ICA anatomy and its relationship to surrounding structures.

This will enable surgeons to more reliably predict the location of the ICA and its relationship to surrounding structures, decreasing the potential for vascular injury.

Conclusions: Patients with microadenomas had higher remission and lower complication rates following PEETS, emphasizing the necessity for early detection and treatment of pituitary adenomas.

PEETS is a discussion worthy method for microprolactinoma treatment. These can be locally aggressive with potential intracranial extension.

Traditionally these lesions have been treated using open surgical techniques, however recently endoscopic approaches have been implemented in hopes of minimizing morbidity.

We recorded the number of operations, estimated blood loss, extent of resection, any complications and length of hospital stay. All are male with an average age of 16 years.

Average follow up is All patients underwent pre operative tumor embolization. One patient underwent an initial open transfacial approach and required a subsequent endoscopic approach.

Patients underwent an average of 2. Mean EBL was cc. A subtotal resection was achieved in all cases. Two patients underwent radiation therapy during the course of their treatment.

There were no mortalities. Open surgical resection can achieve good tumor control, but can be exceedingly morbid. Given the tendency for these lesions to regrow, multiple surgeries are often required.

We believe an endoscopic approach for subtotal resection in combination with pre operative embolization and post operative adjuvant treatment in select patients can achieve good tumor control while minimizing morbidity.

Numerical values were estimates from the french register of CNS tumors, the national institute of statistics, and published series of glioma survivals.

We report a new case in a pediatric patient. Methods: A 4 year old girl presented with generalized seizures.

MRI of the brain revealed an extensive diffuse nonenhancing area of abnormal signal involving the right frontal and temporal lobes.

She was taken to surgery for biopsy, and returned to surgery eight months later for electrocorticography guided seizure focus resection.

Seizure frequency decreased to zero over the following three months. Compared with gemistocytic, protoplasmic astrocytomas have less potential to behave aggressively.

In two case series encompassing 18 patients, average age at presentation was 25 years. Most lesions were in the frontal or temporal lobes.

For 7 patients with unresectable lesions, biopsy was performed; all others underwent attempted gross total resection. Five patients subsequently received radiation therapy and one also had chemotherapy.

The youngest patient age 2 years at diagnosis died 36 months after subtotal resection without further adjuvant therapy; all others were alive with or without residual tumor 2 to months postoperatively.

One additional case report describes a 3 year old with diffuse leptomeningeal disease who died from tumor progression despite chemotherapy. Although all patients presented with seizures, seizure outcomes have not been well documented.

Our patient achieved seizure freedom. Conclusions: Protoplasmic astrocytoma is a rare low grade glioma which can be associated with medically resistant epilepsy.

Tailored surgery for unresectable lesions can be beneficial for seizure control. Conclusions: Patients with silent DLGG are more likely to die from transformation of the silent DLGG to symptomatic glioma than dying from another cause with the silent DLGG, unless patient survival is expected to be less than 4 years.

This epidemiological argumentation supports early surgery for incidentally discovered glioma. To identify patients who had undergone surgery, we used brain tumor surgery ICD 9 codes.

We used the SAS statistical software package Version 9. For brain tumor patients treated without surgery For brain tumor patients treated with surgery 9.

The most common PSIs included postoperative respiratory failure, deep vein thrombosis, and sepsis.

The total number of HACs associated with brain tumor patients was 13,, with 2. For brain tumor patients treated without surgery 3.

For brain tumor patients treated with surgery 7. The most common HACs included falls and trauma and pressure ulcers. Conclusions: Patient safety and delivery of quality care is an important part of our national healthcare agenda.

These data may be used to determine individual institutional improvements or success by comparison. One of the molecular hallmarks of Glioblastomas is genomic instability, which leads to the development catastrophic mutations.

Thus, basic DNA repair mechanisms responsible for the preservation of genomic integrity could be impaired in Glioblastomas. We have previously reported the detection of DNA sequences of the human neurotropic JC Virus and expression of its oncoprotein, T Antigen, in brain tumors of glial and neuroectoermal origin.

Bevacizumab has recently demonstrated encouraging anti tumor effect in the treatment of recurrent and progressive meningiomas. The imaging characteristics of meningiomas undergoing bevacizumab treatment have not been extensively described.

Methods: While undergoing systemic therapy on bevacizumab with a sustained intracranial response, a 55 year old man with a locally recurrent WHO grade III meningioma developed a biopsy proven left sided neck metastasis and radiographic findings consistent 40 Conclusions: Fluorescence guided resection for complex meningiomas have shown to be an effective intraoperative tool to achieve maximal citoreduction.

In meningioma lesions we assume that the breakage of the blood brain barrier increasing vascular permeability and by this mechanism the 5 ALA reaches the peritumoral area.

Results: The primary intracranial meningioma was a homogeneously, avidly enhancing extra axial mass on magnetic resonance imaging MRI.

The recurrent intracranial lesion was isointense to surrounding brain on T1 imaging and hyperintense on T2 weighted images.

The mass was centered in the obliquus capitis inferior muscle and was associated with erosive bony changes. The neck lesion was isointense to muscle on noncontrast T1 imaging, and nearly isointense to gray matter on T2 weighted images.

There were four subcentimeter, nonenhancing parenchymal lung nodules appreciated on chest CT, consistent with pulmonary metastatic disease. Cranial hyperostosis in association with adult meningioma occurs frequently.

The osteopathophysiology of this phenomenon is poorly understood and controversial, with actual bone invasion by tumor or reactive changes due to adjacent tumor having been posited as explanations.

Metalloproteins have also been suggested as playing a role. Hyperostosing meningioma is rarely reported in children. Conclusions: This case illustrates the imaging appearance of intracranial anaplastic meningioma and extracranial metastases while on bevacizumab.

Further study of imaging characteristics of recurrent and progressive meningiomas while undergoing treatment with anti angiogenic therapies is warranted.

Results: We identified patients with a diagnosis of CNS hemangiopericytoma. Age, radiation therapy, and gross total resection plus adjuvant radiation were significantly associated with survival on univariate analysis.

On the multivariable model, age, location and adjuvant radiation therapy were significantly associated with prolonged overall survival.

Older patients had a hazard ratio of 1. Patients with supratentorial lesions were found to have prolonged survival, with infratentorial tumors associated with a hazard ratio of 2.

The only treatment paradigm to confer a survival advantage was gross total resection plus radiation therapy. Patients undergoing this combination therapy were found to have significantly better survival, with a hazard ratio of 0.

Conclusions: Following microsurgical resection of posterior fossa ependymomas, cystic changes and increased peritumoral T2 signal are independent predictors of the rate of neurological recovery.

Further study should examine the biological correlates underlying these radiographic features of adult posterior fossa ependymomas.

However, delineating tumor infiltrated tissue from normal brain remains a challenge. Here we describe the use of Coherent Raman scattering CRS microscopy for differentiating healthy brain from tumor infiltrated brain based on histologic and biochemical differences.

Unlike traditional histopathology, CRS is a label free technique that can be rapidly performed in situ. Methods: All experiments were performed using an established system for CRS microscopy.

To demonstrate the ability of CRS to detect tumor infiltration in unprocessed tissue specimens we imaged fresh 2mm thick tissue sections from normal and tumor bearing mice.

Frozen and fresh tissue CRS imaging demonstrated both normal brain structures and and tumor infiltrated brain with excellent clarity and accuracy.

We also demonstrated, that tumor detection with CRS is possible in vivo, revealing tumor margins that are invisible under the standard operative conditions.

Selective targeting of brain tumor cells by SapC DOPS was observed in astrocyte Gli36 co cultures, a model that better resembles the in vivo tumor environment.

Synergistic anticancer effects were observed after co treatment of glioma cell lines with SapC DOPS and chemotherapeutic drugs that promote PS externalization.

Conclusions: By providing the surgeons with rapid histologic assessment of the operative field, CRS microscopy may ultimately improve the safety and accuracy of tumor surgeries where tumor boundaries are visually indistinct.

CRS microscopy demonstrates a clear distinction between tumor infiltrated areas T and non infiltrated brain N a. Brightfield microscopy demonstrates no gross differences within the same FOV b.

In the multivariate analysis adjusting for age, sex, race, tumor grade, medical Introduction: Though research into the pathogenesis of primary and metastatic brain tumors has advanced, current therapies still show limited efficacy.

Saposin C dioleoylphosphatidylserine SapC DOPS nanovesicles are a novel antitumor agent that selectively target exposed phosphatidylserine PS on brain tumor cell membrane surface and induces cell death.

The authors present analysis of these procedures between to evaluate how procedural volume impacts complication rates.

Methods: The authors performed a retrospective cohort study using data from the Nationwide Inpatient Sample NIS for 62, admissions for biopsy or resection of supratentorial primary brain tumors from to The presence of one or more complications was significantly correlated with increased mortality OR 6.

The mutational profile of a meningioma can largely be predicted based on its anatomical position, serving as the basis for targeted therapeutics.

Conclusions: Consistent with the previous decade, the number of high volume hospitals and surgeons performing craniotomies and needle biopsies for primary brain tumor increased over the study period.

Analysis of outcomes demonstrate that high surgeon and hospital volumes correlate with decreased risk of adverse outcome and support a shift towards regionalization of care.

Introduction: Studies have suggested better outcome after complex surgery at hospitals with larger treatment volume, including meningioma craniotomy.

We investigated whether previously reported US national trends toward neurosurgical centralization, as for intracranial aneurysm treatment, affected meningioma craniotomy practice patterns from We aimed to comprehensively characterize the genomics of meningiomas.

Methods: We performed genome wide genotyping, exome sequencing, ChIP seq and gene expression analyses of 50 tumors, followed by targeted resequencing of an independent cohort of meningiomas.

We correlated the genomic analyses with clinical findings. Among the novel neoplasia genes, TRAF7, a pro apoptotic E3 ubiquitin ligase, is mutated in one fourth of all meningiomas.

These non NF2 meningiomas are nearly always benign, show chromosomal stability, include secretory and meningothelial histology, and mostly originate from the anterior and medial skull base with SMO mutants localizing to midline.

In contrast, the vast majority of NF2 mutant tumors show genomic instability, localize to the cerebral and cerebellar hemispheres and are more likely to be malignant.

In hospital mortality was 1. The number of US hospitals performing meningioma craniotomies remained largely stable: hospitals , After multivariate adjustment age, sex, race, payer, surgery year and admission type , larger hospital volume significantly predicted lower mortality both in OR 0.

Conclusions: Higher hospital volume continues to predict lower mortality after meningioma craniotomy. An increasing proportion of meningioma craniotomies in the US are being performed at high volume centers.

Conclusions: Our results clearly identify clinically relevant meningioma subgroups, distinguishing them based on their mutually exclusive distribution of mutations, distinct potential for 29 It has been proposed that the vascular nature of these tumors is the product of reactive angiogenesis.

Recent studies have shown that the characteristic islands of erythrocytes in VHL associated CNS hemangioblastomas develop from tumor cells.

We hypothesized that a subset of vascular structures within VHL associated lesions are a result of tumor derived vasculogenesis. Methods: Tumor endothelial markers within CNS hemangioblastomas were visualized by immunofluorescence and three dimensional immunohistochemistry.

Additionally, identified vascular elements from human vHL deficient murine xenografts were micro dissected and analyzed for loss of heterozygosity, as well as visualization by co localization immunofluorescence and fluorescence in situ hybridization FISH.

Three dimensional immunohistochemistry identified isolated islands of CD31 expressing structures. Micro dissected vascular structures demonstrated marked allelic imbalance after amplification with VHL gene flanking primers, indicating a loss of VHL and a somatic second hit deletion of the wild type allele.

Co localization by immunofluorescence for HLA and CD31 further confirmed the presence of tumor derived vascular tissue.

Conclusions: The hemangioblast cell was identified as the embryologic progenitor cell for both endothelial cells and erythrocytes. We established that some VHL associated tumor cells differentiate into endothelial cells, confirming that developmentally arrested vHL deficient hemangioblast cells are responsible for VHL associated tumorogenesis, and maintain the potential to develop into endothelial cells.

Introduction: While immunotherapy has demonstrated promise in clinical studies, overcoming immunosuppression within the tumor microenvironment remains a challenge.

Naturally occurring ribonucleoproteins known as vault nanoparticles have been found capable of enclosing, protecting and delivering various antigens and drugs.

In this study, we assay a bioengineered PVI Z vault containing CCL21, a potent lymphocyte chemoattractant, inducing antitumor immunity in glioblastoma in vivo.

Mice were euthanized if tumors were ulcerating or larger than 15mm in diameter. Survival and tumor growth rate were analyzed and compared.

Results: GBM was successfully injected into our animal model. For the other cohort, tumor size decreased on average by day 25, and stabilized until the conclusion of the study on day Conclusions: PVI Z CCL21 vault nanoparticles can be bioengineered efficiently, and treatment with recombinant vaults demonstrated the potential for tumor control.

This study demonstrates the in vivo efficacy of CCL21 vault nanoparticles, and its potential to be used as a potential novel therapy for high grade gliomas.

Because the mTORC1 mammalian target of rapamycin complex 1 pathway is activated in many tumors, we explored the usefulness of mTORC1 inhibition as therapeutic strategy in meningioma cell lines and mouse models.

Introduction: MicroRNAs miRs have been shown to modulate critical gene transcripts involved in tumorigenesis, but their role in tumor mediated immune suppression is largely unknown.

Methods: On the basis of miRNA gene expression in gliomas using tissue microarrays, in situ hybridization, and molecular modeling, miR was identified as the lead candidate for modulating signal transducer and activator of transcription 3 STAT3 signaling, a key pathway mediating immune suppression of the tumor microenvironment.

Results: MiR is down regulated in all grades and pathological types of gliomas. Both systemic administration of miR or adoptive miR transfected T cell transfers exerted potent anti glioma therapeutic effects in clonotypic and genetically engineered murine models of glioblastoma and enhanced effector responses in the local tumor microenvironment.

A significant dosage dependent growth inhibition by temsirolimus was observed in all cell lines which was also affected by NF2 status.

Conclusions: Our findings highlight the potential application of miR as a novel immunotherapeutic agent for neoplasms and serve as a model for identifying miRNAs that can be exploited as immune therapeutics.

We present a case report of a patient who had combination chemotherapy without histological diagnosis and had complete tumour regression.

Methods: The patient's case folder was retrieved and information relating to presentation, the working diagnosis and supporting investigations were sought.

She had pre chemotherapy ventriculo peritoneal shunt insertion for obstructive hydrocephalus. After due consultation with the Radio oncolgist, she had cyclical combination chemotherapy with cisplatin, etoposide and bleomycin.

Results: The patient's clinical condition improved following the ventriculo peritoneal shunt insertion. Post chemotherapy Brain CT scan showed complete tumor regression.

Conclusions: Tissue diagnosis may allow for precise, targeted management of pineal region tumours, however, in the absence of facilities which enable safe neurosurgery, resorting to the traditional chemo radiation is still a viable alternative.

There are several therapeutic options, but selection of the optimal treatment for individual patients remains controversial. Classification schemes such as recursive partitioning analysis RPA , and diagnosis specific graded prognostic assessment DS GPA have been validated, but these provide group, rather than individualized estimates of outcome.

The purpose of this study was to develop and validate a nomogram for individualized patient prognosis which could be used for counseling patients.

Methods: De identified data from 7 randomized controlled trials of brain metastasis in patients was obtained from the RTOG database. Overall survival was estimated using the Cox proportional hazards regression, RPA, and random survival forests RSF methods, and a nomogram was built using a concordance index to identify the best approach for each variable.

Results: The Cox analysis outperformed other methods thus the nomogram was built to estimate survival probabilities and median survival based on the Cox model.

This predictor of outcome could be readily applicable to clinical practice in enabling patients and their physicians to make informed decisions regarding treatment options and will be provided as free software application.

Future directions include external validation in a prospective dataset. The most biologically aggressive subtype is the glioblastoma multiforme GBM , a tumor associated with dismal prognosis.

The current standard of care for GBM patients; surgical resection followed by adjuvant radiation therapy and chemotherapy with the oral alkylating agent temozolomide; produces a median survival of only 15 months.

Even with the addition of the last generation of imaging studies, clinical assessment of tumor progression versus pseudo progression remains difficult.

This, combined with the high cost of these imaging modalities, can pose serious delays in treatment decisions and result in harm to the patient.

Hence, there is urgent need for a sensitive, specific, noninvasive and low cost biomarker which could be used routinely to monitor disease status in patients on treatment.

Methods: It is now well established that circulating mutant DNA cmDNA that originates in the tumor can be detected in the peripheral blood.

We used next generation, paired end sequencing to analyze several GBM genomes and their isogenic controls and identified tumor specific mutations.

These mutations were detected by polymerase chain reaction PCR in the patients; plasma and were used to follow disease progression over time.

Conclusions: Mutation associated biomarkers offer a reliable measure that would be useful for monitoring tumor response to specific therapies, detecting residual disease after surgery, and for long term clinical management.

The endoribonuclease Dicer is crucial for microRNA biogenesis. Low expression of Dicer has been associated with cancer, even though there are no studies in meningiomas.

Methods: We used tissue microarray TMA slides containing 59 samples of meningiomas from patients that underwent surgical resection.

Clinical correlation was made between WHO grade classification, tumor recurrence, post operative radiation therapy, cavernous sinus invasion, Mib1 index and Dicerexpression.

Results: From the total of 59 patients studied, 42 In the high Dicer group, the WHO grade distribution was: 34 The low Dicer group revealed: 7 In addition, the low Dicer group had higher percentage of tumor recurrence Withdrawn The clinical signs and symptoms of spinal meningiomas are typical of slow growing space occupying lesions of the spinal canal.

Clinical symptoms are normally indolent, gradual in presentation, and dependent on the tumor level and breadth. These lesions have the potential to rapidly expand and cause acute neurological decline, often requiring emergent surgical intervention.

There is ample literature on the more common causes of epidural bleeds, but sparse data describing spinal epidural hematomas presenting secondary to cervical meningiomas.

This study describes a patient lacking the common risk factors for a spinal epidural hemorrhage, who presented clinically with acute paraparesis from a spontaneous cervical spinal hemorrhage.

Methods: The patient physical examination was most notable for dense paraparesis. Clinical workup was unremarkable for any typical causes of an acute epidural hematoma.

A cervical spine MRI revealed a meningioma at the C1 2 level, at the proximal portion of the epidural hematoma. We hypothesized the pathogenesis of the meningioma as the causative agent of the acute epidural hematoma.

Conclusions: This case provides evidence that, though not previously considered, spinal meningiomas should be included in the differential diagnosis of spinal hematomas.

This is especially the case when long term indolent pain is followed by acute symptoms without the commonly reported risk factors.

Conclusions: Therefore, low Dicer expression in meningiomas can be related to tumor aggressiveness and a worse clinical course.

Prognosis of affected patients is dependent on age, staging, and the pathology of the neoplasms, and this in turn affects treatment. A review of the literature reveals a constant debate between surgical or non surgical management of these types of neoplasms.

However, the literature unanimously reveals a poor prognosis in patients with severe acute progressive neurological deficits, regardless of treatment type.

The novel case herein reports a 3 month old patient with full resolution of a 4 day history of complete lower extremity paralysis status post neurosurgical intervention.

Methods: Magnetic resonance imaging showed complete spinal cord compression by a thoracolumbar intracanal extradural mass that was contiguous with a paraspinal mass.

Further pathological and radiological analysis, including MIBG and bone scintigraphy, showed that the mass was consistent with a non metastatic neuroblastoma.

The patient subsequently underwent a multilevel laminectomy that allowed for resection of the intraspinal mass and decompression of the spinal cord.

This was followed by adjuvant therapy on a delayed basis. Results: Fortunately, despite their prolonged lower extremity paralysis the patient regained full neurological function with resolution of spinal cord compression on radiographic imaging at 6 months follow up.

Conclusions: Currently, research states that patients with prolonged severe neurological deficits secondary to an intraspinal neuroblastoma have a very slim chance in regaining neurological function, irrespective of surgical or non surgical management.

This novel case seems to suggest that prompt surgical intervention followed by adjuvant therapy is the best treatment for these patients, given the potential benefit of rapid recovery of neurological function.

Meningiomas are benign brain tumors that are also associated with an increased VTE risk. Whether the presence or resection of meningiomas leads to systemic coagulation activation has not been clarified.

Methods: We hypothesize that patients with glioblastoma multiforme GBM demonstrate increased systemic coagulation activation compared to healthy individuals.

We further hypothesize that meningiomas are not associated with a significant increase in systemic coagulation activation and that this may account for the difference in VTE risk.

We will test this hypothesis by measuring surrogate markers of systemic coagulation activation in patients with GBM and meningiomas before and after treatment and in age and sex matched healthy control blood donors.

Markers of coagulation activation assayed for this study will include plasma D dimers, P selectin, tissue factor pathway inhibitor TFPI , thrombin generation via calibrated automated thrombography and tumor tissue factor and TFPI expression by immunohistochemistry.

Results: We are currently actively recruiting to this study and expect to complete arcual by the end of Conclusions: We expect this work to lead to clarification of coagulation abnormalities in patients with primary brain tumors and may result in identification of novel markers of VTE risk in these patients.

This however does not exclude the immunocompromising effect,which includes risks of lymphomatous disease.

He was commenced on Stupp prorocal with concurrent Temozolomide. His treatment completed 2 months after his initial presentation and a month later, he proceeded with first cycle of adjuvant chemotherapy.

This was complicated with large pulmonary embolism and left lower limb deep vein thrombosis. Follow up MRI Brain revealed a recurrence of his tumour.

There was also a new enhancing lesion in the left frontal lobe, measuring 1. He subsequenly underwent further debulking of his original tumour and stereotactic biopsy of the contralateral lesion.

He deteriorated during chemotherapy and died 10 months after his original presentation. Results: We describe herein an interesting case of primary GBM with concurrent primary CNS lymphoma diagnosed 2 months after completion of Temozolomide treatment.

To best of our knowledge, this is the first case reported in literature. This was observed on his surveillance MRI Brain 2 months after completion of treatment, therefore, the suspicion exists that the lesion may have developed while he was on treatment.

Excitatory glutamatergic mechanism are shown to be involved in the generation of epileptic activities in the cortex surrounding gliomas.

However, the contribution of defective Chloride homeostasis and paradoxical excitatory GABAergic mechanisms, crucial in other epilepsies, is unknown.

They can occur anywhere in the cranium and the spine and have varied pathology. Removal of meningiomas in certain locations can be challenging, we explored the use of ALA induced fluorescence to guide intracranial meningiomas; resection and its corrolation to histopathology.

Methods: We studied in neocortical slices from the security margin resected around human brain gliomas, the occurrence, networks, cells, signaling and origin of epileptic activities.

These events were synchronized in superficial layers of cortical columns in the neocortex surrounding glioma areas that presented a tumor infiltration and had a high frequency oscillation signature.

Interictal like events depended on glutamatergic transmission but also on depolarizing GABAergic signaling.

This effect was related to perturbations in Chloride homeostasis, due to an abnormal load by the co transporter NKCC1.

Ictal like activities could be exclusively generated in these epileptogenic areas. Methods: Twenty nine consecutive lesions with MRI differential of meningiomas were included in this analysis, including 17 supratentorial, 10 infratentorial and one thoracic.

Twenty three were females, the mean age was All these patients received 1. Surgical resection was aided by using the blue light of the microscope Pentero, Zeiss, Germany.

The fluorescence was graded into strong very red fluorescent , faint pink and moderate in between red and pink. Results: Fluorescence was detected in 22 Faint signal was observed in six Total excision Simpson grade 1 was achieved in all meningiomas.

There was no correlation between histological type, ALA dose, or time to fluorescence and the intensity of fluorescence.

Only two patients developed significant drop in their blood pressure 7. ALA induced fluorescence is safe and helpful in intracranial meningioma surgical resection, but there was no correlation to histology.

On postoperative day 22 the EVD was clamped, and the patient remained asymptomatic the following day. A new brain MRI showed significantly decreased size of the germinoma along with flow artifact across the floor of the third ventricle, and his EVD was removed.

The patient's hydrocephalus did not recur over the following month. We undertook a multidisciplinary study among brain tumor experts to test this hypothesis.

Methods: The expert group included 2 CNS radiation oncologists, 3 tumor neurosurgeons, and 2 neuro radiologists. CERR Matlab tool was used to compare volumes.

CCC measured inter observer reproducibility. Conclusions: In this pilot substantial inter observer variability exists in meningioma target definition.

Over contouring increases normal tissue exposure. Under contouring increases recurrence risk. Our findings suggest lack of physician consensus regarding target volume.

We suggest a large scale study to confirm these findings and consideration of a multidisciplinary consortium to standardize target volumes.

Gump, MD; Ian Mutchnick, MD Louisville, KY Introduction: Endoscopic third ventriculostomy E3V is an established option for treatment of obstructive hydrocephalus and is often performed concurrently with biopsy of an obstructing mass lesion.

Delayed failure is a known complication. We report the case of a patient whose E3V became functionally patent in a delayed fashion, three weeks postoperatively, when mass effect on the brainstem had been adequately relieved.

Methods: A 13 year old boy presented to the emergency department with symptomatic obstructive hydrocephalus from a pineal region tumor.

Results: Pathology was consistent with pure germinoma. The patient returned to surgery four days later for a secondary E3V. He remained drain dependent, and initiated radiation therapy on postoperative day 7.

Therefore, advancements in research tools, including cell culture and animal models represent a challenge for basic research and are necessary for the development of more effective treatments.

Methods: We are developing the 3 Dimensional cell culture model in which primary Glioblastoma cells are forced to form multi cellular Glio Spheres.

This approach allows cells to grow for several months without losing their glial phenotype, the main problem with Glioblastoma culture. We use Seahorse Analyzer to characterize metabolic properties of Glio Spheres by measuring Extracellular acidification and Oxygen consumption rates; We also evaluate mitochondrial membrane potential, cell survival and response to a common lipid lowering drug, fenofibrate.

Conclusions: Here, we demonstrate a new approach to develop 3 dimentional cell culture system for primary Glioblastoma Glio Spheres and present their metabolic profiles.

We also include studies on fenofibrate, which has strong anti tumoral effect with low systemic toxicity, and could be introduced as a supportive regimen to the conventional therapies.

The Glio Spheres can be also implanted into the brains of immunodeficient mice, providing a clinically relevant model for testing anti tumoral regiments against Glioblastoma.

The tumor suppressor NF2 is disrupted in approximately half of meningiomas, but the complete spectrum of genetic changes remains undefined.

Introduction: Microcystic meningioma is a variant of meningioma with a multicystic appearance that can mimic intrinsic primary brain tumors, hemangioblastomas, and other non meningiomatous tumor types.

Methods: We performed whole genome or whole exome sequencing of 17 Grade I meningiomas and focused sequencing of an additional 48 tumors to comprehensively identify mutations, insertion deletions, copy number alterations, and genetic rearrangements contributing to oncogenesis.

A mutational significance algorithm was used to distinguish driver and passenger events. Methods: 18 subjects with histopathological diagnosis of microcystic meningioma and a cohort of 12 subjects with grade I meningioma and 54 subjects with grade IV primary glioma were considered.

Clinical variables including patient sex, age, extent of resection, surgical blood loss and need for adjunctive therapy were considered. DSC images were acquired at a temporal resolution of either ms 3T or ms 1.

Results: Overall, the tumors showed few somatic genetic events, consistent with their benign clinical status, but underscoring the potential importance of each individual event.

Several tumors harbored more complex patterns of copy number changes and rearrangements including one tumor with chromothripsis. As expected, the NF2 gene was identified as the most frequently altered, with over half of tumors harboring NF2 disruptions.

One sample had a novel translocation affecting the NF2 gene and a nearby region of chr Preoperative DCE analysis demonstrated kTrans values of 0.

Conclusions: This study begins to define the spectrum of genetic alterations in meningiomas. The discovery of novel drivers of meningiomagenesis with existing targeted therapeutics has the potential to rapidly transform the clinical management of meningiomas.

Higher nCBV values are associated with a trend to increased intraoperative blood loss. Introduction: Increasing use of endoscopic approaches for the treatment of various intracranial pathology has necessitated neurosurgeons have a thorough understanding of the anatomy from an endoscopic endonasal perspective.

We present a cadaveric anatomic study of the clinoidal and ophthalmic ICA from an endonasal endoscopic perspective. Methods: Testing of all basal hormone values and magnetic resonance imaging MRI were performed preoperatively and postoperatively in consecutive patients who underwent PEETS in the period between and The series consisted of 37 somatotroph adenomas, 4 prolactinomas, and 8 corticotroph and 72 nonfunctioning adenomas.

Remission was defined as hormonal excess normalization on the third postoperative day in functioning adenomas and as normal MRI findings approximately four months postoperatively in nonfunctioning adenomas.

Hypocortisolism was assessed through necessity for replacement therapy within 3 months postoperatively. Methods: Embalmed heads underwent thin cut CT scans for the purpose of neuronavigation.

The heads were registered with our neuronavigation system. An endonasal endoscopic transsphenoidal exposure was performed. Various measurements were taken some of which include: the inter carotid distance at the level of the distal dural rings DDR , the distance between the ICA at the distal dural ring and the optic chiasm and the distance between the ICA and the pituitary stalk.

The ratio of inter carotid distance to distance between the OCRs was also calculated. Results: A total of 10 cadaver heads were studied.

Neuronavigation was used achieving excellent accuracy in all cases. The average distance between the carotids at the distal dural rings was The average distance between the ICA at the distal dural ring and the optic chiasm is 9.

Endocrinological complications occurred in Seventy five percent of preoperatively present hormonal deficiencies improved after the surgery.

Between tumor types there were no significant differences in remission, complications, and normal pituitary function recovery. Conclusions: Expansion of endonasal endoscopic techniques for treatment of various intracranial pathology necessitates improved understanding of the clinoidal and proximal intradural ICA anatomy and its relationship to surrounding structures.

This will enable surgeons to more reliably predict the location of the ICA and its relationship to surrounding structures, decreasing the potential for vascular injury.

Conclusions: Patients with microadenomas had higher remission and lower complication rates following PEETS, emphasizing the necessity for early detection and treatment of pituitary adenomas.

PEETS is a discussion worthy method for microprolactinoma treatment. These can be locally aggressive with potential intracranial extension. Traditionally these lesions have been treated using open surgical techniques, however recently endoscopic approaches have been implemented in hopes of minimizing morbidity.

We recorded the number of operations, estimated blood loss, extent of resection, any complications and length of hospital stay. All are male with an average age of 16 years.

Average follow up is All patients underwent pre operative tumor embolization. One patient underwent an initial open transfacial approach and required a subsequent endoscopic approach.

Patients underwent an average of 2. Mean EBL was cc. A subtotal resection was achieved in all cases. Two patients underwent radiation therapy during the course of their treatment.

There were no mortalities. Open surgical resection can achieve good tumor control, but can be exceedingly morbid. Given the tendency for these lesions to regrow, multiple surgeries are often required.

We believe an endoscopic approach for subtotal resection in combination with pre operative embolization and post operative adjuvant treatment in select patients can achieve good tumor control while minimizing morbidity.

Numerical values were estimates from the french register of CNS tumors, the national institute of statistics, and published series of glioma survivals.

We report a new case in a pediatric patient. Methods: A 4 year old girl presented with generalized seizures. MRI of the brain revealed an extensive diffuse nonenhancing area of abnormal signal involving the right frontal and temporal lobes.

She was taken to surgery for biopsy, and returned to surgery eight months later for electrocorticography guided seizure focus resection.

Seizure frequency decreased to zero over the following three months. Compared with gemistocytic, protoplasmic astrocytomas have less potential to behave aggressively.

In two case series encompassing 18 patients, average age at presentation was 25 years. Most lesions were in the frontal or temporal lobes. For 7 patients with unresectable lesions, biopsy was performed; all others underwent attempted gross total resection.

Five patients subsequently received radiation therapy and one also had chemotherapy. The youngest patient age 2 years at diagnosis died 36 months after subtotal resection without further adjuvant therapy; all others were alive with or without residual tumor 2 to months postoperatively.

One additional case report describes a 3 year old with diffuse leptomeningeal disease who died from tumor progression despite chemotherapy.

Although all patients presented with seizures, seizure outcomes have not been well documented. Our patient achieved seizure freedom.

Conclusions: Protoplasmic astrocytoma is a rare low grade glioma which can be associated with medically resistant epilepsy.

Tailored surgery for unresectable lesions can be beneficial for seizure control. Conclusions: Patients with silent DLGG are more likely to die from transformation of the silent DLGG to symptomatic glioma than dying from another cause with the silent DLGG, unless patient survival is expected to be less than 4 years.

This epidemiological argumentation supports early surgery for incidentally discovered glioma. To identify patients who had undergone surgery, we used brain tumor surgery ICD 9 codes.

We used the SAS statistical software package Version 9. For brain tumor patients treated without surgery For brain tumor patients treated with surgery 9.

The most common PSIs included postoperative respiratory failure, deep vein thrombosis, and sepsis. The total number of HACs associated with brain tumor patients was 13,, with 2.

For brain tumor patients treated without surgery 3. For brain tumor patients treated with surgery 7. The most common HACs included falls and trauma and pressure ulcers.

Conclusions: Patient safety and delivery of quality care is an important part of our national healthcare agenda. These data may be used to determine individual institutional improvements or success by comparison.

One of the molecular hallmarks of Glioblastomas is genomic instability, which leads to the development catastrophic mutations. Thus, basic DNA repair mechanisms responsible for the preservation of genomic integrity could be impaired in Glioblastomas.

We have previously reported the detection of DNA sequences of the human neurotropic JC Virus and expression of its oncoprotein, T Antigen, in brain tumors of glial and neuroectoermal origin.

Bevacizumab has recently demonstrated encouraging anti tumor effect in the treatment of recurrent and progressive meningiomas.

The imaging characteristics of meningiomas undergoing bevacizumab treatment have not been extensively described.

Methods: While undergoing systemic therapy on bevacizumab with a sustained intracranial response, a 55 year old man with a locally recurrent WHO grade III meningioma developed a biopsy proven left sided neck metastasis and radiographic findings consistent 40 Conclusions: Fluorescence guided resection for complex meningiomas have shown to be an effective intraoperative tool to achieve maximal citoreduction.

In meningioma lesions we assume that the breakage of the blood brain barrier increasing vascular permeability and by this mechanism the 5 ALA reaches the peritumoral area.

Results: The primary intracranial meningioma was a homogeneously, avidly enhancing extra axial mass on magnetic resonance imaging MRI.

The recurrent intracranial lesion was isointense to surrounding brain on T1 imaging and hyperintense on T2 weighted images.

The mass was centered in the obliquus capitis inferior muscle and was associated with erosive bony changes.

The neck lesion was isointense to muscle on noncontrast T1 imaging, and nearly isointense to gray matter on T2 weighted images.

There were four subcentimeter, nonenhancing parenchymal lung nodules appreciated on chest CT, consistent with pulmonary metastatic disease. Cranial hyperostosis in association with adult meningioma occurs frequently.

The osteopathophysiology of this phenomenon is poorly understood and controversial, with actual bone invasion by tumor or reactive changes due to adjacent tumor having been posited as explanations.

Metalloproteins have also been suggested as playing a role. Hyperostosing meningioma is rarely reported in children. Conclusions: This case illustrates the imaging appearance of intracranial anaplastic meningioma and extracranial metastases while on bevacizumab.

Further study of imaging characteristics of recurrent and progressive meningiomas while undergoing treatment with anti angiogenic therapies is warranted.

Methods: Following IRB approval, the medical record of a child with intracranial hyperostosing meningioma was abstracted for diagnostic, treatment and outcome details.

The medical literature on meningioma and hyperostosis conditions was surveyed. Fluorescence Guided Resection Of Complex Meningiomas Results: A 15 year old boy presented with progressive nausea, vomiting and headaches.

Gastroenterologic evaluations were negative and therapy for reflux disease was ineffective. Imaging revealed a lobulated solid cystic mass in the right frontal region, with overlying irregular cranial bone thickening.

Skull palpation revealed painless fullness without scalp changes. Via a large craniotomy flap, the tumor was found to be arising from the dura and adherent to the skull, without gross invasion.

The flap was hyperostotic and the inner table and cancellous bone were drilled out using a high speed air drill. The tumor was microsurgically completely resected and the bone flap was replaced.

The lesion showed classic syncytial features, yet with hypercellularity and an elevated MIB 1 index, consistent with atypical meningioma, W. Tumor was identified in the bone curettings.

Due to the higher grade histology and tumor in the bone, adjuvant radiation therapy was administered. He remains in remission three years later.

The extent of resection in intracranial brain tumors determine survival rate. For extra axial tumors, such as, meningiomas the usefulness of fluorescence guided surgery will help to achieve maximal resection in complex cases where occult tumor cells spreads beyond the arachnoid layer or in to bone structures.

Methods: We present an illustrative case of a 37 year old female with past medical history relevant for overweight and penicillin allergy.

Her symptoms were characterized by headache, nausea, amaurosis fugax, left eye ptosis with facial asymmetry. An MRI was done and a left frontal extra axial lesion was found.

There were no surgical complications. She was discharged 4 days after the tumor resection. Conclusions: Only a paucity of pediatric cases of hyperostosing meningioma have ever been reported.

There is no reported correlation between hyperostosis and histologic tumor grade and bone invasion by tumor. Our report confirms that this phenomenon occurs in children.

The pathophysiologic mechanisms may be the same as in adults. We recommend ongoing reporting of this rare condition in youth, so as to inform of preferred management strategies.

Results: The patient did not experience any additional neurological deficits after surgery. There was no evidence of increased liver function test.

Currently the patient is seen in the outpatient clinic. Most of the general symptoms have remarkable improved. Facial asymmetry has also been substantially reduced.

We aimed to determine the clinical impact of histologically proven transformation. Methods: We retrospectively identified patients with anaplastic gliomas who had surgery at our center upon first radiographic progression.

We examined the impact of clinical and molecular factors on transformation and outcome. Results: Between and , 85 patients met study criteria; 24 with oligodendrogliomas, 22 with oligoastrocytomas, and 39 with astrocytomas.

Transformation was associated with shorter overall survival OS from initial diagnosis median OS 6. Conclusions: Fewer than half of radiographically progressive anaplastic gliomas transformed to glioblastoma histologically.

Transformation is associated with reduced OS from the time of diagnosis and from the second surgery. Tissue diagnosis may be warranted for prognostic counseling at the time of radiographic progression.

A newly emerged field, imaging genomics, links gene expression profiles with MRI phenotypes. Thus, an imaging genomic necrosis screen has the potential to uncover novel molecular determinants of cell death in GBM.

Here, we present the first comprehensive radiogenomic analysis using quantitative necrosis MRI volumetrics and large scale gene and microRNA expression profiling in GBM.

Gender specific analysis was performed and the top concordant genes and microRNAs correlated with high volumes of necrosis were further characterized using Ingenuity Pathway Analysis, whole genome transcriptional factor analysis, and cognate microRNA gene networks were created.

Results: Female patients demonstrated significantly lower volumes of necrosis than male patients. Thus, a gender specific analysis was chosen and revealed in both MRI and histopathology data that female patients with high necrosis had a significantly shorter survival compared to both females with lower necrosis or males with high necrosis.

Survival in males was not statistically different in patients with high versus low tumor necrosis. The survival data was concordant with the genomic analysis suggesting that predominantly MYC driven oncogenic pathways were associated with necrosis in female patients, while male patients showed a strong positive association of the MRI necrosis phenotype with the P53 tumor suppressor pathway.

Gender independent necrosis pathway analysis showed equal distribution of both tumor suppressors and oncogenes.

Conclusions: Here, we propose a novel diagnostic method to screen for molecular correlates of necrosis in GBM.

Our findings suggest distinct oncogenic pathways promoting MRI and histopathology necrosis phenotypes in male versus female GBM patients. In prior studies, depression has been associated with decreased quality of life and shorter overall survival.

Antidepressant therapy is a widespread and generally well tolerated treatment of depression which can increase quality of life.

We investigated whether pharmacologic treatment of depression has an impact on overall survival. Univariate analysis isolated possible predictors of survival.

Results: Median survival was Analysis based on class of antidepressant was not significant. Multivariate analysis controlled for age, tumor grade, extent of resection, Karnofsky Performance Score, reoperation, antidepressant therapy, diabetes, radiation and temazolamide therapy.

Although this effect did not reach significance in multivariate analysis, the trend warrants further investigation.

Prospective studies closely monitoring antidepressant treatment and its effects are necessary to evaluate the potential benefit of both improving quality of life and prolonging survival with a single therapy.

We investigated the feasibility of sonodynamic therapy for malignant glioma by low frequency ultrasound with 5 aminolevulinic acid 5 ALA , a precursor of protoporphyrin IX PpIX in heme synthetic process.

Methods: In vivo tumor model was made by inoculating human glioma cell line U87 MG subcutaneously in nude mice. The tumor was sonicated by 25 kHz ultrasound 4 hours following administration of 5 ALA.

The results showed the therapeutic effect of 25 kHz ultrasound for the glioma in 5 ALA administered tumor bearing mice by inducing apoptotic change of tumor cells.

Conclusions: This is a first report to elucidate the feasibility of therapeutic use of 25 kHz ultrasound in sonodynamic therapy using 5 ALA as a sonosensitizer precursor.

This may be a realistic intraoperative malignant gioma therapy in addition of tumorectomy, since 25kHz is a frequency of ultrasonic aspirator.

We leveraged this unique developmental system to interrogate lncRNA expression and function. By integrating data from chromatin state maps, custom microarrays, and FACS purified cells, we stringently identify lncRNAs with potential roles in adult neurogenesis, and accurately predict their expression patterns in the SVZ and OB.

More broadly, our data and workflow provide a uniquely coherent in vivo lncRNA analysis that will be relevant for future studies of lncRNAs in development and tumorigenesis.

This phenomenon, however, has seldom been documented with an imaging correlate and quantitative evaluation.

Methods: The clinical and radiographic features, quantitative assessments, treatments, and outcomes were reviewed for two patients with lesions in the third ventricle, in which remitting clinical symptoms of raised intracranial pressure were either characteristic of or associated with intermittent ventriculomegaly on imaging.

Additionally, the few documented cases of intermittent obstructive hydrocephalus with concomitant intraventricular cysts are examined.

Results: Two patients, a 3 month and a 9 year old male, presented with paroxysmal symptoms of raised intracranial pressure and imaging confirmation of varying ventriculomegaly with a third ventricular pineal and choroid plexus cyst, respectively.

Both were treated by a primary endoscopic cyst fenestration and remain without symptoms, complications, or placement of an indwelling shunt at 20 and 3 months of follow up, respectively.

Conclusions: Our cases add to a growing body of evidence that a normal sized ventricular system cannot rule out the diagnosis of intermittent hydrocephalus in a patient who presents both with symptoms suggestive of increased intracranial pressure and a lesion that can potentially obstruct CSF flow.

Additionally, an absence of intraventricular cysts on traditional CT or MR imaging should not automatically rule out the possibility of an intermittently obstructive cyst.

Our findings suggest that patients experiencing symptoms of raised intracranial pressure concomitantly with third ventricular cystic masses and normal sized ventricles should be offered cyst decompression.

On radiographic findings, these lesions may present as an osteolytic or osteoblastic skull lesions. Methods: We report a case of a 53 year old female who presented with a gradual onset exopthalmos of the right eye.

The plain radiographs of the skull showed hyperostosis af the right orbital roof and the lateral orbital wall. The computerized tomography CT scan revealed an extra axial, intradiploic orbital roof tumor involving the frontal and temporal bone.

Results: The tumor, including the surrounding normal bone, was totally excised by an extradural route using a basal fronto temporal craniotomy.

The histopathological study confirmed a meningotheliomatous meningioma. A split calvarial frontal bone graft was used to reconstruct the orbit.

The patient was discharged after 6 days. There is no evidence of recurrence after a follow up of 3 months. Conclusions: Intradiploic meningiomas are often asymptomatic, but can cause proptosis and neurological symptoms depending on their size and location.

Radiographic and clinical presentations generate diagnostic suspicion that may assist with preoperative planning.

The majority of these tumors cause hyperostosis that may mimic meningioma en plaque, osteoma, osteosarcoma, Paget disease, and fibrous displasia.

The treatment of choise is resection, which is potentially curative. Tumors that cannot be compleely resected may be require adjuvant therapy, which may include radiation therapy, chemotherapy, or bisphosphonate therapy.

In non contrast enhancing gliomas, and to a lesser extent enhancing tumors, the T2 and FLAIR signals are important targets to determine target volumes for resection margins.

We hypothesized that intraoperatively obtained MRI T2 and FLAIR signal volumes might not reflect corresponding post operative volumes due to tumor edema after resection and brain manipulation.

Methods: We examined 12 low grade gliomas LGG, 9 low grade astrocytomas and 3 oligodendrogliomas and compared them to 13 high grade tumors HGG, 4 anaplastic astrocytomas, 3 anaplastic oligodendrogliomas, and 5 glioblastomas.

When all tumor grades are analyzed together similar trends are found. Conclusions: Postoperative FLAIR signal volumes are significantly lower and T2 signal volumes significantly higher than 44 Methods: We analyzed the relation between the sphenozygomatic suture and the marginal tubercle of the frontal process of the zygoma 60 dried skulls.

Minipterional craniotomy was performed in 10 cadaveric specimens. The approach was utilized to 18 sphenoid wing meningiomas. Anterior to posterior sub periosteal dissection and retraction of the temporalis muscle, and avoiding cuts along the origin of the muscle allows excellent cosmetic outcome.

All 18 meningiomas 3 to 5 cm in size were successfully resected without morbidity or mortality through a 3.

Meningiomas A Population Based Perspective Conclusions: Minipterional approach is an excellent option to approach sphenoid wing meningiomas. The minimally invasive access allows minimal soft tissue trauma, smaller bony opening, less pain, and excellent cosmetic outcome Quinn T.

We used this data to describe the current epidemiology of meningiomas in the United States between the years of and We also calculated survival rates for all malignant menginiomas.

Introduction: Fronto orbital minicraniotomy is the most commonly used minimally invasive approaches for anterior cranial fossa lesions.

Methods: We describe our novel technique with the transpalpebral eyelid incision to obtain access to the anterior cranial fossa. We describe the approach and technique of the transpalpebral eyelid incision in a step by step fashion and discuss the results of retrospectively analyzed eighteen cases.

Results: Meningiomas are the most common type of brain tumor in the United States, compromising There was an overall incidence rate of 7.

They are more common in women than men incidence rates of 9. They are more common in blacks than whites incidence rates of 8. For malignant menginiomas, there were 1, 5 and 10 year survival rates of Results: Incisions in the eyelid region should therefore be as horizontal as possible.

A relative safety zone; free of facial nerve branches was identified that exists up to 2. We apply knowledge of upper eyelid anatomy, which allow us to utilize an avascaular plane of dissection that maintains functionality of the eyelid and avoids disfiguring cosmetic results.

We describe the bony cuts necessary to complete our one piece fronto orbital approach. Complications in one patient who developed deep wound infection required re operation.

Conclusions: Though most menginiomas are not malignant, their frequency and potential resulting morbidity makes them of significant clinical and scientific relevance.

Awareness of the populations most at risk for these tumors assists physicians and scientists in focusing on developing new ways to serve these patient populations.

Mini Pterional Craniotomy: An Alternative Approach For Sphenoid Wing Meningiomas Conclusions: The transpalpebral approach provides dissection in natural anatomical planes, affords preservation of the frontalis muscle, avoids injury to nerve VII branches, and results in an excellent cosmetic outcome.

Khaled M. It provides the same microsurgical exposure as the standard frontotemporal approach. Corinna C.

The goal of our study is to identify which preoperative symptoms and MRI findings are correlated with specific postoperative outcomes in order to better counsel patients pre operatively.

Conclusions: The modified dural incisions are safe, easier to perform and close with lesser complications. We then used univariate and multivariate regression models to analyze the effect of several MRI characteristics including tumor volume, distance to optic chiasm, anterior cerebral artery encasement, paranasal sinus invasion, and sellar invasion on preoperative symptoms and postoperative outcomes, including complication rate and tumor recurrence.

Tumors with nasal sinus invasion are significantly more likely to cause postoperative surgical complications, and tumors with ACA encasement are associated with a higher likelihood of both postoperative complications and tumor recurrence.

In terms of predicting surgical complications, nasal sinus invasion and ACA encasement are associated with higher risk profiles when surgery becomes necessary.

While making these dural incisions we encountered certain difficulties whole opening the dura, while performing the procedure and during closure of dural incisions.

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Pediatric patients were excluded. Routine clinical and radiographic variables were retrospectively collected, including volumetric extent of resection, cystic changes, peritumoral T2 signal changes, progression free survival, and overall survival.

Median progression free survival and overall survival were 5. Greater extent of resection and the adjuvant radiotherapy were both associated with improved survival.

Specifically, patients with cystic changes and increased peritumoral T2 signal recovered their baseline KPS by 1 year, while those without these features improved by 6 weeks.

Most of the literature on this disease consists of single institution case series collected over long periods of time, and thus may reflect selection bias and might not be representative of the outcomes of current treatment paradigms.

Methods: We queried the Surveillance Epidemiology and End Results SEER database to investigate the clinical behavior and prognostic factors for hemangiopericytomas originating within the CNS during the years Results: We identified patients with a diagnosis of CNS hemangiopericytoma.

Age, radiation therapy, and gross total resection plus adjuvant radiation were significantly associated with survival on univariate analysis.

On the multivariable model, age, location and adjuvant radiation therapy were significantly associated with prolonged overall survival.

Older patients had a hazard ratio of 1. Patients with supratentorial lesions were found to have prolonged survival, with infratentorial tumors associated with a hazard ratio of 2.

The only treatment paradigm to confer a survival advantage was gross total resection plus radiation therapy. Patients undergoing this combination therapy were found to have significantly better survival, with a hazard ratio of 0.

Conclusions: Following microsurgical resection of posterior fossa ependymomas, cystic changes and increased peritumoral T2 signal are independent predictors of the rate of neurological recovery.

Further study should examine the biological correlates underlying these radiographic features of adult posterior fossa ependymomas. However, delineating tumor infiltrated tissue from normal brain remains a challenge.

Here we describe the use of Coherent Raman scattering CRS microscopy for differentiating healthy brain from tumor infiltrated brain based on histologic and biochemical differences.

Unlike traditional histopathology, CRS is a label free technique that can be rapidly performed in situ. Methods: All experiments were performed using an established system for CRS microscopy.

To demonstrate the ability of CRS to detect tumor infiltration in unprocessed tissue specimens we imaged fresh 2mm thick tissue sections from normal and tumor bearing mice.

Frozen and fresh tissue CRS imaging demonstrated both normal brain structures and and tumor infiltrated brain with excellent clarity and accuracy.

We also demonstrated, that tumor detection with CRS is possible in vivo, revealing tumor margins that are invisible under the standard operative conditions.

Selective targeting of brain tumor cells by SapC DOPS was observed in astrocyte Gli36 co cultures, a model that better resembles the in vivo tumor environment.

Synergistic anticancer effects were observed after co treatment of glioma cell lines with SapC DOPS and chemotherapeutic drugs that promote PS externalization.

Conclusions: By providing the surgeons with rapid histologic assessment of the operative field, CRS microscopy may ultimately improve the safety and accuracy of tumor surgeries where tumor boundaries are visually indistinct.

CRS microscopy demonstrates a clear distinction between tumor infiltrated areas T and non infiltrated brain N a. Brightfield microscopy demonstrates no gross differences within the same FOV b.

In the multivariate analysis adjusting for age, sex, race, tumor grade, medical Introduction: Though research into the pathogenesis of primary and metastatic brain tumors has advanced, current therapies still show limited efficacy.

Saposin C dioleoylphosphatidylserine SapC DOPS nanovesicles are a novel antitumor agent that selectively target exposed phosphatidylserine PS on brain tumor cell membrane surface and induces cell death.

The authors present analysis of these procedures between to evaluate how procedural volume impacts complication rates. Methods: The authors performed a retrospective cohort study using data from the Nationwide Inpatient Sample NIS for 62, admissions for biopsy or resection of supratentorial primary brain tumors from to The presence of one or more complications was significantly correlated with increased mortality OR 6.

The mutational profile of a meningioma can largely be predicted based on its anatomical position, serving as the basis for targeted therapeutics. Conclusions: Consistent with the previous decade, the number of high volume hospitals and surgeons performing craniotomies and needle biopsies for primary brain tumor increased over the study period.

Analysis of outcomes demonstrate that high surgeon and hospital volumes correlate with decreased risk of adverse outcome and support a shift towards regionalization of care.

Introduction: Studies have suggested better outcome after complex surgery at hospitals with larger treatment volume, including meningioma craniotomy.

We investigated whether previously reported US national trends toward neurosurgical centralization, as for intracranial aneurysm treatment, affected meningioma craniotomy practice patterns from We aimed to comprehensively characterize the genomics of meningiomas.

Methods: We performed genome wide genotyping, exome sequencing, ChIP seq and gene expression analyses of 50 tumors, followed by targeted resequencing of an independent cohort of meningiomas.

We correlated the genomic analyses with clinical findings. Among the novel neoplasia genes, TRAF7, a pro apoptotic E3 ubiquitin ligase, is mutated in one fourth of all meningiomas.

These non NF2 meningiomas are nearly always benign, show chromosomal stability, include secretory and meningothelial histology, and mostly originate from the anterior and medial skull base with SMO mutants localizing to midline.

In contrast, the vast majority of NF2 mutant tumors show genomic instability, localize to the cerebral and cerebellar hemispheres and are more likely to be malignant.

In hospital mortality was 1. The number of US hospitals performing meningioma craniotomies remained largely stable: hospitals , After multivariate adjustment age, sex, race, payer, surgery year and admission type , larger hospital volume significantly predicted lower mortality both in OR 0.

Conclusions: Higher hospital volume continues to predict lower mortality after meningioma craniotomy. An increasing proportion of meningioma craniotomies in the US are being performed at high volume centers.

Conclusions: Our results clearly identify clinically relevant meningioma subgroups, distinguishing them based on their mutually exclusive distribution of mutations, distinct potential for 29 It has been proposed that the vascular nature of these tumors is the product of reactive angiogenesis.

Recent studies have shown that the characteristic islands of erythrocytes in VHL associated CNS hemangioblastomas develop from tumor cells.

We hypothesized that a subset of vascular structures within VHL associated lesions are a result of tumor derived vasculogenesis. Methods: Tumor endothelial markers within CNS hemangioblastomas were visualized by immunofluorescence and three dimensional immunohistochemistry.

Additionally, identified vascular elements from human vHL deficient murine xenografts were micro dissected and analyzed for loss of heterozygosity, as well as visualization by co localization immunofluorescence and fluorescence in situ hybridization FISH.

Three dimensional immunohistochemistry identified isolated islands of CD31 expressing structures. Micro dissected vascular structures demonstrated marked allelic imbalance after amplification with VHL gene flanking primers, indicating a loss of VHL and a somatic second hit deletion of the wild type allele.

Co localization by immunofluorescence for HLA and CD31 further confirmed the presence of tumor derived vascular tissue. Conclusions: The hemangioblast cell was identified as the embryologic progenitor cell for both endothelial cells and erythrocytes.

We established that some VHL associated tumor cells differentiate into endothelial cells, confirming that developmentally arrested vHL deficient hemangioblast cells are responsible for VHL associated tumorogenesis, and maintain the potential to develop into endothelial cells.

Introduction: While immunotherapy has demonstrated promise in clinical studies, overcoming immunosuppression within the tumor microenvironment remains a challenge.

Naturally occurring ribonucleoproteins known as vault nanoparticles have been found capable of enclosing, protecting and delivering various antigens and drugs.

In this study, we assay a bioengineered PVI Z vault containing CCL21, a potent lymphocyte chemoattractant, inducing antitumor immunity in glioblastoma in vivo.

Mice were euthanized if tumors were ulcerating or larger than 15mm in diameter. Survival and tumor growth rate were analyzed and compared.

Results: GBM was successfully injected into our animal model. For the other cohort, tumor size decreased on average by day 25, and stabilized until the conclusion of the study on day Conclusions: PVI Z CCL21 vault nanoparticles can be bioengineered efficiently, and treatment with recombinant vaults demonstrated the potential for tumor control.

This study demonstrates the in vivo efficacy of CCL21 vault nanoparticles, and its potential to be used as a potential novel therapy for high grade gliomas.

Because the mTORC1 mammalian target of rapamycin complex 1 pathway is activated in many tumors, we explored the usefulness of mTORC1 inhibition as therapeutic strategy in meningioma cell lines and mouse models.

Introduction: MicroRNAs miRs have been shown to modulate critical gene transcripts involved in tumorigenesis, but their role in tumor mediated immune suppression is largely unknown.

Methods: On the basis of miRNA gene expression in gliomas using tissue microarrays, in situ hybridization, and molecular modeling, miR was identified as the lead candidate for modulating signal transducer and activator of transcription 3 STAT3 signaling, a key pathway mediating immune suppression of the tumor microenvironment.

Results: MiR is down regulated in all grades and pathological types of gliomas. Both systemic administration of miR or adoptive miR transfected T cell transfers exerted potent anti glioma therapeutic effects in clonotypic and genetically engineered murine models of glioblastoma and enhanced effector responses in the local tumor microenvironment.

A significant dosage dependent growth inhibition by temsirolimus was observed in all cell lines which was also affected by NF2 status.

Conclusions: Our findings highlight the potential application of miR as a novel immunotherapeutic agent for neoplasms and serve as a model for identifying miRNAs that can be exploited as immune therapeutics.

We present a case report of a patient who had combination chemotherapy without histological diagnosis and had complete tumour regression.

Methods: The patient's case folder was retrieved and information relating to presentation, the working diagnosis and supporting investigations were sought.

She had pre chemotherapy ventriculo peritoneal shunt insertion for obstructive hydrocephalus. After due consultation with the Radio oncolgist, she had cyclical combination chemotherapy with cisplatin, etoposide and bleomycin.

Results: The patient's clinical condition improved following the ventriculo peritoneal shunt insertion. Post chemotherapy Brain CT scan showed complete tumor regression.

Conclusions: Tissue diagnosis may allow for precise, targeted management of pineal region tumours, however, in the absence of facilities which enable safe neurosurgery, resorting to the traditional chemo radiation is still a viable alternative.

There are several therapeutic options, but selection of the optimal treatment for individual patients remains controversial.

Classification schemes such as recursive partitioning analysis RPA , and diagnosis specific graded prognostic assessment DS GPA have been validated, but these provide group, rather than individualized estimates of outcome.

The purpose of this study was to develop and validate a nomogram for individualized patient prognosis which could be used for counseling patients.

Methods: De identified data from 7 randomized controlled trials of brain metastasis in patients was obtained from the RTOG database.

Overall survival was estimated using the Cox proportional hazards regression, RPA, and random survival forests RSF methods, and a nomogram was built using a concordance index to identify the best approach for each variable.

Results: The Cox analysis outperformed other methods thus the nomogram was built to estimate survival probabilities and median survival based on the Cox model.

This predictor of outcome could be readily applicable to clinical practice in enabling patients and their physicians to make informed decisions regarding treatment options and will be provided as free software application.

Future directions include external validation in a prospective dataset. The most biologically aggressive subtype is the glioblastoma multiforme GBM , a tumor associated with dismal prognosis.

The current standard of care for GBM patients; surgical resection followed by adjuvant radiation therapy and chemotherapy with the oral alkylating agent temozolomide; produces a median survival of only 15 months.

Even with the addition of the last generation of imaging studies, clinical assessment of tumor progression versus pseudo progression remains difficult.

This, combined with the high cost of these imaging modalities, can pose serious delays in treatment decisions and result in harm to the patient.

Hence, there is urgent need for a sensitive, specific, noninvasive and low cost biomarker which could be used routinely to monitor disease status in patients on treatment.

Methods: It is now well established that circulating mutant DNA cmDNA that originates in the tumor can be detected in the peripheral blood.

We used next generation, paired end sequencing to analyze several GBM genomes and their isogenic controls and identified tumor specific mutations.

These mutations were detected by polymerase chain reaction PCR in the patients; plasma and were used to follow disease progression over time.

Conclusions: Mutation associated biomarkers offer a reliable measure that would be useful for monitoring tumor response to specific therapies, detecting residual disease after surgery, and for long term clinical management.

The endoribonuclease Dicer is crucial for microRNA biogenesis. Low expression of Dicer has been associated with cancer, even though there are no studies in meningiomas.

Methods: We used tissue microarray TMA slides containing 59 samples of meningiomas from patients that underwent surgical resection.

Clinical correlation was made between WHO grade classification, tumor recurrence, post operative radiation therapy, cavernous sinus invasion, Mib1 index and Dicerexpression.

Results: From the total of 59 patients studied, 42 In the high Dicer group, the WHO grade distribution was: 34 The low Dicer group revealed: 7 In addition, the low Dicer group had higher percentage of tumor recurrence Withdrawn The clinical signs and symptoms of spinal meningiomas are typical of slow growing space occupying lesions of the spinal canal.

Clinical symptoms are normally indolent, gradual in presentation, and dependent on the tumor level and breadth.

These lesions have the potential to rapidly expand and cause acute neurological decline, often requiring emergent surgical intervention.

There is ample literature on the more common causes of epidural bleeds, but sparse data describing spinal epidural hematomas presenting secondary to cervical meningiomas.

This study describes a patient lacking the common risk factors for a spinal epidural hemorrhage, who presented clinically with acute paraparesis from a spontaneous cervical spinal hemorrhage.

Methods: The patient physical examination was most notable for dense paraparesis. Clinical workup was unremarkable for any typical causes of an acute epidural hematoma.

A cervical spine MRI revealed a meningioma at the C1 2 level, at the proximal portion of the epidural hematoma. We hypothesized the pathogenesis of the meningioma as the causative agent of the acute epidural hematoma.

Conclusions: This case provides evidence that, though not previously considered, spinal meningiomas should be included in the differential diagnosis of spinal hematomas.

This is especially the case when long term indolent pain is followed by acute symptoms without the commonly reported risk factors.

Conclusions: Therefore, low Dicer expression in meningiomas can be related to tumor aggressiveness and a worse clinical course.

Prognosis of affected patients is dependent on age, staging, and the pathology of the neoplasms, and this in turn affects treatment.

A review of the literature reveals a constant debate between surgical or non surgical management of these types of neoplasms. However, the literature unanimously reveals a poor prognosis in patients with severe acute progressive neurological deficits, regardless of treatment type.

The novel case herein reports a 3 month old patient with full resolution of a 4 day history of complete lower extremity paralysis status post neurosurgical intervention.

Methods: Magnetic resonance imaging showed complete spinal cord compression by a thoracolumbar intracanal extradural mass that was contiguous with a paraspinal mass.

Further pathological and radiological analysis, including MIBG and bone scintigraphy, showed that the mass was consistent with a non metastatic neuroblastoma.

The patient subsequently underwent a multilevel laminectomy that allowed for resection of the intraspinal mass and decompression of the spinal cord.

This was followed by adjuvant therapy on a delayed basis. Results: Fortunately, despite their prolonged lower extremity paralysis the patient regained full neurological function with resolution of spinal cord compression on radiographic imaging at 6 months follow up.

Conclusions: Currently, research states that patients with prolonged severe neurological deficits secondary to an intraspinal neuroblastoma have a very slim chance in regaining neurological function, irrespective of surgical or non surgical management.

This novel case seems to suggest that prompt surgical intervention followed by adjuvant therapy is the best treatment for these patients, given the potential benefit of rapid recovery of neurological function.

Meningiomas are benign brain tumors that are also associated with an increased VTE risk. Whether the presence or resection of meningiomas leads to systemic coagulation activation has not been clarified.

Methods: We hypothesize that patients with glioblastoma multiforme GBM demonstrate increased systemic coagulation activation compared to healthy individuals.

We further hypothesize that meningiomas are not associated with a significant increase in systemic coagulation activation and that this may account for the difference in VTE risk.

We will test this hypothesis by measuring surrogate markers of systemic coagulation activation in patients with GBM and meningiomas before and after treatment and in age and sex matched healthy control blood donors.

Markers of coagulation activation assayed for this study will include plasma D dimers, P selectin, tissue factor pathway inhibitor TFPI , thrombin generation via calibrated automated thrombography and tumor tissue factor and TFPI expression by immunohistochemistry.

Results: We are currently actively recruiting to this study and expect to complete arcual by the end of Conclusions: We expect this work to lead to clarification of coagulation abnormalities in patients with primary brain tumors and may result in identification of novel markers of VTE risk in these patients.

This however does not exclude the immunocompromising effect,which includes risks of lymphomatous disease.

He was commenced on Stupp prorocal with concurrent Temozolomide. His treatment completed 2 months after his initial presentation and a month later, he proceeded with first cycle of adjuvant chemotherapy.

This was complicated with large pulmonary embolism and left lower limb deep vein thrombosis. Follow up MRI Brain revealed a recurrence of his tumour.

There was also a new enhancing lesion in the left frontal lobe, measuring 1. He subsequenly underwent further debulking of his original tumour and stereotactic biopsy of the contralateral lesion.

He deteriorated during chemotherapy and died 10 months after his original presentation. Results: We describe herein an interesting case of primary GBM with concurrent primary CNS lymphoma diagnosed 2 months after completion of Temozolomide treatment.

To best of our knowledge, this is the first case reported in literature. This was observed on his surveillance MRI Brain 2 months after completion of treatment, therefore, the suspicion exists that the lesion may have developed while he was on treatment.

Excitatory glutamatergic mechanism are shown to be involved in the generation of epileptic activities in the cortex surrounding gliomas.

However, the contribution of defective Chloride homeostasis and paradoxical excitatory GABAergic mechanisms, crucial in other epilepsies, is unknown.

They can occur anywhere in the cranium and the spine and have varied pathology. Removal of meningiomas in certain locations can be challenging, we explored the use of ALA induced fluorescence to guide intracranial meningiomas; resection and its corrolation to histopathology.

Methods: We studied in neocortical slices from the security margin resected around human brain gliomas, the occurrence, networks, cells, signaling and origin of epileptic activities.

These events were synchronized in superficial layers of cortical columns in the neocortex surrounding glioma areas that presented a tumor infiltration and had a high frequency oscillation signature.

Interictal like events depended on glutamatergic transmission but also on depolarizing GABAergic signaling.

This effect was related to perturbations in Chloride homeostasis, due to an abnormal load by the co transporter NKCC1. Ictal like activities could be exclusively generated in these epileptogenic areas.

Methods: Twenty nine consecutive lesions with MRI differential of meningiomas were included in this analysis, including 17 supratentorial, 10 infratentorial and one thoracic.

Twenty three were females, the mean age was All these patients received 1. Surgical resection was aided by using the blue light of the microscope Pentero, Zeiss, Germany.

The fluorescence was graded into strong very red fluorescent , faint pink and moderate in between red and pink.

Results: Fluorescence was detected in 22 Faint signal was observed in six Total excision Simpson grade 1 was achieved in all meningiomas.

There was no correlation between histological type, ALA dose, or time to fluorescence and the intensity of fluorescence. Only two patients developed significant drop in their blood pressure 7.

ALA induced fluorescence is safe and helpful in intracranial meningioma surgical resection, but there was no correlation to histology.

On postoperative day 22 the EVD was clamped, and the patient remained asymptomatic the following day. A new brain MRI showed significantly decreased size of the germinoma along with flow artifact across the floor of the third ventricle, and his EVD was removed.

The patient's hydrocephalus did not recur over the following month. We undertook a multidisciplinary study among brain tumor experts to test this hypothesis.

Methods: The expert group included 2 CNS radiation oncologists, 3 tumor neurosurgeons, and 2 neuro radiologists. CERR Matlab tool was used to compare volumes.

CCC measured inter observer reproducibility. Conclusions: In this pilot substantial inter observer variability exists in meningioma target definition.

Over contouring increases normal tissue exposure. Under contouring increases recurrence risk. Our findings suggest lack of physician consensus regarding target volume.

We suggest a large scale study to confirm these findings and consideration of a multidisciplinary consortium to standardize target volumes. Gump, MD; Ian Mutchnick, MD Louisville, KY Introduction: Endoscopic third ventriculostomy E3V is an established option for treatment of obstructive hydrocephalus and is often performed concurrently with biopsy of an obstructing mass lesion.

Delayed failure is a known complication. We report the case of a patient whose E3V became functionally patent in a delayed fashion, three weeks postoperatively, when mass effect on the brainstem had been adequately relieved.

Methods: A 13 year old boy presented to the emergency department with symptomatic obstructive hydrocephalus from a pineal region tumor.

Results: Pathology was consistent with pure germinoma. The patient returned to surgery four days later for a secondary E3V. He remained drain dependent, and initiated radiation therapy on postoperative day 7.

Therefore, advancements in research tools, including cell culture and animal models represent a challenge for basic research and are necessary for the development of more effective treatments.

Methods: We are developing the 3 Dimensional cell culture model in which primary Glioblastoma cells are forced to form multi cellular Glio Spheres.

This approach allows cells to grow for several months without losing their glial phenotype, the main problem with Glioblastoma culture.

We use Seahorse Analyzer to characterize metabolic properties of Glio Spheres by measuring Extracellular acidification and Oxygen consumption rates; We also evaluate mitochondrial membrane potential, cell survival and response to a common lipid lowering drug, fenofibrate.

Conclusions: Here, we demonstrate a new approach to develop 3 dimentional cell culture system for primary Glioblastoma Glio Spheres and present their metabolic profiles.

We also include studies on fenofibrate, which has strong anti tumoral effect with low systemic toxicity, and could be introduced as a supportive regimen to the conventional therapies.

The Glio Spheres can be also implanted into the brains of immunodeficient mice, providing a clinically relevant model for testing anti tumoral regiments against Glioblastoma.

The tumor suppressor NF2 is disrupted in approximately half of meningiomas, but the complete spectrum of genetic changes remains undefined.

Introduction: Microcystic meningioma is a variant of meningioma with a multicystic appearance that can mimic intrinsic primary brain tumors, hemangioblastomas, and other non meningiomatous tumor types.

Methods: We performed whole genome or whole exome sequencing of 17 Grade I meningiomas and focused sequencing of an additional 48 tumors to comprehensively identify mutations, insertion deletions, copy number alterations, and genetic rearrangements contributing to oncogenesis.

A mutational significance algorithm was used to distinguish driver and passenger events. Methods: 18 subjects with histopathological diagnosis of microcystic meningioma and a cohort of 12 subjects with grade I meningioma and 54 subjects with grade IV primary glioma were considered.

Clinical variables including patient sex, age, extent of resection, surgical blood loss and need for adjunctive therapy were considered.

DSC images were acquired at a temporal resolution of either ms 3T or ms 1. Results: Overall, the tumors showed few somatic genetic events, consistent with their benign clinical status, but underscoring the potential importance of each individual event.

Several tumors harbored more complex patterns of copy number changes and rearrangements including one tumor with chromothripsis. As expected, the NF2 gene was identified as the most frequently altered, with over half of tumors harboring NF2 disruptions.

One sample had a novel translocation affecting the NF2 gene and a nearby region of chr Preoperative DCE analysis demonstrated kTrans values of 0.

Conclusions: This study begins to define the spectrum of genetic alterations in meningiomas. The discovery of novel drivers of meningiomagenesis with existing targeted therapeutics has the potential to rapidly transform the clinical management of meningiomas.

Higher nCBV values are associated with a trend to increased intraoperative blood loss. Introduction: Increasing use of endoscopic approaches for the treatment of various intracranial pathology has necessitated neurosurgeons have a thorough understanding of the anatomy from an endoscopic endonasal perspective.

We present a cadaveric anatomic study of the clinoidal and ophthalmic ICA from an endonasal endoscopic perspective. Methods: Testing of all basal hormone values and magnetic resonance imaging MRI were performed preoperatively and postoperatively in consecutive patients who underwent PEETS in the period between and The series consisted of 37 somatotroph adenomas, 4 prolactinomas, and 8 corticotroph and 72 nonfunctioning adenomas.

Remission was defined as hormonal excess normalization on the third postoperative day in functioning adenomas and as normal MRI findings approximately four months postoperatively in nonfunctioning adenomas.

Hypocortisolism was assessed through necessity for replacement therapy within 3 months postoperatively. Methods: Embalmed heads underwent thin cut CT scans for the purpose of neuronavigation.

The heads were registered with our neuronavigation system. An endonasal endoscopic transsphenoidal exposure was performed.

Various measurements were taken some of which include: the inter carotid distance at the level of the distal dural rings DDR , the distance between the ICA at the distal dural ring and the optic chiasm and the distance between the ICA and the pituitary stalk.

The ratio of inter carotid distance to distance between the OCRs was also calculated. Results: A total of 10 cadaver heads were studied.

Neuronavigation was used achieving excellent accuracy in all cases. The average distance between the carotids at the distal dural rings was The average distance between the ICA at the distal dural ring and the optic chiasm is 9.

Endocrinological complications occurred in Seventy five percent of preoperatively present hormonal deficiencies improved after the surgery. Between tumor types there were no significant differences in remission, complications, and normal pituitary function recovery.

Conclusions: Expansion of endonasal endoscopic techniques for treatment of various intracranial pathology necessitates improved understanding of the clinoidal and proximal intradural ICA anatomy and its relationship to surrounding structures.

This will enable surgeons to more reliably predict the location of the ICA and its relationship to surrounding structures, decreasing the potential for vascular injury.

Conclusions: Patients with microadenomas had higher remission and lower complication rates following PEETS, emphasizing the necessity for early detection and treatment of pituitary adenomas.

PEETS is a discussion worthy method for microprolactinoma treatment. These can be locally aggressive with potential intracranial extension.

Traditionally these lesions have been treated using open surgical techniques, however recently endoscopic approaches have been implemented in hopes of minimizing morbidity.

We recorded the number of operations, estimated blood loss, extent of resection, any complications and length of hospital stay.

All are male with an average age of 16 years. Average follow up is All patients underwent pre operative tumor embolization. One patient underwent an initial open transfacial approach and required a subsequent endoscopic approach.

Patients underwent an average of 2. Mean EBL was cc. A subtotal resection was achieved in all cases. Two patients underwent radiation therapy during the course of their treatment.

There were no mortalities. Open surgical resection can achieve good tumor control, but can be exceedingly morbid. Given the tendency for these lesions to regrow, multiple surgeries are often required.

We believe an endoscopic approach for subtotal resection in combination with pre operative embolization and post operative adjuvant treatment in select patients can achieve good tumor control while minimizing morbidity.

Numerical values were estimates from the french register of CNS tumors, the national institute of statistics, and published series of glioma survivals.

We report a new case in a pediatric patient. Methods: A 4 year old girl presented with generalized seizures.

MRI of the brain revealed an extensive diffuse nonenhancing area of abnormal signal involving the right frontal and temporal lobes.

She was taken to surgery for biopsy, and returned to surgery eight months later for electrocorticography guided seizure focus resection.

Seizure frequency decreased to zero over the following three months. Compared with gemistocytic, protoplasmic astrocytomas have less potential to behave aggressively.

In two case series encompassing 18 patients, average age at presentation was 25 years. Most lesions were in the frontal or temporal lobes. For 7 patients with unresectable lesions, biopsy was performed; all others underwent attempted gross total resection.

Five patients subsequently received radiation therapy and one also had chemotherapy. The youngest patient age 2 years at diagnosis died 36 months after subtotal resection without further adjuvant therapy; all others were alive with or without residual tumor 2 to months postoperatively.

One additional case report describes a 3 year old with diffuse leptomeningeal disease who died from tumor progression despite chemotherapy.

Although all patients presented with seizures, seizure outcomes have not been well documented. Our patient achieved seizure freedom.

Conclusions: Protoplasmic astrocytoma is a rare low grade glioma which can be associated with medically resistant epilepsy.

Tailored surgery for unresectable lesions can be beneficial for seizure control. Conclusions: Patients with silent DLGG are more likely to die from transformation of the silent DLGG to symptomatic glioma than dying from another cause with the silent DLGG, unless patient survival is expected to be less than 4 years.

This epidemiological argumentation supports early surgery for incidentally discovered glioma. To identify patients who had undergone surgery, we used brain tumor surgery ICD 9 codes.

We used the SAS statistical software package Version 9. For brain tumor patients treated without surgery For brain tumor patients treated with surgery 9.

The most common PSIs included postoperative respiratory failure, deep vein thrombosis, and sepsis. The total number of HACs associated with brain tumor patients was 13,, with 2.

For brain tumor patients treated without surgery 3. For brain tumor patients treated with surgery 7. The most common HACs included falls and trauma and pressure ulcers.

Conclusions: Patient safety and delivery of quality care is an important part of our national healthcare agenda.

These data may be used to determine individual institutional improvements or success by comparison. One of the molecular hallmarks of Glioblastomas is genomic instability, which leads to the development catastrophic mutations.

Thus, basic DNA repair mechanisms responsible for the preservation of genomic integrity could be impaired in Glioblastomas.

We have previously reported the detection of DNA sequences of the human neurotropic JC Virus and expression of its oncoprotein, T Antigen, in brain tumors of glial and neuroectoermal origin.

Bevacizumab has recently demonstrated encouraging anti tumor effect in the treatment of recurrent and progressive meningiomas.

The imaging characteristics of meningiomas undergoing bevacizumab treatment have not been extensively described. Methods: While undergoing systemic therapy on bevacizumab with a sustained intracranial response, a 55 year old man with a locally recurrent WHO grade III meningioma developed a biopsy proven left sided neck metastasis and radiographic findings consistent 40 Conclusions: Fluorescence guided resection for complex meningiomas have shown to be an effective intraoperative tool to achieve maximal citoreduction.

In meningioma lesions we assume that the breakage of the blood brain barrier increasing vascular permeability and by this mechanism the 5 ALA reaches the peritumoral area.

Results: The primary intracranial meningioma was a homogeneously, avidly enhancing extra axial mass on magnetic resonance imaging MRI. The recurrent intracranial lesion was isointense to surrounding brain on T1 imaging and hyperintense on T2 weighted images.

The mass was centered in the obliquus capitis inferior muscle and was associated with erosive bony changes. The neck lesion was isointense to muscle on noncontrast T1 imaging, and nearly isointense to gray matter on T2 weighted images.

There were four subcentimeter, nonenhancing parenchymal lung nodules appreciated on chest CT, consistent with pulmonary metastatic disease.

Cranial hyperostosis in association with adult meningioma occurs frequently. The osteopathophysiology of this phenomenon is poorly understood and controversial, with actual bone invasion by tumor or reactive changes due to adjacent tumor having been posited as explanations.

Metalloproteins have also been suggested as playing a role. Hyperostosing meningioma is rarely reported in children. Conclusions: This case illustrates the imaging appearance of intracranial anaplastic meningioma and extracranial metastases while on bevacizumab.

Further study of imaging characteristics of recurrent and progressive meningiomas while undergoing treatment with anti angiogenic therapies is warranted.

Methods: Following IRB approval, the medical record of a child with intracranial hyperostosing meningioma was abstracted for diagnostic, treatment and outcome details.

The medical literature on meningioma and hyperostosis conditions was surveyed. Fluorescence Guided Resection Of Complex Meningiomas Results: A 15 year old boy presented with progressive nausea, vomiting and headaches.

Gastroenterologic evaluations were negative and therapy for reflux disease was ineffective. Imaging revealed a lobulated solid cystic mass in the right frontal region, with overlying irregular cranial bone thickening.

Skull palpation revealed painless fullness without scalp changes. Via a large craniotomy flap, the tumor was found to be arising from the dura and adherent to the skull, without gross invasion.

The flap was hyperostotic and the inner table and cancellous bone were drilled out using a high speed air drill. The tumor was microsurgically completely resected and the bone flap was replaced.

The lesion showed classic syncytial features, yet with hypercellularity and an elevated MIB 1 index, consistent with atypical meningioma, W.

Tumor was identified in the bone curettings. Due to the higher grade histology and tumor in the bone, adjuvant radiation therapy was administered.

He remains in remission three years later. The extent of resection in intracranial brain tumors determine survival rate.

For extra axial tumors, such as, meningiomas the usefulness of fluorescence guided surgery will help to achieve maximal resection in complex cases where occult tumor cells spreads beyond the arachnoid layer or in to bone structures.

Methods: We present an illustrative case of a 37 year old female with past medical history relevant for overweight and penicillin allergy.

Her symptoms were characterized by headache, nausea, amaurosis fugax, left eye ptosis with facial asymmetry. An MRI was done and a left frontal extra axial lesion was found.

There were no surgical complications. She was discharged 4 days after the tumor resection. Conclusions: Only a paucity of pediatric cases of hyperostosing meningioma have ever been reported.

There is no reported correlation between hyperostosis and histologic tumor grade and bone invasion by tumor.

Our report confirms that this phenomenon occurs in children. The pathophysiologic mechanisms may be the same as in adults. We recommend ongoing reporting of this rare condition in youth, so as to inform of preferred management strategies.

Results: The patient did not experience any additional neurological deficits after surgery. There was no evidence of increased liver function test.

Currently the patient is seen in the outpatient clinic. Most of the general symptoms have remarkable improved. Facial asymmetry has also been substantially reduced.

We aimed to determine the clinical impact of histologically proven transformation. Methods: We retrospectively identified patients with anaplastic gliomas who had surgery at our center upon first radiographic progression.

We examined the impact of clinical and molecular factors on transformation and outcome. Results: Between and , 85 patients met study criteria; 24 with oligodendrogliomas, 22 with oligoastrocytomas, and 39 with astrocytomas.

Transformation was associated with shorter overall survival OS from initial diagnosis median OS 6. Conclusions: Fewer than half of radiographically progressive anaplastic gliomas transformed to glioblastoma histologically.

Transformation is associated with reduced OS from the time of diagnosis and from the second surgery. Tissue diagnosis may be warranted for prognostic counseling at the time of radiographic progression.

A newly emerged field, imaging genomics, links gene expression profiles with MRI phenotypes. Thus, an imaging genomic necrosis screen has the potential to uncover novel molecular determinants of cell death in GBM.

Here, we present the first comprehensive radiogenomic analysis using quantitative necrosis MRI volumetrics and large scale gene and microRNA expression profiling in GBM.

Gender specific analysis was performed and the top concordant genes and microRNAs correlated with high volumes of necrosis were further characterized using Ingenuity Pathway Analysis, whole genome transcriptional factor analysis, and cognate microRNA gene networks were created.

Results: Female patients demonstrated significantly lower volumes of necrosis than male patients. Thus, a gender specific analysis was chosen and revealed in both MRI and histopathology data that female patients with high necrosis had a significantly shorter survival compared to both females with lower necrosis or males with high necrosis.

Survival in males was not statistically different in patients with high versus low tumor necrosis. The survival data was concordant with the genomic analysis suggesting that predominantly MYC driven oncogenic pathways were associated with necrosis in female patients, while male patients showed a strong positive association of the MRI necrosis phenotype with the P53 tumor suppressor pathway.

Gender independent necrosis pathway analysis showed equal distribution of both tumor suppressors and oncogenes.

Conclusions: Here, we propose a novel diagnostic method to screen for molecular correlates of necrosis in GBM. Our findings suggest distinct oncogenic pathways promoting MRI and histopathology necrosis phenotypes in male versus female GBM patients.

In prior studies, depression has been associated with decreased quality of life and shorter overall survival. Antidepressant therapy is a widespread and generally well tolerated treatment of depression which can increase quality of life.

We investigated whether pharmacologic treatment of depression has an impact on overall survival. Univariate analysis isolated possible predictors of survival.

Results: Median survival was Analysis based on class of antidepressant was not significant. Multivariate analysis controlled for age, tumor grade, extent of resection, Karnofsky Performance Score, reoperation, antidepressant therapy, diabetes, radiation and temazolamide therapy.

Although this effect did not reach significance in multivariate analysis, the trend warrants further investigation.

Prospective studies closely monitoring antidepressant treatment and its effects are necessary to evaluate the potential benefit of both improving quality of life and prolonging survival with a single therapy.

We investigated the feasibility of sonodynamic therapy for malignant glioma by low frequency ultrasound with 5 aminolevulinic acid 5 ALA , a precursor of protoporphyrin IX PpIX in heme synthetic process.

Methods: In vivo tumor model was made by inoculating human glioma cell line U87 MG subcutaneously in nude mice.

The tumor was sonicated by 25 kHz ultrasound 4 hours following administration of 5 ALA. The results showed the therapeutic effect of 25 kHz ultrasound for the glioma in 5 ALA administered tumor bearing mice by inducing apoptotic change of tumor cells.

Conclusions: This is a first report to elucidate the feasibility of therapeutic use of 25 kHz ultrasound in sonodynamic therapy using 5 ALA as a sonosensitizer precursor.

This may be a realistic intraoperative malignant gioma therapy in addition of tumorectomy, since 25kHz is a frequency of ultrasonic aspirator.

We leveraged this unique developmental system to interrogate lncRNA expression and function. By integrating data from chromatin state maps, custom microarrays, and FACS purified cells, we stringently identify lncRNAs with potential roles in adult neurogenesis, and accurately predict their expression patterns in the SVZ and OB.

More broadly, our data and workflow provide a uniquely coherent in vivo lncRNA analysis that will be relevant for future studies of lncRNAs in development and tumorigenesis.

This phenomenon, however, has seldom been documented with an imaging correlate and quantitative evaluation. Methods: The clinical and radiographic features, quantitative assessments, treatments, and outcomes were reviewed for two patients with lesions in the third ventricle, in which remitting clinical symptoms of raised intracranial pressure were either characteristic of or associated with intermittent ventriculomegaly on imaging.

Additionally, the few documented cases of intermittent obstructive hydrocephalus with concomitant intraventricular cysts are examined.

Results: Two patients, a 3 month and a 9 year old male, presented with paroxysmal symptoms of raised intracranial pressure and imaging confirmation of varying ventriculomegaly with a third ventricular pineal and choroid plexus cyst, respectively.

Both were treated by a primary endoscopic cyst fenestration and remain without symptoms, complications, or placement of an indwelling shunt at 20 and 3 months of follow up, respectively.

Conclusions: Our cases add to a growing body of evidence that a normal sized ventricular system cannot rule out the diagnosis of intermittent hydrocephalus in a patient who presents both with symptoms suggestive of increased intracranial pressure and a lesion that can potentially obstruct CSF flow.

Additionally, an absence of intraventricular cysts on traditional CT or MR imaging should not automatically rule out the possibility of an intermittently obstructive cyst.

Our findings suggest that patients experiencing symptoms of raised intracranial pressure concomitantly with third ventricular cystic masses and normal sized ventricles should be offered cyst decompression.

On radiographic findings, these lesions may present as an osteolytic or osteoblastic skull lesions. Methods: We report a case of a 53 year old female who presented with a gradual onset exopthalmos of the right eye.

The plain radiographs of the skull showed hyperostosis af the right orbital roof and the lateral orbital wall. The computerized tomography CT scan revealed an extra axial, intradiploic orbital roof tumor involving the frontal and temporal bone.

Results: The tumor, including the surrounding normal bone, was totally excised by an extradural route using a basal fronto temporal craniotomy.

The histopathological study confirmed a meningotheliomatous meningioma. A split calvarial frontal bone graft was used to reconstruct the orbit.

The patient was discharged after 6 days. There is no evidence of recurrence after a follow up of 3 months. Conclusions: Intradiploic meningiomas are often asymptomatic, but can cause proptosis and neurological symptoms depending on their size and location.

Radiographic and clinical presentations generate diagnostic suspicion that may assist with preoperative planning. The majority of these tumors cause hyperostosis that may mimic meningioma en plaque, osteoma, osteosarcoma, Paget disease, and fibrous displasia.

The treatment of choise is resection, which is potentially curative. Tumors that cannot be compleely resected may be require adjuvant therapy, which may include radiation therapy, chemotherapy, or bisphosphonate therapy.

In non contrast enhancing gliomas, and to a lesser extent enhancing tumors, the T2 and FLAIR signals are important targets to determine target volumes for resection margins.

We hypothesized that intraoperatively obtained MRI T2 and FLAIR signal volumes might not reflect corresponding post operative volumes due to tumor edema after resection and brain manipulation.

Methods: We examined 12 low grade gliomas LGG, 9 low grade astrocytomas and 3 oligodendrogliomas and compared them to 13 high grade tumors HGG, 4 anaplastic astrocytomas, 3 anaplastic oligodendrogliomas, and 5 glioblastomas.

When all tumor grades are analyzed together similar trends are found. Conclusions: Postoperative FLAIR signal volumes are significantly lower and T2 signal volumes significantly higher than 44 Methods: We analyzed the relation between the sphenozygomatic suture and the marginal tubercle of the frontal process of the zygoma 60 dried skulls.

Minipterional craniotomy was performed in 10 cadaveric specimens. The approach was utilized to 18 sphenoid wing meningiomas. Anterior to posterior sub periosteal dissection and retraction of the temporalis muscle, and avoiding cuts along the origin of the muscle allows excellent cosmetic outcome.

All 18 meningiomas 3 to 5 cm in size were successfully resected without morbidity or mortality through a 3. Meningiomas A Population Based Perspective Conclusions: Minipterional approach is an excellent option to approach sphenoid wing meningiomas.

The minimally invasive access allows minimal soft tissue trauma, smaller bony opening, less pain, and excellent cosmetic outcome Quinn T.

We used this data to describe the current epidemiology of meningiomas in the United States between the years of and We also calculated survival rates for all malignant menginiomas.

Introduction: Fronto orbital minicraniotomy is the most commonly used minimally invasive approaches for anterior cranial fossa lesions. Methods: We describe our novel technique with the transpalpebral eyelid incision to obtain access to the anterior cranial fossa.

We describe the approach and technique of the transpalpebral eyelid incision in a step by step fashion and discuss the results of retrospectively analyzed eighteen cases.

Results: Meningiomas are the most common type of brain tumor in the United States, compromising There was an overall incidence rate of 7.

They are more common in women than men incidence rates of 9. They are more common in blacks than whites incidence rates of 8. For malignant menginiomas, there were 1, 5 and 10 year survival rates of Results: Incisions in the eyelid region should therefore be as horizontal as possible.

A relative safety zone; free of facial nerve branches was identified that exists up to 2. We apply knowledge of upper eyelid anatomy, which allow us to utilize an avascaular plane of dissection that maintains functionality of the eyelid and avoids disfiguring cosmetic results.

We describe the bony cuts necessary to complete our one piece fronto orbital approach. Complications in one patient who developed deep wound infection required re operation.

Conclusions: Though most menginiomas are not malignant, their frequency and potential resulting morbidity makes them of significant clinical and scientific relevance.

Awareness of the populations most at risk for these tumors assists physicians and scientists in focusing on developing new ways to serve these patient populations.

Mini Pterional Craniotomy: An Alternative Approach For Sphenoid Wing Meningiomas Conclusions: The transpalpebral approach provides dissection in natural anatomical planes, affords preservation of the frontalis muscle, avoids injury to nerve VII branches, and results in an excellent cosmetic outcome.

Khaled M. It provides the same microsurgical exposure as the standard frontotemporal approach. Methods: Magnetic resonance imaging showed complete spinal cord compression by a thoracolumbar intracanal extradural mass that was contiguous with a paraspinal mass.

Further pathological and radiological analysis, including MIBG and bone scintigraphy, showed that the mass was consistent with a non metastatic neuroblastoma.

The patient subsequently underwent a multilevel laminectomy that allowed for resection of the intraspinal mass and decompression of the spinal cord.

This was followed by adjuvant therapy on a delayed basis. Results: Fortunately, despite their prolonged lower extremity paralysis the patient regained full neurological function with resolution of spinal cord compression on radiographic imaging at 6 months follow up.

Conclusions: Currently, research states that patients with prolonged severe neurological deficits secondary to an intraspinal neuroblastoma have a very slim chance in regaining neurological function, irrespective of surgical or non surgical management.

This novel case seems to suggest that prompt surgical intervention followed by adjuvant therapy is the best treatment for these patients, given the potential benefit of rapid recovery of neurological function.

Meningiomas are benign brain tumors that are also associated with an increased VTE risk. Whether the presence or resection of meningiomas leads to systemic coagulation activation has not been clarified.

Methods: We hypothesize that patients with glioblastoma multiforme GBM demonstrate increased systemic coagulation activation compared to healthy individuals.

We further hypothesize that meningiomas are not associated with a significant increase in systemic coagulation activation and that this may account for the difference in VTE risk.

We will test this hypothesis by measuring surrogate markers of systemic coagulation activation in patients with GBM and meningiomas before and after treatment and in age and sex matched healthy control blood donors.

Markers of coagulation activation assayed for this study will include plasma D dimers, P selectin, tissue factor pathway inhibitor TFPI , thrombin generation via calibrated automated thrombography and tumor tissue factor and TFPI expression by immunohistochemistry.

Results: We are currently actively recruiting to this study and expect to complete arcual by the end of Conclusions: We expect this work to lead to clarification of coagulation abnormalities in patients with primary brain tumors and may result in identification of novel markers of VTE risk in these patients.

This however does not exclude the immunocompromising effect,which includes risks of lymphomatous disease. He was commenced on Stupp prorocal with concurrent Temozolomide.

His treatment completed 2 months after his initial presentation and a month later, he proceeded with first cycle of adjuvant chemotherapy. This was complicated with large pulmonary embolism and left lower limb deep vein thrombosis.

Follow up MRI Brain revealed a recurrence of his tumour. There was also a new enhancing lesion in the left frontal lobe, measuring 1.

He subsequenly underwent further debulking of his original tumour and stereotactic biopsy of the contralateral lesion. He deteriorated during chemotherapy and died 10 months after his original presentation.

Results: We describe herein an interesting case of primary GBM with concurrent primary CNS lymphoma diagnosed 2 months after completion of Temozolomide treatment.

To best of our knowledge, this is the first case reported in literature. This was observed on his surveillance MRI Brain 2 months after completion of treatment, therefore, the suspicion exists that the lesion may have developed while he was on treatment.

Excitatory glutamatergic mechanism are shown to be involved in the generation of epileptic activities in the cortex surrounding gliomas.

However, the contribution of defective Chloride homeostasis and paradoxical excitatory GABAergic mechanisms, crucial in other epilepsies, is unknown.

They can occur anywhere in the cranium and the spine and have varied pathology. Removal of meningiomas in certain locations can be challenging, we explored the use of ALA induced fluorescence to guide intracranial meningiomas; resection and its corrolation to histopathology.

Methods: We studied in neocortical slices from the security margin resected around human brain gliomas, the occurrence, networks, cells, signaling and origin of epileptic activities.

These events were synchronized in superficial layers of cortical columns in the neocortex surrounding glioma areas that presented a tumor infiltration and had a high frequency oscillation signature.

Interictal like events depended on glutamatergic transmission but also on depolarizing GABAergic signaling. This effect was related to perturbations in Chloride homeostasis, due to an abnormal load by the co transporter NKCC1.

Ictal like activities could be exclusively generated in these epileptogenic areas. Methods: Twenty nine consecutive lesions with MRI differential of meningiomas were included in this analysis, including 17 supratentorial, 10 infratentorial and one thoracic.

Twenty three were females, the mean age was All these patients received 1. Surgical resection was aided by using the blue light of the microscope Pentero, Zeiss, Germany.

The fluorescence was graded into strong very red fluorescent , faint pink and moderate in between red and pink. Results: Fluorescence was detected in 22 Faint signal was observed in six Total excision Simpson grade 1 was achieved in all meningiomas.

There was no correlation between histological type, ALA dose, or time to fluorescence and the intensity of fluorescence. Only two patients developed significant drop in their blood pressure 7.

ALA induced fluorescence is safe and helpful in intracranial meningioma surgical resection, but there was no correlation to histology.

On postoperative day 22 the EVD was clamped, and the patient remained asymptomatic the following day. A new brain MRI showed significantly decreased size of the germinoma along with flow artifact across the floor of the third ventricle, and his EVD was removed.

The patient's hydrocephalus did not recur over the following month. We undertook a multidisciplinary study among brain tumor experts to test this hypothesis.

Methods: The expert group included 2 CNS radiation oncologists, 3 tumor neurosurgeons, and 2 neuro radiologists. CERR Matlab tool was used to compare volumes.

CCC measured inter observer reproducibility. Conclusions: In this pilot substantial inter observer variability exists in meningioma target definition.

Over contouring increases normal tissue exposure. Under contouring increases recurrence risk. Our findings suggest lack of physician consensus regarding target volume.

We suggest a large scale study to confirm these findings and consideration of a multidisciplinary consortium to standardize target volumes.

Gump, MD; Ian Mutchnick, MD Louisville, KY Introduction: Endoscopic third ventriculostomy E3V is an established option for treatment of obstructive hydrocephalus and is often performed concurrently with biopsy of an obstructing mass lesion.

Delayed failure is a known complication. We report the case of a patient whose E3V became functionally patent in a delayed fashion, three weeks postoperatively, when mass effect on the brainstem had been adequately relieved.

Methods: A 13 year old boy presented to the emergency department with symptomatic obstructive hydrocephalus from a pineal region tumor.

Results: Pathology was consistent with pure germinoma. The patient returned to surgery four days later for a secondary E3V.

He remained drain dependent, and initiated radiation therapy on postoperative day 7. Therefore, advancements in research tools, including cell culture and animal models represent a challenge for basic research and are necessary for the development of more effective treatments.

Methods: We are developing the 3 Dimensional cell culture model in which primary Glioblastoma cells are forced to form multi cellular Glio Spheres.

This approach allows cells to grow for several months without losing their glial phenotype, the main problem with Glioblastoma culture. We use Seahorse Analyzer to characterize metabolic properties of Glio Spheres by measuring Extracellular acidification and Oxygen consumption rates; We also evaluate mitochondrial membrane potential, cell survival and response to a common lipid lowering drug, fenofibrate.

Conclusions: Here, we demonstrate a new approach to develop 3 dimentional cell culture system for primary Glioblastoma Glio Spheres and present their metabolic profiles.

We also include studies on fenofibrate, which has strong anti tumoral effect with low systemic toxicity, and could be introduced as a supportive regimen to the conventional therapies.

The Glio Spheres can be also implanted into the brains of immunodeficient mice, providing a clinically relevant model for testing anti tumoral regiments against Glioblastoma.

The tumor suppressor NF2 is disrupted in approximately half of meningiomas, but the complete spectrum of genetic changes remains undefined.

Introduction: Microcystic meningioma is a variant of meningioma with a multicystic appearance that can mimic intrinsic primary brain tumors, hemangioblastomas, and other non meningiomatous tumor types.

Methods: We performed whole genome or whole exome sequencing of 17 Grade I meningiomas and focused sequencing of an additional 48 tumors to comprehensively identify mutations, insertion deletions, copy number alterations, and genetic rearrangements contributing to oncogenesis.

A mutational significance algorithm was used to distinguish driver and passenger events. Methods: 18 subjects with histopathological diagnosis of microcystic meningioma and a cohort of 12 subjects with grade I meningioma and 54 subjects with grade IV primary glioma were considered.

Clinical variables including patient sex, age, extent of resection, surgical blood loss and need for adjunctive therapy were considered. DSC images were acquired at a temporal resolution of either ms 3T or ms 1.

Results: Overall, the tumors showed few somatic genetic events, consistent with their benign clinical status, but underscoring the potential importance of each individual event.

Several tumors harbored more complex patterns of copy number changes and rearrangements including one tumor with chromothripsis.

As expected, the NF2 gene was identified as the most frequently altered, with over half of tumors harboring NF2 disruptions.

One sample had a novel translocation affecting the NF2 gene and a nearby region of chr Preoperative DCE analysis demonstrated kTrans values of 0.

Conclusions: This study begins to define the spectrum of genetic alterations in meningiomas. The discovery of novel drivers of meningiomagenesis with existing targeted therapeutics has the potential to rapidly transform the clinical management of meningiomas.

Higher nCBV values are associated with a trend to increased intraoperative blood loss. Introduction: Increasing use of endoscopic approaches for the treatment of various intracranial pathology has necessitated neurosurgeons have a thorough understanding of the anatomy from an endoscopic endonasal perspective.

We present a cadaveric anatomic study of the clinoidal and ophthalmic ICA from an endonasal endoscopic perspective. Methods: Testing of all basal hormone values and magnetic resonance imaging MRI were performed preoperatively and postoperatively in consecutive patients who underwent PEETS in the period between and The series consisted of 37 somatotroph adenomas, 4 prolactinomas, and 8 corticotroph and 72 nonfunctioning adenomas.

Remission was defined as hormonal excess normalization on the third postoperative day in functioning adenomas and as normal MRI findings approximately four months postoperatively in nonfunctioning adenomas.

Hypocortisolism was assessed through necessity for replacement therapy within 3 months postoperatively.

Methods: Embalmed heads underwent thin cut CT scans for the purpose of neuronavigation. The heads were registered with our neuronavigation system.

An endonasal endoscopic transsphenoidal exposure was performed. Various measurements were taken some of which include: the inter carotid distance at the level of the distal dural rings DDR , the distance between the ICA at the distal dural ring and the optic chiasm and the distance between the ICA and the pituitary stalk.

The ratio of inter carotid distance to distance between the OCRs was also calculated. Results: A total of 10 cadaver heads were studied.

Neuronavigation was used achieving excellent accuracy in all cases. The average distance between the carotids at the distal dural rings was The average distance between the ICA at the distal dural ring and the optic chiasm is 9.

Endocrinological complications occurred in Seventy five percent of preoperatively present hormonal deficiencies improved after the surgery.

Between tumor types there were no significant differences in remission, complications, and normal pituitary function recovery. Conclusions: Expansion of endonasal endoscopic techniques for treatment of various intracranial pathology necessitates improved understanding of the clinoidal and proximal intradural ICA anatomy and its relationship to surrounding structures.

This will enable surgeons to more reliably predict the location of the ICA and its relationship to surrounding structures, decreasing the potential for vascular injury.

Conclusions: Patients with microadenomas had higher remission and lower complication rates following PEETS, emphasizing the necessity for early detection and treatment of pituitary adenomas.

PEETS is a discussion worthy method for microprolactinoma treatment. These can be locally aggressive with potential intracranial extension.

Traditionally these lesions have been treated using open surgical techniques, however recently endoscopic approaches have been implemented in hopes of minimizing morbidity.

We recorded the number of operations, estimated blood loss, extent of resection, any complications and length of hospital stay.

All are male with an average age of 16 years. Average follow up is All patients underwent pre operative tumor embolization.

One patient underwent an initial open transfacial approach and required a subsequent endoscopic approach. Patients underwent an average of 2. Mean EBL was cc.

A subtotal resection was achieved in all cases. Two patients underwent radiation therapy during the course of their treatment.

There were no mortalities. Open surgical resection can achieve good tumor control, but can be exceedingly morbid. Given the tendency for these lesions to regrow, multiple surgeries are often required.

We believe an endoscopic approach for subtotal resection in combination with pre operative embolization and post operative adjuvant treatment in select patients can achieve good tumor control while minimizing morbidity.

Numerical values were estimates from the french register of CNS tumors, the national institute of statistics, and published series of glioma survivals.

We report a new case in a pediatric patient. Methods: A 4 year old girl presented with generalized seizures. MRI of the brain revealed an extensive diffuse nonenhancing area of abnormal signal involving the right frontal and temporal lobes.

She was taken to surgery for biopsy, and returned to surgery eight months later for electrocorticography guided seizure focus resection.

Seizure frequency decreased to zero over the following three months. Compared with gemistocytic, protoplasmic astrocytomas have less potential to behave aggressively.

In two case series encompassing 18 patients, average age at presentation was 25 years. Most lesions were in the frontal or temporal lobes.

For 7 patients with unresectable lesions, biopsy was performed; all others underwent attempted gross total resection.

Five patients subsequently received radiation therapy and one also had chemotherapy. The youngest patient age 2 years at diagnosis died 36 months after subtotal resection without further adjuvant therapy; all others were alive with or without residual tumor 2 to months postoperatively.

One additional case report describes a 3 year old with diffuse leptomeningeal disease who died from tumor progression despite chemotherapy.

Although all patients presented with seizures, seizure outcomes have not been well documented. Our patient achieved seizure freedom.

Conclusions: Protoplasmic astrocytoma is a rare low grade glioma which can be associated with medically resistant epilepsy. Tailored surgery for unresectable lesions can be beneficial for seizure control.

Conclusions: Patients with silent DLGG are more likely to die from transformation of the silent DLGG to symptomatic glioma than dying from another cause with the silent DLGG, unless patient survival is expected to be less than 4 years.

This epidemiological argumentation supports early surgery for incidentally discovered glioma. To identify patients who had undergone surgery, we used brain tumor surgery ICD 9 codes.

We used the SAS statistical software package Version 9. For brain tumor patients treated without surgery For brain tumor patients treated with surgery 9.

The most common PSIs included postoperative respiratory failure, deep vein thrombosis, and sepsis. The total number of HACs associated with brain tumor patients was 13,, with 2.

For brain tumor patients treated without surgery 3. For brain tumor patients treated with surgery 7. The most common HACs included falls and trauma and pressure ulcers.

Conclusions: Patient safety and delivery of quality care is an important part of our national healthcare agenda.

These data may be used to determine individual institutional improvements or success by comparison. One of the molecular hallmarks of Glioblastomas is genomic instability, which leads to the development catastrophic mutations.

Thus, basic DNA repair mechanisms responsible for the preservation of genomic integrity could be impaired in Glioblastomas.

We have previously reported the detection of DNA sequences of the human neurotropic JC Virus and expression of its oncoprotein, T Antigen, in brain tumors of glial and neuroectoermal origin.

Bevacizumab has recently demonstrated encouraging anti tumor effect in the treatment of recurrent and progressive meningiomas. The imaging characteristics of meningiomas undergoing bevacizumab treatment have not been extensively described.

Methods: While undergoing systemic therapy on bevacizumab with a sustained intracranial response, a 55 year old man with a locally recurrent WHO grade III meningioma developed a biopsy proven left sided neck metastasis and radiographic findings consistent 40 Conclusions: Fluorescence guided resection for complex meningiomas have shown to be an effective intraoperative tool to achieve maximal citoreduction.

In meningioma lesions we assume that the breakage of the blood brain barrier increasing vascular permeability and by this mechanism the 5 ALA reaches the peritumoral area.

Results: The primary intracranial meningioma was a homogeneously, avidly enhancing extra axial mass on magnetic resonance imaging MRI. The recurrent intracranial lesion was isointense to surrounding brain on T1 imaging and hyperintense on T2 weighted images.

The mass was centered in the obliquus capitis inferior muscle and was associated with erosive bony changes. The neck lesion was isointense to muscle on noncontrast T1 imaging, and nearly isointense to gray matter on T2 weighted images.

There were four subcentimeter, nonenhancing parenchymal lung nodules appreciated on chest CT, consistent with pulmonary metastatic disease. Cranial hyperostosis in association with adult meningioma occurs frequently.

The osteopathophysiology of this phenomenon is poorly understood and controversial, with actual bone invasion by tumor or reactive changes due to adjacent tumor having been posited as explanations.

Metalloproteins have also been suggested as playing a role. Hyperostosing meningioma is rarely reported in children. Conclusions: This case illustrates the imaging appearance of intracranial anaplastic meningioma and extracranial metastases while on bevacizumab.

Further study of imaging characteristics of recurrent and progressive meningiomas while undergoing treatment with anti angiogenic therapies is warranted.

Methods: Following IRB approval, the medical record of a child with intracranial hyperostosing meningioma was abstracted for diagnostic, treatment and outcome details.

The medical literature on meningioma and hyperostosis conditions was surveyed. Fluorescence Guided Resection Of Complex Meningiomas Results: A 15 year old boy presented with progressive nausea, vomiting and headaches.

Gastroenterologic evaluations were negative and therapy for reflux disease was ineffective. Imaging revealed a lobulated solid cystic mass in the right frontal region, with overlying irregular cranial bone thickening.

Skull palpation revealed painless fullness without scalp changes. Via a large craniotomy flap, the tumor was found to be arising from the dura and adherent to the skull, without gross invasion.

The flap was hyperostotic and the inner table and cancellous bone were drilled out using a high speed air drill. The tumor was microsurgically completely resected and the bone flap was replaced.

The lesion showed classic syncytial features, yet with hypercellularity and an elevated MIB 1 index, consistent with atypical meningioma, W.

Tumor was identified in the bone curettings. Due to the higher grade histology and tumor in the bone, adjuvant radiation therapy was administered.

He remains in remission three years later. The extent of resection in intracranial brain tumors determine survival rate. For extra axial tumors, such as, meningiomas the usefulness of fluorescence guided surgery will help to achieve maximal resection in complex cases where occult tumor cells spreads beyond the arachnoid layer or in to bone structures.

Methods: We present an illustrative case of a 37 year old female with past medical history relevant for overweight and penicillin allergy. Her symptoms were characterized by headache, nausea, amaurosis fugax, left eye ptosis with facial asymmetry.

An MRI was done and a left frontal extra axial lesion was found. There were no surgical complications. She was discharged 4 days after the tumor resection.

Conclusions: Only a paucity of pediatric cases of hyperostosing meningioma have ever been reported. There is no reported correlation between hyperostosis and histologic tumor grade and bone invasion by tumor.

Our report confirms that this phenomenon occurs in children. The pathophysiologic mechanisms may be the same as in adults. We recommend ongoing reporting of this rare condition in youth, so as to inform of preferred management strategies.

Results: The patient did not experience any additional neurological deficits after surgery. There was no evidence of increased liver function test.

Currently the patient is seen in the outpatient clinic. Most of the general symptoms have remarkable improved.

Facial asymmetry has also been substantially reduced. We aimed to determine the clinical impact of histologically proven transformation. Methods: We retrospectively identified patients with anaplastic gliomas who had surgery at our center upon first radiographic progression.

We examined the impact of clinical and molecular factors on transformation and outcome. Results: Between and , 85 patients met study criteria; 24 with oligodendrogliomas, 22 with oligoastrocytomas, and 39 with astrocytomas.

Transformation was associated with shorter overall survival OS from initial diagnosis median OS 6. Conclusions: Fewer than half of radiographically progressive anaplastic gliomas transformed to glioblastoma histologically.

Transformation is associated with reduced OS from the time of diagnosis and from the second surgery. Tissue diagnosis may be warranted for prognostic counseling at the time of radiographic progression.

A newly emerged field, imaging genomics, links gene expression profiles with MRI phenotypes. Thus, an imaging genomic necrosis screen has the potential to uncover novel molecular determinants of cell death in GBM.

Here, we present the first comprehensive radiogenomic analysis using quantitative necrosis MRI volumetrics and large scale gene and microRNA expression profiling in GBM.

Gender specific analysis was performed and the top concordant genes and microRNAs correlated with high volumes of necrosis were further characterized using Ingenuity Pathway Analysis, whole genome transcriptional factor analysis, and cognate microRNA gene networks were created.

Results: Female patients demonstrated significantly lower volumes of necrosis than male patients. Thus, a gender specific analysis was chosen and revealed in both MRI and histopathology data that female patients with high necrosis had a significantly shorter survival compared to both females with lower necrosis or males with high necrosis.

Survival in males was not statistically different in patients with high versus low tumor necrosis. The survival data was concordant with the genomic analysis suggesting that predominantly MYC driven oncogenic pathways were associated with necrosis in female patients, while male patients showed a strong positive association of the MRI necrosis phenotype with the P53 tumor suppressor pathway.

Gender independent necrosis pathway analysis showed equal distribution of both tumor suppressors and oncogenes. Conclusions: Here, we propose a novel diagnostic method to screen for molecular correlates of necrosis in GBM.

Our findings suggest distinct oncogenic pathways promoting MRI and histopathology necrosis phenotypes in male versus female GBM patients.

In prior studies, depression has been associated with decreased quality of life and shorter overall survival. Antidepressant therapy is a widespread and generally well tolerated treatment of depression which can increase quality of life.

We investigated whether pharmacologic treatment of depression has an impact on overall survival. Univariate analysis isolated possible predictors of survival.

Results: Median survival was Analysis based on class of antidepressant was not significant. Multivariate analysis controlled for age, tumor grade, extent of resection, Karnofsky Performance Score, reoperation, antidepressant therapy, diabetes, radiation and temazolamide therapy.

Although this effect did not reach significance in multivariate analysis, the trend warrants further investigation. Prospective studies closely monitoring antidepressant treatment and its effects are necessary to evaluate the potential benefit of both improving quality of life and prolonging survival with a single therapy.

We investigated the feasibility of sonodynamic therapy for malignant glioma by low frequency ultrasound with 5 aminolevulinic acid 5 ALA , a precursor of protoporphyrin IX PpIX in heme synthetic process.

Methods: In vivo tumor model was made by inoculating human glioma cell line U87 MG subcutaneously in nude mice. The tumor was sonicated by 25 kHz ultrasound 4 hours following administration of 5 ALA.

The results showed the therapeutic effect of 25 kHz ultrasound for the glioma in 5 ALA administered tumor bearing mice by inducing apoptotic change of tumor cells.

Conclusions: This is a first report to elucidate the feasibility of therapeutic use of 25 kHz ultrasound in sonodynamic therapy using 5 ALA as a sonosensitizer precursor.

This may be a realistic intraoperative malignant gioma therapy in addition of tumorectomy, since 25kHz is a frequency of ultrasonic aspirator.

We leveraged this unique developmental system to interrogate lncRNA expression and function. By integrating data from chromatin state maps, custom microarrays, and FACS purified cells, we stringently identify lncRNAs with potential roles in adult neurogenesis, and accurately predict their expression patterns in the SVZ and OB.

More broadly, our data and workflow provide a uniquely coherent in vivo lncRNA analysis that will be relevant for future studies of lncRNAs in development and tumorigenesis.

This phenomenon, however, has seldom been documented with an imaging correlate and quantitative evaluation. Methods: The clinical and radiographic features, quantitative assessments, treatments, and outcomes were reviewed for two patients with lesions in the third ventricle, in which remitting clinical symptoms of raised intracranial pressure were either characteristic of or associated with intermittent ventriculomegaly on imaging.

Additionally, the few documented cases of intermittent obstructive hydrocephalus with concomitant intraventricular cysts are examined. Results: Two patients, a 3 month and a 9 year old male, presented with paroxysmal symptoms of raised intracranial pressure and imaging confirmation of varying ventriculomegaly with a third ventricular pineal and choroid plexus cyst, respectively.

Both were treated by a primary endoscopic cyst fenestration and remain without symptoms, complications, or placement of an indwelling shunt at 20 and 3 months of follow up, respectively.

Conclusions: Our cases add to a growing body of evidence that a normal sized ventricular system cannot rule out the diagnosis of intermittent hydrocephalus in a patient who presents both with symptoms suggestive of increased intracranial pressure and a lesion that can potentially obstruct CSF flow.

Additionally, an absence of intraventricular cysts on traditional CT or MR imaging should not automatically rule out the possibility of an intermittently obstructive cyst.

Our findings suggest that patients experiencing symptoms of raised intracranial pressure concomitantly with third ventricular cystic masses and normal sized ventricles should be offered cyst decompression.

On radiographic findings, these lesions may present as an osteolytic or osteoblastic skull lesions. Methods: We report a case of a 53 year old female who presented with a gradual onset exopthalmos of the right eye.

The plain radiographs of the skull showed hyperostosis af the right orbital roof and the lateral orbital wall. The computerized tomography CT scan revealed an extra axial, intradiploic orbital roof tumor involving the frontal and temporal bone.

Results: The tumor, including the surrounding normal bone, was totally excised by an extradural route using a basal fronto temporal craniotomy.

The histopathological study confirmed a meningotheliomatous meningioma. A split calvarial frontal bone graft was used to reconstruct the orbit.

The patient was discharged after 6 days. There is no evidence of recurrence after a follow up of 3 months. Conclusions: Intradiploic meningiomas are often asymptomatic, but can cause proptosis and neurological symptoms depending on their size and location.

Radiographic and clinical presentations generate diagnostic suspicion that may assist with preoperative planning. The majority of these tumors cause hyperostosis that may mimic meningioma en plaque, osteoma, osteosarcoma, Paget disease, and fibrous displasia.

The treatment of choise is resection, which is potentially curative. Tumors that cannot be compleely resected may be require adjuvant therapy, which may include radiation therapy, chemotherapy, or bisphosphonate therapy.

In non contrast enhancing gliomas, and to a lesser extent enhancing tumors, the T2 and FLAIR signals are important targets to determine target volumes for resection margins.

We hypothesized that intraoperatively obtained MRI T2 and FLAIR signal volumes might not reflect corresponding post operative volumes due to tumor edema after resection and brain manipulation.

Methods: We examined 12 low grade gliomas LGG, 9 low grade astrocytomas and 3 oligodendrogliomas and compared them to 13 high grade tumors HGG, 4 anaplastic astrocytomas, 3 anaplastic oligodendrogliomas, and 5 glioblastomas.

When all tumor grades are analyzed together similar trends are found. Conclusions: Postoperative FLAIR signal volumes are significantly lower and T2 signal volumes significantly higher than 44 Methods: We analyzed the relation between the sphenozygomatic suture and the marginal tubercle of the frontal process of the zygoma 60 dried skulls.

Minipterional craniotomy was performed in 10 cadaveric specimens. The approach was utilized to 18 sphenoid wing meningiomas.

Anterior to posterior sub periosteal dissection and retraction of the temporalis muscle, and avoiding cuts along the origin of the muscle allows excellent cosmetic outcome.

All 18 meningiomas 3 to 5 cm in size were successfully resected without morbidity or mortality through a 3.

Meningiomas A Population Based Perspective Conclusions: Minipterional approach is an excellent option to approach sphenoid wing meningiomas.

The minimally invasive access allows minimal soft tissue trauma, smaller bony opening, less pain, and excellent cosmetic outcome Quinn T.

We used this data to describe the current epidemiology of meningiomas in the United States between the years of and We also calculated survival rates for all malignant menginiomas.

Introduction: Fronto orbital minicraniotomy is the most commonly used minimally invasive approaches for anterior cranial fossa lesions. Methods: We describe our novel technique with the transpalpebral eyelid incision to obtain access to the anterior cranial fossa.

We describe the approach and technique of the transpalpebral eyelid incision in a step by step fashion and discuss the results of retrospectively analyzed eighteen cases.

Results: Meningiomas are the most common type of brain tumor in the United States, compromising There was an overall incidence rate of 7. They are more common in women than men incidence rates of 9.

They are more common in blacks than whites incidence rates of 8. For malignant menginiomas, there were 1, 5 and 10 year survival rates of Results: Incisions in the eyelid region should therefore be as horizontal as possible.

A relative safety zone; free of facial nerve branches was identified that exists up to 2. We apply knowledge of upper eyelid anatomy, which allow us to utilize an avascaular plane of dissection that maintains functionality of the eyelid and avoids disfiguring cosmetic results.

We describe the bony cuts necessary to complete our one piece fronto orbital approach. Complications in one patient who developed deep wound infection required re operation.

Conclusions: Though most menginiomas are not malignant, their frequency and potential resulting morbidity makes them of significant clinical and scientific relevance.

Awareness of the populations most at risk for these tumors assists physicians and scientists in focusing on developing new ways to serve these patient populations.

Mini Pterional Craniotomy: An Alternative Approach For Sphenoid Wing Meningiomas Conclusions: The transpalpebral approach provides dissection in natural anatomical planes, affords preservation of the frontalis muscle, avoids injury to nerve VII branches, and results in an excellent cosmetic outcome.

Khaled M. It provides the same microsurgical exposure as the standard frontotemporal approach. Corinna C.

The goal of our study is to identify which preoperative symptoms and MRI findings are correlated with specific postoperative outcomes in order to better counsel patients pre operatively.

Conclusions: The modified dural incisions are safe, easier to perform and close with lesser complications. We then used univariate and multivariate regression models to analyze the effect of several MRI characteristics including tumor volume, distance to optic chiasm, anterior cerebral artery encasement, paranasal sinus invasion, and sellar invasion on preoperative symptoms and postoperative outcomes, including complication rate and tumor recurrence.

Tumors with nasal sinus invasion are significantly more likely to cause postoperative surgical complications, and tumors with ACA encasement are associated with a higher likelihood of both postoperative complications and tumor recurrence.

In terms of predicting surgical complications, nasal sinus invasion and ACA encasement are associated with higher risk profiles when surgery becomes necessary.

While making these dural incisions we encountered certain difficulties whole opening the dura, while performing the procedure and during closure of dural incisions.

To overcome these difficulties we modified some of these incisions. The potential benefits and possible complications along with outline of various dural incisions for cranial and spinal tumors will be presented supplemented by personal experience.

Potentially actionable molecular alterations that might be driving the growth of these neoplasms have been reported. To better understand these molecular alterations and their correlation with clinical outcomes in cancer patients, we developed a clinical sequencing program, UNCSeqTM, capable of reporting a broad spectrum of clinically actionable mutations.

Methods: All adult patients with brain tumors including meningioma undergoing surgery are offered enrollment; the collected tumors undergo next generation sequencing of tumor DNAs.

Confirmed, actionable molecular targets are identified and are made available for clinical use. Other potential targets and genetic alterations are also evaluated but not reported to the treating physicians.

Results: 17 patients have been enrolled and will be discussed. As of the submission date, 7 patients have been sequenced and 5 confirmed.

Next generation sequencing can identify targets, providing a personalized approach to meningioma therapy.

Characterization of Haitian neuro oncologic disease patterns will enable productive allocation of neurosurgical resources and training efforts. This study sought to describe disease presentation of patients with CNS masses admitted to a Haitian emergency room ER.

Ethical approval was obtained at both US and Haitian institutions. De identified data on patients with CNS masses was collected using Microsoft Excel and analyzed using standard statistical analysis for disease presentation and prevalence.

Conclusions: Though this is an ongoing study and more sample size is needed for conclusion, our preliminary data indicates that in most of our GBM cases, notch signalling contributes significantly to the process of tumorigenesis, strongly supporting this pathway as a promising therapeutic target for this malignancy.

Results: During the study period, there were ER admissions. A single patient had head CT without and with contrast; two had non contrast CT.

In all 3 cases, images were consistent with brain tumor. No images were obtained in 2 patients; one of which had an exploratory craniotomy revealing a subdural empyema.

Seizures were the most common presenting symptom. While Haitian CNS tumor prevalence cannot be determined by this survey, the data indicates the need to further study this disease pattern.

Limitations on availability of diagnostic tools and neurosurgical resources are significant barriers to the identification and management of patients in Haiti with CNS tumors.

The primary objective is to assess the safety and feasibility in newly diagnosed GBM. This Phase I study includes three cohorts of at least three evaluable patients per cohort.

In spite of optimal treatment, median survival is less than 15 months. Aberrant activation of notch signalling is reported in many human malignancies including GBM and targeted therapy in this disease with pharmacological inhibitors of this pathway is under clinical trial.

Stratification of GBM patients on the basis of notch pathway activity is crucial for targeted therapy with the appropriate inhibitors. For this reason, we sought to classify a series of GBM cases in eastern India based on their expression patterns of HES 1, a key notch target gene.

Toxicity has been minimal and well tolerated. We sub classified only the GBM cases into three subgroups based on their HES 1 gene expression levels High, moderate and low Notch pathway activity 47 All patients experience a recurrence after first line therapy, so improvements in both first line and salvage therapy are critical to enhancing quality of life and prolonging survival.

Temozolomide is an oral alkylating agent often used along with radiation therapy after initial GBM resection. A phase I clinical research trial was designed to test the hypothesis that temozolomide can be safely used by direct intracranial superselective intraarterial cerebral infusion SIACI to increase delivery to the brain and ultimately enhance survival of patients with primary GBM.

Methods: Subjects with primary high grade glioma were treated with mannitol followed by a single SIACI of temozolomide. The maximal tolerated dose has not been reached.

Two patients reported mild headaches and nausea within the first month post infusion. One seizure was reported at 1 week post infusion.

However, particular caution must be used around small end artery infusion to prevent streaming effect which can lead to high level of toxic doses of temozolomide.

They are most commonly encountered in the pediatric population. Due to their proximity to vital neural and vascular structures they pose a significant operative challenge to the neurosurgeon and a malignant clinical course to the patient.

The neurosurgical community has questioned the feasibility of total resection with acceptable morbidity.

The authors present a novel paradigm and case illustration in the treatment of prenatally diagnosed craniopharyngiomas aimed at reducing operative morbidity.

We also review the relevant literature supporting errors in neurulation as the cause of these clinically malignant but histologically benign tumors of childhood.

Methods: We report the case of a prenatally diagnosed craniopharyngioma that has been completely resected without any operative morbidity to illustrate a novel paradigm in management.

Results: An ultrasound at 30 weeks gestation demonstrated a large suprasellar lesion. The patient was born at 35 weeks of gestation via spontaneous vaginal delivery with poor feeding and decreased activity.

He underwent delayed total surgical resection at four months of age without associated morbidity. Conclusions: To our knowledge this is the seventh case of a prenatally diagnosed craniopharyngioma reported in the literature that underwent attempted resection.

The literature has questioned the feasibility of total resection with acceptable morbidity. The trend however based on current literature has advocated attempted total resection.

We present this case to support the feasibility of total resection with limited to no surgical morbidity and postulate that the standard of care should be gross total resection.

The most frequent mutations are missense but the mechanism of tumorigenesis is not known. Methods: We investigated the protein stability and intrinsic E3 ligase function of mutant pVHL that carries pathogenic mutations.

Mutant pVHL is unstable and degraded contemporarily with translation. However, mutant pVHL retains its E3 ligase function, including hypoxia inducible factor degradation.

We found that premature pVHL degradation is due to misfolding and imbalance of chaperonin binding. Conclusions: These findings provide direct insight into the pathobiology of VHL associated tumors, as well as elucidate a new treatment paradigm for VHL.

Successful application of this technique is considered to depend on the level of experience of the surgical team.

In this study the extent of glioma resection EOR is quantitated and compared between a surgical team with 15 and 2 years of experience with stimulation mapping.

Introduction: The purpose of this study was to define recurrence rates and timing of recurrence following endoscopic pituitary adenoma resection to aid in management of imaging surveillance.

Methods: Adult patients with glioma were consecutively included who had resective surgery targeted at the MRI FLAIR hyperintense volume and limited by functional boundaries.

The senior surgical team contributed 56, and the junior team 60 consecutive patients. The surgical technique was very similar including the stimulation mapping.

Because the localization of tumor within the brain is essential in comparing EOR, a novel approach was applied using resection maps that quantitate and compare the likelihood of resection throughout the brain at 1mm resolution.

Considerations for spatial dependence of voxels and multiple comparisons were taken into account. Results: The patient cohorts were comparable in age, preoperative tumor volume, lateralization, and lobe localization.

The resection maps detected 0 of Conclusions: The EOR for patient cohorts can be quantitated using resection maps. These resection maps are similar for surgical teams with 2 and 15 years of experience in stimulation mapping.

This indicates that stimulation mapping is a robust and reproducible technique and supports more universal implementation. Methods: A retrospective review was conducted from November to present for patients undergoing purely endoscopic resection for pituitary adenoma by a single surgeon team.

Patients were followed with serial imaging occurring yearly with one intermediate scan in the first year.

Progression was defined as enlargement on serial imaging or biochemical failure. Data was analyzed using Fisher exact test to determine significance.

Six tumor recurrences occured on or after 5 years. Although gross total resection proved to offer benefit in non secreting tumors, there was no significant difference in recurrence relating to resection in secreting tumors.

Withdrawn 49 The shape and position of cortex white matter architectural volume units can be used to define if the tumor is growing in a single area or spreading to other areas.

Methods: Seventy four patients with diffuse gliomas Grade II IV with serial MR imaging and at least 2 years of follow up were retrospectively reviewed by a consensus of 3 9 neuroradiologists, blinded to survival data.

This was compared to other predictors of survival. Conclusions: Gliomas' shape and location is an independent survival predictor much like the staging of other cancer sites.

This strategy is best demonstrated in common locations, such as near the central sulcus and sylvian fissures, where well defined white matter "stalks" course perpendicular to deep fibers.

This parcellation strategy could group outcomes for research, improve communication and facilitate treatment planning.

We sought to identify preoperative risk factors for CSF leaks and meningitis. Methods: The results of 98 consecutive endoscopic endonasal surgeries performed from were retrospectively analyzed for preoperative comorbidities, intraoperative techniques, and postoperative care.

Univariate and multivariate analysises were performed. Results: Pathologies addressed included pituitary adenoma, meningioma, esthesioneuroblastoma, adenocarcinoma, chondrosarcoma, chordoma, lymphoma, squamous cell carcinoma and angiofibroma.

Conclusions: In this series of endoscopic transphenoidal surgeries preoperative BMI and age are two predictive values for CSF leak and infection.

Risks associated with complex surgical resections when combining open and endoscopic approaches could be minimized by staging these procedures.

After implantation into the brain of nude mice, GSCs formed intracranial tumors more frequently after co culture with GA hMSCs than after co culture with controls.

Conclusions: Our results have shown that surgery for cerebral metastases in the central area can be done safely and improve or stabilize the neurological function of most patients.

Surgery also promptly addresses symptoms related to cerebral edema, mass effect, and midline shift. Microsurgical resection of central area metastases should be a treatment option for patients with single or multiple lesions who present a focal neurological deficit.

In this study, we examined the useful of photodiagnosis PD by 5 ALA for the cases during brain tumor surgery. Methods: In our institute, patients was performed tumor resection using 5 ALA from to The patients received oral doses of 5 ALA 2 hours before induction of anesthesia.

Withdrawn Results: 79 cases showed positive responses, and 21 cases showed negative responses. Malignant brain tumors i.

On the other hand, pilocytic astrocytomas, diffuse astrocytomas, and recurrent high grade gliomas, etc. Central area lesions are often treated with whole brain radiation therapy WBRT or stereotactic radiosurgery SRS because of the concern for causing post operative neurological deficits.

Surgery has an important role in acutely alleviating symptoms from cerebral edema and mass effect that radiation cannot address.

Additionally, there is evidence in the literature that radiation therapy carries significant risk of complications.

We present a series of patients who were symptomatic from a central area metastasis and underwent surgical excision. However, the sensitivity of PD varies among tumors, therefore it is important to use this technique in combination with the other intraoperative support tools.

Methods: During a 2 year period from to , 17 consecutive patients harboring a cerebral metastasis within the central area underwent microsurgical resection.

Cases were selected by reviewing all cases of cerebral metastasis by the senior author and identifying those patients with a central area lesion that was surgically removed.

The prerequisite for neurosurgical treatment was stable systemic disease and life expectancy greater than 6 months as determined by the patient oncologist.

Patients also were required to harbor a symptomatic lesion within the central area, defined as the pre or post central gyri. Results: We present the 3 month neurological outcome for this group of patients.

Surgery was uneventful and without any severe peri operative complications in all 17 patients. Gadolinium enhanced T1 weighted MRI scans obtained on post operative day 1 revealed a gross total resection in all patients.

At 3 month follow up, symptoms had improved or been stabilized in Portions of tumor clearance may occur by lysis.

However, natural killer NK cells may target infected glioma cells and restrict lytic replication. NK cell cytotoxicity is regulated by activating and inhibitory ligands on cell surfaces.

In a large, single center cohort, we tested the hypothesis that 2 distinct subtypes of anaplastic meningiomas, those that arise de novo and those that progress from lower grade tumors, exist and exhibit different clinical behavior.

Methods: Pathology reports and clinical data of 37 patients treated between to for anaplastic meningioma at MSKCC, were retrospectively reviewed.

Patients were divided into those whose tumors arose de novo and those whose tumors progressed from previously documented benign or atypical meningiomas.

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