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DIA and DIG are rare, infantile, supratentorial neoplasms that usually occur in children before 2years of age and are exceedingly rare in older age groups. They appear as hypodense, cystic masseswith solid components showing dural attachment on neuroimaging. They are characterized byreticulin-rich spindle cell stroma containing connective tissue due to meningeal involvement,microscopically. These tumors have potential for misdiagnosis because they contain varyingproportions of neoplastic glial, neuronal and poorly differentiated cells, which causes them to have a“small round blue cell tumor” like appearance, though they have a good prognosis if correctlydiagnosed. The current study report two cases diagnosed at our institution that had very latepresentation with varying complaints which challenged the normally believed dictum of these tumorsbeing entirely infantile.

Background Primary meningeal melanomatosis is a rare leptomeningeal tumor, and the diagnosis is challenging due to nonspecific clinical symptoms and radiologic findings. Case Description A 21-year-old man presented with recurrent seizure and impaired memory. Cranial magnetic resonance imaging showed obvious brain atrophy with bilateral extensive meningeal enhancement in the supratentorial region. Diffusion-weighted imaging and fluid-attenuated inversion recovery showed slightly hyperintensive signals in the cortex. Microscopic examination revealed invasion of pigment into the Virchow-Robin space and cortex. Immunohistochemical examination of biopsy samples showed that cells were immunopositive for HMB45 and S-100 and immunonegative for melan-A with a Ki-67–positive percentage of 3%. No obvious atypia or nuclear mitosis was observed. Pathohistologic results of biopsied meninges confirmed the diagnosis of diffuse meningeal melanomatosis. The disease was aggravated with the occurrence of brain atrophy, recurrent seizure, and declined higher cortical function. Conclusions This case report illustrates that brain atrophy in meningeal melanomatosis is associated with a progressive decline of higher cortical function.

Previously undiagnosed obstructive sleep apnea (OSA) is a known contributor to negative postoperative outcomes. The STOP-Bang questionnaire is a screening tool for OSA that has been validated in both medical and surgical populations. The authors have previously studied this screening tool in a brain tumor population at 30 days. The present study seeks to investigate the effectiveness of this questionnaire, for predicting 90-day readmissions in a population of brain tumor patients with previously undiagnosed OSA.Included for analysis were all patients undergoing craniotomy for supratentorial neoplasm at a multihospital, single academic medical center. Data were collected from supratentorial craniotomy cases for which the patient was alive at 90 days after surgery (n = 238). Simple logistic regression analyses were used to assess the ability of the STOP-Bang questionnaire and subsequent single variables to accurately predict patient outcomes at 90 days.The sample included 238 brain tumor admissions, of which 50% were female (n = 119). The average STOP-Bang score was 1.95 ± 1.24 (range 0-7). A 1-unit higher increase in STOP-Bang score accurately predicted 90-day readmissions (odds ratio [OR] = 1.65, P = 0.001), 30- to 90-day emergency department visits (OR = 1.85, P 0.001), and 30- to 90-day reoperation (OR = 2.32, P 0.001) with fair accuracy as confirmed by the receiver operating characteristic (C-statistic = 0.65-0.76). However, the STOP-Bang questionnaire did not correlate with home discharge (P = 0.315).The results of this study suggest that undiagnosed OSA, as evaluated by the STOP-Bang questionnaire, is an effective predictor of readmission risk and health system utilization in a brain tumor craniotomy population with previously undiagnosed OSA.

Despite research indicating that patients with non-English primary language (NEPL) have increased hospital length of stay (LOS) for craniotomies, there is a paucity of neurosurgical research examining the impact of language on short-term outcomes. This study sought to evaluate short-term outcomes for patients with English primary language (EPL) and NEPL admitted for resection of a supratentorial tumor.Using the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project New Jersey State Inpatient Database, this study included patients 18-90 years old who underwent resection of a supratentorial primary brain tumor, meningioma, or brain metastasis from 2009 to 2017. The primary outcomes were total, preoperative, and postoperative LOS. Secondary outcomes were complications, mortality, and discharge disposition. Univariable and multivariable analyses compared Spanish primary language (SPL), non-English non-Spanish (NENS) primary language, and EPL groups.A total of 7324 patients were included: 2962 with primary brain tumor, 2091 with meningioma, and 2271 with brain metastasis. Patients with SPL (n = 297) were younger and more likely to have noncommercial insurance, lower income, and fewer comorbidities. Patients with NENS (n = 257) had similar age and comorbidities to the EPL group but had a greater proportion of noncommercially insured and low-income patients (P0.001). Multivariable analysis showed that patients with NENS had increased postoperative LOS (adjusted incidence rate ratio, 1.10; P = 0.008) and higher odds of a complication (adjusted odds ratio, 1.36; P = 0.015), and patients with SPL had higher odds of being discharged home (adjusted odds ratio, 1.55; P = 0.017).Patients with NEPL have different short-term outcomes after supratentorial tumor resection that varies based on primary language. More research is needed to understand the mechanisms driving these findings and to clarify unique experiences for different populations with NEPL.

Background and importance Data supporting the use of electrocorticography (ECoG) monitoring during electrical stimulation in awake craniotomies for resection of supratentorial neoplasms is robust, but its applicability during active resection is often limited by the inability to keep the array in place. Given the known survival benefit of gross total resection in glioma surgery, novel approaches to surgical monitoring are warranted to maximize safe resection and optimize surgical outcomes in patients with glioblastoma. Clinical presentation A 68-yr-old right-handed woman presented to the emergency department with confusion. Imaging studies revealed a bifrontal intra-axial brain lesion. She underwent a left-sided awake craniotomy procedure with cortical and subcortical mapping. During surgical resection, multiple electrographic seizures were detected on continuous ECoG monitoring with a customized 22-channel high-density hollow circular array. She remained without clinical evidence of seizures at 3 mo after surgery. Conclusion We report a unique case of serial electrographic seizures detected during continuous intraoperative ECoG monitoring during active surgical resection of a glioblastoma using a novel circular hollow array during an awake craniotomy. The use of continuous ECoG monitoring during active resection may provide additional data, with potential influence in outcomes for patients undergoing resection of high-grade glial neoplasms.

Leptomeningeal metastatic disease (LMD) occurs in 30–50% of newly diagnosed and recurrent pediatric malignant cerebellar tumors and 20–45% of malignant supratentorial tumors. Radiation and chemotherapy often cause substantial long-term neurotoxicity and outcomes remain poor for patients with LMD. At recurrence, LMD is generally minimally responsive to conventional therapies. Immunovirotherapy with engineered oncolytic HSV-1 G207 has emerged as a promising treatment for children with high-grade brain tumors. G207 infects and kills tumor cells while sparing normal cells and stimulates a robust anti-tumor immune response. Intratumoral G207 inoculation demonstrated safety and preliminary efficacy in a pediatric Phase 1 trial in recurrent/progressive high-grade glioma (NCT02457845), and a Phase 2 trial (NCT04482933) is forthcoming. Additionally, a Phase 1 trial of intratumoral G207 in recurrent/progressive malignant pediatric cerebellar tumors is ongoing (NCT03911388). While intratumoral inoculation delivers G207 directly to a primary tumor, it requires neurosurgical procedures thereby limiting repeat doses. Thus, we sought to establish the safety and efficacy of intraventricular G207. Utilizing an immunocompetent, HSV-sensitive murine strain, we determined that a standard 1x107 plaque-forming units (PFU) dose of G207 resulted in damage to the ependymal lining. However, interferon induction with an intraventricular low-dose (1x104 PFU) of G207 or polyinosinic-polycytidylic acid (poly I:C), a toll-like receptor 3 agonist, three days prior to standard treatment dose protected the ependymal lining. This approach enabled safe delivery of multiple subsequent doses. Importantly, with these protective measures, G207 significantly prolonged survival in pediatric patient-derived xenograft models and an immunocompetent murine LMD model of group 3 medulloblastoma, the most aggressive and fatal subtype. Collectively, these data indicate that toxicity from intraventricular G207 can be safely mitigated prior to a therapeutic dose, and that intraventricular G207 effectively targets group 3 medulloblastoma including LMD. These findings provide support for clinical translation of intraventricular G207.

Ependymoma with YAP1-MAMLD1 fusion is a rare, recently described supratentorial neoplasm of childhood, with few cases published so far. We report on 15 pediatric patients with ependymomas carrying YAP1-MAMLD1 fusions, with their characteristic histopathology, immunophenotype and molecular/cytogenetic, radiological and clinical features. The YAP1-MAMLD1 fusion was documented by RT-PCR/Sanger sequencing, and tumor genomes were studied by molecular inversion probe (MIP) analysis. Significant copy number alterations were identified by GISTIC (Genomic Identification of Significant Targets in Cancer) analysis. All cases showed similar histopathological features including areas of high cellularity, presence of perivascular pseudo-rosettes, small to medium-sized nuclei with characteristic granular chromatin and strikingly abundant cells with dot-like cytoplasmic expression of epithelial membrane antigen. Eleven cases presented features of anaplasia, corresponding to WHO grade III. MRI showed large supratentorial multinodular tumors with cystic components, heterogeneous contrast enhancement, located in the ventricular or periventricular region. One of two variants of YAP1-MAMLD1 fusions was detected in all cases. The MIP genome profiles showed balanced profiles, with focal alterations of the YAP1 locus at 11q22.1-11q21.2 (7/14), MAMLD1 locus (Xp28) (10/14) and losses of chromosome arm 22q (5/14). Most patients were female (13/15) and younger than 3 years at diagnosis (12/15; median age, 8.2 months). Apart from one patient who died during surgery, all patients are alive without evidence of disease progression after receiving different treatment protocols, three without postoperative further treatment (median follow-up, 4.84 years). In this to date, largest series of ependymomas with YAP1-MAMLD1 fusions we show that they harbor characteristic histopathological, cytogenetic and imaging features, occur mostly in young girls under 3 years and are associated with good outcome. Therefore, this genetically defined neoplasm should be considered a distinct disease entity. The diagnosis should be confirmed by demonstration of the specific fusion. Further studies on large collaborative series are warranted to confirm our findings.

BACKGROUND: Neurofibromatosis type 1 (NF1) has been identified as a predisposing factor in the development of pilocytic astrocytoma (PA), a common benign central nervous system tumor. Although this is a common association, simultaneous development of multiple lesions is an infrequent finding, especially in nonoptic and hypothalamic locations. CASE DESCRIPTION: A 41-year-old female patient with NF1 and uncontrolled human immunodeficiency virus (HIV) type 1 infection presented with a first generalized seizure and associated headache and ataxia. Imaging studies revealed 2 large intra-axial PAs, nodular-cystic in the supratentorial compartment and solid in the infratentorial compartment. Both lesions were treated by gross total resection in 2 surgeries performed 1 week apart. Despite their different imaging patterns, the tumors were histologically and genetically identical. CONCLUSIONS: We present a unique case involving 2 histologically and genetically identical PAs occurring simultaneously in supratentorial and infratentorial locations. We suggest that an intrinsic predisposition to tumor development in patients with NF1 might have been enhanced by the HIV-related immunosuppression in this case. Strict oncologic surveillance is essential in patients with a tumor predisposition syndrome combined with immunosuppression. info:eu-repo/semantics/publishedVersion

Background Pediatric cerebral ganglioneuroblastoma is an exceedingly rare tumor. Case Description We describe the case of a 4-year-old boy with sudden mental status decline who was found to have a large intracranial lesion with intraventricular extension. Conclusion Management of the case and pathologic findings are discussed, along with a review of the literature on this rare entity.

Purpose Intensive multi-modal regimens have improved survival for patients with atypical teratoid rhabdoid tumor, however relapse rates remain high. A better understanding of clinical and pathologic features associated with tumor relapse is critical to risk-stratifying patients. Patients and Methods ACNS0333 treatment consisted of multi-agent chemotherapy, high-dose chemotherapy, and radiation therapy, lasting approximately 6 months. Variables including patient age, sex, tumor location, M-stage, degree of resection, order of therapy, germline status, and molecular subgroup were analyzed. Cumulative incidence (CI) of event free survival due to relapse was evaluated for each variable. Results Thirty-three of 65 evaluable patients had tumor relapse. For the entire cohort, the CI of relapse was 21.8% at 6 months, 40.6% at one year and 50.3% at 4 years. For patients with infratentorial tumors, CI of relapse was 26.3%, 34.2% and 37.2%, at 6 months, 1 and 4 years respectfully compared to 15.3%, 49.9%, and 69.7% for those with supratentorial tumors (p 0.051). Patients with SHH subtype had no relapses in the first 6 months and CI of relapse of 37.5% at 4 years, while those with TYR and MYC subgroups had CI of relapse of 33.3% and 26.7% at 6 months and 46.3% and 73.3% at 4 years respectfully (p 0.088). Patients with germline mutations had a cumulative incidence of relapse of 20% at 6 months and 60% at 12 months compared to 22.6% and 37.7% respectfully for those without. No obvious trends were noted based on other analyzed variables. Conclusions ACNS0333 was not powered to determine prognostic indicators of relapse, however, this data suggest interesting trends based on tumor location, subtype and germline status. Infratentorial location and SHH subtype maybe associated with lower risk of relapse. Larger data sets must be compiled to further investigate these variables, perform multivariate analyses and inform risk-stratification on future trials.

Ependymoma is the third most common pediatric primary brain tumor. Ependymomas are categorized according to their locations and genetic abnormalities, and these two parameters are important prognostic factors for patient outcome. For supratentorial (ST) ependymomas, RELA fusion-positive ependymomas show a more aggressive behavior than YAP1 fusion-positive ependymomas. Extracranial metastases of intra-axial neuroepithelial tumors are extremely rare. In this paper, we report a case of aggressive anaplastic ependymoma arising in the right frontoparietal lobe, which had genetically 1q25 gain, CDKN2A homozygous deletion, and L1CAM overexpression. The patient was a 10-year-old boy who underwent four times of tumor removal and seven times of gamma knife surgery. Metastatic loci were scalp and temporalis muscle overlying primary operation site, lung, liver, buttock, bone, and mediastinal lymph nodes. He had the malignancy for 10 years and died. This tumor is a representative case of RELA fusion-positive ST ependymoma, showing aggressive behavior.

We investigated the functional status of adult supratentorial superficial low-grade glioma (ASS-LGG) after surgery and analyzed its relevant factors to guide the therapeutic strategy and improve the life quality of these patients. Clinical materials from January 2008 to December 2010 in 104 adults with ASS-LGG were analyzed retrospectively. The follow-up period ranged from 6 months to 1.5 years. The logistic regression was used to evaluate the preoperative and postoperative variation of functional status in patients to disclose the relevant factors affecting postoperative functional status, such as age, gender, the duration of symptom, size and location of the tumor, hemisphere, resection degree, and tumor pathologic grade and preoperative Karnofsky performance status (Pre-KPS). Four out of nine candidate factors are related to the postoperative functional status. They are age less than 40 years, the size of tumor less than 5 cm in diameter, tumor located in the right hemisphere, and limited resection of tumor in the eloquent area. It seems more meaningful to evaluate the functional status of the patients with ASS-LGG on the basis of these clinical features, involving age, tumor size, location, and extent of resection.

The Stupp protocol of post-resection external beam radiation therapy and concomitant temozolomide is the standard of care for patients with newly-diagnosed glioblastoma, with expanded use in anaplastic astrocytoma. However, the optimal interval between surgery and these adjuvant therapies, and its impact on survival, is unknown. To investigate this, de-identified claims from a large, private health insurance database were queried to identify adult patients who underwent index craniotomy for resection of a supratentorial neoplasm during the period 2005-2014 and began postoperative radiation and temozolomide within 13 weeks of surgery. A total of 2535 patients were assigned to groups based on interval from surgery to first radiation treatment of up to 4 weeks, 4-6 weeks, or 6-13 weeks. Of these, 1098 patients began radiation treatment within 4 weeks of craniotomy, 1019 between 4 and 6 weeks, and 418 between 6 and 13 weeks. There was significant regional variation in treatment schedule in the United States. Survival was calculated based on time from first craniotomy to death. Kaplan-Meier plot and multivariate Cox proportional hazard regression demonstrated a statistically significant association between earliest postoperative radiation and decreased survival (hazard ratio 1.31), along with older age and male sex. Earlier initiation of postoperative radiation for high-grade glioma is not associated with increased survival. Rather, beginning radiation treatment within 4 weeks of craniotomy was associated with significantly worse survival compared to initiation of treatment 4-13 weeks after craniotomy. This is the largest population-based study to date regarding timing of Stupp protocol initiation.

Intraoperative electrophysiology is increasingly used for various lesion resections, both in adult and pediatric brain surgery. Subcortical mapping is often used in adult surgery when lesions lie in proximity to the corticospinal tract (CST). We describe a novel technique of continuous subcortical mapping using an electrified Cavitron UltraSonic Aspirator (CUSA) in children with supratentorial lesions.We evaluated the method of subcortical mapping using a CUSA as a stimulation probe. Included in this study were children (18 years of age) with supratentorial lesions in proximity to the CST in which the CUSA stimulator was applied. Data were collected retrospectively.Eleven children were included. Lesions were located in the thalamus (3), basal-ganglia (2), lateral ventricle (1), and convexity (5). Lesions included low-grade gliomas (6), arteriovenous malformation (1), cavernoma (1), cortical dysplasia (1), ependymoma grade II (1), and high-grade glioma (1). Seven patients had positive mapping responses to CUSA-based stimulation at various stimulation intensities. These responses led to a more limited resection in 5 cases. There were no complications related to the mapping technique.Continuous CUSA-based subcortical stimulation is a feasible mapping technique for assessing proximity to the CST during resection of supratentorial lesions in children. Future studies should be performed to better correlate the current threshold for eliciting a motor response with the distance from the CST, as well as the effect of age on this technique.

Enterogenous cysts (ECs) are endodermal lesions resulting from splitting anomalies in the neuroenteric canal. We report the case of a 64-year-old patient who presented with a sudden headache followed by collapse. Brain computed tomography revealed a hyperdense lesion in the anterior part of the third ventricle with obstructive hydrocephalus. A presumptive diagnosis of colloid cyst was made and he underwent a right transcortical approach for lesion resection. The histopathological examination revealed an EC. ECs are common lesions in the cervical-thoracic spine but rare in the supratentorial compartment with only two previously described cases occurring in the third ventricle.

INTRODUCTION In the previous WHO classification of central nervous tumors, the supratentorial tumors comprise small round blue cells with aggressive clinical features had been defined as primitive neuroectodermal tumor (PNET). Recent molecular analysis revealed that they do not belong to a single entity, but they are re-classified as the tumors of other well-defined tumors and newly defined tumor species. These facts were reflected to the new classifications. While, there are few studies those showed the re-consideration of treatments for tumors diagnosed as so-called PNET. In this study, we propose the optimization of treatments for tumors diagnosed by the new classification to clarify which treatments were effective for the tumors those were diagnosed as PNET. MATERIALS AND METHODS The tumor samples diagnosed as so-called PNETs were analyzed. The molecular information was extracted from tumor specimens. We used high throughput analysis with microarray, FISH, and immunohistochemistry. They all had treated in our institution in last 6 years and their clinical courses were followed by medical records. Informed parental consent was obtained from their guardians and this study was approved by the institutional review board of Juntendo university. RESULTS Nine tumor samples were able to be analyzed and they are re-classified into high-grade glioma, neuroblastoma, sarcoma, embryonal tumors with multilayered rosettes, C19MC altered (ETMR). They resembled each other closely in morphology, and therefore, it was not able to be classified by histopathological findings. There was a case of pineoblastoma, whose molecular background suggested that the tumor was re-classified into neuroblastoma. In terms of treatments, we have succeeded in neuroblastoma cases so far, ETMRs were required multiple surgeries and radiations to maintain remissions. CONCLUSIONS Re-classification of diagnosis based on the molecular background is necessary to clarify the optimization of treatments for pediatric brain tumors, and the comprehensive methods is required. We present our methods for molecular diagnosis in clinical field and future plans.

In the United Kingdom widespread adoption of day-case image-guided biopsy (DIB) for brain tumour has yet to develop. We review a decade of experience of DIB for suspected supra-tentorial brain tumour and recommend discharge criteria for patients post-operatively. 30-day complications, post-operative admissions into hospital and patient satisfaction are examined. METHODS Published protocols and procedures for DIB of brain tumours were used. Tissue samples were sent for fixed histological preparation without intraoperative neuropathological assessment. All patients undergoing an image-guided biopsy for tumour were retrospectively identified from operative logbooks (01/10/2006–30/09/2016), and information recorded from online records. Patients completed satisfaction questionnaires. RESULTS 706 image-guided biopsies for supratentorial tumour were performed of which approximately 60% were identified pre-operatively as candidates for DIB. 92% of DIB patients were successfully discharged 6 hours postoperatively. 4.5% of DIB patients were admitted directly from the day-case unit following identification of a postoperative haematoma >2 cm diameter on CT head performed at 4 hours. 3/401 DIB patients (< 1%) required surgical evacuation for the haematoma, all made a full recovery, with no delay to commencing their oncological management. A diagnostic accuracy of 98% was achieved. Overall 90% of patients were satisfied about the timing of their discharge from hospital and 92.5 % felt they had enough medical support following discharge. DISCUSSION Conscious sedation with enhanced recovery techniques, lack of intra-operative neuropathological analysis and a stream lined service with robust communication between patients, carers/families and the oncology allied medical professionals has ensured that DIB for diagnosis of tumour is safe, reliable and feasible for most patients and is not associated with increased morbidity or mortality. The procedure is well tolerated with good patient satisfaction. We recommend that patients with a good pre-operative functional baseline, requiring a supra-tentorial biopsy are offered day-case surgery in a dedicated unit specialising in this procedure.

Young age represents an adverse prognostic factor in children with ependymomas. Their treatment is challenging since beneficial therapeutic options are limited. As ependymomas are considered a biologically heterogeneous group we aimed to characterize infant ependymomas in respect to their histological and genetic features. We analyzed 28 ependymomas in children younger than 18 months at diagnosis treated according to HIT2000-E protocols in which irradiation was postponed until the age of 18 months. All cases underwent neuropathological review, including immunohistochemical characterization. Genome-wide copy number alterations (CNA) were assessed by molecular inversion probe assays and RELA and YAP1 fusions were detected by RT-PCR and sequencing. All infant ependymomas were anaplastic (WHO grade III). Complete resection was accomplished in 57% of cases. 75% of cases were located in the posterior fossa, all of which showing loss of H3-K27me3, characteristic for PFA ependymomas. CNA analysis showed a stable genome in all cases. No gain of chromosome 1q was observed, an adverse prognostic marker in PFA tumors of older children. After a median follow-up of 5.4 years, 71% relapsed, and 43 % died. Seven ependymomas occurred in the supratentorial region of which in only two cases a complete resection could be achieved. Four tumors carried C11orf95-RELA fusions and two cases typical YAP1-MAMLD1 fusions (one case, not analyzable). The RELA-fused cases did not display CDKN2A loss as an adverse indicator of prognosis in this disease entity. Although 43% of infants with supratentorial ependymomas relapsed, all patients survived (median follow-up, 8.0 years). Infant ependymomas seem to consist of three biological entities: supratentorial tumors carrying RELA or YAP fusions and PFA ependymomas. The latter showed a particularly unfavorable outcome even though chromosome 1q gain was not present. Further biological studies are warranted in these neoplasms to identify prognostic markers and suitable targets for a more effective treatment.

Desmoplastic infantile ganglioglioma (DIG) is a rare, distinctive, supratentorial neoplasm with a generally favorable prognosis. Clinical, radiographic, and pathologic features can sometimes mimic those of a malignant tumor and other serious intracranial disorders. The author describes his experience with 3 cases of DIG, each of which initially masqueraded as another neurological disease with a very different prognosis. Case 1 was an infant boy referred for evaluation of a hemorrhagic infarction at birth. Case 2 was an infant girl referred for evaluation of a holohemispheric malignant neoplasm. Case 3 was an infant girl referred for evaluation of an intracranial mass believed to be a subdural empyema or possible sarcoma. In each case the lesion was resected and found to be a WHO grade I DIG. Each child has had a benign postoperative course. DIG can be mistaken for other serious neurological conditions including malignant neoplasm, cerebral infarction, and infection. It is prudent to consider this rare, low-grade resectable tumor in the differential diagnosis of atypical intracranial masses of childhood, as the impact on prognosis can be profound. The author discusses management strategies for DIG, including a role for molecular sequencing.

The LACE+ index (Length of stay, Acuity of admission, Charlson Comorbidity Index score, and Emergency department [ED] visits in the past 6 months) is a tool used to predict 30-day readmissions. We sought to examine this predictive tool in patients undergoing brain tumor surgery.Admissions and readmissions for patients undergoing craniotomy for supratentorial neoplasm at a single multihospital academic medical center were analyzed. All brain tumor cases for which the patient was alive at 30 days after surgery were included (n = 352). Simple logistic regression analyses were used to assess the ability of the LACE+ index and subsequent single variables to accurately predict the outcome measures of 30-day readmission, reoperation, and ED visit. Analysis of the model's or variable's discrimination was determined by the receiver operating characteristic curve as represented by the C-statistic.The sample included admissions for craniotomy for supratentorial neoplasm (n = 352). Assessment of the LACE+ index demonstrates a 1.02× increased odds of 30-day readmission for every 1-unit increase in LACE+ score (P = 0.031, CI = 1.00-1.03). Despite this, analysis of the receiver operating characteristic curve indicates that LACE+ index has poor specificity in predicting 30-day readmission (C-statistic = 0.58). A 1-unit increase in LACE+ score also predicts a 0.98× reduction in odds of home discharge (P0.001, CI = 0.97-0.99, C-statistic = 0.70). But LACE+ index does not predict 30-day reoperation (P = 0.945) or 30-day ED visits (P = 0.218).The results of this study demonstrate that the LACE+ index is not yet suitable as a prediction model for 30-day readmission in a brain tumor population.

Meningiomas are highly vascularized tumors which may recruit pial blood supply. Pial supply complicates tumor treatment in numerous ways. The objective of this study was to establish a reliable MRI-based diagnostic score to predict the existence of pial blood supply in supratentorial intracranial meningiomas and then correlate the score with clinical and surgical outcomes and histopathological findings. We performed a retrospective analysis of supratentorial histologically proven meningiomas in our institution from 2010 to 2018. A score was built based on MRI criteria and correlated with digital subtraction angiography (DSA) pial vascularization assessment. The score was then validated on a second independent population recruited with the same modalities. Logistic regression identified four parameters related to pial blood supply which were used to build the score: skull base location, tumor size > 45 mm, peritumoral flow voids, and incomplete cerebrospinal fluid rim. The overall diagnostic performance in predicting pial blood supply was as follows: sensitivity 97.8%, specificity 76.9%, predictive positive value 88.2%, negative predictive value 95.2%, and accuracy 90.3%. Inter-reader agreement and Cohen’s kappa were good, respectively, of 90.7% and 0.69. A high score was associated with aggressive meningioma (World Health Organization II–III) (p = 0.04) and with greater importance of pial supply relative to dural supply. We have identified a reliable way to use MRI to predict the existence of pial blood supply in supratentorial intracranial meningiomas. A higher score also predicted higher grade meningioma. • Accurate and reproducible MRI score composed of four items to predict the existence of pial blood supply in supratentorial meningioma. • High score is associated with high-grade meningioma (WHO II–III) but also with greater importance of pial supply relative to dural supply.

A 25-year-old female presented with a generalized tonic-clonic seizure. She had no previous history of seizures. A brain magnetic resonance imaging scan revealed a solitary enhancing mass in the right fronto-parietal cortex. During surgery, the mass was noted to be pure cortical with no connection to the ventricular lining. The tumor was completely resected. After surgery, the patient had no further seizures. The biopsy result showed a supratentorial ependymoma, which was C11orf95-RELA-fusionpositive.

OBJECTIVE An unexpectedly high incidence of sarcomas of the Central Nervous System (SCNS) was recently observed in Peru. We describe clinical and biological characteristics of the disease. METHODS Seventy pediatric patients with primary SCNS diagnosed between January 2005 and June 2018 were analyzed. DNA methylation profiling and gene panel sequencing was available from 28 and 27 tumors, respectively. RESULTS Median age was 6 years (range 2–17.5), 66/70 patients had supratentorial tumors, 56 patients intratumoral hemorrhage at diagnosis. Three patients fulfilled clinical criteria of NF1; 35 had café-au-lait spots and/or freckling. DNA-methylation profiling classified 28/28 as “intracranial spindle cell sarcoma with rhabdomyosarcoma-like features and DICER1 mutations”. DICER1 mutations were found in 26/27, TP53 mutations in 22/27, and RAS-pathway gene mutations (NF1, KRAS, NRAS) in 19/27 tumors, all of which were somatic (germline control available in n=19 cases). Survival was analyzed in 57 patients with non-metastatic disease who received adjuvant therapy. Two patients had metastatic disease, eleven did not receive or abandoned treatment. Two-year OS was 66.3% (95%-CI: 54–81%), 2-year PFS 51% (38–67%). PFS was highest in patients treated with postoperative ICE chemotherapy followed by radiotherapy and ICE (2y-EFS 79% [59–100%], n=18) and worse after upfront radiotherapy followed by ICE (40% [19–85%]; n=10) or VAC (50% [28–88%], n=12) and radiotherapy only (21% [6–71%], n=11; p=0.008). CONCLUSION Primary SCNS with DICER1 mutation have an aggressive clinical course. A combination of chemotherapy and radiotherapy seems beneficial. A link to a cancer predisposition syndrome could not be established so far.

OBJECTIVE Our objective was to quantify resection outcomes and operative morbidity in paediatric brain tumour surgery using existing scales, assessing their applicability. METHODS We investigated morbidity using the Clavien-Dindo (CD) scale and the Drake classification. All paediatric patients receiving a biopsy or craniotomy for an intracranial tumour in a single tertiary paediatric neurosurgery centre between January 2008 and December 2018 were studied. Complications up to day 30 post op were graded. RESULTS There were 459 operations: 92 biopsies and 367 craniotomies comprising 166 infratentorial and 292 supratentorial tumours. Median age was 9 years (56% male). The surgical goal was achieved or exceeded in 94% of cases. Thirty-day mortality was 1.31% with all deaths related to disease and none to surgical complications. The overall CD score was 1 in 10.9% of cases, 2 in 18.9%, 3A in 1.7%, 3B in 11.8%, and 4 in 1.1%. There was no operative morbidity in 54% of cases. Using the Drake classification, meningitis was seen in 3.92% of cases, seizures in 3.92%, neurological deficit (that persisted at 30 days) in 8.5%, CSF leak in 5.01%, wound infection in 1.96%, haemorrhage 1.75 %, shunt infection in 1.53%, shunt block in 0.65%, medical complications in 2.4%, and others in 3.05%. CONCLUSIONS This is the largest series presenting morbidity from paediatric brain tumour surgery, and the first to validate the CD scale. Our morbidity on the Drake scale was comparable with other series. There is a need to develop improved tools to quantify morbidity in this high-risk specialty.

Recent progress in neuro-oncology has validated the significance of genetic diagnosis in gliomas. We previously investigated IDH1/2 and TP53 mutations via Sanger sequencing for adult supratentorial gliomas and reported that PCR-based sequence analysis classified gliomas into three genetic subgroups that have a strong association with patient prognosis: IDH mutant gliomas without TP53 mutations, IDH and TP53 mutant gliomas, and IDH wild-type gliomas. Furthermore, this analysis had a strong association with patient prognosis. To predict genetic subgroups prior to initial surgery, we retrospectively investigated preoperative radiological data using CT and MRI, including MR spectroscopy (MRS), and evaluated positive 5-aminolevulinic acid (5-ALA) fluorescence as an intraoperative factor. We subsequently compared these factors to differentiate each genetic subgroup. Multiple factors such as age at diagnosis, tumor location, gadolinium enhancement, 5-ALA fluorescence, and several tumor metabolites according to MRS, such as myo-inositol (myo-inositol/total choline) or lipid20, were statistically significant factors for differentiating IDH mutant and wild-type, suggesting that these two subtypes have totally distinct characteristics. In contrast, only calcification, laterality, and lipid13 (lipid13/total Choline) were statistically significant parameters for differentiating TP53 wild-type and mutant in IDH mutant gliomas. In this study, we detected several pre- and intraoperative factors that enabled us to predict genetic subgroups for adult supratentorial gliomas and clarified that lipid13 quantified by MRS is the key tumor metabolite that differentiates TP53 wild-type and mutant in IDH mutant gliomas. These results suggested that each genetic subtype in gliomas selects the distinct lipid synthesis pathways in the process of tumorigenesis.

Gangliocytoma of the sellar region are extremely rare and often coexist with pituitary adenoma. Aim of this review is to collect all the cases reported in literature and to summarize the most recent literature evidences on the subject. A systematic review was performed through PubMed searching for articles describing gangliocytoma of the sellar region in the adult population, up to September 2015. An analysis of epidemiological data, clinical presentation, histochemical and radiological features and follow-up data was performed. A total of 55 articles were included in our analysis, reporting 129 cases of gangliocytoma of the sellar region. One case identified in our institution was also included. 85% of cases presented in association with pituitary adenomas. A female prevalence was evident. Patients presented most frequently with symptoms of hyperprolactinemia (44%) or visual disturbances (47%) when the sellar gangliocytoma was isolated, or with acromegalic manifestations (67%) when the gangliocytoma was associated with a pituitary adenoma. Immunohistochemistry showed a higher prevalence of mixed GH-PRL adenomas in association with sellar gangliocytomas, followed by GH adenomas. A purely intrasellar localization was found in about 25% of cases and a suprasellar extension in 30% of cases. A more extensive infiltration was present in about 40% of cases. A complete resection was obtained in 56% of collision lesions. The follow-up period was variable but endocrine remission was reported in 81% of cases of associated gangliocytoma and pituitary adenoma. Sellar gangliocytomas are rare lesions and an association with pituitary adenomas should always be searched. Mixed GH PRL adenomas are most frequently isolated. Collision lesions seem to have a behavior similar to isolated adenoma but a more important aggressiveness should be excluded at a molecular level. Further studies will allow advancements in clarifying the pathogenesis of this association.

Objectives Cognitive deficits caused by extra-axial benign brain tumors like meningiomas and the course of these deficits after surgery is not well known. The aim of the study is to assess the pre-operative and post-operative cognitive functions in patients with meningiomas in the supratentorial compartment. Materials and methods In this prospective study, patients with clinico-radiological diagnosis of supratentorial meningioma, operated upon and later confirmed by histopathological examination, were included. The patients were evaluated for cognitive deficits before and after surgery. The various clinical and radiological factors influencing the cognitive status were evaluated. Results A total of 57 patients were enrolled into the study. Out of 57, 22 were males and 35 were females. The frontal group had 22 patients, the parietal group had 10 patients, the temporal group had 10 patients, the occipital group had 6 patients, and the suprasellar group had 9 patients. Meningiomas, although extra-axial, caused significant cognitive deficits in 42 patients (73.7%). The highest frequency of cognitive deficits is seen in the frontal and temporal group of meningiomas (90% each). Frontal meningiomas with volume greater than 35cc and peritumoral edema greater than 40cc caused a higher frequency of cognitive deficits. Also, patients with raised ICP had significant cognitive deficits. Postoperatively there was a significant improvement in the cognitive functions in the frontal and temporal groups. Conclusion Meningiomas cause cognitive deficits in 73.7% of patients. Anatomical location of meningioma, elevated ICP, the volume of meningioma and extent of peritumoral edema significantly influence the incidence of cognitive deficits. Post-operatively, the cognitive deficits improve significantly in the frontal and temporal group.

Gliomas with 1p/19q loss of heterozygosity (LOH) are known to be associated with longer patient survival and higher sensitivity to treatment than tumors without 1p/19q LOH. This study was designed to clarify whether the preoperative finding of calcification on CT was correlated with 1p/19q LOH in patients with suspected WHO grade II and III gliomas. This study included 250 adult patients who underwent resection for primary supratentorial tumors at Tokyo Women’s Medical University Hospital. The tumors were suspected, based on MRI findings, to be WHO grade II or III gliomas. The presence of calcification on the patients’ CT images was qualitatively evaluated before treatment. After surgery, the resected tumors were examined to determine their 1p/19q status and mutations of IDH1 and p53. The presence of calcification was significantly correlated with 1p/19q LOH (P

Objective To identify variables associated with the development of pre- and postoperative seizures in patients who underwent surgical resection of intracranial meningiomas, in a patient cohort not routinely treated prophylactically with antiepileptic drugs (AED). Patients and methods Retrospective cohort study of 295 patients that underwent resection of a supratentorial meningioma at Odense University Hospital in between 2007–2015. Multivariate logistic regression was used to identify variables significantly correlating with pre- and postoperative seizures. Retrospective chart review was used to identify the rates of seizure incidence in patients, and the effect of AED on them. Results The presence of peritumoral edema (OR:18.00, 7.44–43.58) was identified as predictor of preoperative seizure, while headache (OR:0.43, 0.22–0.84) and neurological deficit (OR:0.18, 0.09–0.39) were associated with a reduced incidence of preoperative seizures. The rates of postoperative seizure were increased in meningiomas in the left side (OR:1.91, 1.11–3.29), and reduced for tumor location in the convexity/parasagittal/falx (OR:0.72, 0.59–0.88) as well as in the absence of postoperative complications (OR:0.19, 0.10–0.36). 24.4% of the patients experienced seizures preoperatively, and a complete seizure freedom was achieved in 63.9% of them. 75.6% of the patients did not experience seizures preoperatively, but 15.2% of them then developed seizures postoperatively. A total of 20.3% of the patients experienced seizures after surgery. Time to first seizure in patients that did not experience seizures preoperatively but developed seizures after surgery, was one week (47%). However, first time postoperative seizures were also observed within one month postoperative (21%) and three months after surgery (32%). AED had a treatment success rate of 98.2% in preoperative seizures, and 98.0% in postoperative seizures. Conclusion Seizures after supratentorial meningioma surgery is common also in patients with no seizures preoperatively and mainly occurs within the first three postoperative months. AED are effective in controlling seizures.

Intracranial ependymomas are rare tumors in adults. Thus, factors affecting prognosis are poorly understood. We performed a study to investigate whether tumor location is an important prognostic factor in adults who undergo surgery for intracranial ependymomas. PubMed was searched to identify studies that reported clinical outcomes in adult patients with intracranial ependymoma. Data were extracted for patient and tumor characteristics, extent of resection, progression-free survival (PFS), and overall survival (OS). Tumors were categorized as supratentorial or infratentorial and extraventricular or intraventricular. Presenting clinical features and tumor characteristics were tabulated. Kaplan–Meier and multivariate Cox regression survival analyses were performed to determine PFS and OS by tumor location. Extent of resection was also analyzed by tumor location. A total of 183 patients were included in the metaanalysis. Patients presented at a mean of 8.2 months with a myriad of clinical features. The mean tumor size was 3.38 cm, and 19.3% of tumors were cystic. Supratentorial tumors were most commonly located in the frontal and parietal lobes, and infratentorial tumors in the fourth ventricle. Supratentorial tumors demonstrated significantly poorer PFS (p < 0.001) and OS (p = 0.003) than infratentorial tumors, despite a higher rate of gross total resection (GTR) for the supratentorial tumors (72.6% versus 42.1%). Extraventricular ependymomas displayed significantly poorer PFS than intraventricular ependymomas (p = 0.009). In summary, supratentorial ependymomas have significantly poorer PFS and OS than their infratentorial counterparts, despite being more conducive to GTR, suggesting increased clinical aggressiveness. Extraventricular location is also associated with significantly poorer PFS than intraventricular location.

Ependymona occasionally occurs outside the ventricular structures, which is called ectopic ependymona (EE), while pure cortex location is uncommon. However, cortical anaplastic ependymoma (CE) is rare, especially in children. There were only four primary CEs, which is located in the superficial cortex, were reported the age of the patient under 12 years old. The present case is a 20-month-old boy presenting with simple partial seizure was treated in our department. Cranial magnetic resonance imaging (MRI) revealed a fronto-parietal lobe mass of more than 50mm in diameter with mixed signal intensity. Total removal of the mass lesion was performed without any neurological deficit. Pathological examination of the excised tumor were consistent with anaplastic ependymoma (AE). The patient had a good recovery after his surgical resection. Radiotherapy and chemotherapy were not taken into account in view of his age, the favorable site and the complete resection. The management of this unusual tumor is summarized in this paper.

Germ cell tumors, which constitute approximately 3-5% of tumors of the central nervous system (CNS), can be subdivided into germinomas, embryonal carcinomas, yolk sac tumors, choriocarcinomas, teratomas and mixed germ cell tumors. The diagnosis of intracranial germ cell tumor is based on the clinical symptoms, detection of tumor markers, such as alpha fetoprotein (AFP) and the beta subunit of human chorionic gonadotropin (beta-hCG) in blood and cerebrospinal fluid (CSF), magnetic resonance imaging (MRI) of the brain and spinal cord, CSF cytology and histology. The diagnosis of a secreting germ cell tumor, i.e. a non-germinoma, can be made by the determination of AFP and hCG as tumor markers. Germinomas are radiosensitive but are equally as sensitive to chemotherapy. Teratomas of the CNS are mostly diagnosed in newborns and infants. The most decisive role in the treatment of teratomas is played by as complete a resection as possible. Chemotherapy and irradiation play a subordinate role.Embryonal tumors, which constitute approximately 15-20% of CNS tumors, include medulloblastomas, primitive neuroectodermal tumors (PNET) of the CNS and the atypical teratoid rhabdoid tumor of the CNS. Medulloblastoma is the most common malignant brain tumor in childhood and adolescence. The incidence peak is the fifth year of life with a male predisposition in a ratio of 1.5:1. Medulloblastomas constitute 12-25% of all pediatric CNS tumors and 30-40% of pediatric tumors of the posterior cranial fossa. At the time of diagnosis evidence of dissemination in the CSF cavity is found in approximately 40% of patients. The extreme cell density makes medulloblastomas hyperdense in computed tomography (CT) and can therefore be differentiated from hypodense astrocytomas. The PNETs are histologically related to medulloblastomas, pineoblastomas, atypical teratoid rhabdoid tumors and peripheral neuroblastomas. They are relatively rare in children constituting less than 5% of supratentorial neoplasms. Patients are mostly clinically conspicuous due to macrocephalus and signs of brain pressure and/or seizures. In native CT the solid components of PNETs show a hyperdensity compared to the surrounding brain parenchyma probably due to the high cell density. Cysts and calcification are often detectable. The survival rate of children with CNS tumors has continuously increased in recent years. When corresponding clinical symptoms appear, such as headache, nausea or vomiting when fasting, all of which are evidence of increased intracranial pressure, MRI should be carried out as quickly as possible. Children should be treated in centers with departments of pediatric oncology and hematology and within the framework of studies.

Aim. We reviewed the surgical procedures guided by intraoperative electrocorticography and outcome of 65 patients with onset of supratentorial neoplasms manifesting as epilepsy. Method. Clinical data were obtained for 65 patients with supratentorial neoplasms who received surgery, with the aid of intraoperative electrocorticography to screen epileptogenic foci before and after removal of neoplasms, and depth electrodes when needed. According to electrocorticography findings, appropriate surgical procedures were performed to treat the epileptogenic foci. In the control group, 72 patients received simple lesionectomy. Postoperative seizure outcomes were documented and analysed retrospectively. Results. In the case group, 33 patients received lesionectomy only, while the other 32 patients underwent intraoperative electrocorticography-guided tailored epilepsy surgery. In total, 57 patients (87.7%) in the case group and 38 patients (52.8%) in the control group were seizure-free (Engel Class I). Comparing outcomes of patients with temporal lesions between the two groups, 80.0% patients (12/15) in the case group and 20.0% (3/15) in the control group were seizure-free. Furthermore, comparing the seizure outcomes of patients who finally underwent tailored epilepsy surgery and simple lesionectomy (33 after electrocorticography and 72 without electrocorticography), intraoperative electrocorticography-guided tailored epilepsy surgery demonstrated superiority over lesionectomy (Engel Class I; 87.5% vs. 63.8%, respectively). Conclusions. Electrocorticography plays an important role in the localisation of epileptogenic foci and evaluation of the effects of microsurgical procedures intraoperatively. Isolated lesionectomy is not usually sufficient for better postoperative seizure outcome. In addition, for patients with temporal tumours, especially in the non-dominant hemisphere, a more aggressive strategy, such as an anterior temporal lobectomy, is recommended.

Atypical teratoid/rhabdoid tumor is a rare malignant CNS tumor that most often affects children ≤ 3 years old. The Central Brain Tumor Registry of the United States contains the largest aggregation of population-based incidence data for primary CNS tumors in the US. Its data were used to describe the incidence, associated trends, and relative survival after diagnosis of atypical teratoid/rhabdoid tumor.Using data from 50 cancer registries between 2001 and 2010, age-adjusted incidence rates per 100 000 and 95% CIs were calculated by sex, race, Hispanic ethnicity, age at diagnosis, and location of tumor in the CNS for children aged 0 to 19 years. Relative survival rates and 95% CIs were also calculated.The average annual age-adjusted incidence rate was 0.07 (95% CI: 0.07, 0.08). Incidence rates did not significantly vary by sex, race, or ethnicity. Age had a strong effect on incidence rate, with highest incidence among children1 year, and decreasing incidence with increasing age. The 6-month, 1-year, and 5-year relative survival rates for all ages were 65.0%, 46.8%, and 28.3%, respectively. Atypical teratoid/rhabdoid tumor can occur anywhere in the CNS, but supratentorial tumors were more common with increasing age.We confirm differences in survival by age at diagnosis, treatment pattern, and location of tumor in the brain. This contributes to our understanding of these tumors and may stimulate research leading to improved treatment of this devastating childhood disease.

Object Hospital readmission within 30 days of discharge is a major contributor to the high cost of health care in the US and is also a major indicator of patient care quality. The purpose of this study was to investigate the incidence, causes, and predictors of 30-day readmission following craniotomy for malignant supratentorial tumor resection. Methods The longitudinal California Office of Statewide Health Planning & Development inpatient-discharge administrative database is a data set that consists of 100% of all inpatient hospitalizations within the state of California and allows each patient to be followed throughout multiple inpatient hospital stays, across multiple institutions, and over multiple years (from 1995 to 2010). This database was used to identify patients who underwent a craniotomy for resection of primary malignant brain tumors. Causes for unplanned 30-day readmission were identified by principle ICD-9 diagnosis code and multivariate analysis was used to determine the independent effect of various patient factors on 30-day readmissions. Results A total of 18,506 patients received a craniotomy for the treatment of primary malignant brain tumors within the state of California between 1995 and 2010. Four hundred ten patients (2.2%) died during the index surgical admission, 13,586 patients (73.4%) were discharged home, and 4510 patients (24.4%) were transferred to another facility. Among patients discharged home, 1790 patients (13.2%) were readmitted at least once within 30 days of discharge, with 27% of readmissions occurring at a different hospital than the initial surgical institution. The most common reasons for readmission were new onset seizure and convulsive disorder (20.9%), surgical infection of the CNS (14.5%), and new onset of a motor deficit (12.8%). Medi-Cal beneficiaries were at increased odds for readmission relative to privately insured patients (OR 1.52, 95% CI 1.20–1.93). Patients with a history of prior myocardial infarction were at an increased risk of readmission (OR 1.64, 95% CI 1.06–2.54) as were patients who developed hydrocephalus (OR 1.58, 95% CI 1.20–2.07) or venous complications during index surgical admission (OR 3.88, 95% CI 1.84–8.18). Conclusions Using administrative data, this study demonstrates a baseline glioma surgery 30-day readmission rate of 13.2% in California for patients who are initially discharged home. This paper highlights the medical histories, perioperative complications, and patient demographic groups that are at an increased risk for readmission within 30 days of home discharge. An analysis of conditions present on readmission that were not present at the index surgical admission, such as infection and seizures, suggests that some readmissions may be preventable. Discharge planning strategies aimed at reducing readmission rates in neurosurgical practice should focus on patient groups at high risk for readmission and comprehensive discharge planning protocols should be implemented to specifically target the mitigation of potentially preventable conditions that are highly associated with readmission.

BACKGROUND: Children with recurrent or progressive pediatric CNS tumors have poor prognoses. Optune delivers TTFields, an anti-mitotic FDA-approved cancer therapy, for adult patients with newly diagnosed and recurrent supratentorial GBM. METHODS: This multicenter trial [NCT03033992] examines the feasibility and device-related toxicity of TTFields in 20 children aged 5–21 years with recurrent supratentorial HGG and ependymoma. Secondary objectives include: response rate, event-free survival, compliance and QoL. Feasibility in this trial is defined as the ability of pediatric subjects to wear Optune ≥18 hours/day for at least 23/28 days of cycle one following a 7-day learning period. Treatment may continue up to 26 cycles based on observed benefit and safety. QOL instruments include PROMIS and Neuro-QOL. Following enrollment of the 11(th) evaluable subject, the study will be temporarily suspended to share interim feasibility and safety data with the FDA. RESULTS: This planned interim analysis included 11 patients (7 males/4 females) with supratentorial tumors: ten HGG and one ependymoma. Median age was 14.2 (6.4–21.3) years. Ten patients were evaluable (1 Progressive Disease) during the feasibility period) and 4 remained on study through 4 cycles and one patient is currently on Cycle 14. One grade 5 intracranial hemorrhage not associated with the device and no grade IV toxicities occurred, 3 patients had seizures (grade 1–3), fatigue, scalp pain, localized rash, and headache (none greater than grade 3). Of the 10 evaluable patients, 7 satisfied the feasibility criteria for the Optune therapy, which is above the prespecified threshold of at least 6/11. CONCLUSION: This is the first prospective safety and feasibility trial for Optune in children with recurrent supratentorial HGG and ependymoma. Preliminary results indicate feasibility with minimal toxicity. Accrual to the study is ongoing. An amendment is in progress adding a stratum for newly diagnosed diffuse intrinsic pontine glioma (DIPG) patients.

Ozawa et al. present a murine tumor model resembling the most frequent molecular group of human supratentorial ependymoma, ST-EPN-RELA. Their model shows RELA-fusion-based de novo ependymoma tumorigenesis in the forebrain derived from neural stem cells. : Ozawa et al. present a murine tumor model resembling the most frequent molecular group of human supratentorial ependymoma, ST-EPN-RELA. Their model shows RELA-fusion-based de novo ependymoma tumorigenesis in the forebrain derived from neural stem cells.

Treatment of ependymoma has changed little over the years and is essentially limited to surgery and radiation. Limited preclinical testing has hindered the development of targeted therapies. Our group has identified a variety of potential therapy options for ependymoma based on drug screening using novel human posterior fossa ependymoma cell lines with chromosome 1q gain. Whether these agents were also effective in RELA fusion-driven supratentorial ependymoma was not determined due to of a lack of available supratentorial ependymoma cell lines. Recently we were able to generate a novel supratentorial cell line – MAF1329 - harboring 1q+ as well as the RELA-C11orf95 fusion. Paired with a supratentorial ependymoma cell line (EP1NS) obtained from collaborators, we were able to perform an in vitro screen and to identify supratentorial ependymoma-selective therapies in a panel of 124 FDA-approved oncology drugs, for streamlined clinical application. Additionally, we are able to compare drug sensitivities between supratentorial and posterior fossa ependymoma. Our initial findings indicate that the two ependymoma subgroups differ in response to therapy options with some overlap, notably RTKIs imatinib and pazopanib. We also noted that carmofur, a lypophilic-masked analog of 5-FU, was effective in treating both subgroups. Conversely, 5-FU itself, a top hit in posterior fossa ependymoma, showed very little effect in supratentorial models. Early phase trials of 5-FU resulted in a lack of survival benefit in supratentorial tumors enrolled in the study, and this preclinical finding may explain this lack of response. These data suggest that supratentorial and posterior fossa ependymoma may require subgroup specific targeted therapy options. Further comparative drug screening of other supratentorial cell lines and short term cultures, combined with in vivo testing, will address the need for subgroup-stratified preclinical data to better inform design of clinical trials in ependymoma.

Supratentorial extraventricular anaplastic ependymoma (SEAE) in adults is a relatively rare intracranial tumor. Because of the very low prevalence, only a few cases have been reported. According to a recent study, SEAE is associated with a poor prognosis and there is no definite consensus on optimal treatment. We report a case of an adult SEAE patient who had no recurrence until seven years after a gross total resection (GTR) followed by conventional radiotherapy. A 42-year-old male had a persistent mild headache, left facial palsy, dysarthria, and left hemiparesis. Preoperative neuroimaging revealed an anaplastic astrocytoma or supratentorial ependymoma in the right frontal lobe. A GTR was performed, followed by adjuvant radiotherapy. Histologic and immunohistochemical results revealed anaplastic ependymoma. After seven years of initial therapy, a regular follow-up MRI showed a 3-cm-sized partially cystic mass in the same area as the initial tumor. The patient underwent a craniotomy, and a GTR was performed. Histopathologic examination revealed recurrence of the SEAE. External radiotherapy was performed. The patient has been stable without any disease progression or complications for 12 months since the surgery for recurrent SEAE.

We present a third reported case of intracranial germinomas occurring in two brothers. They underwent chemotherapy and radiotherapy after biopsy and are doing well for 10 years and 20 months, respectively. The pertinent literatures are reviewed, and the possible role of heredity in the pathogenesis of familial occurrence of germinomas is discussed., 症例1(11歳男児)。1年前から視力障害、2ヵ月前から頭痛と嘔吐が出現した。瞳孔反射消失、視力低下、上方注視麻痺、両側乳頭浮腫を認め、MRIで中脳蓋に不均質に増強される腫瘤及び水頭症を認めた。脳室腹腔シャント術を施行後、生検を施行し、2細胞パターンを有する胚細胞腫と診断し、化学療法後に放射線照射を行った。病変は完全に消失し、10年間再発はなかった。症例2(21歳)は症例1の兄。18年前からてんかんと精神遅滞、10年前から低身長及び甲状腺機能低下症、3ヵ月前から食欲不振、体重減少、左眼瞼下垂が出現した。瞳孔不同、左瞳孔反射遅延、左眼球全方向運動障害を認め、MRIで不均等に増強されるトルコ鞍内及び鞍上部腫瘤を認めた。経蝶骨アプローチで生検を行い、純胚細胞腫と診断した。弟と同じ治療を行い、腫瘤は完全に消失し、20ヵ月間再発は認めなかった。環境及び遺伝学的原因は突き止められなかった。

We report the case of a 61-year-old man with supratentorial extraventricular anaplastic ependymoma who presented with repeated intratumoral hemorrhage. The patient was admitted with headache. Computed tomography and magnetic resonance imaging showed an enhancing mass with intratumoral hemorrhage in the right temporal lobe. Gross total resection was performed. The tumor was well demarcated from the brain tissue, and showed no continuity with the ventricular system. Histopathological examination revealed the features of anaplastic ependymoma. Therefore, additional radiation therapy and adjuvant chemotherapy were administered. Ten months later, the tumor recurred with hemorrhage in the spinal canal. This case showed rapid malignant progression and repeated intratumoral hemorrhage within a short period of time, both of which are characteristics of anaplastic ependymomas. Close observation of the central nervous system and adjuvant radiotherapy are mandatory, even if the ependymoma presents with repeated intratumoral hemorrhage.

Ependymomas comprise 8 % of all intracranial tumors in children

Extracranial spread from a glioblastoma is rare. We present a case of a 48year-old man with a previously radiologically-stable left temporal lobe glioblastoma presenting with symptoms referrable to the spinal cord. MRI revealed a spinal cord lesion, with the differential including transverse myelitis and tumour. Open surgical biopsy revealed high-grade astrocytoma. Genetic analysis of both the supratentorial and spinal tumours revealed R132H IDH1 mutations, providing evidence that the spinal cord lesion had spread from the supratentorial tumour.

AIM To study the clinical features, imaging findings, treatment methods and results, and prognosis of supratentorial parenchymal ependymomas in children. MATERIAL AND METHODS Fourteen children with supratentorial parenchymal ependymomas were treated by the senior author at Tiantan Hospital between October 2004 and May 2010. The clinical manifestations, neuroimaging findings, treatment methods, and therapeutic results were retrospectively reviewed. RESULTS The study included 11 boys and three girls. The patients were aged from 1 to 14 years with an average age of 6.1 years. Gross total surgical removal (GTR) was achieved in 10 cases, and subtotal removal (STR) was achieved in four cases. There were six ependymomas, seven anaplastic ependymomas, and one subependymoma. The mean follow-up duration was 78.9 months (range, 4?122 months). During the follow-up period, 10 patients who underwent GTR (71.4%; only 1 patient had a recurrent tumor during this time) had an excellent postoperative outcome (Karnofsky Performance Status ? 80), while four patients who underwent STR (28.6%) developed recurrent tumors and died. CONCLUSION The preoperative diagnosis of supratentorial parenchymal ependymomas is difficult. GTR can be achieved with a favorable long-term outcome using an improved microsurgical technique.

We report a WHO grade III ependymoma of the supratentorial interhemispheric fissure and grew to form a large mass with anaplastic transformation without local recurrence 17 years after the total removal of a fourth ventricular WHO grade II ependymoma. We emphasize the necessity of long-term follow-up, even in benign ependymomas.

Background Pilocytic astrocytoma is a rare tumour, usually occurring in paediatric ages, and mainly located in the posterior fossa. It can cause hydrocephalus and intracranial hypertension and, less frequently, seizures, or a focal neurological deficit. The main imaging study by magnetic resonance imaging, which shows a tumour with solid and cystic components without peri-lesional swelling. The election treatment is surgical, and the patient is considered cured if a total resection is accomplished. Clinical case The case is presented of 22-year-old female patient with a supratentorial pilocytic astrocytoma and epilepsy. Histopathology reported a low grade glial proliferation, with an extensive fibrillar matrix, small cells without atypia, extensive calcifications and piloid areas consisting of bipolar fusiform cells, and some Rosenthal fibres. There were also spongiotic areas consisting of multipolar cells and associated microcysts. The final report was a pilocytic astrocytoma. Conclusions Pilocytic astrocytoma is more frequent in paediatric patients and in the posterior fossa. The case presented is of a young female adult with supratentorial location, making it a special case. The surgery achieved a total resection. The long-term prognosis is good, but it is necessary to perform a follow-up, particularly in adult patients because of a higher risk of recurrence.

An ependymoma is an uncommon glial tumor, which arises from different parts of the neuroaxis. Considerable variation in presentation and survival in tumors in different locations after an optimum treatment indicates inherent molecular and genetic differences in tumorigenesis between them. A number of genetic aberrations have been identified to distinctly characterize different subgroups of ependymomas that include a posterior fossa tumor, a supratentorial tumor, and a pediatric tumor. These different groups have substantial genetic alterations, and also distinct demography, clinical characteristics, and prognosis. This article is intended to review the diverse molecular and genetic aberrations that may be helpful in prognostication and prediction of survival in patients suffering from an ependymoma.