Dysembryoplastic Neuroepithelial Tumor: A Case Report of A Benign Intracranial Lesion Masquerading as Seizure Disorder.

The uncommon, benign dysembryoplastic neuroepithelial tumor (DNET, WHO grade 1) is frequently linked to epilepsy. It is a glioneuronal neoplasm in the cerebral cortex of children or young adults defined by the presence of a pathognomonic glioneuronal element that may be linked to glial nodules and activating mutations of fibroblast growth factor receptor 1 (FGFR1) (CNS WHO grade 1 according to WHO classification of CNS and pituitary tumors, 2021 ). The cerebral cortex is primarily affected. The most frequent areas are the temporal lobe, particularly the medial lobe, frontal lobe, and other cortex. This study reports the instance of a 31-year-old male who had a history of seizures for the past 20 years and complained of a sudden headache and vomiting at the hospital. MRI revealed a cortical-based lesion in the left posterior temporo-occipital region. A biopsy sample was sent for histopathological examination. DNETs are usually benign, non-recurring lesions and rarely can be a malignant transformation. Although they are frequently stable tumors, surgical excision seldom results in recurrence.

Radiosurgery outcomes in infratentorial juvenile pilocytic astrocytomas.

PURPOSE: To assess survival and neurological outcomes for patients who underwent primary or salvage stereotactic radiosurgery (SRS) for infratentorial juvenile pilocytic astrocytomas (JPA). METHODS: Between 1987 and 2022, 44 patients underwent SRS for infratentorial JPA. Twelve patients underwent primary SRS and 32 patients underwent salvage SRS. The median patient age at SRS was 11.6 years (range, 2-84 years). Prior to SRS, 32 patients had symptomatic neurological deficits, with ataxia as the most common symptom in 16 patients. The median tumor volume was 3.22 cc (range, 0.16-26.6 cc) and the median margin dose was 14 Gy (range, 9.6-20 Gy). RESULTS: The median follow-up was 10.9 years (range, 0.42-26.58 years). Overall survival (OS) after SRS was 97.7% at 1-year, and 92.5% at 5- and 10-years. Progression free survival (PFS) after SRS was 95.4% at 1-year, 79.0% at 5-years, and 61.4% at 10-years. There is not a significant difference in PFS between primary and salvage SRS patients (p = 0.79). Younger age correlated with improved PFS (HR 0.28, 95% CI 0.063-1.29, p = 0.021). Sixteen patients (50%) had symptomatic improvements while 4 patients (15.6%) had delayed onset of new symptoms related to tumor progression (n = 2) or treatment related complications (n = 2). Tumor volumetric regression or disappearance after radiosurgery was found in 24 patients (54.4%). Twelve patients (27.3%) had delayed tumor progression after SRS. Additional management of tumor progression included repeat surgery, repeat SRS, and chemotherapy. CONCLUSIONS: SRS was a valuable alternative to initial or repeat resection for deep seated infratentorial JPA patients. We found no survival differences between patients who had primary and salvage SRS.

Differentiation between supratentorial pilocytic astrocytoma and extraventricular ependymoma using multiparametric MRI.

BACKGROUND: The differentiation of supratentorial pilocytic astrocytomas (STPAs) and supratentorial extraventricular ependymomas (STEEs) is clinically pivotal because of distinct therapeutic management and prognosis, which is sometimes challenging to both neuroradiologists and pathologists. PURPOSE: To explore and compare the conventional and advanced magnetic resonance imaging (MRI) features between STPA and STEE. MATERIAL AND METHODS: A total of 23 patients with STPAs and 23 patients with STEEs were reviewed in this study. All patients performed conventional MRI, susceptibility-weighted imaging (SWI), and diffusion-weighted imaging (DWI), and 34 patients (17 with STPAs and 17 with STEEs) examined dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI) in addition. Clinical data, conventional MRI features, minimum relative apparent diffusion coefficient ratio (rADCmin), and maximum relative cerebral blood volume ratio (rCBVmax) were compared between the two groups and subgroups. The optimal cutoff values of rADCmin and rCBVmax with sensitivity and specificity were calculated. RESULTS: STPA manifested similar to STEE as a solid-cystic mass but more frequently presented with a marked enhancing deep nodule (P = 0.02), no peritumoral edema (P = 0.036), higher rADCmin value (2.0 ± 0.5 vs. 0.9 ± 0.2; P < 0.001), and lower rCBVmax value (2.1 ± 0.4 vs. 14.4 ± 5.5; P < 0.001). The cutoff value of >1.39 for rADCmin and ≤ 2.81 for rCBVmax produced a high sensitivity of 95.65% and 100.0%, respectively, and all produced a specificity of 100.0% in differentiating STPAs from STEEs. CONCLUSION: Multiparametric MRI techniques including conventional MRI, DWI, and DSC-PWI contribute to the differential diagnosis of STPA and STEE.

Treatment with endoscopic transnasal resection of hypothalamic pilocytic astrocytomas: a single-center experience.

BACKGROUNDS: Pilocytic astrocytomas (PAs) are World Health Organization (WHO) grade I tumors, which are relatively common, and are benign lesions in children. PAs could originate from the cerebellum, optic pathways, and third ventricular/hypothalamic region. Traditional various transcranial routes are used for hypothalamic PAs (HPAs). However, there are few studies on hypothalamic PAs treated through the endoscopic endonasal approach (EEA). This study reports the preliminary experience of the investigators and results with HPAs via expanded EEAs. METHODS: All patients with HPAs, undergone EEA in our hospital from 2017 to 2019, were retrospectively reviewed. The demographic data, clinical symptoms, complications, skull base reconstruction, prognosis, and endocrinological data were all recorded and analyzed in detail. RESULTS: Finally, five female patients were enrolled. The average age of patients was 28.6 ± 14.0. All patients had complaints about their menstrual disorder. One patient had severe bilateral visual impairment. Furthermore, only one patient suffered from severe headache due to acute hydrocephalus, although there were four patients with headache or dizziness. Four cases achieved gross-total resection, and one patient achieved subtotal resection. Furthermore, there was visual improvement in one patient (case 5), and postoperative worsening of vision in one patient (case 4). However, only one patient had postoperative intracranial infection. None of the patients experienced a postoperative CSF leak, and in situ bone flap (ISBF) techniques were used for two cases for skull base repair. In particular, ISBF combined with free middle turbinate mucosal flap was used for case 5. After three years of follow-up, three patients are still alive, two patients had no neurological or visual symptoms, or tumor recurrence, and one patient had severe hypothalamic dysfunction. Unfortunately, one patient died of severe postoperative hypothalamus reaction, which presented with coma, high fever, diabetes insipidus, hypernatremia and intracranial infection. The other patient died of recurrent severe pancreatitis at one year after the operation. CONCLUSION: Although the data is still very limited and preliminary, EEA provides a direct approach to HPAs with acceptable prognosis in terms of tumor resection, endocrinological and visual outcomes. ISBF technique is safe and reliable for skull base reconstruction.

Demonstration of Microsurgical Technique and Nuances for the Resection of a Midbrain Tectal Glioma via the Transcollicular Approach: 3-Dimensional Operative Video.

Tectal gliomas are a rare subset of intrinsic brainstem lesions. The microsurgical resection of these lesions remains a major challenge.1,2 Transcollicular approaches on one side, via the superior or inferior colliculi or both, are neurologically well tolerated without obvious or major auditory or oculomotor consequences. However, any postoperative acute visually triggered saccadic abnormalities caused by iatrogenic superior colliculus damage generally resolve during the postoperative period, as other oculomotor structures compensate for these functions in unilateral lesions. In this surgical video, we present a 37-yr-old man with long-standing seizures, new onset headaches, progressive ataxic gait, and imbalance. Magnetic resonance imaging (MRI) showed a circumscribed nonenhancing dorsal midbrain cystic mass with compression on the aqueduct causing hydrocephalus. The lesion had a low signal intensity on T1-weighted images and a high signal intensity on T2-weighted images. The patient first underwent an endoscopic third ventriculostomy. Although his headaches greatly improved after the third ventriculostomy, he remained quite symptomatic in terms of gait imbalance and ataxia. The patient underwent a supracerebellar, infratentorial, transcollicular approach for resection of the tectal tumor. Simultaneously, motor and somatosensory evoked potentials were monitored. Both the surgery and the postoperative course were uneventful, with postoperative MRI showing gross total resection of the mass, and histopathology indicating a WHO (World Health Organization) grade I pilocytic astrocytoma. The patient continued to do well without recurrence at 2-yr follow-up. In this video, we demonstrate step-by-step microsurgical techniques for resecting these challenging tectal gliomas via the infratentorial-supracerebellar-transcollicular approach. The patient consented to the procedure and publication of his images.

Paediatric posterior fossa tumour resection rates in a small volume centre: the past decade's experience.

BACKGROUND: Paediatric brain tumour resection rates have been shown to correlate with outcome and, it is argued, are linked to operator volume and caseload. The British paediatric neurosurgery community has previously debated centralisation of paediatric neuro-oncology. At the 2018 British Paediatric Neurosurgery Group (BPNG) meeting, a commitment was made to prospectively collect tumour resection data at each Neurosurgical Unit (NSU). Here we review our prospectively-collected 10-year database of the three commonest paediatric posterior fossa tumours - astrocytomas, medulloblastomas and ependymomas. MATERIALS AND METHODS: Our primary outcome was extent of resection (EOR) on post-operative MRI scans reviewed by neuro-radiologists. Secondary outcomes comprised neurosurgical morbidity including infection, need for cerebrospinal fluid (CSF) diversion and the occurrence of posterior fossa syndrome (PFS). RESULTS: 55 children had 62 operations, where our complete resection rates for pilocytic astrocytomas, medulloblastomas and ependymomas were 77%, 79% and 63%, respectively. Both our primary and secondary outcomes were in keeping with the published literature and we discuss here some of the factors which may contribute towards favourable outcomes in a small volume centre. CONCLUSION: Our results suggest that small volume centres can expect equivalent results to larger volume NSUs with regards to paediatric brain tumour surgery. Continuing efforts nationally for data collection on resection rates and operative outcomes is a key step towards optimising management in these children.

Implications of new understandings of gliomas in children and adults with NF1: report of a consensus conference.

Gliomas are the most common primary central nervous system tumors occurring in children and adults with neurofibromatosis type 1 (NF1). Over the past decade, discoveries of the molecular basis of low-grade gliomas (LGGs) have led to new approaches for diagnosis and treatments. However, these new understandings have not been fully applied to the management of NF1-associated gliomas. A consensus panel consisting of experts in NF1 and gliomas was convened to review the current molecular knowledge of NF1-associated low-grade "transformed" and high-grade gliomas; insights gained from mouse models of NF1-LGGs; challenges in diagnosing and treating older patients with NF1-associated gliomas; and advances in molecularly targeted treatment and potential immunologic treatment of these tumors. Next steps are recommended to advance the management and outcomes for NF1-associated gliomas.

Resolving mystery behind autonomous retrogression of low-grade gliomas: A systematic review.

OBJECTIVE: To review evidence-based data on spontaneous retrogression of low-grade gliomas with respect to interval till regression, type of glioma and patient outcome. METHODS: The systematic review comprised medical literature in English language published from January 1997 to January 2017 on Scopus, PubMed and Google Scholar databases to establish consensus about the possible mechanism of spontaneous regression, the role of therapeutic intervention and failure of management strategies in low-grade gliomas. Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed during the review. RESULTS: Of the 176 articles identified, 73(41.5%) were shortlisted for detailed assessment. Of them, 10(13.7%) were included; 5(50%) case reports and 5(50%) case series. There were 23 cases of spontaneous regression; 15(65.2%) males and 8(34.7%) females. The interval of regression varied from 3 months to 15.5 years, and the most commonly presenting low-grade glioma type was optic pathway glioma 11(47.4%). CONCLUSIONS: The phenomenon of regression was most evident in optic pathway glioma. Literature suggested that low-grade gliomas should undergo serial imaging before implying any therapeutic intervention. However, the evidencebased proof, large-scale experimental studies and ethical considerations are still required to standardise this strategy.

Actionable FGFR1 and BRAF mutations in adult circumscribed gliomas.

PURPOSE: Circumscribed gliomas -pilocytic astrocytomas (PA), gangliogliomas (GG), ependymomas (EP)- are mostly low-grade tumours but may progress to anaplasia and sometimes surgery can be challenging due to deep anatomical localization. Because of the high frequency of MAPK-pathway alterations and availability of targeted therapies for FGFR1 and BRAF-mutated tumors, we investigated these mutational hotspots in a cohort of adult circumscribed gliomas. METHODS: Adult patients (>15 years) with diagnosis of PA, GG, EP and DNET were retrospectively identified from two institutions databases. Genomic DNA was extracted from formalin-fixed paraffin-embedded or frozen samples and exons including codons 546 and 656 of FGFR1 and V600 of BRAF were sequenced. RESULTS: FGFR1 mutations were identified in 15/108 PA and were particularly frequent in optic pathway (6/9 vs. 9/108; p = 10-4). FGFR1 was mutated in 3/75 grade II versus 2/7 grade III GG (p = 0.05), 1/7 DNET, 1/100 EP grade II. We found 3/108 PA with BRAF pVal600Glu and 6/108 with p.Thr599_Val600insThr. The p.Val600Glu was found in 14/75 grade II GG. No EP were BRAF mutated. CONCLUSIONS: We report actionable targets, including frequent FGFR1 mutation in optic-pathway PA that makes them excellent candidates to anti-FGFR therapies, and BRAF non-canonical mutations in PA.

The benefit of surveillance imaging for paediatric cerebellar pilocytic astrocytoma.

OBJECTIVES: Paediatric cerebellar pilocytic astrocytomas (PA) (WHO grade 1) are amongst the most common of childhood brain tumours and are generally amenable to resection, with surgery alone being curative in the majority of cases. There is, however, a lack of consensus regarding the frequency and duration of post-treatment MRI surveillance for these tumours. This is important, as follow-up imaging is a significant use of resources and often associated with patient and family anxiety. We have assessed the utility of MRI surveillance in the detection of cerebellar PA recurrence at our regional paediatric neurosurgical centre. MATERIALS AND METHODS: The tumour register at Alder Hey Children's Hospital was searched to identify all patients diagnosed between 2007 and 2017, with a confirmed histopathological diagnosis of cerebellar PA. Patient demographics, surgical outcome, number of MRI scans and length of follow-up were recorded for each patient. RESULTS: Forty patients met the inclusion criteria. The mean age at diagnosis was 7.8 years (range 2 to 17 years). Complete surgical resection (CR), confirmed by post-operative MRI, was achieved in 36 of the 40 patients, including all 31 cases from 2009 and later for which intraoperative MRI (iMRI) was utilised. There was one case of recurrence after CR (at 2.2 years) out of the 36 cases, whereas all 4 patients with initial partial resections had progressive growth of their tumours and required second surgical interventions. CONCLUSION: This series confirms the very low likelihood of recurrence for completely resected cerebellar PAs and suggests that in such cases the duration and frequency of surveillance imaging could be limited to a maximum of 2.5 to 3 years of follow-up imaging. This report also indicates improved complete resection rates over time, probably associated with technical advances including the routine in-house use of iMRI in 2009.

Integrated DNA methylation analysis identifies topographical and tumoral biomarkers in pilocytic astrocytomas.

Pilocytic astrocytoma (PA) is the most common glioma in pediatric patients and occurs in different locations. Chromosomal alterations are mostly located at chromosome 7q34 comprising the BRAF oncogene with consequent activation of the mitogen-activated protein kinase pathway. Although genetic and epigenetic alterations characterizing PA from different localizations have been reported, the role of epigenetic alterations in PA development is still not clear. The aim of this study was to investigate whether distinctive methylation patterns may define biologically relevant groups of PAs. Integrated DNA methylation analysis was performed on 20 PAs and 4 normal brain samples by Illumina Infinium HumanMethylation27 BeadChips. We identified distinct methylation profiles characterizing PAs from different locations (infratentorial vs supratentorial) and tumors with onset before and after 3 years of age. These results suggest that PA may be related to the specific brain site where the tumor arises from region-specific cells of origin. We identified and validated in silico the methylation alterations of some CpG islands. Furthermore, we evaluated the expression levels of selected differentially methylated genes and identified two biomarkers, one, IRX2, related to the tumor localization and the other, TOX2, as tumoral biomarker.

Incidence, time trends and survival patterns of childhood pilocytic astrocytomas in Southern-Eastern Europe and SEER, US.

Pilocytic astrocytomas (PA) comprise the most common childhood central nervous system (CNS) tumor. Exploiting registry-based data from Southern and Eastern Europe (SEE) and SEER, US, we opted to examine incidence, time trends, survival and tentative outcome disparities of childhood PA by sociodemographic and clinical features. Childhood PA were retrieved from 12 SEE registries (N = 552; 1983-2014) and SEER (N = 2723; 1973-2012). Age-standardized incidence rates (ASR) were estimated and survival was examined via Kaplan-Meier and Cox regression analysis. ASR of childhood PA during 1990-2012 in SEE was 4.2/106, doubling in the USA (8.2/106). Increasing trends, more prominent during earlier registration years, were recorded in both areas (SEE: +4.1 %, USA: +4.6 %, annually). Cerebellum comprised the most common location, apart from infants in whom supratentorial locations prevailed. Age at diagnosis was 1 year earlier in SEE, whereas 10-year survival was 87 % in SEE and 96 % in SEER, improving over time. Significant outcome predictors were age <1 year at diagnosis diagnosis (hazard ratio, HR [95% confidence intervals]: 3.96, [2.28-6.90]), female gender (HR: 1.38, [1.01-1.88]), residence in SEE (HR: 4.07, [2.95-5.61]) and rural areas (HR: 2.23, [1.53-3.27]), whereas non-cerebellar locations were associated with a 9- to 12-fold increase in risk of death. The first comprehensive overview of childhood PA epidemiology showed survival gains but also outcome discrepancies by geographical region and urbanization pointing to healthcare inequalities. The worse prognosis of infants and, possibly, females merits further consideration, as it might point to treatment adjustment needs, whereas expansion of systematic registration will allow interpretation of incidence variations.

Posterior Fossa Intra-Axial Tumors in Adults.

BACKGROUND: The posterior fossa is the site of many types of tumors, and brain metastases are the most common malignancies in that location among adults. Other brain tumors, such as ependymomas, medulloblastomas, and juvenile pilocytic astrocytomas, mostly occur during childhood and are relatively rare in adults. Most primary malignant brain tumors, such as gliomas and lymphomas, tend to be located in the supratentorial compartment. METHODS: This review summarizes prognostic factors, therapeutic management, and molecular data of intra-axial posterior fossa tumors in adults, including ependymomas, medulloblastomas, and pilocytic astrocytomas. RESULTS: The literature on intra-axial posterior fossa tumors in adults relies mainly on limited retrospective clinical studies, and such studies employ a wide range of treatment approaches that are usually based on therapies developed specifically for children or for supratentorial brain tumors. CONCLUSIONS: The clinical course and surgical outcome of adult patients with intra-axial brain tumors in the posterior fossa are summarized in this review. The prognostic factors and therapeutic management of patients with these tumors are controversial because of their rarity, their heterogeneity, and the lack of sufficient data in the literature.

miR-15a and miR-24-1 as putative prognostic microRNA signatures for pediatric pilocytic astrocytomas and ependymomas.

In the current setting, we attempted to verify and validate miRNA candidates relevant to pediatric primary brain tumor progression and outcome, in order to provide data regarding the identification of novel prognostic biomarkers. Overall, 26 resected brain tumors were studied from children diagnosed with pilocytic astrocytomas (PAs) (n = 19) and ependymomas (EPs) (n = 7). As controls, deceased children who underwent autopsy and were not present with any brain malignancy were used. The experimental approach included microarrays covering 1211 miRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate the expression profiles of miR-15a and miR-24-1. The multiparameter analyses were performed with MATLAB. Matching differentially expressed miRNAs were detected in both PAs and EPs, following distinct comparisons with the control cohort; however, in several cases, they exhibited tissue-specific expression profiles. On correlations between miRNA expression and EP progression or outcome, miR-15a and miR-24-1 were found upregulated in EP relapsed and EP deceased cases when compared to EP clinical remission cases and EP survivors, respectively. Taken together, following several distinct associations between miRNA expression and diverse clinical parameters, the current study repeatedly highlighted miR-15a and miR-24-1 as candidate oncogenic molecules associated with inferior prognosis in children diagnosed with ependymoma.

Pediatric brainstem gangliogliomas show BRAF(V600E) mutation in a high percentage of cases.

Brainstem gangliogliomas (GGs), often cannot be resected, have a much poorer prognosis than those located in more common supratentorial sites and may benefit from novel therapeutic approaches. Therapeutically targetable BRAF c.1799T>A (p.V600E) (BRAF(V600E) ) mutations are harbored in roughly 50% of collective GGs taken from all anatomical sites. Large numbers of pediatric brainstem GGs, however, have not been specifically assessed and anatomic-and age-restricted assessment of genetic and biological factors are becoming increasingly important. Pediatric brainstem GGs (n = 13), non-brainstem GGs (n = 11) and brainstem pilocytic astrocytomas (PAs) (n = 8) were screened by standard Sanger DNA sequencing of BRAF exon 15. Five of 13 (38%) pediatric GG harbored a definitive BRAF(V600E) mutation, with two others exhibiting an equivocal result by this method. BRAF(V600E) was also seen in five of 11 (45%) non-brainstem GGs and one of eight (13%) brainstem PAs. VE1 immunostaining for BRAF(V600E) showed concordance with sequencing in nine of nine brainstem GGs including the two cases equivocal by Sanger. The equivocal brainstem GGs were subsequently shown to harbor BRAF(V600E) using a novel, more sensitive, RNA-sequencing approach, yielding a final BRAF(V600E) mutation frequency of 54% (seven of 13) in brainstem GGs. BRAF(V600E) -targeted therapeutics should be a consideration for the high percentage of pediatric brainstem GGs refractory to conventional therapies.

Clinical review of pediatric pilocytic astrocytomas treated at a tertiary care hospital in Pakistan.

BACKGROUND: Pilocytic Astrocytoma (PA) is a common type of brain tumor in the pediatric population. They have a fairly good prognosis. This study describes PAs in detail, with a focus on the demographic factors, presenting features, management and prognosis, and aims, to identify the negative outcome predictors in our population, which can affect the course of the disease. This article will add to the understanding of PAs from a third world perspective. METHODS: The Aga Khan University medical records (1995 - 2007) were reviewed, to study the clinical features, management, and outcome of patients (0 - 15 years) with Pilocytic Astrocytomas (PAs) in our population. After a thorough review of the medical records, all the PAs diagnosed on the basis of histopathology at our Pathology Laboratory, during this period, were included in the study. RESULTS: Twenty-two patients were included with a mean age of 9.25 years. Male-to-female ratio was 1 : 1. The most common presenting feature was a sign of increased intracranial pressure. The most common location was the cerebellum followed by the cerebrum. Fifteen patients underwent maximum surgical resection. Three had recurrence, despite no residual tumor. There were 10 Intensive Care Unit (ICU) admissions and one inpatient mortality. Fifteen patients followed up in the clinic: Eight had recurrence and four underwent repeat surgery (three showed clinical improvement). Hydrocephalus was a predictor of ICU admission. Solid consistency was found to be a marker of recurrence. CONCLUSION: Pilocytic Astrocytomas are the most common pediatric brain tumors in our population, commonly located in the cerebellum. Complete resection is the best treatment option, but some tumors are aggressive and recurrence is not uncommon. The possible negative outcome predictors are age, source of admission, extent of resection, hydrocephalus, and solid consistency.