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To explore factors that might be associated with prognosis of dysembryoplastic neuroepithelial tumors (DNTs). DNTs patients who were admitted to the Department of Neurosurgery of Xiangya Hospital between 1 January 2010 and 31 December 2018 and underwent surgical resection were retrospectively analyzed. Clinical, neuroimaging, and pathological features of DNTs were compared among patients with different outcomes and analyzed using the Kaplan–Meier curves and univariable Cox regression analysis. Thirty-three DNTs patients were included finally, of which the average age at seizure onset was 11.59 ± 7.46 years old and the average duration of seizures prior to surgical resection was 3.00 ± 4.68 years. After surgical resection, the patients were followed up for 2.39 ± 1.97 years, and 28 patients (84.85%) were seizure-free (class I of the Engel Outcome Scale) while five patients (15.15%) were seizure-continuous (class II or III of the Engel Outcome Scale). When compared with seizure-free patients, seizure-continuous patients had greater age at seizure onset and longer duration of seizures before surgical resection (p <.05). No variables were found to be statistically significantly associated with prognosis in univariable Cox regression analysis, but patients with extra-temporal DNTs were found to have better prognosis than those with temporal DNTs (log-rank test p =.048). Elder seizure onset age, longer duration of seizures prior to surgical resection, and a temporal location may be risk factors of poor prognosis for DNTs patients after surgical resection. [ABSTRACT FROM AUTHOR]

The correlation between Presenilin-1 (PSEN1) E280A mutation and clinical characteristics of gliomarelated seizures (GRS) was explored. For this purpose, brain tissue samples were collected from 40 patients diagnosed with glioneuronal tumors (GNTs), including 25 cases of gangliogliomas (GGs) and 15 cases of dysembryoplastic neuroepithelial tumors (DNTs). Then, the DNA of GNTs tissues was extracted, and the PSEN1 E280A mutation was detected by sequencing. Finally, the correlation of PSEN1 E280A mutation with clinical characteristics was analyzed. PSEN1 E280A mutation was detected in 16 GNTs patients (44% in GGs (11/25) and 33.3% in DNTs (5/15)). PSEN1 E280A mutation was obviously elevated in females (10/16, 62.5%) versus in males (6/24, 25%) (P = 0.025). Meanwhile, more extensive seizure types were present in GNTs with PSEN1 mutations versus wilds (P = 0.001), but there was no clear correlation between PSEN1 and clinical manifestations like age of seizure, operative age, duration and absence of seizures after surgery. To conclude, PSEN1 E280A mutation is present in GNTs seizures patients, and greatly associated with multiple types of seizures and gender. The requirement of larger sample studies and long-term follow-up is implemented for further confirmation. [ABSTRACT FROM AUTHOR]

Abstract Background Dysembryoplastic neuroepithelial tumors are rare benign supratentotrial epilepsy-associated glioneuronal tumors of children and young adults. Patients have a long history of seizures. Proper surgical resection achieves long term seizure control. We describe the clinicopathological features of dysembryoplastic neuroepithelial tumor cases reported in our practice and review the published literature. Methods All cases of Pakistani ethnicity were diagnosed between 2015 and 2021 were included. Slides were reviewed and clinicopathological features were recorded. Follow-up was obtained. Extensive literature review was conducted. Results Fourteen cases were reported. There were 12 males and 2 females. Age range was 9–45 years (mean 19 years). Majority were located in the temporal and frontal lobes. Duration of seizures prior to resection ranged from 2 months to 9 years with mean and median duration of 3.2 and 3 years, respectively. Histologically, all cases demonstrated a multinodular pattern, specific glioneuronal component, and floating neurons. Simple and complex forms comprised seven cases each. No significant nuclear atypia, mitotic activity, or necrosis was seen. Ki-67 proliferative index was very low. Cortical dysplasia was noted in adjacent glial tissue in four cases. Follow-up ranged from 20 to 94 months. Seizures continued following resection in all but one case but were reduced in frequency and intensity. In one case, seizures stopped completely following surgery. Conclusion Clinicopathological features were similar to those in published literature. However, a marked male predominance was noted in our series. Seizures continued following resection in all but one case but were reduced in frequency and intensity. This series will help raise awareness among clinicians and pathologists in our part of the world about this seizure-associated tumor of children and young adults.

Background: Dysembryoplastic neuroepithelial tumors are rare benign supratentotrial epilepsy-associated glioneuronal tumors of children and young adults. Patients have a long history of seizures. Proper surgical resection achieves long term seizure control. We describe the clinicopathological features of dysembryoplastic neuroepithelial tumor cases reported in our practice and review the published literature. Methods: All cases of Pakistani ethnicity were diagnosed between 2015 and 2021 were included. Slides were reviewed and clinicopathological features were recorded. Follow-up was obtained. Extensive literature review was conducted. Results: Fourteen cases were reported. There were 12 males and 2 females. Age range was 9–45 years (mean 19 years). Majority were located in the temporal and frontal lobes. Duration of seizures prior to resection ranged from 2 months to 9 years with mean and median duration of 3.2 and 3 years, respectively. Histologically, all cases demonstrated a multinodular pattern, specific glioneuronal component, and floating neurons. Simple and complex forms comprised seven cases each. No significant nuclear atypia, mitotic activity, or necrosis was seen. Ki-67 proliferative index was very low. Cortical dysplasia was noted in adjacent glial tissue in four cases. Follow-up ranged from 20 to 94 months. Seizures continued following resection in all but one case but were reduced in frequency and intensity. In one case, seizures stopped completely following surgery. Conclusion: Clinicopathological features were similar to those in published literature. However, a marked male predominance was noted in our series. Seizures continued following resection in all but one case but were reduced in frequency and intensity. This series will help raise awareness among clinicians and pathologists in our part of the world about this seizure-associated tumor of children and young adults. [ABSTRACT FROM AUTHOR]

Background: Myxoid glioneuronal tumor (MGT) is a benign glioneuronal neoplasm recently introduced in the World Health Organization (WHO) classification of the central nervous system (CNS) tumors. MGTs are typically located in the septum pellucidum, foramen of Monro or periventricular white matter of the lateral ventricle. They were previously diagnosed as dysembryoplastic neuroepithelial tumors (DNT), showing histological features almost indistinguishable from classical cortical DNT. Despite that, MGTs have been associated with a specific dinucleotide substitution at codon 385 in the platelet-derived growth factor receptor alpha (PDGFRA) gene, replacing a lysine residue with either leucine or isoleucine (p. LysK385Leu/Iso). This genetic variation has never been described in any other CNS tumor. Materials and methods: Thirty-one consecutive tumors, previously diagnosed as DNTs at the Meyer Children's Hospital IRCCS between January 2010 and June 2021 were collected for a comprehensive study of their clinical, imaging, pathological features, and molecular profile. Results: In six out of the thirty-one tumors we had previously diagnosed as DNTs, we identified the recurrent dinucleotide mutation in the PDGFRA. All six tumors were typically located within the periventricular white matter of the lateral ventricle and in the septum pellucidum. We then renamed these lesions as MGT, according to the latest WHO CNS classification. In all patients we observed an indolent clinical course, without recurrence. Conclusion: MGT represent a rare but distinct group of neoplasm with a typical molecular profiling, a characteristic localization, and a relative indolent clinical course.

Objective: To determine the predictors and the long-term outcomes of patients with seizures following surgery for dysembryoplastic neuroepithelial tumors (DNTs); Methods: Clinical data were collected from medical records of consecutive patients of the Department of Neurosurgery of Sanbo Brain Hospital of Capital Medical University with a pathological diagnosis of DNT and who underwent surgery from January 2008 to July 2021. All patients were followed up after surgery for at least one year. We estimated the cumulative rate of seizure recurrence-free and generated survival curves. A log-rank (Mantel–Cox) test and a Cox proportional hazard model were performed for univariate and multivariate analysis to analyze influential predictors; Results: 63 patients (33 males and 30 females) were included in this study. At the final follow-up, 49 patients (77.8%) were seizure-free. The cumulative rate of seizure recurrence-free was 82.5% (95% confidence interval (CI) 71.8–91.3%), 79.0% (95% CI 67.8–88.6%) and 76.5% (95% CI 64.8–87.0%) at 2, 5, and 10 years, respectively. The mean time for seizure recurrence-free was 6.892 ± 0.501 years (95% CI 5.91–7.87). Gross total removal of the tumor and a short epilepsy duration were significant predictors of seizure freedom. Younger age of seizure onset, bilateral interictal epileptiform discharges, and MRI type 3 tumors were risk factors for poor prognosis; Conclusions: A favorable long-term seizure outcome was observed for patients with DNT after surgical resection. Predictor analysis could effectively guide the clinical work and evaluate the prognosis of patients with DNT associated with epilepsy. [ABSTRACT FROM AUTHOR]

Neurotrophic tyrosine receptor kinase (NTRK) rearrangements are oncogenic drivers of various types of adult and pediatric tumors, including gliomas. However, NTRK rearrangements are extremely rare in glioneuronal tumors. Here, we report a novel NTRK2 rearrangement in a 24-year-old female with dysembryoplastic neuroepithelial tumor (DNT), a circumscribed WHO grade I benign tumor associated with epilepsy. By utilizing targeted RNA next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), reverse transcriptasePCR (RT-PCR), and Sanger sequencing, we verified an in-frame fusion between NTRK2 and the lipomaHMGIC fusion partner-like 3 (LHFPL3). This oncogenic gene rearrangement involves 5' LHFPL3 and 3' NTRK2, retaining the entire tyrosine kinase domain of NTRK2 genes. Moreover, thetargetedDNANGSanalysis revealed an IDH1(p.R132H) mutation, a surprising finding in this type of tumor. The pathogenic mechanism of theLHFPL3::NTRK2 in this case likely involves aberrantdimerization and constitutive activation of RTK signaling pathways. [ABSTRACT FROM AUTHOR]

Low-grade dysembryoplastic neuroepithelial tumors (DNTs) are a frequent cause of drug-refractory epilepsy. Molecular mechanisms underlying seizure generation in these tumors are poorly understood. This study was conducted to identify altered genes in nonneoplastic epileptogenic cortical tissues (ECTs) resected from DNT patients during electrocorticography (ECoG)-guided surgery. RNA sequencing (RNAseq) was used to determine the differentially expressed genes (DEGs) in these high-spiking ECTs compared to non-epileptic controls. A total of 477 DEGs (180 upregulated; 297 downregulated) were observed in the ECTs compared to non-epileptic controls. Gene ontology analysis revealed enrichment of genes belonging to the following Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways: (i) glutamatergic synapse; (ii) nitrogen metabolism; (iii) transcriptional misregulation in cancer; and (iv) protein digestion and absorption. The glutamatergic synapse pathway was enriched by DEGs such as GRM4, SLC1A6, GRIN2C, GRM2, GRM5, GRIN3A, and GRIN2B. Enhanced glutamatergic activity was observed in the pyramidal neurons of ECTs, which could be attributed to altered synaptic transmission in these tissues compared to non-epileptic controls. Besides glutamatergic synapse, altered expression of other genes such as GABRB1 (synapse formation), SLIT2 (axonal growth), and PROKR2 (neuron migration) could be linked to epileptogenesis in ECTs. Also, upregulation of GABRA6 gene in ECTs could underlie benzodiazepine resistance in these patients. Neural cell-type–specific gene set enrichment analysis (GSEA) revealed transcriptome of ECTs to be predominantly contributed by microglia and neurons. This study provides first comprehensive gene expression profiling of nonneoplastic ECTs of DNT patients and identifies genes/pathways potentially linked to epileptogenesis. [ABSTRACT FROM AUTHOR]

Pilocytic astrocytoma with a predominant oligodendrocyte-like component can be difficult to distinguish from oligodendroglioma, dysembryoplastic neuroepithelial tumors (DNTs), central neurocytoma, and ependymoma (clear cell phenotype). The utility of GFAP immunostaining in this context is not well discussed. All cases with a diagnosis of pilocytic astrocytoma were retrieved from the pathological archives along with the following information: age, sex, and pathological description. The GFAP immunostaining was scored as score 1 (<25%), score 2 (25–50%), score 3 (50–75%), and score 4 (>75%). The comparison group included oligodendrogliomas, DNTs, ependymomas, and central neurocytomas. All 26 cases (16 males and 10 females) of pilocytic astrocytoma showed strong and diffuse (score 4) GFAP immunostaining in the neoplastic cells of both the solid fibrillary and oligodendrocyte-like components. The staining pattern in the neoplastic round cells in the oligodendrocyte-like areas was perinuclear cytoplasmic with no processes. In the comparison group, GFAP immunostaining was mostly restricted to the reactive astrocytes in the background. Focal areas of the neoplastic cells showed scores of 1–3 in the neoplastic cells, but the staining pattern was different from those in pilocytic astrocytoma. In the setting of tumors with predominant oligodendrocyte-like areas, the GFAP immunostaining score and pattern help distinguish pilocytic astrocytoma from its mimickers. [ABSTRACT FROM AUTHOR]

Highlights from the article: Gangliogliomas are uncommon tumors of the central nervous system (CNS) predominantly seen in children and young patients presenting with temporal lobe epilepsy, as these tumors are the most common neoplastic cause of chronic temporal lobe epilepsy [[1]]. Initially, it remained unclear whether MVNTs were true neoplastic processes or malformed dysplastic lesions; however, according to the revised WHO classification of CNS tumors, these tumors have been recognized as low-grade mixed glial neuronal lesions since 2016 [[3], [11]]. Angiocentric gliomas, also known as angiocentric neuroepithelial tumor, are very rare neuroepithelial tumors with low proliferation rates, which are classified as WHO grade I neoplasms [[3], [13]]. Pilocytic astrocytoma, Ganglioglioma, Dysembryoplastic neuroepithelial tumors, Angiocentric glioma, Multinodular and vacuolating neuronal tumor, Hypersalivatory seizures.

The associations between gangliogliomas, dysembryoplastic neuroepithelial tumors (DNETs), and cortical dysplasias remain debatable. We report five cases of drug refractory epilepsy with temporal lobe lesions. On resection, histopathological examination showed distinctive areas of gangliogliomas and DNETs with cortical dysplasia. The coexistence of the above three lesions as distinct entities in a single lesion is virtually unknown. This points to the presence of a possible etiological relationship among them. Finally, we also delve into a plausible hypothesis for such a pathogenesis. [ABSTRACT FROM AUTHOR]

Summary: Objective: Glioneuronal tumors (GNTs) are well‐recognized causes of chronic drug‐resistant focal epilepsy in children. Our practice involves an initial period of radiological surveillance and antiepileptic medications, with surgery being reserved for those with radiological progression or refractory seizures. We planned to analyze the group of patients with low‐grade GNTs, aiming to identify factors affecting seizure and cognitive outcomes. Methods: We retrospectively reviewed the medical records of 150 children presenting to Great Ormond Street Hospital with seizures secondary to GNTs. Analysis of clinical, neuroimaging, neuropsychological, and surgical factors was performed to determine predictors of outcome. Seizure outcome at final follow‐up was classified as either seizure‐free (group A) or not seizure‐free (group B) for patients with at least 12‐months follow‐up postsurgery. Full‐scale intelligence quotient (FSIQ) was used as a measure of cognitive outcome. Results: Eighty‐six males and 64 females were identified. Median presurgical FSIQ was 81. One hundred twenty‐one patients (80.5%) underwent surgery. Median follow‐up after surgery was 2 years, with 92 patients (76%) having at least 12 months of follow‐up after surgery. Seventy‐four patients (80%) were seizure‐free, and 18 (20%) continued to have seizures. Radiologically demonstrated complete tumor resection was associated with higher rates of seizure freedom (P = .026). Higher presurgical FSIQ was related to shorter epilepsy duration until surgery (P = .012) and to older age at seizure onset (P = .043). Significance: A high proportion of children who present with epilepsy and GNTs go on to have surgical tumor resection with excellent postoperative seizure control. Complete resection is associated with a higher chance of seizure freedom. Higher presurgical cognitive functioning is associated with shorter duration of epilepsy prior to surgery and with older age at seizure onset. Given the high rate of eventual surgery, early surgical intervention should be considered in children with continuing seizures associated with GNTs. [ABSTRACT FROM AUTHOR]

Objective: In this systematic review the authors aimed to evaluate the effectiveness and superiority of radiomics in detecting tiny epilepsy lesions and to conduct original research in the use of radiomics for preliminary prediction of postoperative seizures in patients with dysembryoplastic neuroepithelial tumor (DNET)., Methods: The PubMed and Web of Science databases were searched from the earliest record, January 1, 2018, to December 29, 2021, for reports of the detection of epilepsy using radiomics, and the resulting articles were carefully checked according to the PRISMA 2020 guidelines. The authors then conducted original research by evaluating MR images in 18 patients, who were then separated into two groups, the epilepsy recurrence group (ERG) and the epilepsy nonrecurrence group. The tumor region and the edema region were segmented manually by 3D Slicer. The radiomics data were extracted from MR images by using "Slicer Radiomics" running on Mac OS X. Tumor regions were observed with T1-weighted imaging, and edema with FLAIR imaging. Radiomics features with significant differences were selected through comparison according to epilepsy relapses performed with the Mann-Whitney U-test. The edema and tumor regions were also compared within groups to identify their distinctive features. Radiomics features were tested to verify their ability to predict recurrence epilepsy by receiver operating characteristic curve., Results: This systematic review located 9 original articles related to epilepsy and radiomics published from 2018 to 2021. The reported studies demonstrated that radiomics is useful for detecting tiny epilepsy lesions. Among the radiomics features used, the predictive ability of the area under the curve was more than 0.8. The heterogeneity of the peritumoral edema region was found to be higher in the ERG., Conclusions: Satellite lesions in the peritumoral edema region of DNET patients may cause epilepsy recurrence, and radiomics is an emerging method to detect and evaluate these epilepsy-associated lesions.

Dysembryoplastic neuroepithelial tumors (DNT) is a benign (World Health Organisation, WHO, grade I) glioneuronal tumor and it represent one of the most frequent neoplasm in patient affected by seizures. The epileptic neuronal activity can be determined by abnormal synchronization, excessive glutamate excitation and\or inadequate GABA inhibition. Increasing evidence suggests that the astrocytes might be involved in this process even if neurons play a relevant role. In particular astrocytes promote the clearance of glutamate, a potent excitatory neurotransmitter of the central nervous system. Indeed, elevated concentrations of extracellular glutamate may determine iper-excitability and seizures as well as other neurological disorders. So, astrocytes, converting glutamate into glutamine via the enzyme glutamine synthetase (GS), could play a protective anti-seizures role. In the present study, we analyzed the immunohistochemical expression of GS in 20 DNTs specimens documenting a constant immunoistochemical expression of GS in astrocytes of the lesional tissue and of the cerebral cortex. • DNT is a benign glioneuronal tumor. It represents one of the most frequent neoplasm in patient affected by seizures. • GS is expressed in astrocytes and it plays an important role in the regulation of ammonia and glutamate concentration. • Glutamate is the major excitatory neurotransmitter. Its elevated extracellular concentrations may determinate seizures. • In DNTs astrocytes appeared larger and with stronger immunostaining for GS compared to astrocytes present in normal cortex. [ABSTRACT FROM AUTHOR]