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cIMPACT‐NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) was established to provide a forum to evaluate and recommend proposed changes to future CNS tumor classifications. From 2016 to 2019 (Round 1), cIMPACT published four updates. Update 1 clarified the use of the term NOS (Not Otherwise Specified) and proposed use of the additional term NEC (Not Elsewhere Classified). Update 2 issued clarifications regarding two diagnoses: Diffuse Midline Glioma, H3 K27M‐mutant and Diffuse Astrocytoma/Anaplastic Astrocytoma, IDH‐mutant. Update 3 proposed molecular criteria that could be used in the setting of an IDH‐wildtype diffuse or anaplastic astrocytic glioma without histological features of glioblastoma to infer that the tumor would behave similarly to a grade IV glioblastoma. Update 4 suggested that, in children and young adults, subtypes of IDH‐wildtype/H3‐wildtype diffuse gliomas may have distinct clinical features in the setting of a BRAFV600E mutation, FGFR1 alteration, other MAPK pathway alteration, or a MYB or MYBL1 rearrangement. The practical diagnostic relevance of these cIMPACT proposals is highlighted in this summary. [ABSTRACT FROM AUTHOR]

Background: The determinants of outcomes for adult survivors of pediatric low-grade glioma (PLGG) are largely unknown.Methods: This study collected population-based follow-up information for all PLGG patients diagnosed in Ontario, Canada from 1985 to 2012 (n = 1202) and determined factors affecting survival. The impact of upfront radiation treatment on overall survival (OS) was determined for a cohort of Ontario patients and an independent reference cohort from the Surveillance, Epidemiology, and End Results database.Results: At a median follow-up of 12.73 years (range, 0.02-33 years), only 93 deaths (7.7%) were recorded, and the 20-year OS rate was 90.1% ± 1.1%. Children with neurofibromatosis type 1 had excellent survival and no tumor-related deaths during adulthood. Adverse risk factors included pleomorphic xanthoastrocytoma (P < .001) and a thalamic location (P < .001). For patients with unresectable tumors surviving more than 5 years after the diagnosis, upfront radiotherapy was associated with an approximately 3-fold increased risk of overall late deaths (hazard ratio [HR], 3.3; 95% confidence interval [CI], 1.6-6.6; P = .001) and an approximately 4-fold increased risk of tumor-related deaths (HR, 4.4; 95% CI, 1.3-14.6; P = .013). In a multivariate analysis, radiotherapy was the most significant factor associated with late all-cause deaths (HR, 3.0; 95% CI, 1.3-7.0; P = .012) and tumor-related deaths (HR, 4.4; 95% CI, 1.3-14.6; P = 0.014). A similar association between radiotherapy and late deaths was observed in the independent reference cohort (P < .001). In contrast to early deaths, late mortality was associated not with PLGG progression but rather with tumor transformation and non-oncological causes.Conclusions: The course of PLGG is associated with excellent long-term survival, but this is hampered by increased delayed mortality in patients receiving upfront radiotherapy. These observations should be considered when treatment options are being weighed for these patients. [ABSTRACT FROM AUTHOR]

Objective Astrocytic inclusions ( AIs) have been identified on histologic specimens of patients with early onset seizures, and the proteomic contents have been described. The aim of this study was to compare the clinical, electroencephalography ( EEG), magnetoencephalography ( MEG), magnetic resonance imaging ( MRI), and surgical outcomes of AIs relative to focal cortical dysplasia ( FCD). Methods We assessed the clinical manifestations, semiology, ictal and interictal features on video- EEG, MEG, MRI features, and surgical outcomes of children with histologically proven AIs compared to FCD. Results Six children had AIs and 27 had FCD. Children with AIs had an earlier age at seizure onset, periodic spasms (all children), and interictal epileptiform discharges consisting of a mixture of generalized or diffuse hemispheric slow waves, sharp waves, spikes and polyspikes. Children with FCD were less likely to have spasms (4/27 [15%]), and the morphology of the diffuse hemispheric or generalized discharges were different from those of AI, consisting of spike-and-waves, polyspike-and-waves, sharp-and-slow waves, and paroxysmal fast activity. Patients with AIs were less likely to have tightly clustered MEG spike sources (3/6 [50%] vs. 23/27 [85%]), and more likely to demonstrate abnormal sulcation and gyration pattern (4/6 [67%] vs. 2/27 [7%]) and gray matter heterotopia (2/6 [33%] vs. 0/27 [0%]) than patients with FCD. Four children with AIs had resection and two had biopsy but did not undergo resection. Children with AIs had lower rates of seizure freedom after surgery compared to FCD (1/4 [25%] vs. 15/27 [56%], respectively). Significance Although there were some similarities between AIs and FCD, patients with AIs were more likely to present with early onset periodic spasms, have unusual interictal epileptiform discharges, abnormal sulcation, gyration pattern, and gray matter heterotopia, and were less likely to be seizure free following surgical resection relative to FCD. Further study with a larger sample size is needed to validate our findings. [ABSTRACT FROM AUTHOR]

Pediatric high-grade astrocytomas ( HGAs) account for 15-20% of all pediatric central nervous system tumors. These neoplasms predominantly involve the supratentorial hemispheres or the pons-diffuse intrinsic pontine gliomas ( DIPG). Assumptions that pediatric HGAs are biologically similar to adult HGAs have recently been challenged, and the development of effective therapeutic modalities for DIPG and supratentorial HGA hinges on a better understanding of their biological properties. Here, 20 pediatric HGAs (9 DIPGs and 11 supratentorial HGAs) were subject to gene expression profiling following approval by the research ethics board at our institution. Many of these tumors showed expression signatures composed of genes that promote G1/S and G2/M cell cycle progression. In particular, Aurora kinase B ( AURKB) was consistently and highly overexpressed in 6/9 DIPGs and 8/11 HGAs. Array data were validated using quantitative real-time PCR and immunohistochemistry, as well as cross-validation of our data set with previously published series. Inhibition of Aurora B activity in DIPG and in pediatric HGA cell lines resulted in growth arrest accompanied by morphological changes, cell cycle aberrations, nuclear fractionation and polyploidy as well as a reduction in colony formation. Our data highlight Aurora B as a potential therapeutic target in DIPG. [ABSTRACT FROM AUTHOR]

Summary Cerebral hyaline astrocytic inclusions have been observed in a subset of patients with early onset epilepsy, brain structural anomalies, and developmental delay, which indicates that it may represent a unique clinicopathologic entity. To further characterize this condition we use proteomics to investigate differentially expressed proteins in epileptic brain tissue from three pediatric epileptic patients with cerebral hyaline astrocytic inclusions, ranging in age from 5-13 years, and compare to brain tissue from two normal controls. Catalase and carbonic anhydrase I both exhibited increased expression in epileptic brain tissue compared to controls. These findings were confirmed by Western blot analysis. Furthermore, both proteins were localized to astrocytes and in epileptic brain were located within the cerebral hyaline astrocytic inclusions, suggesting a potential role in the generation of this pathologic feature of early onset epilepsy with cerebral hyaline astrocytic inclusions. [ABSTRACT FROM AUTHOR]