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Extensive molecular analyses of ependymal tumors have revealed that supratentorial and posterior fossa ependymomas have distinct molecular profiles and are likely to be different diseases. The presence of C11orf95-RELA fusion genes in a subset of supratentorial ependymomas (ST-EPN) indicated the existence of molecular subgroups. However, the pathogenesis of RELA fusion-negative ependymomas remains elusive. To investigate the molecular pathogenesis of these tumors and validate the molecular classification of ependymal tumors, we conducted thorough molecular analyses of 113 locally diagnosed ependymal tumors from 107 patients in the Japan Pediatric Molecular Neuro-Oncology Group. All tumors were histopathologically reviewed and 12 tumors were re-classified as non-ependymomas. A combination of RT-PCR, FISH, and RNA sequencing identified RELA fusion in 19 of 29 histologically verified ST-EPN cases, whereas another case was diagnosed as ependymoma RELA fusion-positive via the methylation classifier (68.9%). Among the 9 RELA fusion-negative ST-EPN cases, either the YAP1 fusion, BCOR tandem duplication, EP300-BCORL1 fusion, or FOXO1-STK24 fusion was detected in single cases. Methylation classification did not identify a consistent molecular class within this group. Genome-wide methylation profiling successfully sub-classified posterior fossa ependymoma (PF-EPN) into PF-EPN-A (PFA) and PF-EPN-B (PFB). A multivariate analysis using Cox regression confirmed that PFA was the sole molecular marker which was independently associated with patient survival. A clinically applicable pyrosequencing assay was developed to determine the PFB subgroup with 100% specificity using the methylation status of 3 genes, CRIP1, DRD4 and LBX2. Our results emphasized the significance of molecular classification in the diagnosis of ependymomas. RELA fusion-negative ST-EPN appear to be a heterogeneous group of tumors that do not fall into any of the existing molecular subgroups and are unlikely to form a single category.Electronic supplementary materialThe online version of this article (10.1186/s40478-018-0630-1) contains supplementary material, which is available to authorized users.

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A biomarker for early diagnosis of central nervous system (CNS) lymphoma would permit early treatment for attenuation of disease progression and neurological deterioration. High interleukin-10 (IL-10) or an IL-10/IL-6 ratio >1.0 are informative parameters for discriminating intraocular lymphomas from uveitis. Recent reports have also shown that CSF IL-10 is a potential diagnostic biomarker for CNS lymphoma. The purpose of this study was to evaluate the diagnostic value of IL-10 in cerebrospinal fluid (CSF) in patients with CNS lymphoma compared with other CNS diseases, including CNS tumors and inflammatory diseases. CSF IL-10, IL-6, beta-2 microglobulin, soluble IL-2 receptor and FDG-PET SUVmax were measured in 19 patients with CNS lymphoma (15 primary and 4 secondary diffuse large B-cell lymphomas) and 26 non-lymphoma patients with various brain tumors and inflammatory diseases. The diagnostic accuracy of the respective examinations for differentiation of CNS lymphomas from non-lymphomas was evaluated by receiver operating characteristic (ROC) curve analysis. The area under the ROC curve (AUC) was calculated. CSF IL-10 was detected at significant levels (median, 28 pg/ml; range <2-4,100 pg/ml) in all except one patient with CNS lymphoma, but not detected in any non-lymphoma patients. CSF IL-10 had the highest diagnostic accuracy with AUC = 0.974. At an IL-10 cutoff of 3 pg/ml, the sensitivity and specificity were 94.7 and 100 %, respectively. These results indicate that CSF IL-10 is a superior biomarker for initial screening for patients with CNS lymphoma.

Purpose: Craniosynostosis patients treated with one-stage cranioplasty often have bleeding from the dura mater, fluid collection in the extradural space, and poor wound healing due to skin overstretching. To avoid these complications, we began using distraction osteogenesis. To determine the advantages and disadvantages of the procedure, we retrospectively compared distraction osteogenesis with conventional cranioplasty. Patients and Results: We treated 24 patients with fronto-orbital advancement. Fifteen had one-stage cranioplasty; 9 received distraction osteogenesis. The one-stage operation patients averaged 25.5 months of age at surgery, 289 min of operating time, and 154 ml of intraoperative blood loss. For the distraction group, the average age was 16.6 months, average operating time was 196 min, and average blood loss was 76 ml. Conclusions: Compared with one-stage cranioplasty patients, distraction osteogenesis patients had significantly less intraoperative bleeding and shorter operating times. The disadvantages of distraction treatment were the need for multiple surgeries, prolonged hospitalization, wound infection, and dislocation of the distraction device.

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Recent studies in rodents suggest that maternal immune activation (MIA) by viral infection is associated with schizophrenia and autism in offspring. Although maternal IL-6 is though t to be a possible mediator relating MIA induced these neuropsychiatric disorders, the mechanism remains to be elucidated. Previously, we reported that the maternal leukemia inhibitory factor (LIF)–placental ACTH–fetal LIF signaling relay pathway (maternal–fetal LIF signal relay) promotes neurogenesis of fetal cerebrum in rats. Here we report that the maternal–fetal LIF signal relay in mice is suppressed by injection of polyriboinosinic-polyribocytidylic acid into dams, which induces MIA at 12.5 days post-coitum. Maternal IL-6 levels and gene expression of placental suppressor of cytokine signaling 3 (Socs3) increased according to the severity of MIA and gene expression of placental Socs3 correlated with maternal IL-6 levels. Furthermore, we show that MIA causes reduction of LIF level in the fetal cerebrospinal fluid, resulting in the decreased neurogenesis in the cerebrum. These findings suggest that maternal IL-6 interferes the maternal–fetal LIF signal relay by inducing SOCS3 in the placenta and leads to decreased neurogenesis.

We present a case of chordoid glioma involving the third ventricle in a 42-year-old woman. CT and MR showed a homogeneously enhancing mass occupying the third ventricle, with a cystic component. Chordoid glioma should be included in the differential diagnosis of uncommon masses of the third ventricle in middle-aged women.