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Background and purpose: Despite their detrimental impact on the quality of life in autoimmune encephalitis, sleep disorders have not been investigated in anti‐glutamic acid decarboxylase (GAD65) associated neurological syndromes. Methods: Six consecutive adult patients diagnosed with anti‐GAD65‐associated neurological syndromes (four with limbic encephalitis and two with stiff‐person syndrome) and 12 healthy controls were enrolled. Participants underwent sleep interviews and sleep studies including night‐time video‐polysomnography, followed by five daytime multiple sleep latency tests (MSLTs, to assess propensity to fall asleep) and an 18 h bed rest polysomnography (to assess excessive sleep need). Results: Patients reported the need for daily naps and that their cognition and quality of life were altered by sleepiness, but they had normal scores on the Epworth sleepiness scale. Compared with controls, sleep latencies during the MSLT were shorter in the patient group (median 5.8 min, interquartile range [IQR] 4.5, 6.0 vs. 17.7 min, IQR 16.3, 19.7, p = 0.001), and the arousal index was reduced (2.5/h, IQR 2.3, 3.0 vs. 22.3/h, IQR 13.8, 30.0, p = 0.002), although total sleep time was similar between groups (621 min, IQR 464, 651 vs. 542.5 min, IQR 499, 582, p = 0.51). Remarkably, all six patients had MSLT latencies ≤8 min, indicating severe sleepiness. No parasomnia or sleep‐disordered breathing was detected. Conclusion: Central hypersomnia is a relevant characteristic of anti‐GAD65‐associated neurological syndromes. [ABSTRACT FROM AUTHOR]

Aims: The distinction between CNS WHO grade 2 and grade 3 is instrumental in choosing between observational follow‐up and adjuvant treatment for resected astrocytomas IDH‐mutant. However, the criteria of CNS WHO grade 2 vs 3 have not been updated since the pre‐IDH era. Methods: Maximal mitotic activity in consecutive high‐power fields corresponding to 3 mm2 was examined for 118 lower‐grade astrocytomas IDH‐mutant. The prognostic value for time‐to‐treatment (TTT) and overall survival (OS) of mitotic activity and other putative prognostic factors (including age, performance status, pre‐surgical tumour volume, multilobar involvement, post‐surgical residual tumour volume and midline involvement) was assessed for tumours with ATRX loss and the absence of CDKN2A homozygous deletion or CDK4 amplification, contrast enhancement, histological necrosis and microvascular proliferation. Results: Seventy‐one per cent of the samples had <6 mitoses per 3 mm2. Mitotic activity, residual volume and multilobar involvement were independent prognostic factors of TTT. The threshold of ≥6 mitoses per 3 mm2 identified patients with a shorter TTT (median 18.5 months). A residual volume ≥1 cm3 also identified patients with a shorter TTT (median 24.5 months). The group defined by <6 mitoses per 3 mm2 and a residual volume <1 cm3 had the longest TTT (median 73 months) and OS (100% survival at 7 years). These findings were confirmed in a validation cohort of 52 tumours. Conclusions: Mitotic activity and post‐surgical residual volume can be combined to evaluate the prognosis for patients with resected astrocytomas IDH‐mutant. Patients with <6 mitoses per 3 mm2 and a residual volume <1 cm3 were the best candidates for observational follow‐up. [ABSTRACT FROM AUTHOR]

Adult glioblastomas, IDH‐wildtype represent a heterogeneous group of diseases. They are resistant to conventional treatment by concomitant radiochemotherapy and carry a dismal prognosis. The discovery of oncogenic gene fusions in these tumors has led to prospective targeted treatments, but identification of these rare alterations in practice is challenging. Here, we report a series of 30 adult diffuse gliomas with an in frame FGFR3‐TACC3 oncogenic fusion (n = 27 WHO grade IV and n = 3 WHO grade II) as well as their histological and molecular features. We observed recurrent morphological features (monomorphous ovoid nuclei, nuclear palisading and thin parallel cytoplasmic processes, endocrinoid network of thin capillaries) associated with frequent microcalcifications and desmoplasia. We report a constant immunoreactivity for FGFR3, which is a valuable method for screening for the FGFR3‐TACC3 fusion with 100% sensitivity and 92% specificity. We confirmed the associated molecular features (typical genetic alterations of glioblastoma, except the absence of EGFR amplification, and an increased frequency of CDK4 and MDM2 amplifications). FGFR3 immunopositivity is a valuable tool to identify gliomas that are likely to harbor the FGFR3‐TACC3 fusion for inclusion in targeted therapeutic trials. [ABSTRACT FROM AUTHOR]

The integrated diagnosis of anaplastic oligodendroglioma, IDH mutant and 1p/19q co-deleted, grade III (O3id) is a histomolecular entity that WHO 2016 classification distinguished from other diffuse gliomas by specific molecular alterations. In contrast, its cell portrait is less well known. The present study is focused on intertumor and intratumor, cell lineage-oriented, heterogeneity in O3id. Based on pathological, transcriptomic and immunophenotypic studies, a novel subgroup of newly diagnosed O3id overexpressing neuronal intermediate progenitor (NIP) genes was identified. This NIP overexpression pattern in O3id is associated with: (i) morphological and immunohistochemical similarities with embryonic subventricular zone, (ii) proliferating tumor cell subpopulation with NIP features including expression of INSM1 and no expression of SOX9, (iii) mutations in critical genes involved in NIP biology and, (iv) increased tumor necrosis. Interestingly, NIP tumor cell subpopulation increases in O3id recurrence compared with paired newly diagnosed tumors. Our results, validated in an independent cohort, emphasize intertumor and intratumor heterogeneity in O3id and identified a tumor cell subpopulation exhibiting NIP characteristics that is potentially critical in oncogenesis of O3id. A better understanding of spatial and temporal intratumor cell heterogeneity in O3id will open new therapeutic avenues overcoming resistance to current antitumor treatments. [ABSTRACT FROM AUTHOR]