Epileptogenic tumors affecting children and young adults are a morphologically diverse collection of neuroepithelial neoplasms that, as a group, exhibit varying levels of glial and/or neuronal differentiation. Recent advances in molecular profiling technology, including comprehensive DNA sequencing and methylation analysis, have enabled the application of more precise and biologically relevant classification schemes to these tumors. In this report, we describe a morphologically and molecularly distinct epileptogenic neoplasm, the polymorphous low-grade neuroepithelial tumor of the young (PLNTY), which likely accounts for a sizable portion of oligodendroglioma-like tumors affecting the pediatric population. Characteristic microscopic findings most notably include infiltrative growth, the invariable presence of oligodendroglioma-like cellular components, and intense immunolabeling for cluster of differentiation 34 (CD34). Moreover, integrative molecular profiling reveals a distinct DNA methylation signature for PLNTYs, along with frequent genetic abnormalities involving either B-Raf proto-oncogene (BRAF) or fibroblast growth factor receptors 2 and 3 (FGFR2, FGFR3). These findings suggest that PLNTY represents a distinct biological entity within the larger spectrum of pediatric, low-grade neuroepithelial tumors.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-016-1639-9) contains supplementary material, which is available to authorized users.

- Summary:Purpose: Partial seizures in early postnatal life may be catastrophic and associated with poor long-term outcome. Epilepsy surgery can alleviate partial seizures in older children and adults, but there is little experience with surgical therapy in infancy apart from hemispheric epilepsy syndromes.Methods: We analyzed the results of cortical resection to treat medically refractory partial epilepsy in 31 children (16 boys, 15 girls) aged <3 years (mean, 18.3 months). Subjects were included only if seizure relief was the primary indication for surgery.Results: Follow-up of at least 1 year (mean, 4.6 years) in 26 patients revealed that 16 were seizure-free, 4 had >90% seizure reduction, and 6 had <90% reduction. There was no significant difference in seizure outcome between hemispherectomy/ multilobar resections and lobar resections or temporal versus extratemporal resection. Seizure outcome was independent of the amount of cortex removed in nonlesional patients. Only the presence of a discrete lesion on preoperative neuroimaging correlated with a favorable outcome. Family perceptions of accelerated development in seizure-free patients were not confirmed on developmental assessment.Conclusions: We conclude that cortical resection often benefits very young children with catastrophic partial seizures, but does not guarantee enhanced neurological development. The location and extent of the excised cortex may not be critical as long as the entire epileptogenic region and tesion are removed.

We investigated a 6-month-old infant with daily episodes of left hemifacial contraction, head and eye deviation to the right, nystagmoid jerks to the right, autonomic dysfunction, and retained consciousness. The episodes began on day 1 of life and were unresponsive to antiepileptic medication. Interictal and ictal scalp electroencephalographic (EEG) recordings were unremarkable. Magnetic resonance imaging revealed a mass in the left cerebellar hemisphere and peduncle. Ictal single-photon emission computed tomography revealed focal hyperperfusion in the region of the cerebellar mass. Ictal EEG recordings with implanted cerebellar electrodes demonstrated focal seizure discharges in the region of the mass. Resection of the mass resulted in remission of seizures and histopathology revealed ganglioglioma. Six previously reported infants with similar semiology (described as "hemifacial spasm"), imaging findings, and histopathology are reviewed. We believe the previously reported infants and our patient constitute a rare but important clinicopathological syndrome of infancy characterized by epileptic seizures of cerebellar origin.

Findings on cranial magnetic resonance (MR) images were correlated with known histopathologic findings in 42 patients with tuberous sclerosis (TS), 17 of whom received gadopentetate dimeglumine, to extend the range of signs on MR images. Four neuroradiologists recorded the number, sites, configurations, and relative signal intensities of intracranial abnormalities. White matter lesions, found in 39 patients (93%), showed four distinct patterns: (a) straight or curvilinear bands extending radially from the ventricle through the cerebral mantle toward the cortex, (b) wedge-shaped lesions, (c) nonspecific conglomerate foci, and (d) cerebellar radial bands. It is concluded that cortical tubers, white matter lesions, subependymal nodules, and sub-ependymal giant cell astrocytomas (SGCAs) may be enhanced after administration of gadopenetetate dimeglumine. Enhancement of a TS lesion does not indicate neoplastic transformation into SGCA. Imaging surveillance every 12 months appears indicated during the peak ages (8-18 years) of occurrence of SGCA. The appearance of white matter lesions supports the theory that the cerebral lesions of TS may be caused by disordered migration of dysgenetic cells.

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Although chronic vagus nerve stimulation (VNS) is an established treatment for medically-intractable childhood epilepsy, there is considerable heterogeneity in seizure response and little data are available to pre-operatively identify patients who may benefit from treatment. Since the therapeutic effect of VNS may be mediated by afferent projections to the thalamus, we tested the hypothesis that intrinsic thalamocortical connectivity is associated with seizure response following chronic VNS in children with epilepsy. Twenty-one children (ages 5–21 years) with medically-intractable epilepsy underwent resting-state fMRI prior to implantation of VNS. Ten received sedation, while 11 did not. Whole brain connectivity to thalamic regions of interest was performed. Multivariate generalized linear models were used to correlate resting-state data with seizure outcomes, while adjusting for age and sedation status. A supervised support vector machine (SVM) algorithm was used to classify response to chronic VNS on the basis of intrinsic connectivity. Of the 21 subjects, 11 (52%) had 50% or greater improvement in seizure control after VNS. Enhanced connectivity of the thalami to the anterior cingulate cortex (ACC) and left insula was associated with greater VNS efficacy. Within our test cohort, SVM correctly classified response to chronic VNS with 86% accuracy. In an external cohort of 8 children, the predictive model correctly classified the seizure response with 88% accuracy. We find that enhanced intrinsic connectivity within thalamocortical circuitry is associated with seizure response following VNS. These results encourage the study of intrinsic connectivity to inform neural network-based, personalized treatment decisions for children with intractable epilepsy.

Diagnosis and treatment of pediatric CNS tumors necessitate a multi-disciplinary approach and require expertise and diligence of all parties involved. Imaging is an essential component has evolved greatly over the past decade. We are becoming better at making a preoperative diagnosis of that tumor type, detecting recurrence, and guiding surgical management to avoid injury to vital brain structures.

Visual and auditory cortices can be activated in children who have been sedated. Visual responses show negative values in the rostral visual cortex, independent of age. Auditory activation is seen in temporal and frontal lobes.