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Abstract Gliomas are the most common central nervous tumors in children and adolescents. However, spinal cord low-grade gliomas (sLGGs) are rare, with scarce information on tumor genomics and epigenomics. To define the molecular landscape of sLGGs, we integrated clinical data, histology, and multi-level genetic and epigenetic analyses on a consecutive cohort of 26 pediatric patients. Driver molecular alteration was found in 92% of patients (24/26). A novel variant of KIAA1549:BRAF fusion (ex10:ex9) was identified using RNA-seq in four cases. Importantly, only one-third of oncogenic drivers could be revealed using standard diagnostic methods, and two-thirds of pediatric patients with sLGGs required extensive molecular examination. The majority (23/24) of detected alterations were potentially druggable targets. Four patients in our cohort received targeted therapy with MEK or NTRK inhibitors. Three of those exhibited clinical improvement (two with trametinib, one with larotrectinib), and two patients achieved partial response. Methylation profiling was implemented to further refine the diagnosis and revealed intertumoral heterogeneity in sLGGs. Although 55% of tumors clustered with pilocytic astrocytoma, other rare entities were identified in this patient population. In particular, diffuse leptomeningeal glioneuronal tumors (n = 3) and high-grade astrocytoma with piloid features (n = 1) and pleomorphic xanthoastrocytoma (n = 1) were present. A proportion of tumors (14%) had no match with the current version of the classifier. Complex molecular genetic sLGGs characterization was invaluable to refine diagnosis, which has proven to be essential in such a rare tumor entity. Moreover, identifying a high proportion of drugable targets in sLGGs opened an opportunity for new treatment modalities.

Objective: Epilepsy surgery in the operculoinsular cortex is challenging due to the difficult delineation of the epileptogenic zone and the high risk of postoperative deficits., Methods: Pre- and postsurgical data from 30 pediatric patients who underwent operculoinsular cortex surgery at the Motol Epilepsy Center Prague from 2010 to 2022 were analyzed., Results: Focal cortical dysplasia (FCD; n = 15, 50%) was the predominant cause of epilepsy, followed by epilepsy-associated tumors (n = 5, 17%) and tuberous sclerosis complex (n = 2, 7%). In eight patients where FCD was the most likely etiology, the histology was negative. Seven patients (23%) displayed normal magnetic resonance imaging results. Seizures exhibited diverse semiology and propagation patterns (frontal, perisylvian, and temporal). The ictal and interictal electroencephalographic (EEG) findings were mostly extensive. Multimodal imaging and advanced postprocessing were frequently used. Stereo-EEG was used for localizing the epileptogenic zone and eloquent cortex in 23 patients (77%). Oblique electrodes were used as guides for better neurosurgeon orientation. The epileptogenic zone was in the dominant hemisphere in 16 patients. At the 2-year follow-up, 22 patients (73%) were completely seizure-free, and eight (27%) experienced a seizure frequency reduction of >50% (International League Against Epilepsy class 3 and 4). Fourteen patients (47%) underwent antiseizure medication tapering; treatment was completely withdrawn in two (7%). Nineteen patients (63%) remained seizure-free following the definitive outcome assessment (median = 6 years 5 months, range = 2 years to 13 years 5 months postsurgery). Six patients (20%) experienced corona radiata or basal ganglia ischemia; four (13%) improved to mild and one (3%) to moderate hemiparesis. Two patients (7%) operated on in the anterior insula along with frontotemporal resection experienced major complications: pontine ischemia and postoperative brain edema., Significance: Epilepsy surgery in the operculoinsular cortex can lead to excellent patient outcomes. A comprehensive diagnostic approach is crucial for surgical success. Rehabilitation brings a great chance for significant recovery of postoperative deficits., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: We comprehensively characterized a large pediatric cohort with focal cortical dysplasia (FCD) type 1 to expand the phenotypic spectrum and to identify predictors of postsurgical outcomes., Methods: We included pediatric patients with histopathological diagnosis of isolated FCD type 1 and at least 1 year of postsurgical follow-up. We systematically reanalyzed clinical, electrophysiological, and radiological features. The results of this reanalysis served as independent variables for subsequent statistical analyses of outcome predictors., Results: All children (N = 31) had drug-resistant epilepsy with varying impacts on neurodevelopment and cognition (presurgical intelligence quotient [IQ]/developmental quotient scores = 32-106). Low presurgical IQ was associated with abnormal slow background electroencephalographic (EEG) activity and disrupted sleep architecture. Scalp EEG showed predominantly multiregional and often bilateral epileptiform activity. Advanced epilepsy magnetic resonance imaging (MRI) protocols identified FCD-specific features in 74.2% of patients (23/31), 17 of whom were initially evaluated as MRI-negative. In six of eight MRI-negative cases, fluorodeoxyglucose-positron emission tomography (PET) and subtraction ictal single photon emission computed tomography coregistered to MRI helped localize the dysplastic cortex. Sixteen patients (51.6%) underwent invasive EEG. By the last follow-up (median = 5 years, interquartile range = 3.3-9 years), seizure freedom was achieved in 71% of patients (22/31), including seven of eight MRI-negative patients. Antiseizure medications were reduced in 21 patients, with complete withdrawal in six. Seizure outcome was predicted by a combination of the following descriptors: age at epilepsy onset, epilepsy duration, long-term invasive EEG, and specific MRI and PET findings., Significance: This study highlights the broad phenotypic spectrum of FCD type 1, which spans far beyond the narrow descriptions of previous studies. The applied multilayered presurgical approach helped localize the epileptogenic zone in many previously nonlesional cases, resulting in improved postsurgical seizure outcomes, which are more favorable than previously reported for FCD type 1 patients., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Aims: To determine the incidence of children < 2 years old with suspected abusive head trauma, to evaluate usage of dedicated skeletal radiographs and the incidence of clinically occult fractures on dedicated skeletal radiographs., Methods: This is a retrospective single centre study of children < 2 years old with traumatic brain injury, referred to the University Hospital's Social Services Department between December 31, 2012 and December 31, 2020. Clinical and demographic data was retrieved from medical notes and imaging was reviewed by paediatric radiologists., Results: 26 children (17 males), 2 weeks to 21 months of age (median age 3 months) were included. Eleven children (42%) had traumatic history, fourteen children (54%) had one or more bruises, eighteen children (69%) had abnormal neurological findings. 16 children (62%) had dedicated skeletal radiographs, 7 children (27%) had radiographs of part of the skeleton and 3 children (11%) had no skeletal radiographs. 5 out of 16 children (31%) with dedicated skeletal radiographs had a clinically occult fracture. 15 (83%) of clinically occult fractures had high specificity for abuse., Conclusion: The incidence of suspected abusive head trauma in children < 2 years old is low. Clinically occult fractures were detected in one third of children with dedicated skeletal radiographs. The majority of these fractures have high specificity for abuse. Dedicated skeletal imaging is not performed in more than one third of the children and hence fractures may be missed. Efforts should be taken to increase awareness of child abuse imaging protocols., Competing Interests: The authors report no conflicts of interest in this work.