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Objective: Management of ketogenic diet (KD) in case of prolonged anesthesia in children., Methods: We conducted a retrospective study in the pediatric neurosurgery department of Rothschild Hospital Foundation in France. All the children who underwent long term anesthesia (>4h) in case of neurosurgery for drug resistant pediatric epilepsy surgery between September 2020 and January 2024 were included, excluding patients with suspected metabolic disorder or without blood sample. Children were analyzed in three subgroups: Children under regular diet before surgery constituted the Non-KD group; strict maintenance of KD with no carbohydrate intake during surgery constituted the KD-S group (stringent); carbohydrate intravenous intake during surgery in a patient treated by KD represented the KD-B group (broken)., Results: 22 patients were included, among whom 6 under ketogenic diet (KD). After 4 h of anesthesia, children maintained in strict ketogenic diet (KD-S, n = 3) exhibited non-lactic metabolic acidosis (pH 7.13 vs 7.34, p = 1.38x10 -9 ) associated with an increased anionic gap (17.1 mM vs 9.6 mM, p = 1.58 x10 -4 )., Significance: Current recommendations for anesthesia during long term anesthesia (>4h) with strict no-carbohydrate intake during anesthesia in case ok KD may be at risk of life-threatening metabolic acidosis, in a context of absence of protocolized monitoring of variations in hyperketosis throughout a prolonged fast. A KD-management protocol, including routine monitoring of ketosis in addition to usual monitoring (lactacidemia, kaliemia and glycemia), and low carbohydrates intravenous perfusion throughout prolonged general anesthesia, should be implemented throughout prolonged general anesthesia, especially for infants younger than 2 years., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Objectives: Hypothalamic hamartomas (HHs) are rare developmental brain lesions associated with drug-resistant epilepsy and often subjected to epilepsy surgery. Brain somatic variants in genes affecting the Sonic hedgehog (Shh) and primary cilia signaling pathways have been implicated in approximately 50% of nonsyndromic HH cases. This study aims to characterize a new cohort of 9 HH cases and elucidate their genetic etiology., Methods: We recruited 9 HH cases including 8 nonsyndromic cases of which 4 were type IV HH. Genomic DNA was extracted from peripheral blood and surgical brain tissues, and somatic variants were investigated using high-depth whole-exome sequencing., Results: Pathogenic somatic variants in known HH genes ( GLI3 , OFD1 , and PRKACA) were identified in 7 of the 9 cases. In addition, a 2-hit mutational event comprising a germline variant (predicted to impair kinase activity) and a somatic loss-of-heterozygosity was identified in TNK2 , a gene encoding a brain-expressed tyrosine kinase., Discussion: Our findings reinforce the role of somatic variants in Shh and cilia genes in HH cases while also shedding light on TNK2 as a potential novel disease-causing gene. This study emphasizes the increasing importance of brain mosaicism in epilepsy disorders and underscores the critical role of genetic diagnosis derived from resected brain tissue., Competing Interests: The authors report no relevant disclosures. Go to Neurology.org/NG for full disclosures., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

PACS2 pathogenic variants are associated with an autosomal dominant syndrome (OMIM DEE66), associating developmental and epileptic encephalopathy, facial dysmorphism, and cerebellar dysgenesis. However, no malformation of cortical development has been reported yet. We report here a seven-year-old child with a history of infantile epileptic spasm syndrome and a right insular polymicrogyria and pachygyria due to de novo PACS2 recurrent mutation c.625G>A (p.Glu209Lys). Our observation raises the question of the role of PACS2 in the cortical development. It also reminds the importance of cerebellar anomalies in the recognition of PACS-related DEE., (© 2023 International League Against Epilepsy.)

Brain-restricted somatic variants in genes of the mechanistic target of rapamycin signalling pathway cause focal epilepsies associated with focal cortical dysplasia type II. We hypothesized that somatic variants could be identified from trace tissue adherent to explanted stereoelectroencephalography electrodes used in the presurgical epilepsy workup to localize the epileptogenic zone. We investigated three paediatric patients with drug-resistant focal epilepsy subjected to neurosurgery. In the resected brain tissue, we identified low-level mosaic somatic mutations in AKT3 and DEPDC5 genes. We collected stereoelectroencephalography depth electrodes in the context of a second presurgical evaluation and identified 4/33 mutation-positive electrodes that were either located in the epileptogenic zone or at the border of the dysplasia. We provide the proof-of-concept that somatic mutations with low levels of mosaicism can be detected from individual stereoelectroencephalography electrodes and support a link between the mutation load and the epileptic activity. Our findings emphasize future opportunities for integrating genetic testing from stereoelectroencephalography electrodes into the presurgical evaluation of refractory epilepsy patients with focal cortical dysplasia type II to improve the patients' diagnostic journey and guide towards precision medicine., Competing Interests: The authors report no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)