OBJECTIVE:Epilepsies presenting with lateral occipital seizures (LOS) pose diagnostic challenges due to their rarity and association with complex visual symptoms. We performed a systematic review to characterize the ictal semiology, electroencephalographic, imaging, and surgical features of LOS. METHODS:A comprehensive literature search was conducted between 1990 and March 2024 to identify patient-level studies reporting focal seizures originating from the occipital lobe, confirmed whenever possible by invasive EEG, MRI lesion, and postoperative outcome. Cases with occipital semiology due to propagation from extra-occipital onset zones were excluded. RESULTS:A total of 105 abstracts were considered resulting in 13 articles reviewed, and 248 patients were analyzed. Visual symptoms were present in 8%-88% of patients: visual hallucinations and illusions, and oculomotor disturbances being the most frequent manifestations. Oculomotor signs, including eye deviation and eyelid myoclonia, were common but non-specific for lateralization. Scalp EEG frequently demonstrated false lateralization, and only a median of 23% of patients underwent invasive monitoring. LOS originating from the lateral occipital cortex exhibited propagation along ventral and dorsal streams, accounting for associated temporal, parietal, and frontal manifestations. MRI lesions were present in 75%-79% of patients, including focal cortical dysplasia, tumors, and cavernomas. Surgical resection yielded Engel class I outcomes in 22%-70% of cases, with pediatric patients demonstrating higher seizure-free rates. Postoperative visual deficits occurred in 17%-80% of patients. SIGNIFICANCE:LOS represent a clinically and anatomically distinct form of occipital epilepsy. Their hallmark semiology reflects lateral extrastriate cortical activation and propagation through ventral and dorsal pathways. Accurate localization requires integration of semiology, multimodal imaging, and invasive EEG. Tailored surgical interventions achieve favorable seizure outcomes, particularly in pediatric populations, while careful mapping is essential to preserve visual function. Future studies should refine lateral versus mesial occipital differentiation and optimize surgical planning through advanced imaging and electrophysiology.

Objectives Electrical stimulation (ES) during stereoelectroencephalography (SEEG) plays a key role in functional mapping in drug-resistant epilepsy. In pediatrics, protocols must account for neurodevelopmental stage. Moreover, pediatric data remain scarce and protocols vary substantially across centers. Such heterogeneity limits comparability between studies and hinders the evaluation of stimulation efficacy and its prognostic value for postoperative functional deficits. This work aims to provide expert consensus to harmonize SEEG stimulation protocols in the pediatric population. Methods A multidisciplinary task force of French experts from French pediatric epilepsy surgery centers reviewed existing guidelines and integrated current knowledge from developmental neurosciences. Through consensus, pediatric-specific parameters and practices were defined. Results The task force establishes practical guidance for stimulation frequency, intensity, and duration adapted to children, with emphasis on safety, feasibility, and neurodevelopmental context. Suggested protocols are designed to optimize both epileptogenic zone (EZ) delineation and functional mapping while enabling multicenter comparability. Conclusion The proposed methods provide a framework for safe and effective pediatric SEEG stimulation. They aim to standardize clinical practice, improve presurgical evaluations, and support collaborative research in pediatric epilepsy surgery.

A few million words suffice for children to acquire language. Yet, the brain mechanisms underlying this unique ability remain poorly understood. To address this issue, we investigate neural activity recorded from over 7,400 electrodes implanted in the brains of 46 children, teenagers, and adults for epilepsy monitoring, as they listened to an audiobook version of "The Little Prince". We then train neural encoding and decoding models using representations, derived either from linguistic theory or from large language models, to map the location, dynamics and development of the language hierarchy in the brain. We find that a broad range of linguistic features is robustly represented across the cortex, even in 2-5-year-olds. Crucially, these representations evolve with age: while fast phonetic features are already present in the superior temporal gyrus of the youngest individuals, slower word-level representations only emerge in the associative cortices of older individuals. Remarkably, this neuro-developmental trajectory is spontaneously captured by large language models: with training, these AI models learned representations that can only be identified in the adult human brain. Together, these findings reveal the maturation of language representations in the developing brain and show that modern AI systems provide a promising tool to model the neural bases of language acquisition.

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 nocarbohydrate 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 KDmanagement 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.

ObjectivesHypothalamic 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.MethodsWe 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.ResultsPathogenic 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.DiscussionOur 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.

OBJECTIVE:Rasmussen's encephalitis (RE) affects the structure and function of one cerebral hemisphere, typically during childhood. Hemispherotomy is a surgical treatment that functionally disconnects the affected hemisphere. The cognitive consequences of surgery and the potential for postoperative recovery remain poorly understood, however, due to their complex and multifactorial nature. This study aimed to examine the long-term cognitive outcomes of patients with RE following hemispherotomy and identify the clinical factors influencing recovery. METHODS:Forty-four patients who underwent childhood hemispherotomy for RE (28 girls, 23 with left RE) were included in this retrospective study. Neuropsychological assessments were conducted during postoperative follow-up, and verbal (VIQ) and nonverbal (performance IQ [PIQ]) IQ scores from the most recent evaluation were analyzed. The impact of age at seizure onset (ASO), age at hemispherotomy, preoperative epilepsy duration, side of hemispherotomy, age at neuropsychological evaluation, and postoperative follow-up duration on intellectual efficiency scores was assessed using partial least squares analysis. RESULTS:The mean ASO was 5.9 years, the mean age at hemispherotomy was 9.6 years, the mean epilepsy duration was 3.7 years, and the mean postoperative follow-up duration was 9.5 years. After hemispherotomy, 91% of patients were seizure free (Engel class I), and 86% were no longer receiving antiepileptic medication. Patients who underwent hemispherotomy of the language-dominant hemisphere (Hdom) had lower VIQ scores but higher PIQ scores compared to those with hemispherotomy of the nondominant hemisphere (Hnondom). Results showed that higher VIQ was significantly associated with several clinical factors, including a shorter epilepsy duration before surgery, a younger age at surgery, and hemispherotomy of the nondominant hemisphere for language. In contrast, no clear link was found between clinical variables and PIQ. CONCLUSIONS:In RE, early hemispherotomy performed soon after disease onset appears to be associated with better long-term intellectual outcomes. Verbal functions can be recovered following hemispherotomy of the dominant hemisphere, highlighting the preferential reorganization of language in postoperative cognitive recovery. These findings underscore the critical importance of early surgical decision-making in optimizing patient care and maximizing postoperative recovery.

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.

The ketogenic diet (KD) has been shown to be effective in refractory epilepsy after long-term administration. However, its interference with short-term brain metabolism and its involvement in the early process leading to epilepsy remain poorly understood. This study aimed to assess the effect of a short-term ketogenic diet on cerebral glucose metabolic changes, before and after status epilepticus (SE) in rats, by using [ 18 F]-FDG PET. Thirty-nine rats were subjected to a one-week KD (KD-rats, n = 24) or to a standard diet (SD-rats, n = 15) before the induction of a status epilepticus (SE) by lithium-pilocarpine administrations. Brain [ 18 F]-FDG PET scans were performed before and 4 h after this induction. Morphological MRIs were acquired and used to spatially normalize the PET images which were then analyzed voxel-wisely using a statistical parametric-based method. Twenty-six rats were analyzed (KD-rats, n = 15; SD-rats, n = 11). The 7 days of the KD were associated with significant increases in the plasma β-hydroxybutyrate level, but with an unchanged glycemia. The PET images, recorded after the KD and before SE induction, showed an increased metabolism within sites involved in the appetitive behaviors: hypothalamic areas and periaqueductal gray, whereas no area of decreased metabolism was observed. At the 4th hour following the SE induction, large metabolism increases were observed in the KD- and SD-rats in areas known to be involved in the epileptogenesis process late—i.e., the hippocampus, parahippocampic, thalamic and hypothalamic areas, the periaqueductal gray, and the limbic structures (and in the motor cortex for the KD-rats only). However, no statistically significant difference was observed when comparing SD and KD groups at the 4th hour following the SE induction. A one-week ketogenic diet does not prevent the status epilepticus (SE) and associated metabolic brain abnormalities in the lithium-pilocarpine rat model. Further explorations are needed to determine whether a significant prevention could be achieved by more prolonged ketogenic diets and by testing this diet in less severe experimental models, and moreover, to analyze the diet effects on the later and chronic stages leading to epileptogenesis.

Objective: Report of the contribution of invasive EEG (iEEG) and epileptogenicity mappings (EM) in a pediatric cohort of patients with epilepsy associated with focal polymicrogyria (PMG) and candidates for resective surgery. Method: Retrospective pediatric case series of patients presenting focal PMG-related refractory epilepsy undergoing an invasive exploration (iEEG) at Fondation Rothschild Hospital. We reviewed clinical data, structural MRI, and visual analysis of iEEG recordings. Moreover, time-frequency analysis of SEEG signals with a neuroimaging approach (epileptogenicity maps) was used to support visual analysis. Results: Between 2012 and 2019, eight patients were selected. Five patients were explored with stereoelectroencephalography (SEEG) only, one patient with subdural exploration (SDE) only and two patients first underwent SEEG and then SDE. T he mean age at seizure onset was 40.3 months (range 3-120), and the mean age for the iEEG 10.8 years (range 7-15). The epileptogenic zone (EZ) appeared concordant to the PMG lesion in only one case, was larger in three cases, smaller in two cases and different in one case. Four cases were selected for tailored resective surgery and one for total callosotomy. Two patients remained seizure-free at their last follow-up (mean 32.6 months, range 7-98). Epileptogenicity mapping (EM) refined the qualitative analysis, showing in four patients an EZ larger than visually defined. Conclusion: This study is the first pediatric study to analyze the value of iEEG and EM as well as operability in focal PMG-related refractory epilepsy. The results illustrate the complexity of this pathology with variable concordance between the EZ and the lesion and mixed response to surgery.

For a ketogenic diet to be effective, strict control of carbohydrate intake is paramount. Factors such as medications may upset this delicate balance. The aim of this commentary is to provide physicians who are treating patients with a ketogenic diet, with a step-by-step guide. A list of unsuitable excipients was established. A flowchart with the title “Can this drug be prescribed to a patient following a ketogenic diet?” was then drafted. The first step is to determine the international nonproprietary name, dosage, form and composition. The amount of unsuitable excipients is calculated. Suitable alternatives may be discussed with the pharmacist. As a last resort, the ketogenic diet itself may need to be adapted. The answers provided are included in a database. Determining the amount of unsuitable excipients is a complex task requiring pharmaceutical expertise. Our flowchart can be used in order to provide a clear pathway for answering such questions.

Le diagnostic d’encéphalite chez les enfants suivis pour une encéphalopathie épileptique peut être difficile à établir. Décrire les modifications de l’électroencéphalogramme de ces enfants au cours d’un épisode d’encéphalite. Réaliser une recherche bibliographique des cas de récidive d’encéphalite et d’encéphalite aiguë chez des patients suivis pour une encéphalopathie épileptique. Étude descriptive de cohorte rétrospective. Critères d’inclusion : tous les enfants suivis pour une encéphalopathie épileptique, ayant présenté une encéphalite aiguë entre 2011 et 2018. Relecture des électroencéphalogrammes réalisés chez ces enfants avant l’encéphalite, au moment du diagnostic et après traitement. Évaluation des modifications électroencéphalographiques. Nous rapportons le cas de trois enfants suivis pour une encéphalopathie épileptique ayant présenté une encéphalite secondaire. Dans ces trois cas, on note lors de la phase aiguë de l’encéphalite une modification de l’activité de fond préexistante avec régression des patterns épileptiques, ainsi qu’un ralentissement de cette activité de fond. D’après ces résultats sur une faible cohorte rétrospective, en cas de suspicion clinique d’encéphalite chez un patient suivi pour une encéphalopathie épileptique, un ralentissement de l’activité de fond associé à une régression des patterns épileptiques préexistants est évocateur d’encéphalite aigu.

L’objectif principal de cette étude pilote est d’avancer des hypothèses quant au profil neuropsychologique des enfants et adolescents français porteurs du Syndrome de Shwachman-Diamond (SSD), maladie génétique rare. Il s’agit également d’évaluer les capacités métapragmatiques à partir d’épreuves dialoguées de compréhension de trois formes non littérales de demandes indirectes spécifiquement aménagées pour cette population. L’originalité de ce travail réside ainsi dans l’analyse des profils comportementaux et dans l’étude des fonctions cognitives supérieures de 7 enfants SSD. Au-delà du faible potentiel cognitif observé pour notre échantillon, plus de la moitié des enfants SSD présentent des difficultés de cognition sociale et tous manifestent des problèmes comportementaux (notamment d’adaptation sociale) et exécutifs. Les résultats obtenus mettent en évidence des profils particuliers de performances au sein des différentes épreuves évaluant la cognition sociale. L’hypothèse d’une atteinte spécifique de certains aspects de la théorie de l’esprit est ainsi soulevée.

La revue de littérature et l’analyse clinique des profils intellectuels de sept enfants et adolescents porteurs d’un Syndrome de Shwachman-Diamond (SDS) au Wechsler Intelligence Scale for Children - IV (WISC-IV) mettent en évidence un affaiblissement intellectuel. Au-delà de la déficience intellectuelle, l’hypothèse d’un affaiblissement intellectuel lié à la présence de difficultés de raisonnement et d’un dysfonctionnement exécutif chez les enfants SDS ne présentant pas une déficience intellectuelle est soulevée. Ces éléments offrent un cadre d'interprétation intéressant et novateur à l'affaiblissement intellectuel objectivé mais aussi aux troubles comportementaux, sociaux et scolaires décrits dans cette population. Une évaluation spécifique et exhaustive du fonctionnement exécutif de ces enfants est recommandée, s’inscrivant dans une approche intégrative analysant les liens entre efficience intellectuelle, fonctionnements cognitif, émotionnel, comportemental, et performances scolaires.

The Statistical Parametric Mapping (SPM) software is frequently used for the quantitative analysis of patients’ brain images obtained from 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography ([18F]FDG PET). However, its adaptation to small animals is difficult, particularly for the initial step of spatial normalization which requires a specific brain anatomical template. This study was aimed at determining whether SPM analysis can be applied to rat, and more specifically to the lithium-pilocarpine model of epilepsy, by using an adaptive template. This template developed for PET clinical imaging is constructed from a block matching algorithm.

The main objective of this pilot study is to put forth hypotheses on the neuropsychological profile of French children and adolescents with Shwachman-Diamond syndrome (SDS), a rare genetic disease. It also assesses the pragmatic abilities, by means of dialogue comprehension tests of three non-literal forms of indirect requests specifically designed for this population. The originality of this work lies in the analysis of behavioural profiles and in the study of higher cognitive functions of 7 SDS children. In addition to their intellectual disability, over half of SSD children present socio-cognitive difficulties and all exhibit behavioural (notably social adaptation) and executive complaints. The results highlight specific performance profiles within the various tests assessing social cognition. The hypothesis of a specific impairment of certain aspects of the theory of mind is thus raised.

La coexistence d’un syndrome infectieux fébrile et de troubles neurologiques fait évoquer le diagnostique d’encéphalite. L’électroencéphalogramme (EEG) est l’un des examens qui permet de conduire l’enquête étiologique et de suivre l’évolution. Afin d’évaluer la sensibilité et la spécificité de l’EEG dans ces situations chez l’enfant immunocompétent, nous avons relu l’ensemble des EEG d’une cohorte prospective monocentrique d’enfant admis dans le contexte de l’urgence, avec un tableau clinique compatible avec le diagnostique d’encéphalite, de novembre 2013 à octobre 2014, à l’hôpital d’enfants du CHRU de Nancy. L’interprétation de l’EEG est standardisée par l’utilisation d’une trame utilisée par deux interprétateurs en aveugle. Les résultats sont corrélés au diagnostic final retenu au terme de l’hospitalisation. Au total les dossiers de 86 patients ont été relus. Nous présenterons les résultats détaillés en fonction de l’étiologie retenue et de l’évolution à court terme.

Objective: Our goal is to describe the clinical, biological, neurophysiological and brain Magnetic Resonnance Imaging (MRI) features, as well as outcome, of Human Herpes 6 (HHV-6) acute neurological infection in immunocompetent children. Methods: We retrospectively analyse the data of all paediatric patients referred to Nancy Academic Children Hospital between January 2007 and June 2015 for acute neurologic symptoms who exhibit positive HHV-6 DNA polymerase chain reaction (PCR) in cerebrospinal fluid (CSF). Results: Fifteen patients are included. Eight children are under the age of 2. They exhibit clinical encephalitis, associated with white-matter T2 hyper-intensities on early MRI in 5 cases. Three of these patients evolve with clinical sequelae: epilepsy (n=2), hemiparesis (n=1) or learning disabilities (n=2). The 7 other patients are aged of 2 to15. They initially present clinical signs of cranial nerve neuritis (n=4), febrile meningitis (n=3), febrile encephalitis (n=1). Only 1 of them exhibits brain MRI abnormalities consistent with 2nd cranial nerve neuritis. All children over the age of 2 recover completely. Conclusion: This is the first study to describe the age related presentation and outcome of CNS HHV-6 primary infection. Encephalitis that may lead to neurological sequelae concerns younger children. Neuritis is the most common clinical presentation after the age of 2. Management of antiviral therapies remains to be determined.

El objetivo principal de este estudio piloto es proponer hipotesis sobre el perfil neuropsicologico de los ninos y adolescentes franceses portadores del sindrome de Shwachman-Diamond (SSD), una enfermedad genetica rara. Tambien se trata de evaluar las capacidades metapragmaticas sobre la base de pruebas dialogicas de comprension de tres formas no literales de demandas indirectas especificamente disenadas para esta poblacion. La originalidad de este trabajo radica, pues, en el analisis de los perfiles de comportamiento y el estudio de las funciones cognitivas superiores de siete ninos con SSD. Mas alla del bajo potencial cognitivo observado en nuestra muestra, mas de la mitad de los ninos con SSD presentan dificultades en la cognicion social y todos muestran problemas de comportamiento (especialmente de adaptacion social) y ejecutivos. Los resultados obtenidos ponen de relieve perfiles de rendimiento particulares dentro de las diversas pruebas que evaluan la cognicion social. Se plantea asi la hipotesis de un logro especifico de ciertos aspectos de la teoria de la mente.