Single-cell genotyping and transcriptomic profiling of mosaic focal cortical dysplasia.

Focal cortical dysplasia type II (FCDII) is a cortical malformation causing refractory epilepsy. FCDII arises from developmental somatic activating mutations in mTOR pathway genes, leading to focal cortical dyslamination and abnormal cytomegalic cells. Which cell types carry pathogenic mutations and how they affect cell-type-specific transcriptional programs remain unknown.

Harmful metabolic acidosis in children treated by ketogenic diet during prolonged general anesthesia for epilepsy surgery: A single center experience.

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.

Analysis of 1386 epileptogenic brain lesions reveals association with DYRK1A and EGFR.

Lesional focal epilepsy (LFE) is a common and severe seizure disorder caused by epileptogenic lesions, including malformations of cortical development (MCD) and low-grade epilepsy-associated tumors (LEAT). Understanding the genetic etiology of these lesions can inform medical and surgical treatment. We conducted a somatic variant enrichment mega-analysis in brain tissue from 1386 individuals who underwent epilepsy surgery, including 599 previously unpublished individuals with ultra-deep ( > 1600x) targeted panel sequencing.

Targeting pathological cells with senolytic drugs reduces seizures in neurodevelopmental mTOR-related epilepsy.

Cortical malformations such as focal cortical dysplasia type II (FCDII) are associated with pediatric drug-resistant epilepsy that necessitates neurosurgery. FCDII results from somatic mosaicism due to post-zygotic mutations in genes of the PI3K-AKT-mTOR pathway, which produce a subset of dysmorphic cells clustered within healthy brain tissue. Here we show a correlation between epileptiform activity in acute cortical slices obtained from human surgical FCDII brain tissues and the density of dysmorphic neurons.

Outcome of Epilepsy Surgery in MRI-Negative Patients Without Histopathologic Abnormalities in the Resected Tissue.

Background And Objective: Patients with presumed nonlesional focal epilepsy-based on either MRI or histopathologic findings-have a lower success rate of epilepsy surgery compared with lesional patients. In this study, we aimed to characterize a large group of patients with focal epilepsy who underwent epilepsy surgery despite a normal MRI and had no lesion on histopathology. Determinants of their postoperative seizure outcomes were further studied.

Detection of brain somatic mutations in focal cortical dysplasia during epilepsy presurgical workup.

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.

Clinical Features, Neuropathology, and Surgical Outcome in Patients With Refractory Epilepsy and Brain Somatic Variants in the Gene.

Background And Objectives: The gene, located at chromosome Xp11.23, encodes for a uridine diphosphate-galactose transporter. We describe clinical, genetic, neuroimaging, EEG, and histopathologic findings and assess possible predictors of postoperative seizure and cognitive outcome in 47 patients with refractory epilepsy and brain somatic gene variants.

Complete callosotomy in children with drop attacks; A retrospective monocentric study of 50 patients.

Purpose: Corpus callosotomy is a palliative surgical procedure for patients with drug-resistant epilepsy and suffering from drop attacks, which are a source of major deterioration in quality of life and can be responsible for severe traumatic injury. The objective of this study is to identify clinical markers that would predict a better outcome in terms of drop attacks and other types of epileptic seizures.

Methods: We reviewed a retrospective series of children who underwent complete corpus callosotomy at our institution, between January 1998 and February 2019.

Clinical semiology of temporal lobe seizures in preschool children: contribution of invasive recording to anatomical classification.

Focal seizure semiology is often inadequately studied, specifically in preschool children. Among drug-resistant epilepsies amenable to surgery, temporal lobe seizure semiology has been widely described in this age group. Nevertheless, a systematic anatomo-electroclinical study has never been performed.

F-FDG-PET hypometabolic pattern reveals multifocal epileptic foci despite limited unique stereotyped seizures.

Purpose: Interictal positron emission tomography (PET) with F-FDG has largely proved its utility in presurgical evaluation of drug-resistant epilepsies (DRE) and in the surgical outcomes. Interictal hypometabolism topography is related to the neuronal networks involved in the seizure onset zone (SOZ) and spread pathways. F-FDG PET has a good prognostic value for post-surgical outcome, especially in cases with unique focal ictal semiology and a limited extent of hypometabolism.

Focal polymicrogyria in children: Contribution of invasive explorations and epileptogenicity mapping in the surgical decision.

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.

Gradient of brain mosaic RHEB variants causes a continuum of cortical dysplasia.

Focal cortical dysplasia (FCD) and hemimegalencephaly (HME) are related malformations with shared etiologies. We report three patients with a spectrum of cortical malformations associated with pathogenic brain-specific somatic Ras homolog enriched in brain (RHEB) variants. The somatic variant load directly correlated with the size of the malformation, with upregulated mTOR activity confirmed in dysplastic tissues.

Frequent SLC35A2 brain mosaicism in mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE).

Focal malformations of cortical development (MCD) are linked to somatic brain mutations occurring during neurodevelopment. Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) is a newly recognized clinico-pathological entity associated with pediatric drug-resistant focal epilepsy, and amenable to neurosurgical treatment. MOGHE is histopathologically characterized by clusters of increased oligodendroglial cell densities, patchy zones of hypomyelination, and heterotopic neurons in the white matter.

Management and results of epilepsy surgery associated with acyclovir prophylaxis in four pediatric patients with drug-resistant epilepsy due to herpetic encephalitis and review of the literature.

Purpose: Herpes simplex virus encephalitis (HSE) is the most common cause of sporadic viral encephalitis in children and is responsible for epilepsy in approximately half of patients. In addition to medical treatment, epilepsy surgery may be offered to drug-resistant patients but carries a high risk of relapse of herpetic encephalitis. We are reporting our series of patients operated on between 2000 and 2019 with the systematic administration of acyclovir (ACV).

Seizure outcome and prognostic factors for surgical management of hypothalamic hamartomas in children.

Purpose: Hypothalamic hamartomas (HH) are rare benign lesions frequently associated with gelastic seizures early in life. Epilepsy can progress to multiple seizure types with cognitive impairment and behavioural disturbance, leading in some cases to epileptic encephalopathy.

Methods: We reviewed a retrospective series of 112 children treated in a single center, between 1998 and 2017.

Dissecting the genetic basis of focal cortical dysplasia: a large cohort study.

Genetic malformations of cortical development (MCDs), such as mild MCDs (mMCD), focal cortical dysplasia (FCD), and hemimegalencephaly (HME), are major causes of severe pediatric refractory epilepsies subjected to neurosurgery. FCD2 are characterized by neuropathological hallmarks that include enlarged dysmorphic neurons (DNs) and balloon cells (BCs). Here, we provide a comprehensive assessment of the contribution of germline and somatic variants in a large cohort of surgical MCD cases.

Parasagittal hemispherotomy in hemispheric polymicrogyria with electrical status epilepticus during slow sleep: Indications, results and follow-up.

Purpose: Polymicrogyria (PMG), although the most common brain malformation, represents a low percentage among patients operated on for epilepsy. In cases of hemispheric PMG, electrical status epilepticus during slow sleep (ESESS) may occur leading to an aggravation of the neurological condition and a risk of drug resistance. In such cases, surgical treatment can be offered.

SEEG-guided radiofrequency thermocoagulation of epileptic foci in the paediatric population: Feasibility, safety and efficacy.

Purpose: Focal epilepsy in children may be refractory to pharmacological treatment and surgical resection may be an appropriate option. When invasive electroencephalogram is required in the presurgical evaluation, depth electrodes can be used to create focal lesions in the epileptogenic zone using radiofrequency thermocoagulation (RFTC), to disrupt the epileptogenic zone.

Methods: This study aimed to assess the efficacy and safety of RFTC in a paediatric population of 46 patients.

Invasive evaluation in children (SEEG vs subdural grids).

Designed from the 60s to the 80s for adults, and despite the development of many new techniques, invasive explorations still have indications in children with focal drug-resistant epilepsy. The main types are stereoelectroencephalography (SEEG) and subdural explorations (SDE). They provide precise information on the localization of the epileptogenic zone (EZ), its relationships with eloquent cortex, and the feasibility of performing a tailored surgical resection.

Investigation of paediatric occipital epilepsy using stereo-EEG reveals a better surgical outcome than in adults, especially when the supracalcarine area is affected.

Occipital epilepsy is the least common among surgical series because: (1) the location makes it hard to asses by EEG; (2) the seizure semiology often reflects propagation; and (3) surgery entails a high risk of neurological deficits. In children, subjective symptoms are harder to assess, adding to the difficulty of a proper diagnosis. We aimed to determine electroclinical characteristics of occipital lobe epilepsy in a paediatric population by reviewing 20 children between one and 16 years, who had undergone intracranial recordings with depth electrodes.