A5051512765- Epilepsy research and treatment
- Pharmacological Effects and Toxicity Studies
- Neuroscience and Neuropharmacology Research
- Neonatal and fetal brain pathology
- EEG and Brain-Computer Interfaces
- Genomics and Rare Diseases
- Fetal and Pediatric Neurological Disorders
- Neural dynamics and brain function
- Genetics and Neurodevelopmental Disorders
- Metabolism and Genetic Disorders
- Neurological disorders and treatments
- Glioma Diagnosis and Treatment
- Neuroscience and Neural Engineering
- Ion channel regulation and function
- Advanced MRI Techniques and Applications
- Cancer Genomics and Diagnostics
- Functional Brain Connectivity Studies
- Diet and metabolism studies
- Vascular Malformations Diagnosis and Treatment
- Advanced biosensing and bioanalysis techniques
- Tuberous Sclerosis Complex Research
- Ion Transport and Channel Regulation
- Cardiovascular Conditions and Treatments
- Cerebrospinal fluid and hydrocephalus
- Congenital Heart Disease Studies
Fondation de Rothschild
2016-2025
Institut du Cerveau
2011-2024
University of Geneva
2024
Allen Institute for Brain Science
2024
Sorbonne Université
2011-2024
Amsterdam University Medical Centers
2024
Centre National de la Recherche Scientifique
2011-2024
Assistance Publique – Hôpitaux de Paris
2009-2024
Inserm
2009-2024
Stichting Epilepsie Instellingen Nederland
2024
Genetic malformations of cortical development (MCDs), such as mild MCDs (mMCD), focal dysplasia (FCD), and hemimegalencephaly (HME), are major causes severe pediatric refractory epilepsies subjected to neurosurgery. FCD2 characterized by neuropathological hallmarks that include enlarged dysmorphic neurons (DNs) balloon cells (BCs). Here, we provide a comprehensive assessment the contribution germline somatic variants in large cohort surgical MCD cases. We enrolled monocentric study 80...
DEP domain-containing 5 protein (DEPDC5) is a repressor of the recently recognized amino acid-sensing branch mTORC1 pathway. So far, its function in brain remains largely unknown. Germline loss-of-function mutations DEPDC5 have emerged as major cause familial refractory focal epilepsies, with case reports sudden unexpected death epilepsy (SUDEP). Remarkably, fraction patients also develop cortical dysplasia (FCD), neurodevelopmental malformation. We therefore hypothesized that somatic...
PurposeTo define the phenotypic and mutational spectrum of epilepsies related to DEPDC5, NPRL2 NPRL3 genes encoding GATOR1 complex, a negative regulator mTORC1 pathwayMethodsWe analyzed clinical genetic data 73 novel probands (familial sporadic) with epilepsy-related variants in GATOR1-encoding proposed new guidelines for interpretation variants.ResultsThe seizure phenotype consisted mostly focal seizures (e.g., hypermotor or frontal lobe 50%), mean age at onset 4.4 years, often...
Abstract Focal malformations of cortical development (MCD) are linked to somatic brain mutations occurring during neurodevelopment. Mild malformation with oligodendroglial hyperplasia in epilepsy (MOGHE) is a newly recognized clinico-pathological entity associated pediatric drug-resistant focal epilepsy, and amenable neurosurgical treatment. MOGHE histopathologically characterized by clusters increased cell densities, patchy zones hypomyelination, heterotopic neurons the white matter. The...
Abstract 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 dysmorphic cells clustered within healthy brain tissue. Here we show correlation between epileptiform activity acute slices obtained human surgical tissues and density neurons. We uncovered multiple...
Dravet syndrome (DS) is currently considered as an epileptic encephalopathy, a condition in which epilepsy causes deterioration or developmental delay but preliminary data suggested that cognitive course may worsen independently from epilepsy. Our objective was to prospectively analyze the neuropsychological features large cohort of DS patients and its relationships with SCN1A mutation.81 examinations were performed 67 typical (9m-24y, 15 longitudinally studied) using Brunet-Lezine...
<h3>Objective:</h3> To assess the prevalence of somatic <i>MTOR</i> mutations in focal cortical dysplasia (FCD) and germline a broad range epilepsies. <h3>Methods:</h3> We collected 20 blood-brain paired samples from patients with FCD searched for variants using deep-targeted gene panel sequencing. Germline were assessed French research cohort 93 probands epilepsies diagnostic Danish 245 Data sharing among collaborators allowed us to ascertain additional <i>MTOR</i>. <h3>Results:</h3>...
Patients with presumed nonlesional focal epilepsy-based on either MRI or histopathologic findings-have a lower success rate of epilepsy surgery compared lesional patients. In this study, we aimed to characterize large group patients who underwent despite normal and had no lesion histopathology. Determinants their postoperative seizure outcomes were further studied.
We aimed to test the efficacy of ketogenic diet (KD) in patients with Dravet syndrome (DS) not satisfactorily controlled by antiepileptic drugs (AEDs). included prospectively 15 DS aged >3 years partial response AEDs including stiripentol. All had a seizure diary and clinical examination Conners Achenbach scales before KD, at 1 month following onset every 3 months thereafter. At month, 10 (66%) decrease frequency ≥75%. Efficacy was maintained eight responders 6 six 9 months. Five (33%)...
Aim . We report our experience of stereoelectroencephalography (SEEG) in 65 children with drug‐resistant seizures, a particular emphasis on young children. Methods retrospectively studied all SEEG performed between 2009 and 2011 centre. As can have several indications, the patients were classified into three categories, according to probability surgery. The contribution final decision regarding surgery was evaluated for each category separately. also compared main demographic surgical data...
Brain mosaic mutations are a major cause of refractory focal epilepsies with cortical malformations such as dysplasia, hemimegalencephaly, malformation development oligodendroglial hyperplasia in epilepsy, and ganglioglioma. Here, we collected cerebrospinal fluid (CSF) during epilepsy surgery to search for somatic variants cell‐free DNA (cfDNA) using targeted droplet digital polymerase chain reaction. In 3 12 epileptic patients known previously identified brain tissue, here provide evidence...
The SLC35A2 gene, located at chromosome Xp11.23, encodes for a uridine diphosphate-galactose transporter. We describe clinical, genetic, neuroimaging, EEG, and histopathologic findings assess possible predictors of postoperative seizure cognitive outcome in 47 patients with refractory epilepsy brain somatic gene variants.This is retrospective multicenter study where we performed descriptive analysis classical hypothesis testing. included the variables interest significantly associated...
Brain-restricted somatic variants in genes of the mechanistic target rapamycin signalling pathway cause focal epilepsies associated with cortical dysplasia type II. We hypothesized that could be identified from trace tissue adherent to explanted stereoelectroencephalography electrodes used presurgical epilepsy workup localize epileptogenic zone. investigated three paediatric patients drug-resistant subjected neurosurgery. In resected brain tissue, we low-level mosaic mutations AKT3 and...
Abstract Focal cortical dysplasia type II (FCDII) is a malformation causing refractory epilepsy. FCDII arises from developmental somatic mutations in mTOR pathway genes, leading to focal dyslamination and abnormal cytomegalic cells. Which cell types carry pathogenic how they affect cell-type-specific transcriptional programs remains unknown. To address this question, here we combined single-nucleus genotyping transcriptomics morphologically-identified cells using surgical samples...
In the premature infant, somatosensory and visual stimuli trigger an immature electroencephalographic (EEG) pattern, "delta-brushes," in corresponding sensory cortical areas. Whether auditory evoke delta-brushes cortex has not been reported. Here, responses to were studied 46 infants without neurologic risk aged 31 38 postmenstrual weeks (PMW) during routine EEG recording. Stimuli consisted of either low-volume technogenic "clicks" near background noise level neonatal care unit, or a human...
Abstract Focal cortical dysplasia (FCD) and hemimegalencephaly (HME) are related malformations with shared etiologies. We report three patients a spectrum of associated pathogenic brain‐specific somatic Ras homolog enriched in brain ( RHEB) variants. The variant load directly correlated the size malformation, upregulated mTOR activity confirmed dysplastic tissues. Laser capture microdissection showed enrichment RHEB variants dysmorphic neurons balloon cells. Our findings support role...
Lesional focal epilepsy (LFE) is a common and severe seizure disorder caused by epileptogenic lesions, including malformations of cortical development (MCD) low-grade epilepsy-associated tumors (LEAT). Understanding the genetic etiology these lesions can inform medical surgical treatment. We conducted somatic variant enrichment mega-analysis in brain tissue from 1386 individuals who underwent surgery, 599 previously unpublished with ultra-deep ( > 1600x) targeted panel sequencing. Here we...