Rima Nabbout

Rima Nabbout

About

508
Publications
41,012
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
13,318
Citations

Publications

Publications (508)
Article
Tuberous sclerosis complex (TSC) is a rare multi-system genetic disorder characterized by a high incidence of epilepsy and neuropsychiatric manifestations known as tuberous-sclerosis-associated neuropsychiatric disorders (TANDs), including autism spectrum disorder (ASD) and intellectual disability (ID). MicroRNAs (miRNAs) are small regulatory non-c...
Article
Vacuolar-type H+-ATPase (V-ATPase) is a multimeric complex present in a variety of cellular membranes that acts as an ATP-dependent proton pump and plays a key role in pH homeostasis and intracellular signalling pathways. In humans, 22 autosomal genes encode for a redundant set of subunits allowing the composition of diverse V-ATPase complexes with...
Article
Objective: GABAA receptor subunit variants have recently been associated with neurodevelopmental disorders and/or epilepsy. The phenotype linked with each gene is becoming better known. Because of their common molecular structure and physiological role, it seemed interesting to describe a putative phenotype associated with GABAA -receptor-related...
Preprint
Background: Preliminary data suggest that COVID-19 pandemic has generated a switch from face-to-face to remote care for individuals with chronic diseases. However, few data are reported for rare and undiagnosed diseases (RUDs). We aimed to assess the impact of the COVID-19 pandemic on the activities of the French reference network for RUDs in 2020....
Article
Full-text available
The 2017 International League Against Epilepsy classification has defined a three‐tier system with epilepsy syndrome identification at the third level. Although a syndrome cannot be determined in all children with epilepsy, identification of a specific syndrome provides guidance on management and prognosis. In this paper, we describe the childhood...
Article
Full-text available
The goal of this paper is to provide updated diagnostic criteria for the epilepsy syndromes that have a variable age of onset, based on expert consensus of the International League Against Epilepsy Nosology and Definitions Taskforce (2017-2021). We use language consistent with current accepted epilepsy and seizure classifications and incorporate kn...
Article
Full-text available
Epilepsy syndromes have been recognized for >50 years, as distinct electroclinical phenotypes with therapeutic and prognostic implications. Nonetheless, no formally accepted International League Against Epilepsy (ILAE) classification of epilepsy syndromes has existed. The ILAE Task Force on Nosology and Definitions was established to reach consensu...
Article
Full-text available
The International League Against Epilepsy (ILAE) Task Force on Nosology and Definitions proposes a classification and definition of epilepsy syndromes in the neonate and infant with seizure onset up to 2 years of age. The incidence of epilepsy is high in this age group and epilepsy is frequently associated with significant comorbidities and mortali...
Article
Importance: New treatment options are needed for patients with Lennox-Gastaut syndrome (LGS), a profoundly impairing, treatment-resistant, developmental and epileptic encephalopathy. Objective: To evaluate the efficacy and safety of fenfluramine in patients with LGS. Design, setting, and participants: This multicenter, double-blind, placebo-co...
Article
Objectives: To gain consensus from experienced physicians and caregivers regarding optimal diagnosis and management of Dravet syndrome (DS), in the context of recently-approved, DS-specific therapies and emerging disease-modifying treatments. Methods: A core working group was convened consisting of 6 physicians with recognized expertise in DS an...
Article
Full-text available
In 2017, the International League Against Epilepsy (ILAE) Classification of Epilepsies described the “genetic generalized epilepsies” (GGEs), which contained the “idiopathic generalized epilepsies” (IGEs). The goal of this paper is to delineate the four syndromes comprising the IGEs, namely childhood absence epilepsy, juvenile absence epilepsy, juv...
Article
Full-text available
In the last few years, with the advent of next generation sequencing (NGS), our knowledge of genes associated with monogenic epilepsies has significantly improved. NGS is also a powerful diagnostic tool for patients with epilepsy, through gene panels, exomes and genomes. This has improved diagnostic yield, reducing the time between the first seizur...
Article
We aimed to describe epilepsy and EEG patterns related to vigilance states and age, in chromosome15-long-arm-duplication-syndrome (dup15q) children with epilepsy, in both duplication types: interstitial (intdup15) and isodicentric (idic15). Methods: Clinical data and 70 EEGs of 12 patients (5 intdup15, 7 idic15), followed from 4.5m.oto 17y4m (media...
Article
Background and objective: Multiple factors have been found to contribute to the high risk of epilepsy in infants with Tuberous Sclerosis Complex (TSC), including evolution of EEG abnormalities, TSC gene mutation and MRI characteristics. The aim of the present prospective multi-center study was to: 1) identify early MRI biomarkers of epilepsy in in...
Article
Background The EPIGENE network was created in 2014 by four multidisciplinary teams composed of geneticists, pediatric neurologists and neurologists specialized in epileptology and neurophysiology. The ambition of the network was to harmonize and improve the diagnostic strategy of Mendelian epileptic disorders using next-generation sequencing, in Fr...
Article
Background and Objectives Pathogenic variants in the neuronal sodium-channel α1-subunit gene ( SCN1A ) are the most frequent monogenic cause of epilepsy. Phenotypes comprise a wide clinical spectrum including the severe childhood epilepsy, Dravet syndrome, characterized by drug-resistant seizures, intellectual disability and high mortality, and the...
Article
Objective We aimed to identify genes associated with genetic generalized epilepsy (GGE) by combining large cohorts enriched with individuals with a positive family history. Secondarily, we set out to compare the association of genes independently with familial and sporadic GGE. Methods We performed a case–control whole exome sequencing study in un...
Article
Aim KCNB1 encephalopathy encompasses a broad phenotypic spectrum associating intellectual disability, behavioral disturbances, and epilepsies of various severity. Using standardized parental questionnaires, we aimed to capture the heterogeneity of the adaptive and behavioral features in a series of patients with KCNB1 pathogenic variants. Methods...
Article
Full-text available
Background The growing use of Electronic Health Records (EHRs) is promoting the application of data mining in health-care. A promising use of big data in this field is to develop models to support early diagnosis and to establish natural history. Dravet Syndrome (DS) is a rare developmental and epileptic encephalopathy that commonly initiates in th...
Article
Full-text available
Objective Epilepsy is highly prevalent in patients with tuberous sclerosis complex (TSC). Everolimus showed higher efficacy than placebo for seizures in the primary analysis of the EXIST-3 study. Here, we present the long-term outcomes of everolimus at the end of the postextension phase (PEP; data cutoff date: October 25, 2017). Methods After comp...
Article
Full-text available
Aim To describe the evolution of electroencephalogram (EEG) characteristics in infants with tuberous sclerosis complex (TSC) and the relationship with neurodevelopmental outcome at 24 months. Method Eighty-three infants were enrolled in the EPISTOP trial and underwent serial EEG follow-up until the age of 24 months (males n=45, females n=37, media...
Article
Full-text available
Background: Epilepsy is the most common neurological manifestation in individuals with tuberous sclerosis complex (TSC). However, real-world evidence on diagnosis and treatment patterns is limited. Here, we present data from TuberOus Sclerosis registry to increase disease Awareness (TOSCA) on changes in patterns of epilepsy diagnosis, treatments, a...
Article
Full-text available
Objective Appetite disturbance and growth abnormalities are commonly reported in children with Dravet syndrome (DS). Fenfluramine (Fintepla) has demonstrated profound reduction in convulsive seizure frequency in DS and was recently approved for use in DS in the US and EU. Prior to its use in epilepsy, fenfluramine was approved to suppress appetite...
Article
Epilepsy is one of the main symptoms affecting the lives of individuals with tuberous sclerosis complex (TSC), causing a high rate of morbidity. Individuals with TSC can present with various types of seizures, epilepsies, and epilepsy syndromes that can coexist or appear in relation to age. Focal epilepsy is the most frequent epilepsy type with two...
Article
Full-text available
Objective Individuals with Dravet syndrome (DS) experience frequent pharmacoresistant seizures beginning in infancy. Most exhibit poor neurodevelopmental outcomes including motor function difficulties, behavior problems, and cognitive impairment. Cognitive deficits in children with DS have been associated with seizure frequency and antiseizure medi...
Article
Objective Add-on cannabidiol (CBD) reduced seizures associated with Dravet syndrome (DS) in two randomized, double-blind, placebo-controlled trials: GWPCARE1 Part B (NCT02091375) and GWPCARE2 (NCT02224703). Patients who completed GWPCARE1 Part A (NCT02091206) or Part B, or GWPCARE2, were enrolled in a long-term open-label extension trial, GWPCARE5...
Article
Channelopathies caused by mutations in genes encoding ion channels generally produce a clear change in channel function. Accordingly, mutations in KCNC1, which encodes the voltage-dependent Kv3.1 potassium channel, result in Progressive Myoclonus Epilepsy as well as other Developmental and Epileptic Encephalopathies, and these have been shown to re...
Article
Objective The aim of this study is the investigation of early-life EEG background abnormalities or “dysmature” traits in infants with tuberous sclerosis complex (TSC) and their capacity to predict autism spectrum disorder or neurodevelopmental outcome. Methods EEG data were prospectively collected from TSC patients during the EPISTOP trial (NCT020...
Article
Full-text available
Background Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant disorder caused by pathogenic variants in either the TSC1 or TSC2 gene. Common manifestations of TSC have been grouped into major and minor clinical diagnostic criteria and assessed in clinical routine workup. However, case studies point towards the existence of ra...
Article
Levetiracetam is a broad‐spectrum antiepileptic drug that exhibits high interindividual variability in serum concentrations in children. A population pharmacokinetic approach can be used to explain this variability and optimize dosing schemes. The objectives are to identify the best predictive population pharmacokinetic model for children and to ev...
Article
Purpose: Analyzing parents’ and physicians’ opinions regarding phone-based encounters in emergency shifts of a French pediatric epilepsy center compared to traditional face-to-face encounters during the first lockdown of the COVID-19 pandemic . Methods : Prospective monocentric study on remote encounters at Necker rare epilepsy reference center fr...
Article
The role of inflammation is increasingly recognized in triggering or sustaining epileptic activity. In the last decades, increasing research has provided definite evidence to support the link between immunity, inflammatory process, and epilepsy. Neuro- and systemic inflammation play a pivotal role in driving epileptogenesis through different pathog...
Article
Objective To study the association between timing and characteristics of the first electroencephalography (EEG) with epileptiform discharges (ED‐EEG) and epilepsy and neurodevelopment at 24 months in infants with tuberous sclerosis complex (TSC). Methods Patients enrolled in the prospective Epileptogenesis in a genetic model of epilepsy – Tuberous...
Article
Full-text available
This non-interventional post-authorisation safety study (PASS) assessed the long-term safety of everolimus in patients with tuberous sclerosis complex (TSC) who participated in the TuberOus SClerosis registry to increase disease Awareness (TOSCA) clinical study and received everolimus for the licensed indications in the European Union. The rate of...
Preprint
Full-text available
Background Dravet syndrome (DS) is a developmental and epileptic encephalopathy. Patients rapidly develop drug resistant seizures but patients with DS develop non-seizures disorders that are often age related. We aimed to identify the caregivers’ opinion on the outcome measures that matters in clinical trials in individuals with DS and their correl...
Article
Full-text available
Objective: To characterize the electro-clinical presentation of patients with pyridoxine-dependent epilepsy (PDE) and pyridoxal phosphate (PLP)-dependent epilepsy in order to determine whether some of them could be diagnosed as de novo West syndrome, i. e., West syndrome that starts after the age of 2 months without other types of seizures (focal s...
Article
Objective We aimed to describe epilepsy and EEG patterns related to vigilance states and age, in chromosome15-long-arm-duplication-syndrome (dup15q) children with epilepsy, in both duplication types: interstitial (intdup15) and isodicentric (idic15). Methods Clinical data and 70 EEGs of 12 patients (5 intdup15, 7 idic15), followed from 4.5m.o to 1...
Article
Introduction: Management of individuals with Dravet Syndrome has evolved significantly over the past 10 years. Progress has been made in understanding the pathophysiology, the long-term outcome and possible consequences of inappropriate therapies, new drugs have been approved by the regulatory authorities and patients and families expressed their n...
Article
Epileptic myoclonus (EM) is reported in many paediatric epilepsies from neonatal period to adolescence. Myoclonus can be the only seizure type or may occur among others, independently or in combination as a single ictal event. We report two children presenting with absences associated with myoclonus, predominating on one side, in a setting of two d...
Article
Objective This study was undertaken to investigate how gain of function (GOF) of slack channel due to a KCNT1 pathogenic variant induces abnormal neuronal cortical network activity and generates specific electroencephalographic (EEG) patterns of epilepsy in infancy with migrating focal seizures. Methods We used detailed microscopic computational m...
Article
Objective To further delineate the electroclinical features of individuals with SYNGAP1 pathogenic variants. Methods Participants with pathogenic SYNGAP1 variants and available video-electroencephalogram (EEG) recordings were recruited within five European epilepsy reference centers. We obtained molecular and clinical data, analyzed EEG recordings...
Article
Full-text available
Objective To correlate fetal brain MRI findings with epilepsy characteristics and neurodevelopment at two years of age in children with Tuberous Sclerosis Complex (TSC) in order to improve prenatal counseling Study design This retrospective cohort study was performed in a collaboration between centers of the EPISTOP consortium. We included childre...
Article
Full-text available
Purpose: Electronic health records are gaining popularity to detect and propose interdisciplinary treatments for patients with similar medical histories, diagnoses, and outcomes. These files are compiled by different nonexperts and expert clinicians. Data mining in these unstructured data is a transposable and sustainable methodology to search for...
Preprint
Full-text available
Background Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant genetic disorder caused by pathogenic mutations in either the TSC1 or TSC2 gene. Common manifestations of TSC have been grouped into major and minor clinical diagnostic criteria and assessed in clinical routine workup. However, case studies point towards the existe...
Preprint
Full-text available
Background The growing use of Electronic Health Records (EHRs) is promoting the application of data mining in health-care. A promising use of big data in this field is to develop models to support early diagnosis and to establish natural history. Dravet Syndrome (DS) is a rare Developmental and Epileptic Encephalopathy that commonly initiates in th...
Article
Full-text available
We explored the impact of coronavirus virus 2019 (COVID‐19) pandemic on patients with Dravet Syndrome (DS) and their family. With European patient advocacy groups (PAGs), we developed an online survey in 10 languages to question health status, behavior, personal protection, and health services before and after lockdown. Approximately 538 European P...
Article
Full-text available
Objective Clinical care of rare and complex epilepsies is challenging, because evidence‐based treatment guidelines are scarce, the experience of many physicians is limited and interdisciplinary treatment of comorbidities is required. The pathomechanisms of rare epilepsies are, however, increasingly understood, which potentially fosters novel target...
Article
Objective The aim of this study was to investigate attachment behavior in a population of infants with infantile spasms (ISs) using the Strange Situation Procedure (SSP) and to explore factors associated with the infants' attachment behavior. Methods The SSP was assessed in a population of 29 children with ISs during the second year of life. In mo...
Article
Lamotrigine is a broad-spectrum antiepileptic drug with high interindividual variability in serum concentrations in children. The aims of this study were to evaluate the predictive performance of pediatric population pharmacokinetic (PPK) models published on lamotrigine, to build a new model with our monitoring data and to evaluate the current reco...
Article
Full-text available
Dravet Syndrome (DS) is burdened by high epilepsy-related premature mortality due to status epilepticus (SE). We surveyed centres within Europe through the Dravet Italia Onlus and EpiCARE network (European Reference Network for Rare and Complex Epilepsies). We collated responses on seven DS SCN1A+ patients who died following refractory SE (mean age...
Article
Full-text available
Objective Epilepsy develops in 70–90% of children with Tuberous Sclerosis Complex (TSC) and is often resistant to medication. Recently, the concept of preventive antiepileptic treatment to modify the natural history of epilepsy has been proposed. EPISTOP was a clinical trial designed to compare preventive versus conventional antiepileptic treatmen...
Article
Purpose The purpose of the study was to describe epileptologists' opinion on the increased use of remote systems implemented during the COVID-19 pandemic across clinics, education, and scientific meetings activities. Methods Between April and May 2020, we conducted a cross-sectional, electronic survey on remote systems use before and during the CO...
Article
Full-text available
Febrile infection‐related epilepsy syndrome (FIRES) is a rare catastrophic epileptic encephalopathy that presents suddenly in otherwise normal children and young adults causing significant neurological disability, chronic epilepsy and high rates of mortality. To suggest a therapy protocol to improve outcome of FIRES, workshops were held in conjunct...
Article
Over the last decade, advances in genetics, neuroimaging and EEG have enabled the aetiology of epilepsy to be identified earlier in the disease course than ever before. At the same time, progress in the study of experimental models of epilepsy has provided a better understanding of the mechanisms underlying the condition and has enabled the identif...
Article
Full-text available
Objective Fenfluramine has been shown to provide clinically meaningful and statistically significant reductions in convulsive seizure frequency in children and adolescents (aged 2‐18 years) with Dravet syndrome in two randomized, placebo‐controlled clinical trials. The objective of this analysis was to assess longer‐term safety and efficacy of fenf...
Article
Full-text available
Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder with a high risk of early-onset epilepsy and a high prevalence of neurodevelopmental comorbidities, including intellectual disability and autism spectrum disorder (ASD). Therefore, TSC is an interesting disease model to investigate early biomarkers of neurodevelopmental comorbiditie...
Article
Objective: We aimed to delineate the phenotypic spectrum and long-term outcome of individuals with KCNB1 encephalopathy. Methods: We collected genetic, clinical, electroencephalographic, and imaging data of individuals with KCNB1 pathogenic variants recruited through an international collaboration, with the support of the family association "KCN...
Article
Full-text available
Background: Tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) have unique, individual patterns that pose significant challenges for diagnosis, psycho-education, and intervention planning. A recent study suggested that it may be feasible to use TAND Checklist data and data-driven methods to generate natural TAND clusters...
Article
Full-text available
Objective To quantify whole‐brain functional organization after complete hemispherotomy, characterizing unexplored plasticity pathways and the conscious level of the dissected hemispheres. Methods Evaluation with multimodal magnetic resonance imaging in two pediatric patients undergoing right hemispherotomy including complete callosotomy with a pe...
Article
Full-text available
Renal angiomyolipomas are one of the most common renal manifestations in patients with tuberous sclerosis complex (TSC), with potentially life-threatening complications and a poor prognosis. Despite the considerable progress in understanding TSC-associated renal angiomyolipomas, there are no large scale real-world data. The aim of our present study...
Article
Full-text available
Objective: To assess adverse events (AEs) and efficacy of add-on cannabidiol (CBD) with a slower titration protocol in pediatric clinical practice. Methods: We conducted a prospective, open-label, multicenter study in seven French reference centers for rare epilepsies. Patients had slow titration to reach a target dose of 10 mg/kg/day within at lea...
Article
Full-text available
Research on tuberous sclerosis complex (TSC) to date has focused mainly on the physical manifestations of the disease. In contrast, the psychosocial impact of TSC has received far less attention. The aim of this study was therefore to examine the impact of TSC on health, quality of life (QoL), and psychosocial well-being of individuals with TSC and...
Article
Full-text available
Objective To evaluate the effect of the COVID-19 pandemic on global access to care and practice patterns for children with epilepsy. Methods We conducted a cross-sectional, online survey of pediatric neurologists across the world affiliated with the International Child Neurology Association, the Chinese Child Neurology Society, the Child Neurology...