Impact of epilepsy on executive functions and attention in preschool children

Cette thèse a pour objectifs d'approfondir les connaissances sur le développement des fonctions exécutives et attentionnelles chez des enfants d'âge préscolaire présentant une épilepsie et d'explorer quels facteurs liés à la maladie épileptique perturbent ce développement. Ces fonctions de haut niveau, majeures pour le développement des êtres-humains, leur bien-être et leur autonomie au quotidien sont fréquemment déficitaires chez les enfants et adolescents présentant une épilepsie mais sont encore peu étudiées dans leur développement précoce notamment à l'âge préscolaire. La première étude a visé à développer un outil d'évaluation des fonctions exécutives et attentionnelles afin de travailler à une détection précoce des troubles dans la tranche d'âge préscolaire. Une batterie de tests cognitifs ciblant ces fonctions et adaptée aux jeunes enfants a été administrée à 67 enfants au développement typique âgés entre 3 et 7 ans. Les résultats nous ont permis de confirmer la forte dynamique développementale de ces fonctions dans cette fenêtre temporelle. Nous étudions également le lien entre l'évaluation au moyen de tests cognitifs et une évaluation plus écologique au moyen de questionnaires parentaux. L'évolution des différentes fonctions dans le temps et l'influence du sexe, du niveau socio-culturel et des compétences intellectuelles sont étudiés. Dans une seconde étude, nous avons administré la batterie précédemment constituée, associée à des questionnaires parentaux, à 34 enfants présentant une épilepsie débutant à l'âge préscolaire. Quatre enfants présentant une épilepsie focale frontale, 8 enfants présentant une épilepsie absence de l'enfant et 22 enfants présentant une épilepsie myoclono-atonique ont ainsi été inclus. Les profils attentionnels et exécutifs sont présentés, montrant des hétérogénéités inter-groupes. Les résultats sont en faveur d'une vulnérabilité des fonctions exécutives et attentionnelles dans ces populations avec des disparités liées au syndrome épileptique, aux crises épileptiques, aux facteurs temporels (durée de la maladie, âge à la première crise) mais aussi aux traitements antiépileptiques. Notre troisième étude apporte une perspective développementale à ces travaux à travers une méthodologie d'étude de cas multiples longitudinale. Trois enfants présentant une épilepsie myoclono-atonique ont été évalués en trois points temporels avec la même batterie de tests. Une analyse individuelle des processus atteints est réalisée et les dynamiques évolutives des compétences attentionnelles et exécutives sont explorées, toujours au regard des caractéristiques de l'épilepsie et de son évolution. Pour conclure, ces travaux confirment la vulnérabilité cérébrale et cognitive précoce. La survenue de la pathologie épileptique pendant la période clé de développement des fonctions exécutives et attentionnelles est délétère pour ces fonctions. Ces fragilités cognitives peuvent être décelées dès l'âge préscolaire au moyen d'évaluations ciblées, permettant d'ouvrir des perspectives d'accompagnement précoce et spécifique de ces enfants et de leur famille.This work aims to extend our knowledge on executive and attention development in preschool children with epilepsy and to explore the links with epilepsy characteristics. These high order cognitive functions are central for development of humans, their well-being and autonomy in daily life. Children and adolescents with epilepsy often show deficits in attention or executive functions but these functions are scarcely studied especially in preschool children. The first study aimed to develop an evaluation tool of executive and attention functions to enable a precocious detection of deficits in preschool age. A cognitive test battery targeting these functions and adapted to young children was administrated to 67 children with typical development from 3 to 7 years old. Results enabled to confirm the strong developmental dynamic of these functions in this age range. We also studied the link between cognitive tests and parental questionnaires. The evolution of executive function and attention through ages and the links with sex, socio-cultural level and intelligence are studied. In a second study, we administered the battery, with parental questionnaires, to 34 children with an epilepsy starting at preschool age. Four children with focal frontal epilepsy, 8 children with childhood absence epilepsy and 22 children with myoclonic-atonic epilepsy were recruited. Attentional and executive profiles are reported and show a heterogeneity between groups. Results are in favor of a vulnerability of executive functions and attention in these populations with discrepancies linked to epileptic syndrom, epileptic seizures, temporal factors (epilepsy duration, age at first seizure) and antiepileptic drugs. Our third study offers a developmental dynamic to our work using a longitudinal multiple case study methodology. Three children with myoclonic-atonic epilepsy were assessed at three time points using the same test battery. An individual study of the cognitive processes is produced and the evolutionary dynamics of executive function and attention through time are explored aknowledging the characteristics of the epilepsy and its evolution. In conclusion, this work confirms the precocious cerebral and cognitive vulnerability. The onset of epilepsy during the key period of development of executive functions and attention have an adverse impact on these functions. This vulnerability can be detected as soon as preschool age using targeted evaluations and enabeling perspective of precocious and specific care for these children and their family

Transition of patients with childhood onset epilepsy: Perspectives from pediatric and adult neurologists

International audienceTransition from pediatric to adult care systems is a major challenge in the management of adolescents with epilepsy. The comparison of pediatric and adult physicians' points of view on this issue is scarcely described. The aim of this study was to understand pediatric and adult neurologists' experience and opinions on transition in epilepsy in France. We investigate the age at which they usually transfer patients, their opinion on the factors that positively or negatively impact transition, on the help provided during this transition period, and their propositions to improve this process. We prepared a targeted questionnaire with two versions, one adapted for neurologists and the other for child neurologists. The questionnaires were diffused through the Reference Centre for Rare Epilepsies, the French Chapter of the League Against Epilepsy, the French Association for Office-based Neurologists, and the French Pediatric Neurology Society. A total of sixty-eight physicians involved mostly in epilepsy care answered this questionnaire: 39 child neurologists and 29 neurologists. Questionnaires were filled at 96.8%. Twenty-six child neurologists followed patients aged over 18 years (70%), and 18 neurologists followed patients under the age of 12 years (66.6%). Cognitive impairment in childhood led significantly to a later transfer to adult care. The major factors believed to delay the transfer were attachment between child neurologists and families as reported in 96.3% by neurologists and in 81.1% by child neurologists, p = 0.07 and lack of adaptation of adult neurology facilities to adolescents especially with intellectual disability (59.3% neurologists, 75.7% child neurologists, p = 0.16). Factors that helped a transfer around 18-19 years were mainly pharmacoresistant epilepsy (71% for neurologists vs. 19% for child neurologists, p 65% of providers) and development of care networks between pediatric and adult care for patients with epilepsy (>55%) to improve transition as well as introducing courses on transition. Few physicians were aware of transition and transfer recommendations. Although child and adult neurologists still have some preconceived beliefs, they were able to identify the strengths and weaknesses of both care systems paving the way for proposals to improve transition and transfer of patients with epilepsy from pediatric to adult care

Adaptive behavior and psychiatric comorbidities in KCNB1 encephalopathy

International audienceAim: 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: We included 25 patients with a KCNB1 encephalopathy, aged from 3.2 to 34.1 years (median = 10 years). Adaptive functioning was assessed in all patients using the French version of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) questionnaire. We screened global behavior with the Childhood Behavioral Check-List (CBCL, Achenbach) and autism spectrum disorder (ASD) with the Social Communication Questionnaire (SCQ). We used a cluster analysis to identify subgroups of adaptive profiles.Results: VABS-II questionnaire showed pathological adaptive behavior in all participants with a severity of adaptive deficiency ranging from mild in 8/20 to severe in 7/20. Eight out of 16 were at risk of Attention Problems at the CBCL and 13/18 were at risk of autism spectrum disorder (ASD). The adaptive behavior composite score significantly decreased with age (Spearman’s Rho=-0.72, p<0.001) but not the equivalent ages, suggesting stagnation and slowing but no regression over time. The clustering analysis identified two subgroups of patients, one showing more severe adaptive behavior. The severity of the epilepsy phenotype predicted the severity of the behavioral profile with a sensitivity of 70% and a specificity of 90.9%.Conclusion: This study confirms the deleterious consequences of early-onset epilepsy in addition to the impact of the gene dysfunction in patients with KCNB1 encephalopathy. ASD and attention disorders are frequent. Parental questionnaires should be considered as useful tools for early screening and care adaptation

Expanding the genetic and phenotypic relevance of KCNB1 variants in developmental and epileptic encephalopathies: 27 new patients and overview of the literature

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Developmental and epilepsy spectrum of KCNB1 encephalopathy with long-term outcome.

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 "KCNB1 France." Patients were classified as having developmental and epileptic encephalopathy (DEE) or developmental encephalopathy (DE). In addition, we reviewed published cases and provided the long-term outcome in patients older than 12 years from our series and from literature. RESULTS: Our series included 36 patients (21 males, median age = 10 years, range = 1.6 months-34 years). Twenty patients (56%) had DEE with infantile onset seizures (seizure onset = 10 months, range = 10 days-3.5 years), whereas 16 (33%) had DE with late onset epilepsy in 10 (seizure onset = 5 years, range = 18 months-25 years) and without epilepsy in six. Cognitive impairment was more severe in individuals with DEE compared to those with DE. Analysis of 73 individuals with KCNB1 pathogenic variants (36 from our series and 37 published individuals in nine reports) showed developmental delay in all with severe to profound intellectual disability in 67% (n = 41/61) and autistic features in 56% (n = 32/57). Long-term outcome in 22 individuals older than 12 years (14 in our series and eight published individuals) showed poor cognitive, psychiatric, and behavioral outcome. Epilepsy course was variable. Missense variants were associated with more frequent and more severe epilepsy compared to truncating variants. SIGNIFICANCE: Our study describes the phenotypic spectrum of KCNB1 encephalopathy, which varies from severe DEE to DE with or without epilepsy. Although cognitive impairment is worse in patients with DEE, long-term outcome is poor for most and missense variants are associated with more severe epilepsy outcome. Further understanding of disease mechanisms should facilitate the development of targeted therapies, much needed to improve the neurodevelopmental prognosis