Developmental outcome of electroencephalographic findings in encephalopathy.
Journal: Frontiers in cell and developmental biology
Volume: 12
Issue:
Year of Publication:
Affiliated Institutions:
Pediatric Neurology Department Sant Joan de Déu (SJD) Children's Hospital, Barcelona, Spain.
Department of Genetics, Microbiology and Statistics, University of Barcelona, Barcelona, Spain.
Pediatric Neurology Department, Hospital Universitario Miguel Servet, Zaragoza, Spain.
Pediatric Neurology Department, Arrixaca University Hospital, Murcia, Spain.
Pediatric Neurology Department - IBIMA Group, Hospital Regional Universitario de Málaga, Málaga, Spain.
Pediatric Neurology Department, Hospital Universitario Reina Sofía, Córdoba, Spain.
Pediatric Neurology Department, Hospital Universitario Infantil del Niño Jesús, Madrid, Spain.
Pediatric Neurology Department, Neurogenetics Section, Hospital Universitario Quironsalud, Madrid, Spain.
Mental Health in Intellectual Disability Specialized Service Althaia, Xarxa Assistencial, Manresa, Spain.
Pediatric Neurology Department, Hospital de Octubre, Universidad Complutense de Madrid, Madrid, Spain.
Paediatric Department, Arnau de Vilanova University Hospital, Lleida, Spain.
Pediatric Neurology Department, Hospital General Universitario de Jerez de la Frontera, Jerez de la Frontera, Spain.
Pediatrics Department, Arnau de Vilanova University Hospital, Lleida, Spain.
Pediatric Neurology Department, Hospital Universitario Donostia, San Sebastian, Spain.
Pediatric Neurology Department, Complejo Asistencial Universitario de Salamanca, Salamanca, Spain.
Pediatric Neurology Department, Hospital de Manises, Valencia, Spain.
Pediatric Neurology Department, Hospital Clínico Universitario Santiago de Compostela, Santiago de Compostela, Spain.
Pediatric Neurology Department, Sevilla, Spain.
Neurology Department, Hospital Universitario de Burgos, Burgos, Spain.
Pediatric Neurology Department, Puerta de Hierro Majadahonda Universitary Hospital, Madrid, Spain.
Paediatric Department Hospital Universitario Virgen del Rocío, Sevilla, Spain.
Pediatric Neurology Department, Vall d'Hebron University Hospital, Universitat Autónoma de Barcelona, Bercelona, Spain.
Department of Clinical and Molecular Genetic Vall d'Hebron University Hospital, Universitat Autónoma de Barcelona, Bercelona, Spain.
Molecular Physiology of the Synapse Laboratory, Institut de Recerca Sant Pau (IR Sant Pau), Universitat Autònoma de Barcelona, Barcelona, Spain.
Eurecat, Technology Center of Catalonia, Multimedia Technologies, Barcelona, Spain.
Pediatric Neurometabolism: Neural Communication Mechanisms and Personalized Therapies Pediatric Neurology Department: Neural Communication Mechanisms and Personalized Therapies Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain.
Department of Child Neurology, Epilepsy and Neurophysiology Unit, Member of the ERN EpiCARE, Hospital Sant Joan de Dèu, Barcelona, Spain.
Abstract summary
haploinsufficiency results in a developmental and epileptic encephalopathy (DEE) causing generalized epilepsies accompanied by a spectrum of neurodevelopmental symptoms. Concerning interictal epileptiform discharges (IEDs) in electroencephalograms (EEG), potential biomarkers have been postulated, including changes in background activity, fixation-off sensitivity (FOS) or eye closure sensitivity (ECS). In this study we clinically evaluate a new cohort of 36 SYNGAP1-DEE individuals. Standardized questionnaires were employed to collect clinical, electroencephalographic and genetic data. We investigated electroencephalographic findings, focusing on the cortical distribution of interictal abnormalities and their changes with age. Among the 36 SYNGAP1-DEE cases 18 presented variants in the gene that had never been previously reported. The mean age of diagnosis was 8 years and 8 months, ranging from 2 to 17 years, with 55.9% being male. All subjects had global neurodevelopmental/language delay and behavioral abnormalities; 83.3% had moderate to profound intellectual disability (ID), 91.7% displayed autistic traits, 73% experienced sleep disorders and 86.1% suffered from epileptic seizures, mainly eyelid myoclonia with absences (55.3%). A total of 63 VEEGs were revised, observing a worsening of certain EEG findings with increasing age. A disorganized background was observed in all age ranges, yet this was more common among older cases. The main IEDs were bilateral synchronous and asynchronous posterior discharges, accounting for ≥50% in all age ranges. Generalized alterations with maximum amplitude in the anterior region showed as the second most frequent IED (≥15% in all age ranges) and were also more common with increasing age. Finally, diffuse fast activity was much more prevalent in cases with 6 years or older. To the best of our knowledge, this is the first study to analyze EEG features across different age groups, revealing an increase in interictal abnormalities over infancy and adolescence. Our findings suggest that haploinsufficiency has complex effects in human brain development, some of which might unravel at different developmental stages. Furthermore, they highlight the potential of baseline EEG to identify candidate biomarkers and the importance of natural history studies to develop specialized therapies and clinical trials.
Authors & Co-authors:
Ribeiro-Constante
Tristán-Noguero
Martínez Calvo
Ibañez-Mico
Peña Segura
Ramos-Fernández
Moyano Chicano
Camino León
Soto Insuga
González Alguacil
Valera Dávila
Fernández-Jaén
Plans
Camacho
Visa-Reñé
Martin-Tamayo Blázquez
Paredes-Carmona
Marti-Carrera
Hernández-Fabián
Tomas Davi
Sanchez
Herraiz
Pita
Gonzalez
O'Callaghan
Iglesias Santa Polonia
Cazorla
Ferrando Lucas
González-Meneses
Sala-Coromina
Macaya
Lasa-Aranzasti
Cueto-González
Valera Párraga
Campistol Plana
Serrano
Alonso
Del Castillo-Berges
Schwartz-Palleja
Illescas
Ramírez Camacho
Sans Capdevila
García-Cazorla
Bayés
Alonso-Colmenero
Study Outcome
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