Marina Trivisano1,2, Nicola Pietrafusa1, Alessandra Terracciano3, Carla Marini4, Davide Mei4, Francesca Darra5, Patrizia Accorsi6, Domenica Battaglia7, Lorella Caffi8, Maria P Canevini9,10, Simona Cappelletti11, Elisabetta Cesaroni12, Luca de Palma1, Paola Costa13, Raffaella Cusmai1, Lucio Giordano6, Annarita Ferrari14, Elena Freri15, Lucia Fusco1, Tiziana Granata15, Tommaso Martino2, Massimo Mastrangelo16, Stefania M Bova16, Lucio Parmeggiani17, Francesca Ragona15, Federico Sicca14, Pasquale Striano18, Luigi M Specchio2, Ilaria Tondo11, Elena Zambrelli9,10, Nelia Zamponi12, Caterina Zanus13, Clementina Boniver19, Marilena Vecchi19, Carlo Avolio2, Bernardo Dalla Bernardina5, Enrico Bertini20, Renzo Guerrini4, Federico Vigevano1, Nicola Specchio1. 1. Neurology Unit, Department of Neuroscience, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. 2. Clinic of Nervous System Diseases, University of Foggia, Foggia, Italy. 3. Laboratory of Medical Genetics, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. 4. Pediatric Neurology Unit and Laboratories, Children's Hospital Meyer-University of Florence, Florence, Italy. 5. Department of Life and Reproduction Sciences, University of Verona, Verona, Italy. 6. Child Neuropsychiatric Unit, Civilian Hospital, Brescia, Italy. 7. Child Neurology and Psychiatry, Catholic University, Rome, Italy. 8. Neuropsychiatric Unit, University of Bergamo, Bergamo, Italy. 9. Epilepsy Center, San Paolo Hospital, Milan, Italy. 10. Department of Health Sciences, University of Milan, Milan, Italy. 11. Unit of Clinical Psychology, Department of Neuroscience, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. 12. Child Neuropsychiatric Unit, University of Ancona, Ancona, Italy. 13. Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy. 14. Department of Developmental Neuroscience, Clinical Neurophysiology Laboratory, IRCCS Stella Maris Foundation, Pisa, Italy. 15. Department of Pediatric Neuroscience, IRCCS Foundation, Carlo Besta Neurological Institute, Milan, Italy. 16. Pediatric Neurology Unit, Vittore Buzzi Hospital, ASST Fatebenefratelli Sacco, Milan, Italy. 17. Department of Neuropediatrics, Regional Hospital of Bolzano, Bolzano, Italy. 18. Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health, G. Gaslini Institute, University of Genoa, Genoa, Italy. 19. Child Neurology and Clinical Neurophysiology Unit, Department of Women's and Children's Health, University Hospital of Padua, Padua, Italy. 20. Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Abstract
OBJECTIVE: PCDH19-related epilepsy is an epileptic syndrome with infantile onset, characterized by clustered and fever-induced seizures, often associated with intellectual disability (ID) and autistic features. The aim of this study was to analyze a large cohort of patients with PCDH19-related epilepsy and better define the epileptic phenotype, genotype-phenotype correlations, and related outcome-predicting factors. METHODS: We retrospectively collected genetic, clinical, and electroencephalogram (EEG) data of 61 patients with PCDH19-related epilepsy followed at 15 epilepsy centers. All consecutively performed EEGs were analyzed, totaling 551. We considered as outcome measures the development of ID, autistic spectrum disorder (ASD), and seizure persistence. The analyzed variables were the following: gender, age at onset, age at study, genetic variant, fever sensitivity, seizure type, cluster occurrence, status epilepticus, EEG abnormalities, and cognitive and behavioral disorders. Receiver operating characteristic curve analysis was performed to evaluate the age at which seizures might decrease in frequency. RESULTS: At last follow-up (median = 12 years, range = 1.9-42.1 years), 48 patients (78.7%) had annual seizures/clusters, 13 patients (21.3%) had monthly to weekly seizures, and 12 patients (19.7%) were seizure-free for ≥2 years. Receiver operating characteristic analysis showed a significant decrease of seizure frequency after the age of 10.5 years (sensitivity = 81.0%, specificity = 70.0%). Thirty-six patients (59.0%) had ID and behavioral disturbances. ASD was present in 31 patients. An earlier age at epilepsy onset emerged as the only predictive factor for ID (P = 0.047) and ASD (P = 0.014). Conversely, age at onset was not a predictive factor for seizure outcome (P = 0.124). SIGNIFICANCE: We found that earlier age at epilepsy onset is related to a significant risk for ID and ASD. Furthermore, long-term follow-up showed that after the age of 10 years, seizures decrease in frequency and cognitive and behavioral disturbances remain the primary clinical problems. Wiley Periodicals, Inc.
OBJECTIVE:PCDH19-related epilepsy is an epileptic syndrome with infantile onset, characterized by clustered and fever-induced seizures, often associated with intellectual disability (ID) and autistic features. The aim of this study was to analyze a large cohort of patients with PCDH19-related epilepsy and better define the epileptic phenotype, genotype-phenotype correlations, and related outcome-predicting factors. METHODS: We retrospectively collected genetic, clinical, and electroencephalogram (EEG) data of 61 patients with PCDH19-related epilepsy followed at 15 epilepsy centers. All consecutively performed EEGs were analyzed, totaling 551. We considered as outcome measures the development of ID, autistic spectrum disorder (ASD), and seizure persistence. The analyzed variables were the following: gender, age at onset, age at study, genetic variant, fever sensitivity, seizure type, cluster occurrence, status epilepticus, EEG abnormalities, and cognitive and behavioral disorders. Receiver operating characteristic curve analysis was performed to evaluate the age at which seizures might decrease in frequency. RESULTS: At last follow-up (median = 12 years, range = 1.9-42.1 years), 48 patients (78.7%) had annual seizures/clusters, 13 patients (21.3%) had monthly to weekly seizures, and 12 patients (19.7%) were seizure-free for ≥2 years. Receiver operating characteristic analysis showed a significant decrease of seizure frequency after the age of 10.5 years (sensitivity = 81.0%, specificity = 70.0%). Thirty-six patients (59.0%) had ID and behavioral disturbances. ASD was present in 31 patients. An earlier age at epilepsy onset emerged as the only predictive factor for ID (P = 0.047) and ASD (P = 0.014). Conversely, age at onset was not a predictive factor for seizure outcome (P = 0.124). SIGNIFICANCE: We found that earlier age at epilepsy onset is related to a significant risk for ID and ASD. Furthermore, long-term follow-up showed that after the age of 10 years, seizures decrease in frequency and cognitive and behavioral disturbances remain the primary clinical problems. Wiley Periodicals, Inc.
Authors: Medine I Gulcebi; Emanuele Bartolini; Omay Lee; Christos Panagiotis Lisgaras; Filiz Onat; Janet Mifsud; Pasquale Striano; Annamaria Vezzani; Michael S Hildebrand; Diego Jimenez-Jimenez; Larry Junck; David Lewis-Smith; Ingrid E Scheffer; Roland D Thijs; Sameer M Zuberi; Stephen Blenkinsop; Hayley J Fowler; Aideen Foley; Sanjay M Sisodiya Journal: Epilepsy Behav Date: 2021-02-10 Impact factor: 3.337