Clinical dissection of early onset absence epilepsy in children and prognostic implications

Summary Purpose To investigate whether patients with typical absence seizures (TAS) starting in the first 3 years of life, conformed to Panayiotopoulos's definition of childhood absence epilepsy (CAE), show different electroclinical course than those not fulfilling CAE criteria. Methods In this multicenter retrospective study, we choose a fixed duration follow-up of 36 months to examine the electroclinical course of epilepsy in all children with TAS starting before 3 years of age. The probands who fulfilled Panayiotopoulos's criteria for CAE were classified as having pure early onset absence epilepsy (P-EOAE), whereas those who did not as nonpure EOAE (NP-EOAE). In addition, these two groups of patients were further stratified according to the number of antiepileptic drugs taken to obtain initial seizure control (mono-, bi-, and tritherapy). Key Findings Patients with P-EOAE (n = 111) showed earlier initial seizure control (p = 0.030) and better seizure-free survival curve (p = 0.004) than those with NP-EOAE (n = 77). No mutation in SLC2A1 gene or abnormal neuroimaging was observed in P-EOAE. Among patients with NP-EOAE, those receiving tritherapy showed increased risk of structural brain abnormalities (p = 0.001) or SLC2A1 mutations (p = 0.001) but fewer myoclonic features (p = 0.031) and worse seizure-free survival curve (p = 0.047) than those treated with mono- and bitherapy. Children with NP-EOAE had 2.134 the odds of having relapse during the follow-up compare to those with P-EOAE. Significance Children with early onset TAS who did meet Panayiotopoulos's criteria showed a favorable course of epilepsy, whereas patients not fulfilling Panayiotopoulos's criteria showed increased risk of relapse at long-term follow-up. © Wiley Periodicals, Inc. © 2013 International League Against Epilepsy

Clinical dissection of early onset absence epilepsy in children and prognostic implications

Summary Purpose To investigate whether patients with typical absence seizures (TAS) starting in the first 3 years of life, conformed to Panayiotopoulos's definition of childhood absence epilepsy (CAE), show different electroclinical course than those not fulfilling CAE criteria. Methods In this multicenter retrospective study, we choose a fixed duration follow-up of 36 months to examine the electroclinical course of epilepsy in all children with TAS starting before 3 years of age. The probands who fulfilled Panayiotopoulos's criteria for CAE were classified as having pure early onset absence epilepsy (P-EOAE), whereas those who did not as nonpure EOAE (NP-EOAE). In addition, these two groups of patients were further stratified according to the number of antiepileptic drugs taken to obtain initial seizure control (mono-, bi-, and tritherapy). Key Findings Patients with P-EOAE (n = 111) showed earlier initial seizure control (p = 0.030) and better seizure-free survival curve (p = 0.004) than those with NP-EOAE (n = 77). No mutation in SLC2A1 gene or abnormal neuroimaging was observed in P-EOAE. Among patients with NP-EOAE, those receiving tritherapy showed increased risk of structural brain abnormalities (p = 0.001) or SLC2A1 mutations (p = 0.001) but fewer myoclonic features (p = 0.031) and worse seizure-free survival curve (p = 0.047) than those treated with mono- and bitherapy. Children with NP-EOAE had 2.134 the odds of having relapse during the follow-up compare to those with P-EOAE. Significance Children with early onset TAS who did meet Panayiotopoulos's criteria showed a favorable course of epilepsy, whereas patients not fulfilling Panayiotopoulos's criteria showed increased risk of relapse at long-term follow-up. © Wiley Periodicals, Inc. © 2013 International League Against Epilepsy

Molecular Genetics and Interferon Signature in the Italian Aicardi Goutières Syndrome Cohort: Report of 12 New Cases and Literature Review

Aicardi-Goutières syndrome (AGS) is a genetically determined early onset encephalopathy characterized by cerebral calcification, leukodystrophy, and increased expression of interferon-stimulated genes (ISGs). Up to now, seven genes (TREX1, RNASEH2B, RNASEH2C, RNASEH2A, ADAR1, SAMHD1, IFIH1) have been associated with an AGS phenotype. Next Generation Sequencing (NGS) analysis was performed on 51 AGS patients and interferon signature (IS) was investigated in 18 AGS patients and 31 healthy controls. NGS identified mutations in 48 of 51 subjects, with three patients demonstrating a typical AGS phenotype but not carrying mutations in known AGS-related genes. Five mutations, in RNASEH2B, SAMHD1 and IFIH1 gene, were not previously reported. Eleven patients were positive and seven negatives for the upregulation of interferon signaling (IS > 2.216). This work presents, for the first time, the genetic data of an Italian cohort of AGS patients, with a higher percentage of mutations in RNASEH2B and a lower frequency of mutations in TREX1 than those seen in international series. RNASEH2B mutated patients showed a prevalence of negative IS consistent with data reported in the literature. We also identified five novel pathogenic mutations that warrant further functional investigation. Exome/genome sequencing will be performed in future studies in patients without a mutation in AGS-related genes

Symptomatic and presumed symptomatic focal epilepsies in childhood: An observational, prospective multicentre study

none44noOBJECTIVE: To describe the clinical, neuropsychological, and psychopathologic features of a cohort of children with a new diagnosis of symptomatic or presumed symptomatic focal epilepsy at time of recruitment and through the first month. The selected population will be followed for 2-5 years after enrollment to investigate the epilepsy course and identify early predictors of drug resistance. METHODS: In this observational, multicenter, nationwide study, children (age 1 month-12.9 years) with a new diagnosis of symptomatic or presumed symptomatic focal epilepsy were consecutively enrolled in 15 Italian tertiary childhood epilepsy centers. Inclusion criteria were as follows: (1) diagnosis of symptomatic focal epilepsy due to acquired and developmental etiologies, and presumed symptomatic focal epilepsy; (2) age at diagnosis older than 1 month and 3 to 6 years, and >6 years. Clinical, electroencephalography (EEG), neuroimaging, and neuropsychological variables were identified for statistical analyses. RESULTS: Two hundred fifty-nine children were enrolled (116 female and 143 male). Median age: 4.4 years (range 1 month-12.9 years); 46.0% (n = 119) of children were younger than 3 years, 24% (61) from 3 to 6 years of age, and 30% (79) older than 6 years. Neurologic examination findings were normal in 71.8%. Brain magnetic resonance imaging (MRI) was abnormal in 59.9%. Children age ≤3 years experienced the highest seizure frequency in the first month after recruitment (p < 0.0001). Monotherapy in the first month was used in 67.2%. Cognitive tests at baseline revealed abnormal scores in 30%; behavioral problems were present in 21%. At multivariate analysis, higher chances to exhibit more than five seizures in the first month after epilepsy onset was confirmed for younger children and those with temporal lobe epilepsy. SIGNIFICANCE: In this prospective cohort study, an extensive characterization of epilepsy onset in children with symptomatic or presumed symptomatic focal epilepsies is reported in relation to the age group and the localization of the epileptogenic zone.noneVecchi, Marilena; Barba, Carmen; De Carlo, Debora; Stivala, Micol; Guerrini, Renzo; Albamonte, Emilio; Ranalli, Domiziana; Battaglia, Domenica; Lunardi, Giada; Boniver, Clementina; Piccolo, Benedetta; Pisani, Francesco; Cantalupo, Gaetano; Nieddu, Giuliana; Casellato, Susanna; Cappanera, Silvia; Cesaroni, Elisabetta; Zamponi, Nelia; Serino, Domenico; Fusco, Lucia; Iodice, Alessandro; Palestra, Filippo; Giordano, Lucio; Freri, Elena; De Giorgi, Ilaria; Ragona, Francesca; Granata, Tiziana; Fiocchi, Isabella; Bova, Stefania Maria; Mastrangelo, Massimo; Verrotti, Alberto; Matricardi, Sara; Fontana, Elena; Caputo, Davide; Darra, Francesca; Dalla Bernardina, Bernardo; Beccaria, Francesca; Capovilla, Giuseppe; Baglietto, Maria Pia; Gagliardi, Alessandra; Vignoli, Aglaia; Canevini, Maria Paola; Perissinotto, Egle; Francione, StefanoVecchi, Marilena; Barba, Carmen; DE CARLO, Debora; Stivala, Micol; Guerrini, Renzo; Albamonte, Emilio; Ranalli, Domiziana; Battaglia, Domenica; Lunardi, Giada; Boniver, Clementina; Piccolo, Benedetta; Pisani, Francesco; Cantalupo, Gaetano; Nieddu, Giuliana; Casellato, Susanna; Cappanera, Silvia; Cesaroni, Elisabetta; Zamponi, Nelia; Serino, Domenico; Fusco, Lucia; Iodice, Alessandro; Palestra, Filippo; Giordano, Lucio; Freri, Elena; De Giorgi, Ilaria; Ragona, Francesca; Granata, Tiziana; Fiocchi, Isabella; Bova, Stefania Maria; Mastrangelo, Massimo; Verrotti, Alberto; Matricardi, Sara; Fontana, Elena; Caputo, Davide; Darra, Francesca; Dalla Bernardina, Bernardo; Beccaria, Francesca; Capovilla, Giuseppe; Baglietto, Maria Pia; Gagliardi, Alessandra; Vignoli, Aglaia; Canevini, Maria Paola; Perissinotto, Egle; Francione, Stefan