Analysis of a child with neurodevelopmental disorders due to variant of HNRNPU gene and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic variant in a child with neurodevelopmental disorders (NDDs).@*METHODS@#Clinical data of a child who had presented at Xiaogan Hospital Affiliated to Wuhan University of Science and Technology in December 2020 due to intermittent convulsions for over a year were retrospectively analyzed. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. "HNRNPU gene", "epilepsy", "epileptic encephalopathy", "hereditary epilepsy", "neurodevelopmental disorder", "neurodevelopmental syndrome", "HNRNPU", and "NDDs" were used as the key words to search the CNKI, Wanfang and PubMed databases dated from January 1, 1994 to February 10, 2022.@*RESULTS@#The patient was a 2-year-old boy who had developed seizure at the age of 5 months. His clinical features had included abnormal appearance, recurrent seizures, and low developmental quotients of each functional area as evaluated by the Gesell scale. The child was given sodium valproate for the antiepileptic treatment and rehabilitation training. He had become seizure-free within half a year of follow-up, but his intelligence and motor development did not improve significantly. Genetic testing revealed that he has harbored a heterozygous c.1720_1722delCTT (p.Lys574del) variant of the HNRNPU gene, which was not found in either of his parents. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PS2+PM2_Supporting+PM4). A total of 13 articles were retrieved, and the types of HNRNPU gene mutations have included splice site mutation, nonsense mutation, missense mutation, in-frame deletion, gene duplication, frameshifting mutation, and multiple exon deletion. The main clinical manifestations have included mental retardation, language delay, global developmental delay, epilepsy, craniofacial deformity, mental and behavioral abnormalities.@*CONCLUSION@#The c.1720_1722delCTT variant of the HNRNPU gene probably underlay the NDDs in this child. Above finding has enriched the mutational spectrum of the HNRNPU gene.

Clinical features of children with febrile seizures caused by Omicron variant infection / 中国当代儿科杂志

OBJECTIVES@#To study the clinical features of children with febrile seizures after Omicron variant infection.@*METHODS@#A retrospective analysis was performed on the clinical data of children with febrile seizures after Omicron variant infection who were admitted to the Department of Neurology, Children's Hospital Affiliated to the Capital Institute of Pediatrics, from December 1 to 31, 2022 (during the epidemic of Omicron variant; Omicron group), and the children with febrile seizures (without Omicron variant infection) who were admitted from December 1 to 31, in 2021 were included as the non-Omicron group. Clinical features were compared between the two groups.@*RESULTS@#There were 381 children in the Omicron group (250 boys and 131 girls), with a mean age of (3.2±2.4) years. There were 112 children in the non-Omicron group (72 boys and 40 girls), with a mean age of (3.5±1.8) years. The number of children in the Omicron group was 3.4 times that in the non-Omicron group. The proportion of children in two age groups, aged 1 to <2 years and 6-10.83 years, in the Omicron group was higher than that in the non-Omicron group, while the proportion of children in two age groups, aged 4 to <5 years and 5 to <6 years, was lower in the Omicron group than that in the non-Omicron group (P<0.05).The Omicron group had a significantly higher proportion of children with cluster seizures and status convulsion than the non-Omicron group (P<0.05). Among the children with recurrence of febrile seizures, the proportion of children aged 6-10.83 years in the Omicron group was higher than that in the non-Omicron group, while the proportion of children aged 3 years, 4 years, and 5 years in the Omicron group was lower than that in the non-Omicron group (P<0.05).@*CONCLUSIONS@#Children with febrile seizures after Omicron variant infection tend to have a wider age range, with an increase in the proportion of children with cluster seizures and status convulsion during the course of fever.

Mutación en el gen SCN9Aasociado con el síndrome de Dravet: presentación de un caso pediátrico / Mutation in the SCN9A Gene Associated with Dravet Syndrome: A Pediatric Case Report / Mutação no gene SCN9A associada à síndrome de Dravet: relato de um caso pediátrico

Introducción:el síndrome de Dravet, también conocido como epilepsia mioclónica grave de la infancia, corresponde a una encefalopatía epiléptica resistente a fármacos que inicia generalmente en el primer año de vida. Se caracteriza por crisis epilépticas que suelen tener múltiples desencadenantes; el más asociado es la presencia de episodios febriles previos. Se considera una enfermedad rara, debido a su baja incidencia y prevalencia. Presentación del caso: niño de 10 años de edad con un cuadro de epilepsia de origen estructural, asociada con un retraso en el neurodesarrollo y anomalías craneofaciales meno-res, con antecedente de cardiopatía congénita no corregida, colpocefalia y agenesia del cuerpo calloso. Debido a la persistencia de las crisis convulsivas y su consiguiente resistencia farmacológica, se le rea-lizó un exoma genético que evidenció una mutación del gen SCN9. Discusión: el síndrome de Dravet debe ser sospechado en todo paciente menor de un año que tenga crisis convulsivas a repetición asociadas con episodios febriles cuantificados. Aproximadamente, entre el 70 % y el 85 % de los pacientes con el diagnóstico de síndrome de Dravet presenta una mutación en el gen SCN1A, por lo que mutaciones en otros genes que codifican para canales de sodio, ubicados en el mismo cromosoma, como el SCN9A, podrían contribuir de forma multifactorial a dicha entidad

Introduction: Dravet syndrome, also known as severe myoclonic epilepsy in infancy, is a drug resistant epileptic encephalopathy that usually begins in the first year of life. It is characterized by the presence of epileptic seizures that usually have multiple triggers; the most currently associated is the presence of previous febrile episodes. It is considered as a rare disease due to its low incidence and prevalence. Case presentation: We reported the case of a ten-year-old boy with structural epilepsy associated with a neuro-developmental delay and minor craniofacial anomalies. He had a history of uncorrected congenital heart disease, colpocephaly, and agenesis of the corpus callosum. Due to the persistence of seizures secondary to drug resistance, it was decided to perform a genetic exome that evidenced a mutation of the SCN9A gene. Conclusions: Dravet syndrome should be suspected in all patients under one year of age who have recu-rrent seizures associated with fever that does not respond to medication and modifies its presentation. Approximately 70%−85% of the patients diagnosed with Dravet syndrome have a mutation in the SCN1A gene; therefore, mutations in other genes that encode sodium channels located on the same chromosome, such as SCN9A, could contribute in a multifactorial way.

Introdução: a síndrome de Dravet, também conhecida como epilepsia mioclônica grave da infância, corresponde a uma encefalopatia epiléptica resistente a medicamentos que geralmente se inicia no primeiro ano de vida. É caracterizada pela presença de crises epilépticas que costumam ter múltiplos detonantes, sendo que o mais associado atualmente é a presença de episódios febris prévios. É conside-rada uma doença rara devido à sua baixa incidência e prevalência. Apresentação do caso: é apresentado o caso de um menino de 10 anos de idade com quadro de epilepsia de origem estrutural, associada a atraso no desenvolvimento neurológico e pequenas anomalias craniofaciais; com histórico de cardio-patia congênita não corrigida, colpocefalia e agenesia do corpo caloso. Devido à persistência das crises epilépticas e consequente resistência farmacológica, optou-se pela realização de um exoma genético que apresenta uma mutação do gene SCN9. Discussão: a síndrome de Dravet deve ser suspeitada em todos os pacientes com menos de um ano de idade que apresentam convulsões repetidas associadas a episódios febris quantificados. Aproximadamente 70 a 85% dos pacientes com diagnóstico de síndrome de Dravet apresentam mutação no gene SCN1A, portanto mutações em outros genes que codificam canais de sódio, localizados no mesmo cromossomo, como o SCN9A, poderiam contribuir de forma multifatorial para essa entidade

Clinical and genetic analysis of PACS2 gene variant in two child patients with developmental and epileptic encephalopathy 66 / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical phenotype and genetic characteristics of two children with developmental epileptic encephalopathy type 66.@*METHODS@#Genomic DNA was extracted from peripheral blood samples of the two children and their parents. Whole exome sequencing (WES) was carried out and suspected variant was verified by Sanger sequencing.@*RESULTS@#The main manifestations of the two children were neonatal onset seizures, hypotonia, global developmental delay, and facial dysmorphisms. Cranial MRI showed delayed myelination in case 1 and cerebellar dysgenesis in case 2. WES has identified a de novo pathogenic variant in the PACS2 gene in both patients, namely c.625G>A (p.Glu209Lys)(NM_001100913.3), which was reported as a pathogenic variant before. This variant was predicted to be pathogenic according to the American College of Medical Genetics and Genomics guideline (PS2+PM2+PP3). The seizures were controlled after combination treatment of sodium valproate and levetiracetam in both cases. At last follow-up, the motor and intellectual development of the 2 cases were improved. Compared with the cases reported, the clinical symptoms and signs of our cases were relatively mild, and the treatment effects were fairly good.@*CONCLUSION@#The variant of c.625G>A (p.Glu209Lys) in PACS2 gene is a hotspot variant of developmental epileptic encephalopathy 66. Gene testing can facilitate the clinical diagnosis and treatment.

Delayed Diagnosis of Chromosome 22q11.2 Deletion Syndrome Due to Late-Onset Generalized Epilepsy

No abstract available.

Crisis epiléptica en la obra Transfiguración de Rafael Sanzio / Epileptic seizure depicted in The Transfiguration a work by Raphael Sanzio

Entre 1516 y 1520 Rafael Sanzio (1483-1520) realizó la obra Transfiguración. Es un cuadro de gran formato que representa un relato de los evangelios de Lucas, Mateo y Marcos con dos escenarios principales, el primero en la parte superior muestra la transfiguración de Cristo en el Monte Tabor; el segundo en la parte inferior expone la escena de un niño endemoniado que varios apóstoles intentan curar infructuosamente, lo cual solo ocurrió cuando Jesús lo hizo. Esta composición, en otras palabras, muestra un milagro fallido que no es habitual en el arte sacro. Un análisis desde la semiología neurológica permite aseverar que el niño poseído está presentando una crisis epiléptica tónica postural. Este artículo analiza la obra, la semiología neurológica en ella y su relación con la historia de la neurología

Raphael Sanzio (1483-1520) painted The Transfiguration between 1516 and 1520. It is a large format painting that illustrates two main scenes as described in the Gospel accounts of Luke, Mathew and Mark. The first scene, in the upper half, shows Christ ́s transfiguration on Mount Tabor; the lower half, shows the devil-possessed child with the apostles who had attempted unsuccessfully to heal him, but Christ heals the boy. In other words, this composition shows a failed miracle which is unusual in sacred art. Based on a neurological semiology analysis we can assert that the possessed boy is experiencing a tonic postural seizure. This article analyzes the painting, the neurological features depicted in it and its relationship with the history of neurology.

Cambios estructurales cerebrales en epilepsia generalizada idiopática identificados por análisis de imágenes de resonancia magnética automatizados / Cerebral structural changes in generalized idiopathic epilepsy identified by automated magnetic resonance imaging analysis

El objetivo de este estudio fue combinar dos métodos automatizados de análisis estructural de imágenes de resonancia magnética para identificar cambios estructurales en pacientes nacidos en Argentina con epilepsia generalizada idiopática (EGI) en comparación con un grupo control de adultos sanos. Fueron incluidos 28 pacientes con EGI y 26 controles sin diferencias demográficas significativas. El análisis de las estructuras cerebrales se realizó con dos métodos automatizados de análisis de imágenes de resonancia magnética: la morfometría basada en vóxel y con la herramienta de segmentación y registro integrada FSL (FSL-FIRST). FSL mostró una disminución del volumen en ambos tálamos en EGI en comparación con el grupo control (tálamo izquierdo: 8092 mm³ grupo control vs. 7424 mm³ EGI, p = 0.0015; tálamo derecho: 7951 mm³ grupo control vs. 7247 mm³ EGI, p = 0.0016). Se observó una reducción en el volumen de ambos núcleos caudados (izquierdo: 3612 mm³ grupo control vs. 3376 mm³ EGI, p = 0.01; derecho 3683 mm³ grupo control vs. 3459 mm³ EGI, p = 0.04). La morfometría basada en vóxel mostró una disminución del volumen en ambos núcleos caudados en EGI en comparación con el grupo control. Las otras estructuras cerebrales analizadas no mostraron diferencias significativas entre los grupos. Este estudio muestra la reducción en el volumen en las estructuras subcortical, tálamos y núcleos caudados en pacientes con EGI comparado con un grupo control.

The purpose of this study was to combine two automated methods of magnetic resonance imaging (MRI) structural analysis in order to identify structural changes in patients born in Argentina with idiopathic generalized epilepsy (IGE) compared to a healthy adult control group. Twenty-eight patients with IGE and 26 controls with no significant demographic differences were included. The analysis of the brain structures was conducted with two automated methods of magnetic resonance image analysis: voxel-based morphometry and FSL-integrated registration and segmentation toolbox (FSL-FIRST). FSL showed volume decrease in both thalamus in patients with IGE compared to the control group (left: 8092 mm³ control group vs. 7424 mm³ IGE, p = 0.0015; right: 7951 mm³ control group vs. 7247 mm³ IGE, p = 0.0016). A reduction in the volume of both caudate nuclei was also seen (left: 3612 mm³ control group vs. 3376 mm³ IGE, p = 0.01; right: 3683 mm³ control group vs. 3459 mm³ IGE, p = 0.04). Voxel-based-morphometry showed a volume decrease in both caudate nuclei in patients with IGE compared to the control group. The other cerebral structures analyzed did not show significant differences between the groups. In conclusion, this study shows the reduction in volume in the subcortical, thalamic, and caudate nuclei structures in patients with IGE in comparison to control group. This study conducted in our country delves into the analysis of brain structural changes in patients with EGI compared to healthy subjects.

Photosensitive tonic-clonic seizures:a continuum between focal and generalized seizures / 北京大学学报(医学版)

OBJECTIVE@#To investigate whether the tonic-clonic seizure (TCS) induced by intermittent photic stimulation (IPS)was generalized tonic-clonic seizure (GTCS)or partial secondarily tonic-clonic seizure (PGTCS),and to analyze the relationship between them.@*METHODS@#Video-electroencephalogram (VEEG)database of Peking University First Hospital from March 2010 to October 2018 were reviewed. Fifteen cases with idiopathic epilepsy who had TCS induced by IPS were included in this study, and their clinical and electroencephalogram (EEG)characteristics were retrospectively analyzed.@*RESULTS@#In this study, 4 of the 15 cases were boys and 11 were girls. The age of seizure onset ranged from 1 to 13 years. According to the medical records: 12 cases were considered as GTCS,while the remaining 3 cases were considered as PGTCS. The age at VEEG monitoring ranged from 2.5 to 16.0 years. All backgrounds of the VEEG were normal. Interictal discharges:generalized discharges in 11 cases, of which 4 cases coexisted with posterior discharges, 2 cases coexisted with Rolandic discharges, the other 5 cases merely had generalized discharges; merely focal discharges in two cases, one in the Rolandic area and the other in the posterior area; no interictal discharge in the remaining 2 cases. IPS induced photoparoxysmal response (PPR)results: 2 cases without PPR,the remaining 13 cases with PPR of generalized discharges, and 6 of the 13 cases coexisted with posterior discharges. IPS induced photoconvulsive response (PCR)results: GTCS in one case (contradictory to medical history),PGTCS in 11 cases (consistent with medical history),and GTCS and PGTCS hardly to distinguish in the remaining 3 cases. Of the three conditions above, there were generalized myoclonic seizures induced by IPS before TCS in 7 cases.@*CONCLUSION@#The medical history was unreliable in determining whether TCS was generalized or focal. Myoclonic seizures can coexist with PGTCS, and sometimes GTCS was indistinguishable from PGTCS, indicating that the dichotomy of seizure types need to be improved. Photosensitive TCS should be regarded as a continuum between focal and generalized seizures.

Association Analysis of Interleukin-1β, Interleukin-6, and HMGB1 Variants with Postictal Serum Cytokine Levels in Children with Febrile Seizure and Generalized Epilepsy with Febrile Seizure Plus

BACKGROUND AND PURPOSE: Febrile seizure (FS) is a unique type of seizure that only occurs during childhood. Genelized epilepsy with febrile seizure plus (GEFS+) is a familial epilepsy syndrome associated with FS and afebrile seizure (AFS). Both seizure types are related to fever, but whether genetic susceptibility to inflammation is implicated in them is still unclear. To analyze the associations between postictal serum cytokine levels and genetic variants in the cytokine genes interleukin (IL)-1β, IL-6, and high mobility group box-1 (HMGB1) in FS and GEFS+. METHODS: Genotyping was performed in 208 subjects (57 patients with FS, 43 patients with GEFS+, and 108 controls) with the SNaPshot assay for IL-1β-31 (rs1143627), IL-1β-511 (rs16944), IL-6-572 (rs1800796), and HMGB1 3814 (rs2249825). Serum IL-1β, IL-6, and HMGB1 levels were analyzed within 2 hours after seizure attacks using the ELISA in only 68 patients (38 FS, 10 GEFS+, and 20 controls). The allele distribution, genotype distribution, and correlations with serum cytokine levels were analyzed. RESULTS: Near-complete linkage disequilibrium exists between IL-1β-31 and IL-1β-511 variants. CT genotypes of these variants were associated with significantly higher postictal serum IL-1β levels than were CC+TT genotypes in FS (both p<0.05). CT genotypes of IL-1β-31 and IL-1β-511 variants were more strongly associated with FS than were CC+TT genotypes (odds ratio=1.691 and 1.731, respectively). For GEFS+, serum IL-1β levels after AFS for CT genotypes of IL-1β-31 and IL-1β-511 were also higher than for CC+TT genotypes. No significant associations were found for IL-6 and HMGB1. CONCLUSIONS: Genetic variants located in IL-1β-31 and IL-1β-511 promotor regions are correlated with higher postictal IL-1β levels in FS. These results suggest that IL-1 gene cluster variants in IL-1β-31 and IL-1β-511 are a host genetic factor for provoking FS in Korean children.

Advance in molecular genetic research on generalized epilepsies / 中华医学遗传学杂志

Genetic generalized epilepsies (GGEs) are a group of epilepsy syndromes caused by genetic factors. A few of GGEs conform to the Mendelian patterns, while most of them show polygene inheritance. Researchers initially found that most of the genes associated with GGEs are related to ion channels including voltage-gated sodium channels, potassium channels, calcium channels and chloride channels, and ligand-gated gamma-aminobutyric acid receptor channels. Further researches have shown that certain non-ion channel genes are also related to GGEs, and that de novo mutations and copy number variants also play an important role in the pathogenesis of GGEs. Application of next- and third-generation sequencing promoted delineation of the molecular genetics of the GGEs, but also brought more challenges. Genetic findings have provided an important basis for the elucidation of the pathogenesis, clinical diagnosis and precise treatment of GGEs. This paper provided a review for recent progress made in molecular genetics of GGEs.

Variantes genéticas de susceptibilidad en epilepsia genética generalizada en familias colombianas / Susceptibility gene variants in genetic generalized epilepsy in Colombian families

INTRODUCCIÓN: las epilepsias genéticas generalizadas (EGG) siguen patrones de herencia compleja. Este fenotipo es producto de la interacción de diferentes genes con factores ambientales. Los genes/loci más consistentemente asociados con este grupo de epilepsias son ECA1, ECA2-GABRG2, ECA3-CLCN2 (también conocido como JME6-CLCN2), JME1-EFHC1 y JME5-GABRA1. En Colombia poco se sabe sobre la contribución de las variantes genéticas en estos genes a la susceptibilidad para ser afectado por cualquiera de las formas de EGG. Nuestro propósito fue evaluar el papel de los cinco genes/loci más consistentemente asociados en otros estudios en un grupo de familias colombianas con EGG. MÉTODOS: se evaluaron dos marcadores para cada locus/gen. Los genotipos se obtuvieron mediante las técnicas de PCR-RFLP y ARMS-Tetraprimer. Los análisis estadísticos incluyeron pruebas de asociación alélica y haplotípica, además de pruebas de interacción gen-gen. RESULTADOS: se incluyeron 98 familias, de las cuales 51 fueron epilepsia de ausencias, mientras que 47 fueron epilepsia mioclónica juvenil. Se identificó una interacción significativa entre el alelo G del marcador rs4428455 (valor P=0,0008; gen GABRA1) y el alelo G de marcador rs719395 (valor P=0,002; gen EFHC1). CONCLUSIÓN: estos dos marcadores parecen incrementar el riesgo de EGG en población colombiana. Otros genes no analizados aquí podrían estudiarse con una muestra de mayor tamaño

INTRODUCTION: Generalized genetic epilepsies (GGE) follow complex inheritance patterns. This phenotype is due to interaction of several genes with environmental factors. The genes/loci most consistently associated with this group of epilepsies are ECA1, ECA2-GABRG2, ECA3-CLCN2 (also known as JME6-CLCN2), JME1-EFHC1 and JME5-GABRA1. In Colombia, little is known about the contribution of gene variants to susceptibility to GGE forms. Our purpose was to evaluate the role of the five most consistently associated genes /loci in other studies, in Colombian families set with GGE. METHODS: Genotypes were obtained by means of PCR-RFLP and ARMS-Tetraprimer. Statistical analyses included both allelic and haplotypic association tests, in addition to gene-gene interaction tests. Two genetic markers were tested for each gene/locus. RESULTS: Ninety-eight families were included, from which 51 had absence epilepsy, and 47 had juvenile myoclonic epilepsy. A significant interaction was identified between allele G at marker rs4428455 (P-value= 0.0008; gene GABRA1) and allele G at marker rs719395 (P-value= 0.002; gene EFHC1). CONCLUSION: Our results suggest that these two markers are associated with GGE in the Colombian population. Other genes not analyzed could be tested using a larger sample size.

Electroencephalography abnormalities in generalized epilepsy and their predictors: A multicenter experience

Background: In spite of the overwhelming significance of knowledge of basic elements of electroencephalography (EEG) in its application to the diagnostic workup and the management of patients with suspected or already established generalized epilepsy (GE), there is a dearth of data on the pattern and utility of clinical variables that can independently determine EEG abnormalities in GE. Objective: The study was designed to evaluate the frequency and pattern of EEG abnormality as well as assess the utility of clinical variables in predicting the likelihood of an abnormal EEG in GE. Methods: It was a cross-sectional study involving the analysis of EEGs of consecutive patients with clinical diagnosis of idiopathic GE from three centers over a 7-year period. Information on sociodemographic and seizure variables was obtained. The International Federation of Societies for Electroencephalography and Clinical Neurophysiology definition of interictal epileptiform discharges (interictal epileptiform activity [IEA]) was adopted in the study. Results: A total of 403 patients comprising 242 (60%) males and 161 (40%) females with clinical diagnosis of GE had EEG. Their age ranged between 2 weeks and 70 years, with a median age of 21 years and an interquartile age of 26 years. Two hundred and thirty-seven (58.8%) and 213 (52.9%) patients had abnormal EEG and IEA, respectively. Before adjustment for confounders, female gender (P = 0.0001), pediatric age group (P = 0.0388), duration of epilepsy of 1­4 years (P = 0.01387), uncontrolled seizure (P = 0.0060), and seizure frequency (P = 0.0001) were significantly associated with the presence of abnormal EEG. However, age, female gender, poor seizure control, and seizure frequencies were the independent predictors of EEG abnormality. Conclusion: The study showed that about 58% of patients with GE patients had abnormal EEG. Age, poor seizure control, and high frequency of seizure were independent predictors of the presence of EEG abnormality

Agenesis of the Internal Carotid Artery Associated with Generalized Epilepsy

No abstract available.

Cognitive Function and Neuropsychological Comorbidities in Children with Newly Diagnosed Idiopathic Epilepsy

BACKGROUND: In this study, we aimed to identify cognitive function and neuropsychological comorbidities in children with newly diagnosed idiopathic epilepsy. METHODS: We retrospectively reviewed the records of 97 antiepileptic drug-naïve children (9.7 ± 2.9 years; 54 males and 43 females) with newly diagnosed idiopathic epilepsy, all of whom underwent a neuropsychological battery. The battery consisted of the Korean Wechsler Intelligence Scale, Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale, ADHD Diagnostic System, Children's Depression Inventory, and State-Trait Anxiety Inventory for Children. We investigated association between scores of the neuropsychological battery and epilepsy classification, lateralization of interictal epileptiform discharges (IEDs) on electroencephalography (EEG), and variables related to seizures. RESULTS: Thirteen patients (14.3%) had ADHD symptoms. Three patients (4.1%) had depressive symptoms, and 9 (12.3%) had anxiety symptoms. Patients with idiopathic generalized epilepsy (IGE) had significantly lower full-scale intelligence and performance intelligence quotient scores than patients with idiopathic localization-related epilepsy (ILRE) (89.0 ± 17.6 vs. 96.3 ± 14.8; P = 0.030 and 88.9 ± 16.3 vs. 97.0 ± 16.4; P = 0.016, respectively). Patients with ILRE having unilateral IEDs had significantly higher full-scale intelligence quotient scores than patients with ILRE having bilateral IEDs and patients with IGE (99.9 ± 12.2 vs. 93.7 ± 16.1 vs. 89.0 ± 17.6; P = 0.039, respectively). CONCLUSION: Our results suggest that idiopathic epilepsy may be accompanied by various neuropsychological comorbidities even at initial diagnosis. Patients with IGE and ILRE having bilateral IEDs on EEG appear more likely to be at high risk of decreased cognitive function.

Transient Abnormalities on Magnetic Resonance Imaging after Absence Seizures / 대한소아신경학회지

Magnetic resonance imaging (MRI) is recommended for patients with epileptic seizures to rule out an underlying focal lesion. However, abnormalities in idiopathic generalized epilepsy, including childhood absence epilepsy, cannot usually be identified using brain imaging modalities such as MRI. Peri-ictal MRI abnormalities have been most commonly reported secondary to status epilepticus and are rarely observed in patients with focal seizures and generalized tonic-clonic seizures. Transient peri-ictal MRI abnormalities in absence epilepsy are extremely rare. A five-year-old girl presented with a three-day history of absence seizures that persisted despite continued treatment with sodium valproate. Electroencephalography showed bursts of generalized 3-Hz spike-and-wave discharges, during and after hyperventilation. Abnormal cortex thickening in the left perisylvian region was detected on T2-weighted brain MRI, and cortical dysplasia or a tumor was suspected. The patient started treatment with lamotrigine and was seizure-free after one month. The abnormal MRI lesion was completely resolved at the two-month follow-up. We report on a patient with childhood absence epilepsy and reversible brain MRI abnormalities in the perisylvian region. To our knowledge, this is the first report of transient MRI abnormalities after absence seizures. Transient peri-ictal MRI abnormalities should be considered for differential diagnosis in patients with absence seizures and a focal abnormality on brain MRI.

long-term prognosis of epilepsy patients with medically treated over a period of eight years in Turkey

Objective: The aim of this study was to investigate the effect of demographic and clinical characteristics on temporal changes in seizure control and frequency in medically treated epilepsy patients to guide treatment modalities

Methods: We retrospectively analyzed the association between clinical and demographic characteristics and seizure frequency in 1329 epilepsy patients who were followed up at an outpatient clinic for one to eight years, 2008-2015

Results: Younger age at first seizure [p = 0.0465] and a long disease duration [p = 0.0406] had a negative effect on seizure control in all the epilepsy patients. Febrile convulsions [PCs] [p > 0.0001], perinatal risk [PNR] [p > 0.0002], a family history of epilepsy [FHE] [p > 0.0016], antiepileptic drug [AED] use [p > 0.001], mental retardation [MR] [p > 0.001], and psychiatric disorders [p > 0.0478] were prognostic indictors of temporal changes in seizure frequency. The presence of PNR [p = 0.0416], age at onset of epilepsy [p = 0.034], central nervous system infection [CNSI] [p = 0.04], and AEDs number [p = 0.0282] were prognostic indicators of not remaining seizure free for one year. In those with partial epilepsy, a trauma history [p = 0.05], a longer epilepsy duration [p = 0.0057], and FHE [p = 0.0466] increased the frequency of seizures, whereas cerebrovascular event [CVE] history decreased the seizure frequency [p = 0.0413]. In addition, FHE [p = 0.0438] and psychotic disorders [p = 0.0416] increased generalized seizures frequency

Conclusion: In all the epilepsy patients, a younger age at onset and longer duration of epilepsy were associated with a poor prognosis. The presence of PNR, age at onset of epilepsy, CNSI, and AEDs numbers were prognostic indicators of not remaining seizure free for one year. Increasing AEDs number was not effective in controlling seizures in partial epilepsy, but it was effective in controlling seizures in generalized epilepsy

Epilepsia occipital / Occipital lobe epilepsy

Se han hecho innumerables intentos para lograr una definición que incluya toda la semiología y fisiología que envuelve la epilepsia, y tratar de hacerlo ha sido una tarea que ha tomado muchos años. Aunado a ello se ha propuesto una clasificación en diferentes grupos según su inicio y desencadenamiento, como lo son focales y generalizadas. La presente revisión versará acerca de la epilepsia occipital, clasificada antes dentro de las crisis parciales, en las que se han identificado un curso y un pronóstico favorables en el transcurso del tiempo, y que tienen en común un inicio en la edad temprana. Ha sido descrito que algunos de estos trastornos pudieran tener una base genética hereditaria o bien esporádica en otros, lo cual requiere una investigación exhaustiva. Por lo anterior se hace necesaria una revisión completa acerca de la epilepsia occipital, con el fin de dar claridad conceptual, clínica y diagnóstica de este desorden, así como para hacer aportes al conocimiento de la misma en pro de mejorar la calidad de vida y el tratamiento en la práctica clínica de pacientes que se encuentren dentro del espectro de esta enfermedad.

Epilepsy and its overall semiology and physiology have been subject to Innumerable definition attempts which have taken many years of effort. Likewise, a proposal for an epilepsy classification based on onset and precipitating factors was developed dividing seizures into focal and generalized seizures. This article reviews occipital lobe epilepsy which was formerly classified in the partial seizures group characterized by a favorable course and prognosis over time and by onset during early childhood. A possible genetic hereditary origin and that they may be sporadic has been described for some of these problems and still require a thorough investigation. Thus, it is necessary to conduct an extensive review on occipital lobe epilepsy for obtaining conceptual, clinical and diagnostic clarity as well as, to enhance knowledge on this illness for improving quality of life and clinical treatment in patients experiencing this spectrum of disorders.

A Case Report of Occipital Lobe Epilepsy and Related Optical Coherence Tomography Findings

PURPOSE: In the present case report, visual pathway damage confirmed by retinal ganglion cell layer (GCL) damage on optical coherence tomography (OCT) in occipital lobe epilepsy was described. CASE SUMMARY: A 25-year-old female with idiopathic generalized epilepsy developed visual blurring followed by a generalized seizure. On brain magnetic resonance imaging (MRI), very subtle changes of the cortex in the left parietooccipital lobe were observed. Two days after the attack, even after the disappearance of epileptiform wave on electroencephalogram (EEG), visual acuity in both eyes was 0.5 and a perimetry revealed nearly complete visual defect in both eyes. OCT showed severe thinning of GCL and mild thinning of retinal nerve fiber layer (RNFL). No additional seizure attack occurred thereafter. One month after the attack, her visual acuity was recovered to 1.0 in both eyes and her left visual hemifield defect was recovered. However, even 6 months after the attack, her right visual hemifield defect and GCL damage persisted in both eyes. CONCLUSIONS: We reported a case in which the visual pathway damage caused by occipital lobe epilepsy was identified using OCT, despite very subtle changes in brain imaging. This case indicated GCL thinning is an objective and prognostic index for the irreversible visual field defect in occipital lobe epilepsy.

The Mechanism of Anti-Epileptogenesis by Levetiracetam Treatment is Similar to the Spontaneous Recovery of Idiopathic Generalized Epilepsy during Adolescence

OBJECTIVE: The anti-epileptogenic drug levetiracetam has anticonvulsant and anti-epileptogenesis effects. Synergy between cell death and inflammation can lead to increased levels of apoptosis inhibitory factors and brain-derived neurotrophic factor, aberrant neurogenesis and extended axon sprouting. Once hyperexcitation of the neural network occurs, spontaneous seizures or epileptogenesis develops. This study investigated whether the anti-epileptogenic effect of levetiracetam is due to its alternate apoptotic activity. METHODS: Adult male Noda epileptic rats were treated with levetiracetam or vehicle control for two weeks. mRNA quantification of Bax, Bcl-2 and GAPDH expression were performed from prefrontal cortex and hippocampus tissue samples. RESULTS: The levetiracetam-treated group showed a significant increase of Bax/Bcl-2 mRNA expression ratio in the prefrontal cortex than the control group, but no change in the Bax/Bcl-2 mRNA expression ratio in hippocampus. CONCLUSION: Idiopathic generalized epilepsy including childhood absence epilepsy develop at childhood and recover spontaneously during adolescence. The aberrant neural excitable network is pruned by a neural-maturing action. This study suggests the mechanism of acquired anti-epileptogenesis by levetiracetam treatment may be similar to spontaneous recovery of idiopathic generalized epilepsy during adolescence.

Seizure Aggravation Following Adjunctive Levetiracetam Therapy in Children with Epilepsy: a Single Tertiary Center Experience / 대한소아신경학회지

PURPOSE: The aim of this study is to evaluate the prevalence and risk factors of seizure aggravation of adjunctive levetiracetam therapy in children with epilepsy. METHODS: We retrospectively identified 125 children (0.3–18 years) with epilepsy who were newly treated with adjunctive levetiracetam therapy from November 2008 to July 2014 in Pusan National University Hospital, and 44 patients were excluded according to the exclusion criteria. Aggravation was diagnosed if the seizure frequency increased by more than 50% of baseline or there were new types of seizures after 1 month of adjunctive levetiracetam therapy. RESULTS: Eighty-one patients (male:female, 44:37) were enrolled, including 27 (33.5%) with generalized seizures and 54 (66.7%) with focal seizures. Twelve patients (14.8%) exhibited seizure aggravation and 69 patients (85.2%) had improvement or no change after 1 month of levetiracetam therapy. Eleven patients (91.7%) in seizure aggravation group and 16 patients (23.2%) in non-seizure aggravation group had generalized seizures, with aggravation significantly more frequent in patients with generalized seizures (P < 0.001). Other factors such as age at diagnosis, age at adding levetiracetam, sex, baseline seizure frequency, etiology, electroencephalography and magnetic resonance imaging abnormalities, and concomitant drug use were not identified as risk factors. CONCLUSION: Although levetiracetam is an effective antiepileptic drug in children with epilepsy, adjunctive levetiracetam therapy was associated with worsening of seizures in 14.8 % of included patients, especially those with generalized seizures. Careful monitoring for increased seizure frequency or the onset of a new type of seizures is advised for patients prescribed levetiracetam add-on treatment.