La epilepsia mioclónica juvenil y las disfunciones neurocognitivas y ejecutivas asociadas / Juvenile myoclonic epilepsy and associated neurocognitive and executive dysfunctions

Resumen La epilepsia mioclónica juvenil (EMJ) es un trastorno benigno con buena respuesta a la medicación antiepiléptica. Evaluaciones neuropsicológicas revelaron trastornos cognitivos leves. El objetivo de este estudio es determinar el desempeño cognitivo y síntomas anímicos de la EMJ comparados con controles normales. Se evaluaron en forma prospectiva 30 pacientes con EMJ y 29 controles pareados por edad, género, y escolaridad. Se analizaron las características clínicas de la EMJ. Se administró una batería cognitiva completa, un cuestionario auto-administrado de dificultades ejecutivas (DEX), un inventario de depresión validado para epilepsia NDDI-E, escala de depresión de Beck (BDI), escala de ansiedad (GAD-7) y escala de riesgo de suicidio (MINI). Sin diferencias significativas en edad y escolaridad ent re EMJ y controles. Tiempo medio de evolución de la enfermedad, 18 años. El 53% presentó tres tipos de crisis, mioclonías, ausencias y convulsiones tónico-clónicas generalizadas. Hubo diferencias significativas con mayores fallas en atención, funciones ejecutivas, un puntaje significativamente mayor en el DEX en pacientes con EMJ. Se encontró un mayor puntaje en el NDDI-E, BDI y GAD-7 en EMJ. No se hallaron diferencias en el riesgo de suicidio respecto a controles. El estudio confirma que la EMJ presenta mayores fallas en el funcionamiento atencional y las habilidades ejecutivas relacionadas con la flexibilidad e inhibición, siendo en la mayoría de los casos los pacientes conscientes de sus dificultades. Conocer estas dificultades permitirá un mejor abordaje terapéutico, y mejorar síntomas muchas veces desestimados.

Abstract Juvenile myoclonic epilepsy (JME) is a benign disorder with a good response to antiepileptic drugs. Neurop sychological evaluations revealed mild cognitive deficits. The objective of this study is to determine the cognitive profile and mood symptoms in JME compared to normal controls. 30 patients with JME and 29 controls matched for age, gender, and education level were prospectively evaluated. The clinical characteristics were analysed. They were given a complete cognitive battery, a self-administered questionnaire of executive difficulties (DEX), the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), Beck Depression Inventory (BDI), Generalized Anxiety Disorder Scale (GAD-7) and suicide risk scale (MINI). No significant differences in age and education were observed between JME and controls. Average time of evolution of the disease 18 years, 53% have three types of seizures: myoclonic, absence seizures and tonic-clonic seizures. Significant differences were found with greater failures in attention, executive function, a significantly higher score values in DEX in JME subjects. A higher score was found in the NDDI-E; BDI and GAD-7. No differences were found in the risk of suicide with respect to controls. The study confirms that JME presents greater failures in attentional functioning and executive skills related to flexibility and inhibition, with patients being aware of their difficulties in most cases. Knowing these difficulties would allow a better therapeutic approach to improve symptoms usually dismissed.

Anthropometric Profile and Nutritional Status in Children with Generalized Epilepsy

Background: Epilepsy is widespread in developing countriescompared to that in developed countries. The reason ofepilepsy in most cases is unknown. Considering the factthat the nutritional status of children in developing countriesis generally poor, our objective was to determine possiblerelationship between nutritional status and epilepsy.Material and methods: Towards this, we gather a datasetof 34 Cases from the Department of Pediatric and as manyControls from the local populace. The age group (5-8.5 years),sex, and gender data is also augmented with educationaland socioeconomic history along with the results of clinicalexaminations, such as, weight, height and body mass index.Results: Our statistical results unveil insignificantdifference in socioeconomic status and educational levels inbetween the parents of Cases and Controls. Additionally, asignificantly higher value of anthropometric measurementsin Controls is observed compared to that of the Casesi.e.Height (117.38±6.05 vs. 112.21±6.82 cm; p value 0.002),Weight (21.29±2.83 vs. 18.14±2.94 kg; p value <0.001) andBody mass index(15.39±1.03 vs.14.33±1.26 kg/m2; p value<0.001).Conclusion: Our results show that generalized epilepsymay have effect on growth and development of children,reflecting that nutritional programs are required to improvethe nutritional status in children with generalized epilepsy soas to optimize their growth and development.

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.

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.

Decision-making impulsivity in patients with idiopathic generalized epilepsy / 中华行为医学与脑科学杂志

Objective To explore the decision-making impulsivity in patients with idiopathic generalized epilepsy.Methods 39 patients with idiopathic generalized epilepsy and 40 healthy controls completed delay discounting task.The participants were demanded to make a series of choices between two different rewards after a delayed period (a smaller sooner reward or a larger longer reward).Results The delay discount rate k was transformed to common logarithm lg (k),and lg (k)=-1.75±0.86 in IGE group was more larger than that in HC group lg (k)=-2.21±0.72(t=2.58,P=0.01).IGE group performed worse than HC group in verbal fluency test-semantic (M (P25,P75):16.00 (14.00,19.00) vs 18.00 (16.00,22.75),Z =-2.86,P＜0.01),verbal fluency test-voice (M (P25,P75):4.00 (3.00,6.00) vs 7.00 (6.00,10.00),Z =-4.26,P＜0.01) and digital span backward test (M(P25,P75):5.00(5.00,7.00) vs 6.00 (5.00,8.00),Z=-2.48,P=0.01).In addition,lg (k) had significant correlation with verbal fluency test-semantic (r=0.32,P=0.048).Conclusion IGE group prefer immediate rewards and show more impulsive than HC group in delay discounting task.IGE group has cognitive deficit in frontal lobe language function and attention function.In addition,impulsivity is correlated with frontal lobe function.

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.

Study of fractional amplitude of low frequency fluctuation and regional homogeneity in idiopathic generalized epilepsy based on resting-state functional MRI / 实用放射学杂志

Objective To observe the changes of whole brain function in idiopathic generalized epilepsy(IGE).Methods Three-dimensional structure scan and resting-state functional scan were performed in 23 cases of IGE patients and 23 health controls at 3.0T super-conducting MRI scanner.Brain functional analysis by fALFF and ReHo methods were obtained and the changes of brain areas were compared.Correlation analysis between different brain regions of IGE patients with the course of disease were performed.Results Compared with normal controls,IGE group showed increasd fALFF in the bilateral precentral gyrus,left supplementary motor area, left cingulate gyrus,left paracentral lobule,left superior occipital gyrus,left calcarine cortex,left middle occipital gyrus and right precuneus;decreased fALFF in the bilateral inferior temporal gyrus,right parahippocampa gyrus,right insula,right precuneus and left inferior parietal lobule(P<0.005).IGE group showed increasd ReHo in the left calcarine cortex,left superior parietal lobule, left postcentral gyrus,right precentral gyrus;decreased ReHo in the right fusiform gyrus,left lentiform nucleus,right inferior frontal gyrus,right superior medial frontal gyrus,left middle occiptal gyrus,right insula and bilateral inferior parietal lobule(P<0.005). These different brain regions in fALFF and ReHo results for IGE patients were no correlated with the course of disease.Conclusion IGE patients having wide range of brain areas with abnormal changes in function is the basis of the IGE complex clinical manifestations of the nerve.Combined application of two analysis methods of RS-fMRI can evaluate the change of brain function more comprehensively, and provide functional neuroanatomical evidence for the researches on neuro pathogenesis mechanism of IGE.

Epilepsia infanto-juvenil y comorbilidad neurocognitiva: Impacto de la atención, memoria y procesos ejecutivos del lenguaje / Childhood epilepsy and neurocognitive comorbidity: Impact on attention, memory, and executive language processing

El objetivo del trabajo es profundizar en el conocimiento de procesos atencionales mnésicos y ejecutivos en pacientes con epilepsia. Comparados con un grupo control de similar edad y nivel educativo se encontraron diferencias significativas en atención, memoria, funciones ejecutivas y lenguaje. Entre epilepsias generalizadas y parciales no hubo diferencias. Los déficits encontrados impactan sobre el área académica. Es por tanto necesario implementar adecuaciones pedagógicas que modulen los contenidos académicos (AU)

The aim of this study was to enhance our knowledge on new attentional numerical and executive processes in patients with epilepsy. Compared to an age- and education-matched control group, significant differences in attention, memory, executive functions, and language development were observed. No differences were found between generalized and partial epilepsies. These deficits have an impact on academic performance. Therefore it is necessary to tailor educational therapy modulating the academic contents (AU)

Qualitative palmar dermatoglyphic patterns in cases of idiopathic generalized epilepsy.

Background: Genetic etiology has been proposed for both idiopathic epilepsy and dermatoglyphics. Hence, the present study has been undertaken to find out the existence of any correlation between dermatoglyphics and idiopathic generalized epilepsy. Objective of current study was to find out an association, if any, between dermatoglyphic patterns of hands in idiopathic generalized epilepsy of both sexes. Methods: The study was conducted in the department of anatomy and department of neurology, Himalayan institute of medical sciences, Swami Ram Nagar, Dehradun. Fingertip patterns (whorls, loops, arches) and Main line (A, B, C, D) terminations were analysed by utilizing finger and palmar prints. Results: The present study showed a significant decrease in whorls and an increase in arches in both the hands of male and female IGE patients. Loops were increased in both hands of female patients. Main line D was mostly confined to sectors 11, 9 and 7 in both sexes among the cases and controls. Main line C terminated quite often in sectors 9 & 7 in males and females of the case series. Main line B terminated most frequently in sectors 5'' & 7 in control and case groups. Main line A terminated most frequently in sector 5' in males and females. Conclusion: Therefore, we can conclude and hypothesize merely by observing decrease in the whorl and increase in the arch patterns in the fingerprints (as observed in the present study) that persons with high risk of idiopathic generalized epilepsy can be identified early and preventive measures can be taken against serious complications.

Screening of SCN1A gene mutation in 10 families with generalized epilepsy accompanied by febrile seizure / 解放军医学杂志

Objective To analyze the phenotypes and to identify SCN1A gene mutation in families with generalized epilepsy accompanied by febrile seizures (GEFS+). Methods The clinical data were collected, and genomic DNA was extracted from peripheral blood lymphocytes of the proband and available members in the GEFS+ families. The phenotypes of the related members were analyzed. The coding regions and flanking intronic regions of the SCN1A gene were screened for mutations using PCR and direct DNA sequencing. Results Thirty-three related members from 10 GEFS+ families, ranged from 2 to 7 members in each family received the examination. T heir phenotypes included febrile seizures (FS) in 11 persons (33.3%), febrile seizures plus (Fs+) in 11 (33.3%), FS with partial seizures in 1 (3.0%), afebrile generalized tonic-clonic seizures (AGTCS) in 3 (9.1%), Dravet syndrome in 1 (3.0%), childhood absence epilepsy in 1 (3.0%), and unclassified seizures in 5 members (15.2%). SCN1A mutations were found in 3 families, including one family with missense mutation (glu1444-lys), and silent mutation: synonymous mutation existed in exon 15 (c.2592G>A), with synonymous mutation in exon 9 (c.1212 G>A) and exon 26 (c.5385 G>A) in two families. Conclusions A new missense mutation and three synonymous mutation have been found in the coding regions of SCN1A gene in three families. One of the families has synonymous mutation in two exons. Genetic mechanism is complicated in GEFS families.

Epileptic events in the XIX century as reported by the Brazilian Royal Family / Eventos epilépticos no século XIX segundo relatos da Família Real Brasileira

Members of the Brazilian Royal Family carry a rich medical history of epileptic seizures and alike. OBJECTIVE: To present the medical knowledge about epilepsy by the time of the Brazilian Empire, as reported by the royal family. METHOD: Narrative review of historical facts about D. Pedro I's family health. RESULTS: The Royal Family, since D. João VI's generation is full of members with epilepsy or acute symptomatic seizures of different etiologies. CONCLUSION: The reported cases suggest that Dom Pedro I's family presented epilepsy with tonic-clonic generalized seizures, besides psychogenic, organic non epileptic events and acute symptomatic seizures. As a whole, this familial epilepsy could fit the diagnosis of generalized epilepsy with febrile convulsion plus.

Há uma história médica rica de crises epilépticas e similares nos membros da família real brasileira. OBJETIVO: Apresentar o conhecimento médico sobre epilepsia à época do Império no Brasil, conforme informado pelos acometidos da família real. MÉTODO: Revisão narrativa de fatos históricos sobre a saúde da família de D. Pedro I. RESULTADOS: A genealogia da família real, desde a geração de D. João VI é repleta de pessoas acometidas por epilepsia ou crises sintomáticas agudas de diversas etiologias. CONCLUSÃO: O relato de casos sugere que Dom Pedro I e sua família apresentavam epilepsia de incidência familiar predominantemente com crises tônico-clonicas generalizadas, além de eventos sintomáticos agudos, psicogênicos e orgânicos não epilépticos. Como um todo, a epilepsia dessa família poderia ser enquadrada no diagnóstico de epilepsia generalizada com convulsão febril plus.

Epileptic seizures in a descendant of Dom Pedro I / Crises epilépticas em uma descendente de Dom Pedro I

Intrauterine seizure is a rare event. Genetic predisposition and trauma are possible risk factors. OBJECTIVE: To review and comment on the historical description of intrauterine events of a bastard daughter of Dom Pedro I (Maria Isabel Alcântara Brasileira - 1830-1896). METHOD: Review of historical facts about the health of Dom Pedro I's daughter according to primary and secondary historical data. RESULTS: According to historical accounts, Dom Pedro I's daughter suffered trauma during the intrauterine period that provoked intrauterine seizures. At the age of eight years, she developed self-limited and benign generalized epilepsy. Like her father, she had mood problems and also learning difficulties. CONCLUSION: Dona Maria Isabel's own report does not shown sufficient evidence to support the diagnosis of post-traumatic intrauterine seizures. Nevertheless, her family history suggests a genetic basis for her epilepsy.

A convulsão intra-uterina é evento raro, sendo possíveis fatores de risco a genética e o traumatismo. OBJETIVO: Rever e comentar a descrição histórica de eventos intra-uterinas de uma filha bastarda de D. Pedro I (Maria Isabel Alcântara Brasileira - 1830-1896). MÉTODO: Revisão dos fatos históricos sobre a saúde da filha do D. Pedro I, de acordo com dados históricos primários e secundários. RESULTADOS: A filha de Dom Pedro I, de acordo com relatos históricos teria sofrido um traumatismo durante o período intra-uterino, o que provocou convulsões intra-uterinas. Na idade de oito anos a menina desenvolveu uma epilepsia generalizada limitada e benigna. Como seu pai, teve problemas do humor e, também, dificuldades de aprendizagem. CONCLUSÃO: O relato de Dona Maria Isabel não gera prova suficiente para sustentar o diagnóstico de convulsões intra-uterinas de origem traumática. Não obstante, seus antecedentes familiares sugerem uma base genética para sua epilepsia.

Tratamento das epilepsias generalizadas idiopáticas / Idiopathic generalized epilepsies treatment

As epilepsias generalizadas idiopáticas (EGIs) correspondem a um-terço de todas as epilepsias. Apesar desta elevada freqüência, as EGIs permanecem pouco reconhecidas. As características clínicas são fundamentais para o diagnóstico. Neste grupo de epilepsias, todos os tipos de crises generalizadas podem ocorrer especialmente as crises tônico-clônicas generalizadas, as crises mioclônicas e as crises de ausência. O eletroencefograma é bastante sugestivo do diagnóstico quando evidencia os típicos complexos espículas ou poliespículas-onda lenta, generalizados, simétricos e com atividade de base normal. De acordo com o tipo de crise predominante e com a idade de início das crises, as EGIs são divididas em subsíndromes. A importância do diagnóstico preciso está relacionada com a elevada porcentagem de indivíduos livre de crises quando tratados com a medicação antiepiléptica apropriada. Por outro lado, o uso de algumas medicações antiepilépticas como carbamazepina e fenitoína pode exacerbar as crises ou até mesmo induzir estado de mal epiléptico em determinadas subsíndromes. Neste artigo, revisamos as principais medicações antiepilépticas utilizadas no tratamento das EGIs bem como alguns aspectos práticos no tratamento das subsíndromes mais freqüentes.

Idiopathic generalized epilepsies (IGEs) correspond to one-third of all epilepsies. Despite of this high frequency, IGEs remains underdiagnosed. Clinical features are the cornerstone to diagnosis. In this group all types of generalized seizures may occur such as generalized tonic-clonic, absences and myoclonic seizures. EEG is very supportive of IGEs diagnosis when it shows the typical generalized symmetrical, spike or polispyke and waves complexes with normal background. According to the main seizure type and the age of onset, IGEs are divided in subsyndromes. The importance of the correct diagnosis is supported by the high rate of seizure free patients under appropriate antiepileptic drug therapy. On the other hand, the use of some antiepileptic drugs such as carbamazepine or phenytoin may exacerbate the seizures or even induce status epilepticus in some subsyndromes. In this article, the main antiepileptic drugs used in the treatment of IGEs are reviewed as well as some practical issues for IGEs subsyndromes treatment.

Brain-derived Neurotrophic Factor(BDNF) SNP 6265 Polymorphisms in Febrile Seizure and GEFS+ / 대한소아신경학회지

PURPOSE: Febrile seizure(FS) is one of the most common neurological conditions during childhood, but the pathogenesis of FS remains ambiguous. Various studies have shown that brain-derived neurotrophic factor(BDNF) increased neuronal excitability. In this study, to determine whether the polymorphisms of SNP 6265 within the gene encoding BDNF are associated with susceptibility to FS, the frequencies of the polymorphisms were investigated in children with FS and control subjects. In addition, we analyzed the SNP 6265 polymorphisms in Generalized epilepsy with febrile seizures plus (GEFS+) that hasn't been studied as yet in Korea. METHODS: A total of 79 children selected throughout a collaborative study of Catholic Child Neurology Research Group were divided into three groups: (1) FS(n=30); (2) GEFS+ (n=19); (3) control subjects(n=30). Genotypes and allelic frequencies for the polymorphisms of SNP 6265 located at nucleotide 196 was analyzed and compared among the groups. RESULTS: In this study, proportions for A homozygote, A/G heterozygote and G homozygote for BDNF were as follows: in FS, 46.7%, 36.7% and 16.7%, in GEFS+, 26.3%, 47.4% and 26.3% and in control subjects, 60.0%, 16.7% and 23.3%. The allele A and G frequencies for BDNF in FS were 65.0% and 35.0%, in GEFS+ were 50% and 50%, and in control subjects were 68.3% and 31.7%. However, these differences in genotype proportions and allele frequencies among three groups were not significant. CONCLUSION: These results suggest that genomic variations of BDNF might not be the susceptibility factor for FS and GEFS+ in Korean population.

Association Analysis of Voltage-gated Chloride Channel Gene CLCN2 Polymorphism with Idiopathic Generalized Epilepsy / 대한소아신경학회지

PURPOSE: The channelopathies has been implicated in the pathogenesis of idiopathic generalized epilepsy(IGE). Recently, nonsense and missense mutations in a voltage-gated chloride channel gene(CLCN2) have been shown to be associated with IGE. Loss of CLCN2 function results in loss of sustained GABA inhibition, increasing the risk of uncontrolled firing leading to seizure activity. This study assessed the relevance of mutations in the CLCN2 gene in the Korean patients with IGE. METHODS: Twenty seven patients with IGE were recruited in the Seoul National University Boramae Hospital. PCR and direct sequencing of genomic DNA were done to analyze the complete coding region of CLCN2. 99 controls were tested for two identified polymorphisms. Genotypes and allelic frequencies were compared to controls with epilepsy patients and subgroup of IGE: 10 generalized epilepsy with febrile seizure plus(GEFSP), 9 childhood absence epilepsy(CAE) and 8 other IGE patients. RESULTS: Twelve CLCN2 polymorphisms: 3 exonic, 2 promotor and 7 intronic, were found in 22 patients(81%) and 2 polymorphisms were noble. Two polymorphisms in the exonic region with changes of amino acid, p.L15P and p.T668S and 2 polymorphisms in the promoter regions(c.1-1990T>C, c.1-693G>A) may affect on the CLCN channel function. The odds ratio for developing other IGE in patients with RS9820367-CG type was 4.2 compared to individuals with CC type. In addition, the odds ratio for developing other GEFSP in patients with RS9820367-CC type was 4.0 compared with individuals with CG type. CONCLUSION: Our findings suggest that genomic variations of CLCN2 may be implicated in the pathogenesis of IGE.

Quality of life and the self-perception impact of epilepsy in three different epilepsy types

PURPOSE: This study aimed to evaluate the quality of life (QOL) and verify the domains of greater impact in patients with focal and generalized epilepsies. METHODS: The sample, composed by 57 subjects from Hospital São Paulo da Universidade Federal de São Paulo, was divided into 3 groups, temporal lobe epilepsies (TLE), extra-temporal epilepsies (Extra-TLE) and idiopathic generalized epilepsy (IGE). They answered a preliminary self-reported questionnaire to identify the perception of the most impaired aspects in their lives. The QOL was evaluated through the validated Brazilian version of the Quality of Life Epilepsy Inventory 31 (QOLIE-31). The correlation of the QOLIE-31 domains with epilepsy duration and seizure frequency was defined by dispersion graphics and also Pearson’s and Spearman’s correlation. RESULTS: The most frequently identified impact of epilepsy was related to interpersonal, familial and social relationships mentioned by 13 (22.81 percent) patients. The seizure frequency per patient in Extra-TLE group was significantly greater (p = 0.007) than in the other groups. The Cognition Functioning scores were lower for the Extra-TLE group (38.4) when compared with TLE (52.6) and IGE (62.6) (p = 0.01). The correlation between epilepsy duration and QOLIE-31 domains did not demonstrate statistical significance; however, seizure frequency was correlated with Seizures Worry (p = 0.0463, alpha = 0.05) and Medication Effects (p = 0.0476, alpha = 0.05) domains. CONCLUSIONS: 1) Interpersonal, familial, and social relationships were the dimension which most impacted daily life; 2) Cognition domain in Extra-TLE group showed the worst scores; 3) QOL scores were similar in the three groups for the majority of the QOLIE-31 domains; 4) The seizure frequency in the Extra-TLE group was significantly greater; 5) Seizure frequency was associated with worse QOLIE-31 scores in the domains Seizure Worry and Medication Effects.

OBJETIVO: Este estudo teve como objetivo avaliar a qualidade de vida (QV) em três diferentes grupos de epilepsia e verificar a esfera percebida como de maior impacto na vida diária. METODOLOGIA: A amostra foi composta por 57 pacientes com epilepsias focais e generalizadas do Hospital São Paulo, Universidade Federal de São Paulo, divididos em três grupos, epilepsias do lobo temporal (ELT), extratemporais (Extra-ELT) e generalizadas idiopáticas (EGI). Os pacientes responderam a um questionário preliminar para identificar a percepção sobre os aspectos mais comprometidos em suas vidas. A QV foi avaliada por meio da versão brasileira do Quality of Life in Epilepsy Inventory 31 (QOLIE-31). A correlação dos domínios do QOLIE-31 com a duração da epilepsia e freqüência de crises foi definida pela inspeção dos gráficos de dispersão e pela correlação de Pearson e de Spearman. Foram considerados significantes os valores de p < 0,05. RESULTADOS: Dificuldades nas relações interpessoais, familiares e sociais foram apontadas como a esfera de maior impacto relacionado à epilepsia, citada por 13 (22,81 por cento) pacientes. O QOLIE-31 mostrou resultado semelhante nos três diferentes tipos de epilepsia, com exceção do domínio Funcionamento Cognitivo. Os escores deste domínio foram significativamente menores (p = 0,01) no grupo com Extra-ELT (38,4) do que nos grupos ELT (52,6) e EGI (62,6). A duração da epilepsia não influenciou na QOL nesta amostra, porém foi observada uma correlação estatística significante entre a freqüência de crises e os domínios Efeitos da Medicação (p = 0,0476, alfa = 0,05) e Preocupação com Crises (p = 0,0463, alfa = 0,05). A freqüência de crises mostrou ainda uma diferença estatisticamente significante (p = 0.007) no grupo com Extra-ELT, que apresentou mais crises/paciente, quando comparado aos demais grupos. CONCLUSÕES: Os pacientes identificaram as relações interpessoais, familiares e sociais como sendo a área mais afetada pela...

Calosotomia em paciente com epilepsia generalizada primária e crises tônico-clônicas generalizadas refratárias: relato de caso / Callosotomy in patients with primary generalized epilepsy and generalized tonic-clonic seizures: case report

INTRODUÇÃO: Pacientes com epilepsia generalizada primária (idiopática) podem, raramente, não responder ao tratamento medicamentoso e assim apresentar crises tônico-clônicas generalizadas (CTCG) recorrentes, incapacitantes e que colocam o paciente em risco de complicações graves. OBJETIVO: Nesse artigo é relatado o caso de um paciente com epilepsia generalizada primária e CTCG semanais, refratárias a diversos esquemas medicamentosos, que foi submetido a uma calosotomia. RESULTADO: No curto espaço de 3 meses de seguimento pós-operatório, o paciente não mais apresentou CTCG. CONCLUSÃO: A calosotomia pode ser um procedimento útil na redução da freqüência de CTCG refratárias, mesmo em pacientes com epilepsia generalizada primária.

INTRODUCTION: Patients with idiophatic generalized epilepsy (IGE) may occasionally have frequent generalized tonic-clonic seizures (GTCS) which are not adequantely controlled by antiepileptic drugs. Frequent GTCS pose a significant risk of injury and other complications. In symptomatic generalized epilepsies, corpus callosotomy (CC) has been shown to be effective in reducing the number of generalized seizures. OBJECTIVE: We report a patient with refractory, weekly GTCS in the context of a primary generalized epilepsy syndrome who underwent subtotal CC. RESULT: In the 3 months since operation, no GTCS occurred. CONCLUSION: Corpus callosotomy can be helpful in reducing medically-refractory GTCS, even in patients with primary generalized epilepsies.

Clinical Analysis and Gene Mutation Screening of Voltage-Gated Sodium Channel ?1 Subunit in 2 Generalized Epilepsy with Febrile Seizures Plus Families / 实用儿科临床杂志

Objective To explore the mutation of voltage-gated sodium channel ?1 subunit(SCN1B)gene in Chinese Han families with generalized epilepsy with febrile seizures plus(GEFS+).Methods Two families pedigrees were established and disease history,physical examination were collected in order to analyze the mode of inheritance.The mutation sites of reported SCN1B gene exon 3-(C46T,G47A,C156G)were detected by polymerase chain reaction sequence special primers(PCR-SSP)method after genomic DNA were extracted.Results There were 13 patients in the 2 families,all were Han people and 9 cases were living.The results showed the mode of inheritance basically corresponds with autosomal dominant inheritance complicated with incomplete penetrance,and leaded to different kinds of phenotype.The mutation sites of SCN1B gene exon 3 were detected by using PCR-SSP method,and heterozygote was not found,and point mutations were also not found in the 2 families.Conclusions GEFS+ is a complex disorder with genetic heterogeneity.There were no gene mutations of SCNIB in the 2 GEFS+ families,which might suggets the possibility of insufficient samples as the patients came from Henan province and the possibility of differences from races and regions of other countries.

Analysis of Gene Mutation of Voltaged-Gated Sodium Channel ?1 Subunit in 2 Generalized Epilepsy with Febrile Seizures Plus Families / 实用儿科临床杂志

Objective To collect the families with generalized epilepsy with febrile seizures plus(GEFS+) and analyze the clinical status and heredity features of Chinese GEFS+.Voltaged-gated sodium channel ?1 subunit(SCN1B) gene of 2 families were detected,and expect to find new mutation sites.Methods All participant in the study of 2 families members were informed of voluntary participate in this investigation,health examination and blood sampling.All 6 gene exons of proband,patients and healthy control group were sequenced.The sequencing result was compared and analyzed with the normal sequence of genomic exon fragment and exon fragment sequencing result of control group through internet(BLAST).Results 1.A new G/A heterozygous polymorphism (G181A)was found in the 181th basyl of SCN1B gene exon 3,and codon was changed from TCG to TCA,both encoding serine (Ser,S).It was synonymous mutation.2.A new G/A heterozygous polymophism(G15A)was found in the 15th basyl of SCN1B gene exon 3,and codon was changed from GAG to GAA,both encoding glutamic acid(Glu,E).It belonged to synonymous mutation.3.A new T/C heterozygous polymorphism (T37C)was found in the 37th basyl of SCN1B gene exon 6.The patients genetype were:5 cases with T/C heterozygote,3 cases with T/T homozygote,2 cases with C/C homozygote.Healthy control group were all T/T homozygote.Allele frequency distribution for T was 55.0%,and 45.0% for C.4.A new A/C heterozygous polymorphism (A81C)was found in the 81th basyl of SCN1B gene exon 6.The patients genetype were:5 cases with A/C heterozygote,3 cases with A/A homozygote,2 cases with C/C homozygote.Healthy control group were all A/A homozygote.Allele frequency distribution for A was 55.0%,and 45.0% for C.Conclusions Two new heterozygous polymorphism (G181A),(G15A) were found in SCN1B gene exon 3.Two new heterozygous polymorphism (T37C),(A81C) were found in SCN1B gene exon 6.These 4 polymorphism enriched single nucleotide polymorphism(SPN) database and provided candidate sites for the research of epilepsy susceptbility polymorphisms.