Academic literature on the topic 'Infantile seizures'

Objective:To describe electroclinical features and outcome of 6 patients harboring KCNB1 mutations.Methods:Clinical, EEG, neuropsychological, and brain MRI data analysis. Targeted next-generation sequencing of a 95 epilepsy gene panel.Results:The mean age at seizure onset was 11 months. The mean follow-up of 11.3 years documented that 4 patients following an infantile phase of frequent seizures became seizure free; the mean age at seizure offset was 4.25 years. Epilepsy phenotypes comprised West syndrome in 2 patients, infantile-onset unspecified generalized epilepsy, myoclonic and photosensitive eyelid myoclonia epilepsy resembling Jeavons syndrome, Lennox-Gastaut syndrome, and focal epilepsy with prolonged occipital or clonic seizures in each and every one. Five patients had developmental delay prior to seizure onset evolving into severe intellectual disability with absent speech and autistic traits in one and stereotypic hand movements with impulse control disorder in another. The patient with Jeavons syndrome evolved into moderate intellectual disability. Mutations were de novo, 4 missense and 2 nonsense, 5 were novel, and 1 resulted from somatic mosaicism.Conclusions:KCNB1-related manifestations include a spectrum of infantile-onset generalized or focal seizures whose combination leads to early infantile epileptic encephalopathy including West, Lennox-Gastaut, and Jeavons syndromes. Long-term follow-up highlights that following a stormy phase, seizures subside or cease and treatment may be eased or withdrawn. Cognitive and motor functions are almost always delayed prior to seizure onset and evolve into severe, persistent impairment. Thus, KCNB1 mutations are associated with diffuse brain dysfunction combining seizures, motor, and cognitive impairment.

DEFINITION Ohtahara syndrome (early infantile epileptic encephalopathy with suppression bursts), is the earliest developing form of epileptic encephalopathy. ETHIOLOGY It considered to be a result of static structural developing brain damage. CLINICAL PICTURE Variable seizures develop mostly within the first 10 days of life, but may occur during the first hour after delivery. The most frequently observed seizure type are epileptic spasms, which may be either generalized and symmetrical or lateralized. The tonic spasms may occur in clusters or singly, while awake and during sleep alike. The duration of spasms is up to 10 seconds, and the interval between spasms within cluster ranges from 9 to 15 seconds. In one third of cases, other seizure types include partial motor seizures or hemiconvulsions The disorder takes a progressively deteriorating course with increasing frequency of seizures and severe retardation of psychomotor development. DIAGNOSTIC WORKUP In the initial stage of Ohtahara syndrome, interictal EEG shows a pattern of suppression-burst with high-voltage paroxysmal discharges separated by prolonged periods of nearly flat tracing that last for up to 18 seconds. PROGNOSIS AND THREATMENT Half of the reported children having Ohtahara syndrome die in infancy. Anticonvulsant helps little in controlling the seizures and halting the deterioration of psychomotor development. Severe psychomotor retardation is the rule. With time, the disorder may evolve into West syndrome or partial epilepsy. Psychomotor development may be slightly better if the infants do not develop West and later Lennox-Gastaut syndrome.

Infantile spasms is one of the “catastrophic childhood epilepsies” because of the difficulty in controlling seizures and the association with mental retardation. However, early recognition, a careful diagnostic evaluation, and proper treatment may allow some children to attain seizure control and to achieve a normal, or at least much improved, level of development. Thus, there is the opportunity to have an important impact in the lives of these unfortunate children and their families.

We describe a term female infant who presented with multiple seizures early in infancy. The clinical and electrical seizures were refractory to traditional antiepileptic medications. After extensive workup, seizure panel testing revealed KCNT1 gene mutation, which is associated with nocturnal frontal lobe epilepsy and epilepsy of infancy with migrating focal seizures. The infant’s condition improved with the combination of traditional as well non-traditional antiepileptic therapy.

Infantile spasms and Lennox-Gastaut syndrome are rare but are important to child neurologists because of the intractable nature of the seizures and the serious neurologic comorbidities. New antiepileptic drugs offer more alternatives for treating both infantile spasms and Lennox-Gastaut syndrome. Selected children with infantile spasms are candidates for epilepsy surgery. Vagus nerve stimulation, corpus callosotomy, and the ketogenic diet are all options for selected children with Lennox-Gastaut syndrome. The epidemiology, clinical manifestations of the seizures, electroencephalographic characteristics, prognosis, and treatment options are reviewed for infantile spasms and Lennox-Gastaut syndrome. Additional therapies are needed for both infantile spasms and Lennox-Gastaut syndrome as many children fail to achieve adequate seizure control in spite of newer treatments. (J Child Neurol 2002;17:2S9—2S22).

Objective: Children with infantile spasms may develop Lennox-Gastaut syndrome. The diagnostic criteria for Lennox-Gastaut syndrome are vague, and many experts use varying combinations of the following criteria for diagnosis: paroxysmal fast activity on electroencephalography (EEG), slow spike and wave on EEG, developmental delay, multiple seizure types, and nocturnal tonic seizures. Our objective was to determine the prevalence of Lennox-Gastaut syndrome in a high-risk cohort of children with a history of infantile spasms and the characteristics of infantile spasms that were associated with the diagnosis of Lennox-Gastaut syndrome. Methods: Children with infantile spasms who were diagnosed and treated at Children’s Hospital Colorado between 2012 and 2018 were included. Lennox-Gastaut syndrome was defined as having 3 of 5 of the following characteristics: paroxysmal fast activity, slow spike and wave, current developmental delay, multiple seizure types, or tonic seizures. Descriptive statistics were performed using median and interquartile range. Univariable analysis was performed with Pearson chi-square, Fisher exact, or the Kruskal-Wallis test. Results: Ninety-seven children met inclusion criteria, and 36% (35/97) met criteria for Lennox-Gastaut syndrome. Developmental delay and history of seizures prior to the onset of infantile spasms were identified as risk factors for the development of Lennox-Gastaut syndrome ( P = .003) as was poor response to first treatment for spasms ( P = .004). Children with an unknown etiology of infantile spasms were less likely to develop Lennox-Gastaut syndrome ( P = .019). Eighty percent (28/35) of the children who met Lennox-Gastaut syndrome criteria lacked a documented diagnosis. Conclusions: Thirty-six percent of children with infantile spasms met criteria for Lennox-Gastaut syndrome. Risk factors for development of Lennox-Gastaut syndrome were developmental delay and seizures prior to the onset of infantile spasms and poor response to first treatment for infantile spasms. Children with an unknown etiology of infantile spasms were less likely to develop Lennox-Gastaut syndrome. Eighty percent of the children who met our criteria were not given a documented diagnosis of Lennox-Gastaut syndrome, which highlights the fact that many children may not be receiving a diagnosis of Lennox-Gastaut syndrome. We recommend establishing clear guidelines for the diagnosis of Lennox-Gastaut syndrome to ensure that the diagnosis is being made accurately.

Seizures are a major neurologic disorder in infants and children. It can affect children at any age, from birth through adolescence. Early onset of seizures at birth or in the first few months of life can cause severe cerebral dysfunction. Also, recurrent and persistent seizures lead to severe cognitive and behavioral impairment in children. Hence, control of seizures is crucial for optimal neurodevelopment. Genetic aetiology of seizures is suspected in early onset recurrent seizures below one year of age, refractory to multiple anticonvulsants. Genetic testing in children with recurrent and therapy resistant seizures provides clue to aetiology, helps in treatment, has prognostic value. It also helps to estimate risk of seizure recurrence and helps avoid unnecessary investigations. We hereby report a case of early onset recurrent seizures with global developmental delay. Next generation sequencing revealed heterozygous missense mutation in SLC1A2 gene which is identified as an epileptic encephalopathy (EE) associated gene.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Objetivos: avaliar a evolução clínica e eletrencefalográfica em 28 pacientes que tiveram diagnóstico de Síndrome de West (SW). Métodos: estudo retrospectivo no qual foram incluídos pacientes que tiveram diagnóstico clínico e eletrográfico de SW e admitidos para seguimento no Hospital São Paulo da Universidade Federal de São Paulo / Escola Paulista de Medicina, entre março de 2006 e dezembro de 2007. Todos foram submetidos a avaliações periódicas durante o tratamento da SW, incluindo VEEG e, no mínimo, um exame de VEEG, com duração de 6 a 12 horas, após o controle da SW por pelo menos um ano. Foram analisados dados demográficos, freqüência e semiologia das crises. Os EEGs e os VEEGs foram revisados para a quantificação e classificação das alterações eletrencefalográficas e das crises epilépticas. Resultados: a amostra foi composta por 28 pacientes com tempo médio de seguimento de 46,5 ± 13 meses, sendo 19 do sexo masculino (68%) e 9 (32%) do sexo feminino. A média de idade na admissão foi 10,5 ± 6,3 meses. Todos os pacientes apresentaram algum grau de atraso no DNPM. Os pacientes foram subdivididos em 2 grupos, criptogênicos (5 casos) e sintomáticos (23 casos). Dos 28 pacientes 16 (57%) evoluíram com crises epilépticas ao final do estudo e 12 (43%) evoluíram sem crises. Do total, 13 (46%) tiveram recidiva da SW. Dentre os 5 criptogênicos 4 (80%) evoluíram com controle de crises e dentre os 23 sintomáticos, apenas 8 (34,7%) evoluíram com controle das crises. Apenas 10,7% dos pacientes evoluíram para SLG (todos do grupo sintomático), permanecendo com crises de difícil controle até o final do seguimento. Dos que permaneceram com crises, 35,7% evoluíram para epilepsia focal, 14,2% com epilepsia generalizada e 7,1% tiveram ambos tipos de crises, focal e generalizada, sendo classificados como epilepsia indeterminada. Conclusões: A maioria dos casos de SW evoluiu para epilepsia focal, portanto, a SLG não foi a síndrome mais freqüente em nosso estudo. O grupo de pacientes sintomáticos apresentou pior evolução quanto ao controle das crises quando comparado com o grupo criptogênico. O tempo de duração da SW também influenciou na evolução. Recidiva da SW tem alta correlação com pior prognóstico.
Objectives: The goal of this study was to evaluate the clinical and electroencephalographic evolution of 28 patients that had WS. Patients and Methods: Retrospective study in which we included patients who had clinical diagnosis and electrographic of WS and admitted in the Hospital São Paulo, Federal University of São Paulo / Escola Paulista de Medicina, between March 2006 and December 2007, who had been submitted to periodic evaluations during treatment of SW, including video-EEG (VEEG) and, after controlling the same, at least, an examination of VEEG, lasting from 6 to 12 hours after the SW under control for at least 1 year. They were revised the handbooks of these patients for analysis of demographic data, frequency and semiology of seizures. The EEGs along the follow-up and the VEEGs were also reviewed for the quantification and classification of electroencephalographic changes and of epileptic seizures. Results: The sample consisted of 28 patients with mean follow-up of 46,5 ± 13 months, with 19 males (68%) and 9 (32%) female. The mean age at admission was 10,5 ± 6,3 months. All patients had some degree of delay in DNPM. The patients were divided into 2 groups, cryptogenics (5 cases) and symptomatics (23 cases). Of the 28 patients 16 (57%) evolved with seizures the end of the study and 12 (43%) evolved without crises. Of the total of patients, 13 (46%) had recurrence of the SW. Of the 5 cryptogenics 4 (80%) evolved with control of seizures and of the 23 symptomatic patients, only 8 (34,7%) evolved with control of the seizures. Only 10,7% of patients evolved to SLG (all of the symptomatic group) and remained with these crises difficult to control until the end of follow up. Of those who remain with crises, 35,7% evolved to focal epilepsy, 14,2% with generalized epilepsy and 7,1% had both types of crises, focal and generalized, being classified as undetermined epilepsy. Conclusions: The SLG wasn’t the evolution most frequent of the SW in our study. The most of these cases evolved with focal epilepsy. The group of symptomatic patients presented worse evolution in the control of seizures when compared with the group criptogenic. The time in which the patient remained in SW seems also influence the evolution. Recurrence of the SW has high correlation with poor prognosis.
TEDE
BV UNIFESP: Teses e dissertações

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The purpose of this paper was to study patients with congenital and acquired hemiparesis, their clinical aspects, the presence or not of epileptic seizures, and electroencephalographic (EEG) and Magnetic Resonance Imaging (MRI) findings. We analyzed the interrelation between etiology, the presence and seriousness of epileptic seizures (ES) and the possible causes of refractoriness. This is a prospective study using the clinical diagnosis of a child neurologist, who attested to the presence of unilateral motor lesions. We compared the electroencephalographic findings in patients with or without epileptic seizures, and investigated if among the former, these seizures were controlled or not, their likely etiology and risks of refractoriness. EEG background activity on the lesion and contralateral side was analyzed, in addition to the presence of concomitant epileptiform activity. Encephalon MRIs of all the patients were studied to correlate etiology and the control or not of epileptic seizures. The disorganization of bilateral EEG activity correlated with the difficult-to-control epileptic seizures. Suitably organized background activity contralateral to the lesion is a good prognosis in relation to epileptic seizures. Focal epileptogenic activity does not necessarily predispose to epileptic manifestation. The MRI is more important in determining etiology than in prognosing epileptic seizures. This study used a multidisciplinary approach involving child neurologists, a physical therapist and a neuroradiologist. This meets the criteria of multidisciplinarity of the Postgraduate Program in Health Sciences
O objetivo do nosso trabalho foi estudar pacientes com hemiparesia, cong?nitas e adquiridas, seus aspectos cl?nicos e epidemiol?gicos, a presen?a ou n?o de crises epil?pticas e os achados eletrencefalogr?ficos e de neuroimagem por Resson?ncia Nuclear Magn?tica. Tentando relacionar a etiologia ? presen?a e gravidade de crises epil?pticas e as poss?veis causas de refratariedade. Trata-se de um estudo prospectivo a partir do diagn?stico cl?nico por um neurologista infantil que atestou a presen?a de les?o motora unilateral. Compararam-se os achados eletrencefalogr?ficos em pacientes sem ou com crises epil?pticas, e dentre esses ?ltimos, se h? ou n?o controle das crises, sua prov?vel etiologia e riscos de refratariedade. Analisou-se a atividade de base do EEG do lado da les?o e contra lateral a esta, al?m da presen?a de atividade epileptiforme concomitante. Estudaram-se as RNM do enc?falo realizadas em todos os pacientes, tentando relacionar a etiologia e controle ou n?o de crises epil?pticas. A desorganiza??o da atividade de base bilateral no EEG correlacionou-se com crises epil?pticas de dif?cil controle. A atividade de base adequadamente organizada contra lateral a les?o ? de bom prognostico em rela??o ?s crises epil?pticas. A atividade epileptog?nica focal n?o necessariamente predisp?e a manifesta??o epil?ptica. A RNM ? mais importante na determina??o da etiologia do que no progn?stico das crises epil?pticas. A realiza??o deste estudo foi concretizada pela abordagem multidisciplinar, envolvendo neurologistas infantis, fisioterapeuta e neurorradiologista. Este aspecto preenche os requisitos de multidisciplinaridade do programa de p?s-gradua??o em Ci?ncias da Sa?de

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The epilepsy is one of the neurological disorders more common in the pediatric period, and which interferes significantly in the psycho and social life of children and teenagers. The objective of this study was analyzing the practice of sedentary practices, physicals, traditional infant fun and games of children and teenagers with and without epilepsy. The study was prospective, transversal descriptive, done with 60 children and teenagers with epilepsy (Epileptic Group - EG) patients from Pediatric Neurology Clinic of the Centre Integrated Health Lineu Ara?jo and 60 children and teenagers without epilepsy (Control Group - CG) students from municipal public school, both of the two groups paired with the same age (age group 7 to 14 years) of both the genders (female = 25/41,6% and male = 35/58,3%) of the Teresina city Piau?. It was done two pattern questionnaires, one applied to children and teenagers of the EG and CG to identify the sedentary activities, physical and traditional infant games and other to the parents/responsible of the EG about the clinical and demographic information. The results permitted the elaboration of two manuscripts: a) the first one titled The Practice of Sedentary and Physical Activities of Children and Teenagers with Epilepsy which showed significant difference in the sedentary activities of playing with car toy (p=0,021) to the EG and reading to the CG (p=0,001); in the physical activities the school physical education (p=0,001) and riding a bike (p=0,014) to the CG; b) the second one The Practice of Infant Games and Fun the children and teenagers with and without Epilepsy in this one the playing with marble presented significant difference (p=0,016) to the CG, despite the girls of the two groups don t do this activity. Observing the distribution of frequencies, it was verified that in the play catch-up and hide-and-seek and burn the EG plays more than the CG both in female and male gender. The girls of the EG play less skip, 60 while the boys of the two groups don t play. Elastic jump the girls of the two groups play in a same frequency and the boys don t participate of this fun. The seizures were found to occur during: soccer (23,3%); hide-and-seek (6,6%) and running (3,3%). In the sedentary activities, seizures were reported to occur: resting and watching TV (18,3%), sleeping (36,0%); sitting (13,3%) and lying down (11,7%). Our results showed that the epileptic group and the controls group engage in the same activities, although the epileptic group participates less than the controls. Although the EG had presented a bigger percentage of generalized attacks, they don t occur during the practice of formal physical activities. The research was developed by a multidisciplinary team, and this contributed a lot to the realization of this study
A epilepsia ? uma das desordens neurol?gicas mais comuns na faixa pedi?trica e que interfere significativamente na vida psico-social de crian?as e adolescentes. O objetivo deste estudo foi analisar a pr?tica de atividades sedent?rias, f?sicas, brincadeiras e jogos infantis de crian?as e adolescentes com e sem epilepsia. O estudo foi prospectivo, transversal descritivo, realizado com 60 crian?as e adolescentes com epilepsia (Grupo Epilepsia - GE) pacientes do Ambulat?rio de Neuropediatria do Centro Integrado de Sa?de Lineu Ara?jo e 60 crian?as e adolescentes sem epilepsia (Grupo Controle - GC), escolares de uma escola p?blica municipal, sendo os dois grupos pareados com a mesma idade (faixa et?ria 7 a 14 anos) de ambos os g?neros (feminino = 25/41,6% e masculino = 35/58,3%) da cidade de Teresina Piau?. Utilizou-se dois question?rios padr?o, um aplicado as crian?as e adolescentes dos GE e GC para identificar as atividades sedent?rias, f?sicas e jogos tradicionais infantis, e outro aos pais/respons?veis do GE sobre as informa??es cl?nicas e demogr?ficas. Os resultados permitiram a elabora??o de dois manuscritos: a) o primeiro intitulado - A Pr?tica de Atividades Sedent?rias e F?sicas de Crian?as e Adolescentes com Epilepsia - que mostrou diferen?a significante nas atividades sedent?rias de brincar de carrinho (p=0,021) para o GE e leitura para o GC (p=0,001); nas atividades f?sicas a educa??o f?sica escolar (p=0,001) e andar de bicicleta (p=0,014) para o GC; b) o segundo A Pr?tica de Jogos e Brincadeiras Infantis de crian?as e adolescentes com e sem Epilepsia neste, o brincar com bola de gude apresentou diferen?a significante (p=0,016) para o GC, apesar das meninas dos dois grupos n?o brincarem dessa atividade. Observando as distribui??es de freq??ncias, verificou-se que nas brincadeiras de pega-pega, esconde-esconde e queimada o GE brinca mais que o GC tanto no g?nero feminino como no masculino. Pular corda, as meninas do GE brincam menos, enquanto os meninos dos dois grupos n?o brincam. Pular el?stico, as meninas dos dois grupos brincam numa mesma freq??ncia e os meninos n?o participam desta brincadeira. Quanto ?s crises epil?pticas, elas aconteceram durante as brincadeiras livres como: jogando bola (23,3%); esconde-esconde (6,6%); correndo (3,3%). Nas atividades sedent?rias: assistindo TV (18,3%); dormindo (36,0%); sentado (13,3%); deitado (11,7%) e em mais de uma atividade: jogando bola/assistindo TV (6,6%); dormindo/assistindo TV (3,3%) e correndo/dormindo (2/3,3%). De um modo geral, conclui-se que as crian?as e adolescentes dos dois grupos praticam os mesmos tipos de atividades, sendo que o GE pratica numa freq??ncia menor. Embora o GE tenha apresentado um maior percentual de crises generalizadas, elas n?o ocorreram durante a pr?tica de atividades f?sicas formais. Esta pesquisa foi desenvolvida por uma equipe multidisciplinar, o que muito contribuiu para a realiza??o deste estudo

INTRODUÇÃO: As crises não-epilépticas psicogênicas são uma condição médica complexa que pode se apresentar como sintomas físicos ou neurológicos porém sem achados orgânicos correspondentes, evidenciando a presença de fatores psicológicos como base dos sintomas. Elas podem ocorrer isoladamente ou se repetir de forma sistemática. Quando se repetem podem estar associadas à baixa auto-estima, perda de emprego, dificuldade nas relações amorosas e sociais. A esta condição clínica denomina-se transtorno de crises não-epilépticas psicogênicas (TCNEP). Dentre os fatores de risco para TCNEP, os mais amplamente estudados são a história de trauma e os fenômenos dissociativos. MÉTODOS: Neste estudo caso-controle, cujos dados foram obtidos entre janeiro de 2003 e setembro de 2009, foram avaliados 20 pacientes portadores de TCNEP e 20 pacientes com epilepsia do lobo t e m p o r a l , a p ó s m o n i t o r a ç ã o p r o l o n g a d a em u n i d a d e d e vídeo-eletroencefalografia (VEEG). Foram excluídos os sujeitos com associação das duas patologias. Os grupos foram pareados quanto ao gênero, faixa etária, anos de escolaridade formal e classe social. Também foram avaliados: idade de início das crises, idade do diagnóstico, pior frequência de crises e classificação social. Os pacientes responderam também a dois instrumentos estruturados e validados no Brasil, um quanto à história de trauma na infância e adolescência (QUESI), e outro sobre a presença de fenômenos dissociativos (DES) ao longo da vida. RESULTADOS: 1) Não houve diferença significativa do ponto de vista estatístico no que diz respeito ao gênero, faixa etária, classificação social, e frequência de crises; 2) Houve diferença estatisticamente significativa na escolaridade (p=0,006); 3) No grupo caso, a idade de início foi superior (22,25 DP 9,19) à do grupo controle (11,62 DP 9,59), p=0,007. Assim como a idade do diagnóstico, que foi de 30,79 (DP 11,33) no grupo de pacientes com TCNEP e de 15,97 (DP 9,67) nos pacientes com epilepsia, p<0,001; 4) A DES teve valores também estatisticamente significativos, sendo 53,35 (DP 23,15) no grupo com TCNEP e de 22,02 (DP 16,37) no grupo com epilepsia, p<0,001. Quanto às subescalas, todas tiveram resultados significativos entre os grupos; 5) O QUESI apresentou também resultados médios significativos, com média de 60,30 (DP 21,75) no grupo de TCNEP e de 45,40 (DP 12,27) no grupo com epilepsia, p=0,014, mas somente as subescalas que identificaram a negligência e o abuso emocionais foram estatisticamente significativas (p=0,013 e p=0,014 respectivamente). CONCLUSÕES: Fenômenos dissociativos e história de trauma na infância são mais frequentes nos pacientes com TCNEP do que nos pacientes com epilepsia. Todavia, em relação à história de trauma, apenas a negligência e o abuso emocionais podem estar associados à TCNEP
INTRODUCTION: Psychogenic non-epileptic seizures are a complex medical condition that may present as physical or neurologic symptoms but without corresponding organic findings, suggesting the presence of psychological factors as the basis of symptoms. They can occur alone or recur systematically. When recurrent they can be associated with low self-esteem, loss of employment, difficulty in intimate and other social relationships. This clinical condition is called a psychogenic non-epileptic seizures disorder (PNESD). Among the risk factors for PNESD, the most widely studied are the history of trauma and the presence of dissociative phenomena. METHODS: In this case-control study, with data obtained between January 2003 and September 2009, 20 patients with PNESD and 20 patients with temporal lobe epilepsy were evaluated after monitoring in video-electroencephalography unit. We excluded subjects with a combination of both conditions. The groups were matched for gender, age, length of school education and social class. We also evaluated age of onset, age at diagnosis and worse seizure frequency. Patientes of both groups responded two structured instruments for history of trauma in childhood and adolescence (QUESI) and FOR the presence of dissociative phenomena (DES) throughout life, both valitaded in Brazil. RESULTS: 1) There was no statistical significant difference between both groups regard to gender, age, social status and seizure frequency; 2) There was a statistical significant difference in education (p = 0.006); 3) Age of onset and at diagnosis in PNESD group were significantly higher (22.25 SD 9, 19) than the control group (11.62 SD 9.59), p = 0.007, as well as age of diagnosis were higher in patients with PNESD (30.79 SD 11.33) than in patients with epilepsy (15.97 SD 9.67), p <0.001; 4) DES values were also significantly higher in the PNESD group (53.35 SD 23.15) than control group (22.02 SD 16.37), p <0.001. As for the subscales all had significant results between groups; 5) QUESI\'s results were also significantly higher in the PNESD group (60.30 SD 21.75) than in epilepsy group (45.40 SD 12.27), p = 0.014, but only the subscales that identify emotional neglect and emotional abuse were statistical significantly in PNESD group (p = 0.013 and p =0.014 respectively). CONCLUSIONS: History of childhood trauma and dissociative phenomena are more common in patients with PNESD than in patients with epilepsy. However, in relation to history of trauma, only emotional neglect and emotional abuse may be associated with PNESD.

Over the past decade and a half, considerable advances have been made in the understanding of the molecular mechanisms underlying the idiopathic epilepsies. Technological advances and completion of the Human Genome Project have enabled continued progress. Much of this has impacted on families with epilepsies developing in infancy. Benign familial neonatal seizures (BFNS) is often caused by mutations in either of two potassium channel subunit genes, KCNQ2 and KCNQ3. Twenty-three of 36 families investigated (65%) were found to have mutations in one of these genes detectable by sequencing. Multiplex ligation-dependent probe amplification, which detects deletions and duplications affecting a specific gene, was applied to solve a further 17% of families. This revealed that deletions and duplications in KCNQ2 are a common mechanism for the pathogenesis of BFNS. The remaining unsolved BFNS families were analysed further to seek other mechanisms. A novel microduplication was identified in one family with BFNS and intellectual disability. This was characterised by comparative genome hybridisation (CGH) and fluorescence in-situ hybridisation and demonstrated the value of applying these technologies to familial as well as sporadic cases. A patient with neonatal seizures and long-QT syndrome (LQTS) was found to have a unique combination of changes in two genes associated with LQTS, supporting speculation that he had a “cardio-cerebral” channelopathy. Two “BFNS” families had mutations in SCN2A, the gene usually associated with benign familial neonatal-infantile seizures (BFNIS). BFNIS is distinguished from BFNS by a higher age of seizure onset distribution. The initial clinical misclassification highlights the phenotypic overlap between these two disorders. These families are now reclassified on molecular criteria as BFNIS families with an earlier than usual age of onset. This distinction is of clinical significance since unlike BFNIS with SCN2A mutations 15% of BFNS patients with KCNQ2 mutations have seizures later in life. The remaining three BFNS families are unsolved. For two families, genotyping of microsatellite markers linked to known BFNS loci showed that they could not have mutations at those loci. Linkage to these loci was excluded by recombination, demonstrating that at least one other gene associated with BFNS exists. The parental origin of de novo mutations in SCN1A was investigated. These mutations cause Dravet Syndrome (DS), a severe childhood epileptic encephalopathy. The mutations were found to originate on the paternal chromosome in approximately 75% of cases. The effect of parental age on mutagenesis in SCN1A was investigated and found not to be a contributing factor. This is the only epilepsy syndrome where sufficient de novo mutations have been identified for meaningful analysis of their parental origin. Finally, the causative gene for benign familial infantile seizures (BFIS) mapped to chromosome 16p11.2-q12.1 remains elusive. Array CGH revealed no pathogenic copy number changes. Sequence capture and next-generation sequencing of the genes in the linkage region did not detect a mutation in a coding region. Several unique, but nonpathogenic, variants were identified in BFIS families. This paves the way for the next steps aimed at detecting rarer molecular defects such as recurrent inversions or unstable repeats.
Thesis (Ph.D.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2010

Tese de Mestrado, Biologia Evolutiva e do Desenvolvimento, 2021, Universidade de Lisboa, Faculdade de Ciências
A epilepsia de ausência infantil é uma síndrome não convulsiva, caraterizada por crises de ausência relatadas como breves interrupções de consciência e movimento. É descrita como uma génese multifatorial, afetando 2 a 8 crianças em cada 100 000 com idade inferior a 15 anos. As crises de ausência iniciam-se entre os 3 e 8 anos, podendo ocorrer múltiplas vezes por dia, podendo a sua frequência ser superior a 200 por dia. De entre todos os casos de epilepsia identificados em crianças em idade escolar, 10 a 17 % devem-se à epilepsia de ausência infantil. É diagnosticada por padrões de disparo neuronal anómalos e síncronos detetáveis por eletroencefalograma na rede talamocortical. A nível molecular, vários genes estão envolvidos na etiologia desta patologia, tais como os genes que codificam para os canais de cálcio tipo T, genes que codificam para as subunidades dos recetores GABAA; bem como o gene SLC6A1, que codifica para o transportador de GABA do subtipo 1 (GAT1). Em crianças com mutação no gene SLC6A1 o fenótipo de crises de ausência é o mais comum. Para além das crises de ausência, descrevem-se dificuldades cognitivas em 60 % das crianças com epilepsia de ausência infantil, tais como deficiências de atenção, hiperatividade, dificuldade de leitura, ou na realização de tarefas visuoespaciais. No entanto, dados relativos a perturbação de memória são inconsistentes, uma vez que nem todos os estudos englobam comparações com crianças desguarnecidas de tratamento. Relativamente à terapia farmacológica da epilepsia de ausência, esta baseia-se na administração individual de etosuximida, ácido valpróico ou lamotrigina, ou na combinações de dois destes fármacos. No geral, a ausência de resposta é de aproximadamente 30%, sendo que o ácido valpróico, quando administrado, está associado a efeitos neuropsiquiátricos adversos. Assim mesmo, quando o tratamento farmacológico permite o controlo das crises de ausência, déficies cognitivos são ainda relatados em 70% dos casos, não sendo claro se os fármacos anti-crises (antiseizure) têm efetivamente efeitos naqueles. Já os mecanismos patofisiológicos não são completamente identificados sabendo-se, no entanto, que as crises de ausência têm o seu início na rede talamocortical. Uma transmissão GABAérgica anormal, aumentada nos neurónios talamocorticais, está envolvida no processo das crises de ausência, sendo a transmissão GABAérgica regulada por transportadores de GABA (GATs), como por exemplo o GAT1, que são responsáveis pela recaptação de GABA da fenda sináptica. A disfunção do GAT1 nos astrócitos do tálamo observa-se em animais com crises de ausência, levando ao aumento da inibição tónica, sendo este aumento necessário e suficiente para a geração daquelas. Ainda, no tálamo, o GAT1 é expresso exclusivamente nos astrócitos sendo a recaptação de GABA quase exclusiva destas células da glia. Uma vez que esta síndrome está associada a défices cognitivos e a ausência de resposta a fármacos é comum, torna-se essencial a identificação de novos fármacos para esta doença. O Fator Neurotrófico Derivado do Cérebro (Brain-derived neurotrophic factor - BDNF) pode ser um novo alvo terapêutico para esta patologia, uma vez que é essencial para plasticidade sináptica, um processo necessário na aprendizagem e memória. O BDNF tem também a capacidade de aumentar o transporte de GABA mediado por GAT1 para os astrócitos, podendo contribuir para uma diminuição na inibição tónica. Como tal, neste trabalho utilizaram-se dois modelos animais de epilepsia de ausência: os ratos GAERS e respectivos ratos controlo não epilético (NEC), e ratos Wistar (como segundo controlo); murganhos Stargazer (STG) e respectivos controlo WT. Os ratos GAERS é um modelo animal de epilepsia de ausência, apresentando spike and wave discharges bilaterais de 7-9 Hz, com interrupções de movimento a partir do dia pós natal 30 e respondem de forma semelhante a fármacos anti-crises comparativamente com humanos. O modelo animal de murganho, os STG, apresentam spike and wave discharges de 6-7 Hz, com interrupções de movimento, caraterizadas também por disfunção do canal de cálcio CACNG2, bem como comportamentos maladaptativos e ataxia. Os objetivos principais deste trabalho foram: 1) identificar as comorbilidades comportamentais dos GAERS e dos STG, avaliando ansiedade, bem como aprendizagem e memória; 2) estudar a plasticidade sináptica em fatias do hipocampo, bem como avaliar a função do BDNF na potenciação a longo-prazo (LTP) nos GAERS e STG; 3) identificar diferenças a nível molecular e celular entre GAERS, Wistar e NEC, determinando a expressão de proteínas por western blot, nomeadamente transportadores de GABA, GAT1, GAT3 e GFAP (Glial fibrillary acidic protein). Recorrendo a imunohistoquímica, a quantificação de alterações de complexidade morfológica dos astrócitos foi também analisada em regiões cerebrais envolvidas na rede talamocortical e /ou memória. Os resultados obtidos contribuem para uma definição fenotípica precisa do modelo mais representativo de epilepsia de ausência infantil. Confirmaram-se deficiências de memória em animais GAERS jovem adultos e adultos a nível de memória de trabalho (Y Maze, acquisition Barnes), memória de reconhecimento de novos objetos (NOR), memória cross-modal contemplando memoria texturial e visual (CMOR) e ainda memória de referência espacial (Barnes Maze). Foram também observados défices na memória de referência espacial (Barnes Maze) para o modelo animal de murganho. De igual forma, a ausência de níveis de ansiedade (Open Field, EPM, Emergence Test) demonstra que os resultados observados não foram enviesados por deficiências de locomoção e/ou ansiedade. De modo a complementar os resultados observados in vivo, foi induzida potenciação a longo prazo em fatias de hipocampos de animais GAERS, Wistar e NEC, e registaram-se potenciais excitatórios pós sinápticos de campo (fEPSP) nas fibras colaterais de Schaffer na região CA1 do hipocampo. A plasticidade sináptica foi avaliada, e identificadas diferenças significativas entre os animais controlo e os epiléticos a nível de LTP, sendo significativamente reduzida nos GAERS, corroborando os resultados comportamentais. Deficiências de LTP no hipocampo foram também observadas nos murganhos STG. Nos GAERS, o BDNF recuperou a perda de magnitude da LTP para valores semelhantes ao controlo. Visto que o GAT1 está associado à perda de função e contribui para um aumento da inibição tónica nos animais epiléticos, e que no tálamo é meramente expresso em astrócitos, foi importante confirmar esta expressão única nos astrócitos talâmicos, visualizar a expressão destes transportadores nos astrócitos, bem como perceber se a morfologia dos astrócitos estaria alterada nas diversas áreas envolvidas nas crises de ausência, nomeadamente o córtex motor, somatosensorial, visual, talamo e ainda hipocampo, fundamental nos circuitos subjacentes à memória. Observou-se um aumento da complexidade morfológica dos astrócitos a nível do córtex motor, visual, hipocampo e tálamo, relativamente ao número de interseções à volta do soma, número de processos e comprimento total das ramificações nos GAERS. Foi ainda fundamental compreender se existem diferenças de expressão dos transportadores de GABA dos astrócitos. GAT3 também foi analisado, servindo de controlo, bem como analise de GFAP, visto que se observaram diferenças significativas a nível morfológico. A expressão de GAT1 nos GAERS não está alterada em nenhuma área cerebral, exceto no córtex motor, que é acompanhada por um aumento significativo de expressão de GFAP comparado com ambos os controlos. A expressão de GFAP está ainda significativamente aumentada no hipocampo, no talamo comparado com ambos os controlos, e no córtex visual, comparado com os Wistar. Um aumento do rácio do peso cérebro- corpo foi ainda observado para os animais epiléticos. Em suma, os resultados deste trabalho permitem inferir deficites de memória de nível comportamental em modelos animais de epilepsia de ausência, em circuitos subjacentes à rede talamocortical, nomeadamente córtex e tálamo, bem como as conexões dependentes do hipocampo. A nível de circuitos intrínsecos do hipocampo, uma reduzida indução de LTP foi observada nos animais epiléticos e esta função sináptica deficiente recuperou-se em perfusão com BDNF em fatias do hipocampo. Observou se a nível molecular que no talamo a expressão de GAT 1 é meramente observada em astrócitos e ausente em neurónios, e que a expressão de GAT1 e GAT3 não está alterada entre os animais epiléticos e os controlos, excepto no córtex motor. Finalmente, a nível celular foram ainda identificados aumentos de complexidade morfológica astrocitica, bem como de expressão de GFAP em diversas areas cerebrais de GAERS, envolvidas nas crises de epilepsia de ausência e nos circuitos de memória alterados.
Typical absence seizures (ASs), characterized by 3-4 Hz spike-wave discharges in thalamocortical network, are the hallmark of Childhood Absence Epilepsy (CAE). In ASs animal models, dysfunction of thalamic GABA transporter-1 (GAT1), exclusively expressed in thalamic astrocytes and responsible for GABA reuptake, enhances tonic inhibition. This enhancement is essential and sufficient for the generation of ASs. A neuropsychological impairment is observed in 60% of children with CAE. Using an ASs animal model, the Genetic Absence Epilepsy Rat from Strasbourg (GAERS), the respective Non-Epileptic control (NEC), and Wistar rats, as well as STARGAZER mice, behaviour tests were carried out to assess anxiety-like behaviour, learning, and memory. Hippocampal synaptic plasticity was evaluated by performing long-term potentiation (LTP) experiments where field excitatory postsynaptic potentials were recorded in control hippocampal slices and perfusion with a possible target to CAE, BDNF (Brain-derived neurotrophic factor). Immunohistochemistry and Western blot assays were used to assess molecular and cellular morphological differences between epileptic and non-epileptic animals. In Novel object recognition, Cross-modal object recognition, Y-Maze, and Barnes Maze tests, we observed significant differences between GAERS and controls, suggesting an impairment in the prefrontal cortex, thalamus, parahippocampal regions, and hippocampal-dependent memory. LTP magnitude in GAERS was significantly lower than from Wistar and NEC, being rescued in perfusion with BDNF. GAERS display an increase in astrocytic morphological complexity, mainly in the hippocampus, thalamus, motor cortex, and visual cortex, and increase GFAP expression levels, compared to Wistar and NEC. No differences were found for GABA transporters expression. This work results suggest memory deficits in GAERS, especially in spatial working memory, object recognition, long-term memory, and reference memory, in line with the reduced LTP magnitude. Since GAT1 is expressed in astrocytes and there is an increase in morphological complexity and GFAP expression in GAERS, the involvement of astrocytes in the pathology of ASs is reinforced.

碩士
台北醫學院
細胞及分子生物研究所
86
Infantile spasm (IS), is a form of epilepsy specifically occurring at infant s tage, is refractory to conventional anticonvulsant treatment but is exceptiona lly sensitive to adrenocorticotropic hormone (ACTH) treatment. Corticotropin- releasing hormone (CRH), a major regulatory factor of ACTH secretion in pituit ary, has been implicated as an important neuro-hormone participating in seizur e generation particularly in early life of both human and animals. In human, excessive production of CRH is speculated as one of the pathological mechanism s underlying the generation of IS. In animal, intracerebral injection of CRH potently produces seizure behavior since early life. Recently, cytokines also participated in communication between immunity and central nerve system disea ses. To further understand the role of CRH in pathological mechanisms of seiz ure, we investigated whether increased plasma CRH level is associated with IS and whether seizure activity will increase the expression of CRH and cytokines (IL-1(, IL-6 and TNF-() in circulation and in brain of neonatal rats. Plasma CRH level in IS patients (0.546(0.184 ng/ml, n=12, P<0.001) or seizure patien ts (0.294(0.032 ng/ml, n=13, P<0.01) is significantly higher as compared to co ntrol (0.135(0.022 ng/ml, n=12). The plasma CRH level of postnatal 30-day (P3 0) rats at 3h after kainate (KA)-injection (0.368(0.06 ng/ml, n=4) is signific antly higher (p<0.05) than that of control, whereas, plasma CRH level show no statistically difference in P14 rats at 1h after KA-injection (0.260(0.04 ng/m l, n=6) when compare to that of control. Furthermore, an 7.84 and 1.55 fold i ncreased expression of CRH mRNA in cortex was observed in P7 and P14 rats with KA-induced seizure by RT-PCR analysis. In addition, IL-1(, IL-6 and TNF-( mR NA expression were increased in cortex of P7 rats with KA-induced seizure. The se data support the hypothesis that over-production of CRH is likely associate d with IS, and seizure activity induced by KA may also upregulate the CRH and cytokines expression in neonatal developing brain. Given that CRH is a pro-co nvulsant in developing brain, increase of CRH in cortex elicited by seizure ma y further potentiate the progression of the activity of seizure.

Tuberous sclerosis complex is an autosomal dominant multi-system disease that involves the skin, brain, heart, lungs, and kidneys and is associated with seizures including infantile spasms, intellectual disability, autism and pulmonary and heart disease. Skin lesions can be particularly disfiguring and infantile spasms can be associated with marked cognitive decline. The outlook for patients has improved markedly with the recognition that TSC is caused by upregulation of the mammalian target of rapamycin (mTOR) enzyme, which connects energy needs and supply with cellular and neuronal growth. mTOR is upregulated in TSC because of mutations in hamartin or tuberin, which normally serve as a brake on mTOR. The drug rapamycin is commonly used as an immunosuppressive for patients undergoing kidney transplants; it has also found a new use in patients with TSC. Although the drug is immunosuppressive for non-TSC patients, careful titration of the drug in TSC patients corrects its upregulation but is not particulary immunosuppressive. Additional mTOR inhibitors such as everolimus have been developed and have been shown to be effective for pulmonary disease associated with TSC. Rapamycin in ointment form is dramatically effective in suppressing skin lesions of TSC and studies are underway to test the effect of mTOR inhibitors on seizures, brain tubers, intellect, and features of autism. Infantile spasms associated with TSC are very responsive to vigabatrin.

Primary CoQ10 deficiencies are usually diagnosed in childhood, but late-onset forms are recognized. The expression of all clinical symptoms is extremely variable, but six major phenotypes are recognized: (1) encephalomyopathy, seizures, and ataxia; (2) infantile-onset multisystem disease; (3) cerebellar ataxia; (4) isolated myopathy; (5) Leigh syndrome; and (6) isolated nephrotic syndrome. Early treatment with exogenous CoQ10 supplementation may result in a good outcome.

Symptomatic generalized epilepsies represent a group of challenging epilepsy syndromes, most often seen in children, which share the hallmark of a triad encompassing multiple seizure types, electroencephalographical (EEG) evidence of diffuse brain involvement, and dysfunction in the intellectual domain (global developmental delay or mental retardation). SGEs include the early myoclonic encephalopathy, early infantile epileptic encephalopathy (Ohtahara syndrome), West syndrome, epilepsy with myoclonic-astatic seizures, epilepsy with myoclonic absence, Lennox-Gastaut syndrome, and the progressive myoclonic epilepsies. SGEs may arise from various genetic, developmental, or acquired brain pathologies and also can be associated with other cerebral or systemic defects and thus being part of a broader epilepsy syndrome phenotype. SGEs are associated with significant mortality and morbidity and most patients with SGE grow up to have intractable epilepsy, mental retardation, and depend on parents and institutions for the activities of the daily living. The mechanisms of SGE are numerous and heterogeneous and the EEG findings usually reflect the age-related changes as the brain matures.

Neuronal ceroid lipofuscinoses (NCL) are a group of autosomal recessive genetic disorders which represent the most common form of childhood neurodegenerative disease. Classically the disease was described according to the age of diagnosis resulting in four common phenotypes: (i) infantile or Santavuori-Haltia, (ii) late infantile or Jansky-Bielschowsky, (iii) juvenile or Spielmeyer-Vogt, and (iv) adult or Kufs. With advances in genetic mutational analysis techniques and improved understanding of NCL disease as a whole, disease classification now focuses on which of the known genetic defects is responsible for the disease. Regardless of genetic defect or age of onset, patients typically present with language delay, seizures, blindness, and ataxia. The term “Batten disease” is used to refer to the group as a whole in addition to specifically referring to the juvenile form. Anesthetic implications focus on disease symptoms at presentation, with special attention to maintaining normorthermia and the possibility of bradycardia.

Surgery for intractable seizures originating from the sensorimotor cortex is associated with a risk of permanent deficit and a risk of incomplete epileptogenic tissue removal. Depth electrode implantation in the sensorimotor region has been performed over several decades with acceptable morbidity. Motor, sensory, premotor, supplementary motor area, and connected areas (parietal lobe, cingulate gyrus, and insular cortex) are explored with orthogonal and oblique electrodes. Implantation strategy is guided by ictal semiology and by the type of epileptogenic lesion identified on imaging. SEEG may identify (1) an MRI-negative focal cortical dysplasia, frequently localized in the sensorimotor region, (2) the epileptogenic part of a heterotopia or a polymicrogyria, (3) the extent of cortex resection in infantile hemiplegia, as an alternative to hemispherotomy, and may guide stereotactic radiofrequency thermocoagulations of a focal lesion as an alternative to surgical resection.

The ketogenic diet (KD) provides an alternative strategy for seizure control in medication-resistant epilepsy. It is particularly valuable for those medication-resistant patients who are not surgical candidates. Years of observational evidence have been recently supported by a randomized controlled study indicating the benefit of diet treatment in children with refractory epilepsy, compared with a control group who delayed diet treatment for 3 months. Well-established uses include children with refractory, nonsurgical epilepsies, as well as epileptic encephalopathies, including infantile spasms and West syndrome, Lennox-Gastaut syndrome, and Dravet and Doose syndromes. The efficacy and role of diet therapy in these conditions are discussed.

Context: We present a patient diagnosed with Tuberous Sclerosis (TS) who developed West Syndrome (WS) early on. Early diagnosis of TS is important for genetic counseling and WS requires early intervention to avoid neurodevelopmental deficits. Case report: Y.S.L.C., female, 45 days old, presented cardiac rhabdomyoma and 9 hypomelanotic lesions, being diagnosed with TS. At 2 months old, she presented epileptic seizures of flexion spasms, which progressed in 1 week to neuropsychomotor development (NP) regression and hypsarrhythmia. She was diagnosed with WS and treated with vigabatrin. There was suppression of hypsarrhythmic pattern at 8 months old. Currently 8 years old, she has hypochromic stains, hemangiomyolipomas in the right kidney, bilateral renal cysts, sebaceous adenomas, facial angiofibromas, cortical tubers, subependymal nodules, Intellectual Disability and Focal Epilepsy. Conclusions: ET is an autosomal dominant disease caused by mutations in TSC1 and TSC2 genes leading neurodevelopmental changes and cellular hyperplasias. TE diagnosis is clinical, based on major (such as facial angiofibromas, nail fibroma and hypopigmented macules) and minor criteria and molecular tests in doubtful cases. TE is associated with epilepsy in 80-90% of cases (30 to 50% of infantile spasms). WS is an encephalopathy of infantile spasms, NP arrest/regression and hypsarrhythmia. Early diagnosis and use of anti-epileptic drugs are necessary to avoid cognitive impairment.

Introdução. Transmitido pelo mosquito Aedes aegypti e Aedes albopictus infectado, entre 2015 e 2016, o Zika vírus foi responsável por um aumento nos casos de microcefalia nas Américas, transformando-se em um grande problema de saúde pública. Além das manifestações típicas da infecção viral, o vírus foi relacionado com alterações no desenvolvimento infantil de fetos em gestantes que se infectaram, com destaque para a microcefalia, convulsões, dentre outras malformações congênitas. Objetivo. O presente artigo objetiva analisar sistematicamente o conhecimento atual sobre a relação entre a síndrome congênita do Zika Vírus (SCZV) e o desenvolvimento de crises convulsivas. Material e métodos. Para a realização desta revisão, utilizou-se as bases de dados PubMed e Scielo, onde foi realizado um levantamento periódico utilizando descritores previamente estabelecidos, respeitando a seguinte fórmula de pesquisa: Congenital AND Zika Virus AND Seizures AND Children. Após leitura do título e resumo foram selecionados 27 artigos. Foram incluídos estudos de coorte, estudos transversais, séries de caso, relatos de caso e estudos de caso controle de pacientes diagnosticadas com a Síndrome Congênita do Zika Vírus. Resultados. Dentre os diversos aspectos que permeiam as alterações clínicas e morfológicas provocadas pela SCZV, foi possível observar uma associação entre a infecção, principalmente durante o primeiro trimestre da gestação, e o surgimento de eventos epileptogênicos. Os tipos de convulsões mais frequentes foram os espasmos epilépticos, seguidos pelas convulsões tônico-clônicas generalizadas e/ou convulsões focais. Além disso, no exame físico foi possível notar sinais motores,neuromusculares ou discinéticos, sendo os mais comuns: aumento dos reflexos tendinosos profundos, hipertonia, clônus, sinais de babinski e hoffman. A presença de microcefalia demonstrou ser um importante fator de risco juntamente com outras alterações morfológicas do sistema nervoso central (calcificações, ventriculomegalia, hidrocefalia, anomalias do corpo caloso, etc.). Conclusão. Nesta revisão, descrevemos a relação entre a SCZV e o desenvolvimento de quadros convulsivos, relatando as características clínicas desses pacientes, a idade de início e sua correlação com malformações cerebrais. Ademais, foi possível demonstrar que grande parte das manifestações convulsionais começaram antes dos 6 meses de vida, tendendo a quadros epiléticos precoces e refratários ao longo do tratamento farmacológico.

Objectives. Uncontrolled seizures in children 1 to 36 months old have serious short-term health risks and may be associated with substantial developmental, behavioral, and psychological impairments. We evaluated the effectiveness, comparative effectiveness, and harms of pharmacologic, dietary, surgical, neuromodulation, and gene therapy treatments for infantile epilepsies. Data sources. We searched Embase®, MEDLINE®, PubMed®, the Cochrane Library, and gray literature for studies published from January 1, 1999, to August 19, 2021. Review methods. Using standard Evidence-based Practice Center methods, we refined the scope and applied a priori inclusion criteria to the >10,000 articles identified. We ordered full text of any pediatric epilepsy articles to determine if they reported any data on those age 1 month to <36 months. We extracted key information from each included study, rated risk of bias, and rated the strength of evidence. We summarized the studies and outcomes narratively. Results. Forty-one studies (44 articles) met inclusion criteria. For pharmacotherapy, levetiracetam may cause seizure freedom in some patients (strength of evidence [SOE]: low), but data on other medications (topiramate, lamotrigine, phenytoin, vigabatrin, rufinamide, stiripentol) were insufficient to permit conclusions. Both ketogenic diet and the modified Atkins diet may reduce seizure frequency (SOE: low for both). In addition, the ketogenic diet may cause seizure freedom in some infants (SOE: low) and may be more likely than the modified Atkins diet to reduce seizure frequency (SOE: low). Both hemispherectomy/hemispherotomy and non-hemispheric surgical procedures may cause seizure freedom in some infants (SOE: low for both), but the precise proportion is too variable to estimate. For three medications (levetiracetam, topiramate, and lamotrigine), adverse effects may rarely be severe enough to warrant discontinuation (SOE: low). For topiramate, non-severe adverse effects include loss of appetite and upper respiratory tract infection (SOE: moderate). Harms of diets were sparsely reported. For surgical interventions, surgical mortality is rare for functional hemispherectomy/hemispherotomy and non-hemispheric procedures (SOE: low), but evidence was insufficient to permit quantitative estimates of mortality or morbidity risk. Hydrocephalus requiring shunt placement after multilobar, lobar, or focal resection is uncommon (SOE: low). No studies assessed neuromodulation or gene therapy. Conclusions. Levetiracetam, ketogenic diet, modified Atkins diet, and surgery all appear to be effective for some infants. However, the strength of the evidence is low for all of these modalities due to lack of control groups, low patient enrollment, and inconsistent reporting. Future studies should compare different pharmacologic treatments and compare pharmacotherapy with dietary therapy. Critical outcomes underrepresented in the literature include quality of life, sleep outcomes, and long-term development.