Les mutations du gène SCN1A, sont impliquées dans des épilepsies du nourrisson : le Syndrome de Dravet (SD), une épilepsie rare et pharmaco-résistante ou l’Epilepsie généralisée avec crises fébriles plus (GEFS+), une épilepsie plus légère. GEFS+ et SD sont associés à des crises épileptiques fébriles dès l’âge de 6 mois. Dans le SD on voit apparaitre des retards mentaux mais également des déficits moteurs, visuels, langagiers et mnésiques au cours de l’évolution de la maladie. L’impact des crises épileptiques au cours l’enfance sur ces déficits cognitifs n’est pas connu. Le SD est considéré comme une encéphalopathie épileptique où les crises étaient les principales responsables du phénotype à l’âge adulte. Récemment, un rôle potentiel de la mutation dans les troubles cognitifs a été mis en évidence changeant la définition de SD d’encéphalopathie épileptique à une canalopathie. La question est quel est le rôle des crises épileptiques répétées sur les fonctions cognitives à l’âge adulte ? Nous avons utilisé un modèle murin de la maladie portant une mutation du gène Scn1a, et qui présente une pathologie très légère. Nous avons induit des crises épileptiques par hyperthermie à l’âge de 21 jours (10 jours) et testé les effets à long-terme à l’âge adulte. Nos résultats révèlent que l’induction de crises induit une hyperactivité, des altérations dans les interactions sociales et des déficits en mémoires hippocampo et cortex préfronto-dépendantes. Ainsi nous avons mis en évidence que les crises épileptiques répétées pendant le développement ont un fort impact sur la fonction cérébrale et qu’il est donc capital de les prévenir afin de diminuer, voir de prévenir, ces déficits. / The SCN1A gene codes for the voltage-gated sodium channel Nav1.1 α-subunit. SCN1A mutations cause genetic epilepsies, as Generalized Epilepsy with Febrile Seizures plus (GEFS+), a mild epilepsy, or Dravet Syndrome (DS), a rare, severe and drug-resistant epileptic encephalopathy (EE). DS patients show severe cognitive/behavioral impairments that, according to the definition of EE, should be caused by the recurrent epileptic activity. Yet, this causal relationship has never been proved and it is been challenged by studies in mouse models showing that the genetic mutation itself, which causes a decrease in GABAergic activity, can be responsible for DS cognitive outcome. We studied the implication of repeated seizures during childhood to the later long-term modifications on cognitive/behavioral and epileptic phenotypes by submitting the Scn1a mouse model carrying the R1648H missense mutation and presenting mild phenotype to a protocol of repeated seizures induction by hyperthermia (10 days/one seizure per day). We observed that early life seizures can worsen the epileptic phenotype and induce cognitive/behavioral defects notably by inducing hyperactivity, sociability deficits and hippocampus- and prefrontal cortex-dependent memory deficits. We found that early life seizures can worsen the epileptic phenotype and induce cognitive/behavioral defects. Although the effect of NaV1.1 dysfunction in altering brain synchrony and the effect of repeated seizure activity in the young brain are not mutually exclusive, we thus conclude that epileptic seizures are sufficient to convert a Scn1a mouse model carrying a mild phenotype into a severe phenotype.

Title: Assessment of the attachment style as a part of the differential diagnosis of psychogenic non-epileptic seizures (PNES) Author: Bc. et Bc. Jana Heidingerová Thesis supervisor: doc. PhDr. Lenka Krámská, Ph.D. Pages: 101 Number of sources: 93 The thesis deals with the topic of psychogenic non-epileptic seizures (PNES) and their differential diagnosis in the context of attachment and its measuring. Based on theoretical knowledge, the relation between attachment disorders and the diagnosis of PNES was assumed. This connection was examined by comparing the results of three groups of respondents with different diagnoses (PNES, PNES and epilepsy, epilepsy) and a control group. The theoretical part deals with the problematics of attachment, PNES and epilepsy. The empirical part examines differences between groups of respondents, correlations of the variables with socio-demographic factors and correlations between results of each used method. Three questionnaires, PBI, ECR and ECR-RS were used for the research. The data were collected in the Epilepsy Centre at the Na Homolce Hospital. The research sample consisted of a total of 84 respondents. The results were statistically significant for numerous hypotheses. Research suggest that there are correlations of some subscales with socio-demographic...

Made available in DSpace on 2014-12-17T14:13:34Z (GMT). No. of bitstreams: 1 AnaMCS.pdf: 1887892 bytes, checksum: 05f9c6bffc3d95915a924712e4e7b5c7 (MD5) Previous issue date: 2007-12-19 / 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

Apresentamos dados e argumentos que indicam que: a) as crises epilépticas apresentadas por Trinomys yonenagae em campo e em cativeiro são espontâneas e idiopáticas; e b) elas podem ser decorrentes de processos evolutivos. A epilepsia nesta espécie foi caracterizada em cativeiro a partir de um cadastro iniciado há 16 anos, formado por progenitores e descendentes de seis colônias de T. yonenagae, coletados na Caatinga de Ibiraba (BA), e adultos (129,90 ± 5,92g) e filhotes nascidos em cativeiro num total de 295 indivíduos. A prevalência e a incidência em indivíduos epilépticos (EE) foram estimadas e as crises epilépticas foram analisadas por meio das manifestações comportamentais, baseando-se na escala de Racine. Aspectos da procriação (n=11), a locomoção, a ansiedade (testes de arena, n= 35) e índices fisiológicos (balanço hídrico-alimentar, n=6), importantes ao fitness, foram mensurados. Somente duas colônias apresentaram EE representando 9% e 28% dos nascimentos. Do total de indivíduos (165 e 130) 9,8% são EE (n=29; 14 e 15), sendo que as representam 52% e os 48%. A prevalência é de 20 a 30% e a incidência variou de 2 a 10 casos/ano, nos últimos cinco anos. As crises são observadas somente em adultos (n=24) a menor latência é de 13m e a frequência é variável (1 a 24 em seis anos). A maioria iniciou-se por congelamento e 50% atingiram o estágio 5 da escala de Racine. Em todos os casais, de 5 a 50% dos filhotes são EE e ocorreu estro pós-parto, como esperado para a espécie. Os filhotes são saudáveis e tanto a média de filhotes por ninhada (1,9±0,3), como a média do número de ninhadas por casal (6,5±5,0) é igual à de casais não epilépticos (NE). O teste de arena indica que descendentes de EE (DE) e as EE são menos ansiosas que as NE. Não há diferença entre os grupos dos índices fisiológicos estimados. A diferença no número de EE nas colônias, a alta prevalência e % de filhotes EE, e a diferença de comportamento das fêmeas DE indicam a base genética desta epilepsia. Neste contexto, consideramos que em Trinomys yonenagae, a epilepsia límbica não compromete o fitness, o que abre possibilidades de ser decorrente de processos evolutivos envolvendo o escalonamento de respostas de anti-predação / We present data and discuss the possibility that: a) the seizures presented by Trinomys yonenagae in the wild and in captivity are spontaneous and idiopathic, and b) they may be due to evolutionary processes. Epilepsy was characterized in this species in captivity from a survey started 16 years ago, made up of parents and descendants from six colonies of T. yonenagae collected in the Caatinga of Ibiraba (BA), and adults (129.90 ± 5.92 g) and pups born in captivity in a total of 295 individuals. The prevalence and incidence in individuals with epilepsy (EE) were estimated and seizures were analyzed by behavioral manifestations, based on Racine´s scale. Locomotion and anxiety indexes (open-field test, n = 35), as well as aspects of breeding (n = 11) and physiological indicators (balance food and water, n = 6), important to fitness were measured. Only two colonies showed EE, representing 9% and 28% of births. Approximately 10% of total individuals (165 and 130 ) are EE (n = 29, 14 and 15 ), and the represent 52 and 48%. In the last five years prevalence is 20-30%, and incidence ranged from 2 to 10 cases/ year. Seizures are only observed in adults (n = 24), the lowest latency is 13 months and the frequency is variable (1 to 24 in six years). The first stage is freezing and 50% reached stage 5 of Racine´s scale. In all couples, 5-50% of puppies are EE and occurred postpartum estrus, as expected for the species. The puppies are healthy and both the average offspring per litter (1.9 ± 0.3), as well as the average number of litters per couple (6.5 ± 5.0) is equal to values presented by non-epileptic couples (NE). The open-field test indicates that descendants of EE (DE) and EE are less anxious than NE. There is no difference between EE and NE regarding food and water intake. The difference in the number of EE in the colonies, the high percentage of EE pups, and the difference in the behavior of DE indicate the genetic basis of this epilepsy. In this context, we consider that in Trinomys yonenagae the limbic epilepsy seems to not compromise the fitness, which opens possibilities to be the result of evolutionary processes involving the escalation of antipredator responses

Apresentamos dados e argumentos que indicam que: a) as crises epilépticas apresentadas por Trinomys yonenagae em campo e em cativeiro são espontâneas e idiopáticas; e b) elas podem ser decorrentes de processos evolutivos. A epilepsia nesta espécie foi caracterizada em cativeiro a partir de um cadastro iniciado há 16 anos, formado por progenitores e descendentes de seis colônias de T. yonenagae, coletados na Caatinga de Ibiraba (BA), e adultos (129,90 ± 5,92g) e filhotes nascidos em cativeiro num total de 295 indivíduos. A prevalência e a incidência em indivíduos epilépticos (EE) foram estimadas e as crises epilépticas foram analisadas por meio das manifestações comportamentais, baseando-se na escala de Racine. Aspectos da procriação (n=11), a locomoção, a ansiedade (testes de arena, n= 35) e índices fisiológicos (balanço hídrico-alimentar, n=6), importantes ao fitness, foram mensurados. Somente duas colônias apresentaram EE representando 9% e 28% dos nascimentos. Do total de indivíduos (165 e 130) 9,8% são EE (n=29; 14 e 15), sendo que as representam 52% e os 48%. A prevalência é de 20 a 30% e a incidência variou de 2 a 10 casos/ano, nos últimos cinco anos. As crises são observadas somente em adultos (n=24) a menor latência é de 13m e a frequência é variável (1 a 24 em seis anos). A maioria iniciou-se por congelamento e 50% atingiram o estágio 5 da escala de Racine. Em todos os casais, de 5 a 50% dos filhotes são EE e ocorreu estro pós-parto, como esperado para a espécie. Os filhotes são saudáveis e tanto a média de filhotes por ninhada (1,9±0,3), como a média do número de ninhadas por casal (6,5±5,0) é igual à de casais não epilépticos (NE). O teste de arena indica que descendentes de EE (DE) e as EE são menos ansiosas que as NE. Não há diferença entre os grupos dos índices fisiológicos estimados. A diferença no número de EE nas colônias, a alta prevalência e % de filhotes EE, e a diferença de comportamento das fêmeas DE indicam a base genética desta epilepsia. Neste contexto, consideramos que em Trinomys yonenagae, a epilepsia límbica não compromete o fitness, o que abre possibilidades de ser decorrente de processos evolutivos envolvendo o escalonamento de respostas de anti-predação / We present data and discuss the possibility that: a) the seizures presented by Trinomys yonenagae in the wild and in captivity are spontaneous and idiopathic, and b) they may be due to evolutionary processes. Epilepsy was characterized in this species in captivity from a survey started 16 years ago, made up of parents and descendants from six colonies of T. yonenagae collected in the Caatinga of Ibiraba (BA), and adults (129.90 ± 5.92 g) and pups born in captivity in a total of 295 individuals. The prevalence and incidence in individuals with epilepsy (EE) were estimated and seizures were analyzed by behavioral manifestations, based on Racine´s scale. Locomotion and anxiety indexes (open-field test, n = 35), as well as aspects of breeding (n = 11) and physiological indicators (balance food and water, n = 6), important to fitness were measured. Only two colonies showed EE, representing 9% and 28% of births. Approximately 10% of total individuals (165 and 130 ) are EE (n = 29, 14 and 15 ), and the represent 52 and 48%. In the last five years prevalence is 20-30%, and incidence ranged from 2 to 10 cases/ year. Seizures are only observed in adults (n = 24), the lowest latency is 13 months and the frequency is variable (1 to 24 in six years). The first stage is freezing and 50% reached stage 5 of Racine´s scale. In all couples, 5-50% of puppies are EE and occurred postpartum estrus, as expected for the species. The puppies are healthy and both the average offspring per litter (1.9 ± 0.3), as well as the average number of litters per couple (6.5 ± 5.0) is equal to values presented by non-epileptic couples (NE). The open-field test indicates that descendants of EE (DE) and EE are less anxious than NE. There is no difference between EE and NE regarding food and water intake. The difference in the number of EE in the colonies, the high percentage of EE pups, and the difference in the behavior of DE indicate the genetic basis of this epilepsy. In this context, we consider that in Trinomys yonenagae the limbic epilepsy seems to not compromise the fitness, which opens possibilities to be the result of evolutionary processes involving the escalation of antipredator responses