Base teórica: O Acidente Vascular Cerebral (AVC) é a causa mais comum de novos diagnósticos de epilepsia no idoso. Embora a epilepsia pós-AVC seja um fenômeno clínico reconhecido há muito tempo, seguem muitas questões não resolvidas. Além disso, nas últimas duas décadas, o tratamento do AVC isquêmico sofreu mudanças radicais com a introdução da trombólise e da hemicraniectomia descompressiva (HD) para o tratamento do infarto maligno de artéria cerebral média (ACM). As consequências destas duas novas abordagens terapêuticas nas características da epilepsia pós-AVC ainda são pouco exploradas. Objetivo: Estudar as características e estimar fatores de risco para as crises epilépticas ou a epilepsia pós-AVC em pacientes submetidos ao tratamento agudo (Estudo 1) ou HD para infarto maligno de ACM (Estudo 2). Métodos: O estudo 1 é uma coorte de 153 pacientes submetidos a trombólise. Variáveis estudadas incluiram fatores de risco para o AVC e variáveis associadas ao AVC isquêmico agudo e trombólise. Utilizamos a análise de regressão de Cox para o estudo das variáveis que se associaram de forma independente com crises epilépticas, epilepsia pós-AVC e o desfecho do AVC. O estudo 2 é também uma coorte que retrospectivamente avaliou 36 pacientes com infarto maligno de ACM tratados com HD. Tempo, incidência e fatores de risco para crises epilépticas e desenvolvimento de epilepsia foram analisados. Resultados: Estudo 1: 74 pacientes (48,4%) eram mulheres; média de idade foi 67,2 anos (DP=13,1). Média do NIHSS na chegada foi 10,95 (DP=6,25) e 2,09 (DP=3,55) após 3 meses. Transformação hemorrágica ocorreu em 22 (14,4%) dos pacientes. Foi considerado desfecho bom classificação na escala modificada de Rankin (mRS) 0-1, sendo encontrado em 87 (56,9%) dos pacientes. Vinte e um pacientes (13,7%) tiveram crises epilépticas e 15 (9,8%) desenvolveram epilepsia após a trombólise. Crises epilépticas foram associadas de forma independente com transformação hemorrágica e desfecho não favorável (mRS ≥ 2) em três meses após o AVC. Transformação hemorrágica e mRS ≥ 2 avaliados em 3 meses, associaram-se de forma independente com epilepsia pós-AVC. Crises epilépticas surgiram como um fator de risco independente para desfecho pobre. Estudo 2. A média de seguimento dos pacientes foi de 1.086 (DP= 1.172) dias. Nove pacientes morreram antes de receberem alta hospitalar e no período de um ano, 11 pacientes haviam morrido. Quase 60% alcançaram mRS ≤ 4. Treze pacientes desenvolveram crises dentro da primeira semana após o AVC. No total, crises epilépticas ocorreram em 22 (61%) dos 36 pacientes. Dezenove pacientes (56%) dos 34, sobreviveram ao período agudo e desenvolveram epilepsia após infarto da ACM e HD. Questionamos aos pacientes ou responsáveis se eles se arrependeram de terem autorizado a HD no momento do AVC. Também foi perguntado se eles autorizariam a HD novamente. Trinta e dois (89%) não se arrependeram de ter autorizado a HD no momento do infarto agudo da ACM, e autorizaria novamente em retrospecto. Conclusão: Confirmamos que as frequências de crises ou epilepsia pós-AVC e trombolítico são comparáveis com as frequências das décadas da era pré-trombólise e confirmamos a alta incidência de crises epilépticas e epilepsia após infartos malignos de ACM submetidos a HD. Em nosso estudo, as crises epilépticas associaram-se de forma independente com pior prognóstico após terapia trombolítica. / Background: The most common cause of newly diagnosed epilepsies in the elderly is stroke. Although post-stroke epilepsy is a well-studied stroke complication, many questions remain unsolved. In addition, during the past two decades, the treatment of stroke has changed dramatically with the introduction of thrombolysis for treatment of acute ischemic stroke (AIS) and decompressive hemicraniectomy (DHC) for malignant middle cerebral artery infarction (MCA). The consequences of these two new therapeutic approaches for characteristics of post-stroke epilepsy remains poorly explored. Objective: To study characteristics and estimate risk factors for acute seizures or post-stroke epilepsy in patients submitted to thrombolysis for treatment of acute stroke (Study 1) or DHC for malignant MCA infarction. Methods: Study 1 is a cohort study of 153 patients submitted to thrombolysis. Variables studied included risk factors for stroke, and variables related to acute stroke and thrombolysis. Variables independently associated with seizures, pos-stroke epilepsy or stroke outcome were defined using Cox regression analysis. Study 2 is also a cohort study that retrospectively assessed 36 patients with malignant stroke of the MCA submitted to DHC. Timing, incidence and plausible risk factors for seizure and epilepsy development were analyzed in these patients. Results: Study 1. Seventy-four patients (48.4%) were female; mean age of patients was 67.2 years-old (SD=13.1). Initial NIHSS mean score was 10.95 (SD=6.25) and 2.09 (SD=3.55) after three months. Hemorrhagic transformation occurred in 22 (14.4%) patients. A good outcome, as defined by a modified Rankin Scale (mRS) of 0-1, was observed in 87 (56.9%) patients. Twenty one (13.7%) patients had seizures and 15 (9.8%) patients developed epilepsy after thrombolysis. Seizures were independently associated with hemorrhagic transformation and with mRS ≥ 2 three months after stroke. Hemorrhagic transformation and unfavorable outcome, as measured by mRS ≥ 2 after three months, were variables independently associated with post-stroke epilepsy. Seizures emerged as an independent factor for poor outcome in stroke thrombolysis. Study 2. Mean patient follow-up time was of 1.086 (SD=1.172) days. Nine patients died before being discharged and after one year eleven patients died. Almost 60% had the modified Rankin score ≤ 4. Thirteen patients developed seizures within the first week after stroke. In total, seizures occurred in 22 (61%) of 36 patients. Nineteen patients (56%) out of 34 patients who survived the acute period developed epilepsy after MCA infarcts and DHC. Also, we asked patients or the person responsible for them whether they regretted, in retrospect, having authorized DHC at the time of the stroke. It was also asked whether they would authorize DHC again. Thirty- two (89%) did not regret having authorized DHC at the time of acute MCA infarct, and would authorize DHC again in retrospect. Conclusion: We confirm that seizures or post-stroke epilepsy rates after thrombolysis are comparable with rates from pre-thrombolysis decades and a high incidence of seizures and epilepsy after malignant MCA infarcts submitted to DHC. In our study, seizures were an independent risk factor associated with worst outcome after thrombolysis therapy.

Base teórica: O Acidente Vascular Cerebral (AVC) é a causa mais comum de novos diagnósticos de epilepsia no idoso. Embora a epilepsia pós-AVC seja um fenômeno clínico reconhecido há muito tempo, seguem muitas questões não resolvidas. Além disso, nas últimas duas décadas, o tratamento do AVC isquêmico sofreu mudanças radicais com a introdução da trombólise e da hemicraniectomia descompressiva (HD) para o tratamento do infarto maligno de artéria cerebral média (ACM). As consequências destas duas novas abordagens terapêuticas nas características da epilepsia pós-AVC ainda são pouco exploradas. Objetivo: Estudar as características e estimar fatores de risco para as crises epilépticas ou a epilepsia pós-AVC em pacientes submetidos ao tratamento agudo (Estudo 1) ou HD para infarto maligno de ACM (Estudo 2). Métodos: O estudo 1 é uma coorte de 153 pacientes submetidos a trombólise. Variáveis estudadas incluiram fatores de risco para o AVC e variáveis associadas ao AVC isquêmico agudo e trombólise. Utilizamos a análise de regressão de Cox para o estudo das variáveis que se associaram de forma independente com crises epilépticas, epilepsia pós-AVC e o desfecho do AVC. O estudo 2 é também uma coorte que retrospectivamente avaliou 36 pacientes com infarto maligno de ACM tratados com HD. Tempo, incidência e fatores de risco para crises epilépticas e desenvolvimento de epilepsia foram analisados. Resultados: Estudo 1: 74 pacientes (48,4%) eram mulheres; média de idade foi 67,2 anos (DP=13,1). Média do NIHSS na chegada foi 10,95 (DP=6,25) e 2,09 (DP=3,55) após 3 meses. Transformação hemorrágica ocorreu em 22 (14,4%) dos pacientes. Foi considerado desfecho bom classificação na escala modificada de Rankin (mRS) 0-1, sendo encontrado em 87 (56,9%) dos pacientes. Vinte e um pacientes (13,7%) tiveram crises epilépticas e 15 (9,8%) desenvolveram epilepsia após a trombólise. Crises epilépticas foram associadas de forma independente com transformação hemorrágica e desfecho não favorável (mRS ≥ 2) em três meses após o AVC. Transformação hemorrágica e mRS ≥ 2 avaliados em 3 meses, associaram-se de forma independente com epilepsia pós-AVC. Crises epilépticas surgiram como um fator de risco independente para desfecho pobre. Estudo 2. A média de seguimento dos pacientes foi de 1.086 (DP= 1.172) dias. Nove pacientes morreram antes de receberem alta hospitalar e no período de um ano, 11 pacientes haviam morrido. Quase 60% alcançaram mRS ≤ 4. Treze pacientes desenvolveram crises dentro da primeira semana após o AVC. No total, crises epilépticas ocorreram em 22 (61%) dos 36 pacientes. Dezenove pacientes (56%) dos 34, sobreviveram ao período agudo e desenvolveram epilepsia após infarto da ACM e HD. Questionamos aos pacientes ou responsáveis se eles se arrependeram de terem autorizado a HD no momento do AVC. Também foi perguntado se eles autorizariam a HD novamente. Trinta e dois (89%) não se arrependeram de ter autorizado a HD no momento do infarto agudo da ACM, e autorizaria novamente em retrospecto. Conclusão: Confirmamos que as frequências de crises ou epilepsia pós-AVC e trombolítico são comparáveis com as frequências das décadas da era pré-trombólise e confirmamos a alta incidência de crises epilépticas e epilepsia após infartos malignos de ACM submetidos a HD. Em nosso estudo, as crises epilépticas associaram-se de forma independente com pior prognóstico após terapia trombolítica. / Background: The most common cause of newly diagnosed epilepsies in the elderly is stroke. Although post-stroke epilepsy is a well-studied stroke complication, many questions remain unsolved. In addition, during the past two decades, the treatment of stroke has changed dramatically with the introduction of thrombolysis for treatment of acute ischemic stroke (AIS) and decompressive hemicraniectomy (DHC) for malignant middle cerebral artery infarction (MCA). The consequences of these two new therapeutic approaches for characteristics of post-stroke epilepsy remains poorly explored. Objective: To study characteristics and estimate risk factors for acute seizures or post-stroke epilepsy in patients submitted to thrombolysis for treatment of acute stroke (Study 1) or DHC for malignant MCA infarction. Methods: Study 1 is a cohort study of 153 patients submitted to thrombolysis. Variables studied included risk factors for stroke, and variables related to acute stroke and thrombolysis. Variables independently associated with seizures, pos-stroke epilepsy or stroke outcome were defined using Cox regression analysis. Study 2 is also a cohort study that retrospectively assessed 36 patients with malignant stroke of the MCA submitted to DHC. Timing, incidence and plausible risk factors for seizure and epilepsy development were analyzed in these patients. Results: Study 1. Seventy-four patients (48.4%) were female; mean age of patients was 67.2 years-old (SD=13.1). Initial NIHSS mean score was 10.95 (SD=6.25) and 2.09 (SD=3.55) after three months. Hemorrhagic transformation occurred in 22 (14.4%) patients. A good outcome, as defined by a modified Rankin Scale (mRS) of 0-1, was observed in 87 (56.9%) patients. Twenty one (13.7%) patients had seizures and 15 (9.8%) patients developed epilepsy after thrombolysis. Seizures were independently associated with hemorrhagic transformation and with mRS ≥ 2 three months after stroke. Hemorrhagic transformation and unfavorable outcome, as measured by mRS ≥ 2 after three months, were variables independently associated with post-stroke epilepsy. Seizures emerged as an independent factor for poor outcome in stroke thrombolysis. Study 2. Mean patient follow-up time was of 1.086 (SD=1.172) days. Nine patients died before being discharged and after one year eleven patients died. Almost 60% had the modified Rankin score ≤ 4. Thirteen patients developed seizures within the first week after stroke. In total, seizures occurred in 22 (61%) of 36 patients. Nineteen patients (56%) out of 34 patients who survived the acute period developed epilepsy after MCA infarcts and DHC. Also, we asked patients or the person responsible for them whether they regretted, in retrospect, having authorized DHC at the time of the stroke. It was also asked whether they would authorize DHC again. Thirty- two (89%) did not regret having authorized DHC at the time of acute MCA infarct, and would authorize DHC again in retrospect. Conclusion: We confirm that seizures or post-stroke epilepsy rates after thrombolysis are comparable with rates from pre-thrombolysis decades and a high incidence of seizures and epilepsy after malignant MCA infarcts submitted to DHC. In our study, seizures were an independent risk factor associated with worst outcome after thrombolysis therapy.

<p>The following thesis will focus on understanding the downstream behavioral effects of δORmediated β-arrestinsignaling. δORagonists have been implicated as effective targets for a variety of diseases, however detrimental side effects of opioid-targeting agonists limit their clinical use. δORagonists specifically can induce seizures, however the underlying mechanism contributing to this  behavior  is  unknown.  We  review  this  phenomenon  in  more  detail,  highlighting  current agonists known to induce seizures and potential circuits and pathways involved. Our work suggests β-arrestinsignaling  is  involved,  specifically β-arrestin2  mediated  signaling  may  be  largely contributing  to δORagonist-induced  seizure  behavior.  As  it  is  possible  the β-arrestinisoforms have unique roles in seizure behavior, we also analyzed methods in which to provoke β-arrestinisoform bias of δORtargeting compounds. Though the full mechanism relating δORagonists with seizures remains unknown, our work provides foundational detail of this behavior, implicating the importance of β-arrestinisoform signaling through δOR; allowing for future studies to full define this seizure pathway and develop δORsafer agonists.  </p>

In die studie is besin oor die wyse waarop die opvoedkundige sielkundige die probleme wat deur die epileptiese adolessente dogter ondervind word, kan aanspreek. 'n Groepterapeutiese begeleidingsprogram is ten doel gestel sodat die intra- en inter-psigiese effek daarvan op die epileptiese adolessente dogter bepaal kon word. Agt epileptiese adolessente dogters is vir die doel van hierdie studie geselekteer, waama hulle aan 'n reeks psigometriese toetse onderwerp is. Voorts het die onderskeie vakonderwysers 'n evalueringsvraelys voltooi. Daar is bevind dat die dogters in die algemeen 'n negatiewe selfkonsep het. Die meeste proefpersone was angstig en depressief. Verhoudingsprobleme en 'n gebrek aan doelstellings het ook onder hulle voorgekom. Volgens die literatuurstudie blyk dit 66k dat die epileptiese kind oor die algemeen 'n hoe voorkoms van psigo-sosiale probleme toon en <lat <lit dikwels lei tot 'n negatiewe selfkonsep. Faktore wat die psigo-sosiale wording van die epileptiese kind kan bei'nvloed, is neuroIV biologiese faktore (byvoorbeeld die tipe toeval), psigo-sosiale faktore (byvoorbeeld stigmatisering) en farmakologiese faktore (byvoorbeeld newe-effekte van medikasie ). Die proefpersone is onderwerp aan 'n groepterapeutiese begeleidingsprogram van tien sessies. Die program het gefokus op intra-psigiese aspekte soos die regstelling van negatiewe selfspraak, asook op die bewusmaking en oefening van interpersoonlike vaardighede. Uit die resultate van die na-toetsing kan afgelei word dat persoonlike groei plaasgevind het - in die algemeen was daar 'n verhoging ten opsigte van die selfkonsep. Interpersoonlike verhoudinge het skynbaar ook verbeter, terwyl angs afgeneem en depressie verminder het. Voorts het die proefpersone se skolastiese prestasie met 5,1 persent verbeter. Die groepterapeutiese begeleidingsprogram het dus 'n positiewe intra- en inter-psigiese effek op die epileptiese adolessente dogter gehad. / This study addressed the ways in which the educational psychologist can address the problems experienced by epileptic adolescent girls. Eight epileptic adolescent girls were subjected to a series of psychometric tests. The results indicated that in general, the majority of the girls were suffering from a negative self-concept, depression and anxiety. They experienced problems with relationships and reflected a lack of goals. The epileptic adolescent girls were subjected to a group therapeutic guidance programme. The programme focussed on intra- and interpsychological aspects such as the modification of negative self-talk and the exercising of interpersonal skills. The results of follow-up tests revealed that in general there had been an improvement of the self-concept. Apparently inter-personal relations had improved, whereas anxiety and depression had declined. At the same time, school performance had increased. Hence, the group therapeutic guidance programme had a positive intra- and interpsychological effect on the epileptic adolescent girls. / Psychology of Education / M.Ed.

Αντικείμενο αυτής της εργασίας είναι η μελέτη τεχνικών για την ανάλυση δεδομένων που προέρχονται από συστήματα απεικόνισης της λειτουργίας του ανθρώπινου εγκεφάλου όπως το ηλεκτροεγκεφαλογράφημα. Σκοπός των τεχνικών ανάλυσης είναι η ανίχνευση συγκεκριμένων μορφών αυτών των σημάτων όπως για παράδειγμα οι επιληπτικές κρίσεις. Μία κρίση είναι μια παρέκκλιση στην ηλεκτρική δραστηριότητα του εγκεφάλου που παράγει αποδιοργανωτικά συμπτώματα για το άτομο και εκδηλώνεται κλινικά από εναλλαγή στη συμπεριφορά, στην κίνηση, στις αισθήσεις και στη συνειδητότητα. Οι κλινικές συμπεριφορές προηγούνται και στη συνέχεια συνοδεύονται από ηλεκτροεγκεφαλογραφικές αλλαγές. Η αυτόματη ανίχνευση των επιληπτικών κρίσεων μπορεί να αντιμετωπιστεί ως ένα πρόβλημα κατηγοριοποίησης των σημάτων σε κρίσεις ή όχι. Η ανίχνευση μπορεί να πραγματοποιηθεί σε δύο βήματα. Αρχικά εξάγονται χαρακτηριστικά που συλλαμβάνουν την μορφή και στη συνέχεια το διάνυσμα των χαρακτηριστικών δίνεται σε έναν εκπαιδευμένο κατηγοριοποιητή. / The subject of this work is the research of analysis techniques on data coming from neuroimaging systems such as Electroencephalogram. The aim of the data analysis techniques is the detection of specific morphologies of these signals such as the epileptic seizures. A seizure is a sudden breakdown of the neuronal activity of the brain that is clinically manifested by an involuntary alteration in behavior, movement, sensation, or consciousness. These clinical behaviors are preceded and then accompanied by electroencephalographic alterations. The automatic detection of epileptic seizures can be faced as a classification problem of the signals into seizures or non seizures. The detection can be carried out in two steps. Firstly, features which capture the morphology of the epileptic seizures are extracted and then the feature vector is given to an appropriately trained classifier.

<p>УВОД: Епилепсију карактерише појава рекурентних непровоцираних напада који су манифестација појачане активности појединих епилептички измењених неуронских група у мозгу. Електроенцефалографија (EEG), је једина метода која може открити присуство фокалних или генерализованих епилептиформних пражњења, и пружити податке који су неопходни за синдромску класификацију епилепсија. МАТЕРИЈАЛ И МЕТОДЕ: Истраживање је обухватило 229 oсоба након првог епилептичког напада. Све особе су испитиване према дијагностичком протоколу који је обухватио анамнестичке и клиничке податке као и резултате допунских EEG и неурорадиолошких (CT, MRI) испитивања. Патолошки EEG налаз је описан као епилептиформан или неепилептиформан, генерализованог, нелатерализованог или фокалног типа. Неурорадиолошки снимак је сматран патолошким уколико је откривена потенцијално епилептогена лезија. Класификација типа и етиологије првог епилептичког напада је извршена у односу на важеће критеријуме. РЕЗУЛТАТИ: Нападе непознатог узрока је имало 51% особа, док је 49% особа имало симптоматске нападе. Најчешћи су били напади генерализованог типа (примарни или секундарни). Патолошки измењен EEG је регистрован код 76% особа, 47% је имало регистровану интерикталну епилептиформну активност (28% фокалну, 16% генерализовану), а&nbsp; у 31% EEG регистрација је бележена спора интериктална активност. Након депривације спавања, епилептиформна активност која је регистрована на EEG-у код 60% особа, била је најчешће фокалног типа (37%). Фактори који су дали статистички значајан допринос појави интерикталне епилептиформне активности су били старост (р 0,000; OR 1,036; 95%CI 1,021-1,051) и тип првог напада (р 0,016; OR 1,00a - 1,937; 95%CI 1,130-3,319). Ризик од рекурентних напада је био највиши код жаришних лезија (р=0,012) које су смештене у фронталном или темпоралном региону (р=0,012).&nbsp; ЗАКЉУЧАК: У периоду након првог непровоцираног напада епилептиформна активност је била чешћа код особа млађе старостне доби са генерализованим типом напада у односу на старије особе са жаришним типом напада. Иако EEG може помоћи у сагледавању епилептичке природе кризе свести, посебно код млађих особа, ипак код многих, дијагноза епилепсије зависи од појаве поновног епилептичког напада.</p> / <p>UVOD: Epilepsiju karakteriše pojava rekurentnih neprovociranih napada koji su manifestacija pojačane aktivnosti pojedinih epileptički izmenjenih neuronskih grupa u mozgu. Elektroencefalografija (EEG), je jedina metoda koja može otkriti prisustvo fokalnih ili generalizovanih epileptiformnih pražnjenja, i pružiti podatke koji su neophodni za sindromsku klasifikaciju epilepsija. MATERIJAL I METODE: Istraživanje je obuhvatilo 229 osoba nakon prvog epileptičkog napada. Sve osobe su ispitivane prema dijagnostičkom protokolu koji je obuhvatio anamnestičke i kliničke podatke kao i rezultate dopunskih EEG i neuroradioloških (CT, MRI) ispitivanja. Patološki EEG nalaz je opisan kao epileptiforman ili neepileptiforman, generalizovanog, nelateralizovanog ili fokalnog tipa. Neuroradiološki snimak je smatran patološkim ukoliko je otkrivena potencijalno epileptogena lezija. Klasifikacija tipa i etiologije prvog epileptičkog napada je izvršena u odnosu na važeće kriterijume. REZULTATI: Napade nepoznatog uzroka je imalo 51% osoba, dok je 49% osoba imalo simptomatske napade. Najčešći su bili napadi generalizovanog tipa (primarni ili sekundarni). Patološki izmenjen EEG je registrovan kod 76% osoba, 47% je imalo registrovanu interiktalnu epileptiformnu aktivnost (28% fokalnu, 16% generalizovanu), a&nbsp; u 31% EEG registracija je beležena spora interiktalna aktivnost. Nakon deprivacije spavanja, epileptiformna aktivnost koja je registrovana na EEG-u kod 60% osoba, bila je najčešće fokalnog tipa (37%). Faktori koji su dali statistički značajan doprinos pojavi interiktalne epileptiformne aktivnosti su bili starost (r 0,000; OR 1,036; 95%CI 1,021-1,051) i tip prvog napada (r 0,016; OR 1,00a - 1,937; 95%CI 1,130-3,319). Rizik od rekurentnih napada je bio najviši kod žarišnih lezija (r=0,012) koje su smeštene u frontalnom ili temporalnom regionu (r=0,012).&nbsp; ZAKLJUČAK: U periodu nakon prvog neprovociranog napada epileptiformna aktivnost je bila češća kod osoba mlađe starostne dobi sa generalizovanim tipom napada u odnosu na starije osobe sa žarišnim tipom napada. Iako EEG može pomoći u sagledavanju epileptičke prirode krize svesti, posebno kod mlađih osoba, ipak kod mnogih, dijagnoza epilepsije zavisi od pojave ponovnog epileptičkog napada.</p> / <p>INTRODUCTION: Epilepsy is characterized by recurrent, unprovoked seizures defined as the manifestation of epileptic excessive activity of neurons in the brain. Electroencephalography (EEG) provides a different focal and generalized epileptiform discharges and essential information for the syndromic classification of epilepsy. MATERIALS AND METHODS: The investigation included 229 patients with first epileptic seizure. Assesment of the first seizure presentation requires systematic clinical approach and diagnostic tests such as EEG and neuroradiological methods. In all the patients first time EEG had been performed within a month of the event. The presence of abnormal EEG activity was classified as epileptic or non-epileptic, of focal, nonlateralized or generalized type. RESULTS: 51% of all persons had a presumed seizure of unknown origin and 49% had presumed remote symptomatic seizures. About 73% had generalized seizures (primarily or secondarily). Abnormal single EEGs were present in 76%, with epileptiform activity in 47% (28% focal, 16% generalized), and nonepileptic slowing activity in 31%. Epileptiform EEG activity was present in 60%, and was predominantely focal (37%) if registration was done after sleep-deprivation. Statistical significance on interictal epileptorm activity was registered in younger age of first seizure oncet (р 0,000; OR 1,036; 95%CI 1,021-1,051) and with generalized seizures (р 0,016; OR 1,00a - 1,937; 95%CI 1,130-3,319). Reccurence risk increased in presence of focal type first seizure (p=0,012), and in frontal or temporal localization of epileptogenic lesions (p=0,012). CONCLUSION: Following a single unprovoked presumed seizure epileptiform activity was most common in younger patients with generalized seizures compared with older individuals with focal seizures. Reccurence risk increased in focal frontal and temporal seizures. Although the EEG is particularly helpful in supporting the epileptic nature of the event in younger patients, still many patients need further seizure reccurence, to be diagnosed.</p>

Présentée comme une nouvelle arme de lutte contre la fraude, la procédure de flagrance fiscale instaurée par la loi de finances rectificative pour 2007 et codifiée à l'article L. 16-0 BA du Livre des procédures fiscales (LPF) marque la rupture avec les moyens de traque jusqu'alors mis à la disposition de l'administration fiscale en ce qu'elle permet d'intervenir en amont de toute obligation déclarative pour garantir le recouvrement d'éventuelles créances de contrôle fiscal et sanctionner, dans le même temps, les contribuables déviants. Ce procédé original qui prétend remédier aux agissements de certaines entreprises dites « éphémères », créées dans un but frauduleux et amenées à disparaître promptement pour échapper à toute obligation déclarative, participe du phénomène de pénalisation du droit fiscal observé ces dernières années. Si le champ d'application du dispositif se veut strictement délimité par la loi, l'imprécision des textes laisse néanmoins subsister de nombreuses interrogations quant à la mise en œuvre et à l'efficacité de la procédure. L'absence d'autonomie du dispositif pourrait, notamment, soulever quelques difficultés dirimantes. D'autant que l'établissement du procès-verbal de flagrance autorise la prise de saisies conservatoires sans intervention préalable du juge judiciaire et entraîne pour le contribuable, outre l'application d'une amende, la perte de régimes de faveur et une extension des pouvoirs de contrôle de l'administration, prérogatives que les deux voies de recours spécifiquement créées pour permettre au contribuable de saisir a posteriori le juge du référé administratif ne sauraient suffire à contrebalancer / Introduced as a new weapon in the fight against tax fraud, the tax flagrancy procedure instituted by article 15 of the French amending finance law for 2007 and codified into article L. 16-0 BA in the French tax procedure code shows a break with the tracking means given until now to the tax administration's officers because it allows them to intervene before any declaratory obligation, to guarantee the recovery of possible debts arising from tax audit and to punish, in the same time, deviant taxpayers. This original process which claims to relieve the corrupt practice of some short-lived companies created for a fraudulent purpose and destined to disappear quickly, before any deadline requirements, participates in the criminalizing phenomenon of tax law observed in recent years. If the scope of procedure is strictly defined by law, the fact remains that the imprecise nature of the legislation leaves several interrogations about the implementation and effectiveness of the method. The procedure's lack of autonomy could raise some dissuasive difficulties. All the more so as the establishment of the flagrancy report involves, besides conservatory seizures without any court order, the loss of preferential treatments, an extension of powers of tax authorities and penalty tax. However both courses of action, specifically created by the legislator to entitle taxpayers to apply to an administrative summary proceeding judge after the event, are insufficient compensations

Introdução: A vigabatrina (VGB - Gama-Vinil-GABA) é um fármaco que eleva os níveis de GABA no organismo, por inibição irreversível da GABA transaminase, cuja eficácia foi bem demonstrada no controle dos espasmos epilépticos em lactentes, especialmente na síndrome de West secundária à esclerose tuberosa. Há escassez de estudos clínicos evidenciando um possível papel deste fármaco no controle de crises epilépticas neonatais e pouco se sabe sobre o potencial impacto do seu uso nessa faixa etária, seus possíveis efeitos adversos, ou se sua introdução teria associações positivas com controle mais adequado das crises na evolução e melhor desenvolvimento neuropsicomotor da criança. A VGB foi introduzida em nosso serviço como terapia de adição para o controle de crises neonatais refratárias, há vários anos, instigando nossa impressão sobre a eficácia deste medicamento no período neonatal. Objetivos: Avaliar a efetividade do uso da VGB como adjuvante no controle das crises eletrográficas e eletroclínicas do período neonatal e seus efeitos sobre o padrão do eletroencefalograma (EEG); Avaliar a evolução clínica e eletrográfica das crianças durante seguimento ambulatorial; Pesquisar associação entre \"controle de crises neonatais com introdução de VGB\" e diversas características demográficas, clínicas e evolutivas destes recém nascidos; Quantificar e caracterizar a ocorrência de efeitos adversos precoces e durante o seguimento. Pacientes e métodos: Estudo transversal retrospectivo, envolvendo o levantamento dos prontuários de uma amostra de recém-nascidos que receberam VGB como tratamento para crises neonatais refratárias aos fármacos convencionais e status epilepticus, no período de janeiro de 2007 a março de 2014, no Serviço de Neonatologia e Terapia Intensiva Neonatal do HCFMRP-USP, mantendo seguimento ambulatorial por pelo menos 1 ano. Foram avaliados os dados demográficos, etiologia e semiologia clínico-eletroencefalográfica das crises, esquema terapêutico prescrito, indicação da introdução da VGB, tempo de internação e tempo para atingir o controle das crises, evolução clínica e eletrencefalográfica durante a internação e no seguimento ambulatorial, época da suspensão da VGB, além de seus efeitos adversos. Resultados: De 48 recém-nascidos avaliados, 34 (79,2 %) obtiveram controle de crises eletrográficas e/ou clínicas durante o período neonatal, havendo melhora no padrão eletrográfico após a introdução da VGB em 79%. Quanto aos critérios para sua indicação, 33,3% (16 indivíduos) iniciaram VGB devido a falha terapêutica no controle das crises com fenobarbital e/ou fenitoína; 27,1% (13 recém nascidos), pela presença de estado de mal epilético e, em 12 crianças (25%), por falha terapêutica do midazolam. Ao final do primeiro ano de vida, a atividade de base do EEG mostrou-se desorganizada em 58,1% (18 de 29 pacientes que o realizaram aos 12 meses de vida). No seguimento ambulatorial de 38 pacientes, algum grau de atraso do desenvolvimento neuropsicomotor foi detectado em 20 crianças (52,6%); 19 lactentes (39,5%) mantiveram o uso da VGB em politerapia, tendo 22 crianças (57,9%) evoluído com persistência das crises epilépticas. Já 37,8% (14 pacientes) enquadraram-se em um padrão de encefalopatia epiléptica, que correspondeu à síndrome de West em 13,9% (5 de 36 crianças). Quanto ao EEG realizado em 34 crianças nessa fase, 17,6% (6 casos) demonstraram a presença de hipsarritmia, enquanto anormalidades focais ou multifocais foram detectadas em 50% (17 lactentes). A taxa de óbito ao final do primeiro ano foi de 23,3% (10 de 43 crianças analisadas quanto a este dado). Não foi possível comprovar déficit visual relacionado diretamente ao uso da VGB. A variável \"controle de crises no período neonatal com o uso da VGB\" foi associada aos seguintes desfechos clínicos favoráveis: melhora no padrão eletrográfico (92,1%), proporção menor de crianças evoluindo para síndrome de West e outras encefalopatias epilépticas (71,9% não tiveram tal desfecho); menor frequência de hipsarritmia no EEG (92,9% sem hipsarritmia), maior alcance de desenvolvimento neuropsicomotor normal (56,2% com bom desenvolvimento neurológico), menor índice de óbito neonatal (97,4% vivos nesta fase) e durante os primeiros doze meses de vida (87,9%). Conclusão: Acreditamos que a VGB seja uma opção terapêutica efetiva e com adequada relação custo-benefício, a ser implementada no controle de crises epilépticas neonatais refratárias como fármaco adjuvante aos convencionais. Entretanto, estudos randomizados e controlados são necessários para confirmar sua eficácia quando comparada a outros medicamentos disponíveis para uso nesta população, bem como para avaliar seus possíveis efeitos adversos a longo prazo. / Introduction: Vigabatrin (VGB - Gama-Vinil-GABA) is an antiepileptic drug which increases systemic GABA levels by irreversibly inhibiting GABA transaminase, with well demonstrated efficacy in the control of infantile epileptic spasms, specially related to West syndrome due to tuberous sclerosis. Clinical studies demonstrating a possible role of VGB in the control of neonatal seizures are still very scarce and very little is known on the impact of its use at this early age, as well as on its possible side effects or eventual positive associations from its use with more adequate seizure control or better neuropsychomotor development in the outcome. VGB has been used in our service as an add-on therapy for refractory neonatal seizures arising the impression that this could be an effective antiepileptic medication in the neonatal period. Objectives: To evaluate the use of VGB as an add-on medication regarding its effectiveness for the control of neonatal electrographic and electroclinical seizures, as well as its effects over the EEG pattern; To evaluate clinical and electrographic evolution of the children in follow-up; To estimate VGB efficacy on the control of neonatal seizures in relation to the demographical and clinical characteristics of those newborns; To quantify and characterize the occurrence of early and late side effects of this medication along follow-up. Patients and methods: This is a transverse retrospective study carried out through charts analysis from a sample of newborns who received VGB as add-on medication for seizures and/or status epilepticus refractory to conventional drugs, from January 2007 through March 2014, at the Neonatal Intensive Care Service of HCFMRP-USP, keeping follow-up in our institution for at least 1 year. Demographical and etiological data were analyzed, as well as clinical-electrographical semiology, VGB prescription indication, therapeutic schedule, time to reach seizure control, clinical and electrographical evolution while in hospital and at the follow-up, age at VGB withdrawal, besides adverse effects. Results: Among 48 newborns evaluated, 34 (79.2%) reached control of electrographic and/or clinical seizures during neonatal period, with improvement of the EEG pattern after VGB introduction in 79%. As for drug introduction criteria, 33.3% (16 children) were started on VGB due to therapeutic failure of phenobarbital and/or phenytoin; 27.1% (13 newborns), due to status epilepticus and, in 12 babies (25%), due to therapeutic failure of midazolam. By the end of the first year of life, EEG background activity was disorganized in 58.1% (18 out of 29 children who had EEG registered at 12 month of life). Along the one year follow-up of 38 patients, 20 infants (52.6%) showed some degree of neurodevelopmental delay; 19 children (39.5%) remained on VGB in polytherapy, with seizure persistence in 22 (57.9%). Evolution to an epileptic encephalopathy was found in 14 kids (37.8%), with West Syndrome being characterized in 13.9% (5 out of 36 kids). As for the EEG carried out in 34 children at the follow-up, 17.6% (6 cases) showed hypsarrhythmia while focal or multifocal abnormalities were seen in 50% (17 infants). Up to 12 month of life, the death rate was 23.3% (10 out of 43 children evaluated for such endpoint). Visual deficit directly related to VGB use could not be determined. The variable \"seizure control during the neonatal period after VGB use\" was associated to the following endpoints: improvement of the EEG pattern (92,1% of children with seizure control after VGB), lower proportion of children evolving into West syndrome and other epileptic encephalopathies (71.9% did not show such endpoint), lower frequency of hypsarrhythmia in the EEG (92.9% without hypsarrhythmia), better milestones reached regarding neuropsychomotor development (56.2% with good neurological outcome), lower rate of neonatal death (97.4% alive by the end of neonatal period) and along the first year of life (87.9%). Conclusion: VGB is an effective therapeutic option with adequate cost-benefit relationship which should be implemented for the control of refractory neonatal seizures as add-on therapy to conventional drugs. However, controlled randomized studies are necessary to confirm such efficacy as compared to other drugs available for use in the neonatal period, as well as to evaluate its possible long term side effects.

As convulsões febris complexas durante a infância representam um fator de risco relevante para o desenvolvimento da epilepsia. Apesar desse fato, as alterações moleculares induzidas por essas crises febris, que tornam o cérebro susceptível ao processo de epileptogênese, ainda são pouco conhecidas. Nesse contexto, a utilização de modelos animais de crises febris induzidas por hipertermia (HS) permite o estudo das alterações moleculares a partir de uma análise temporal desse processo. Assim, neste trabalho foram investigadas as alterações temporais nos perfis de microRNAs e de expressão gênica em explantes da região CA3 hipocampal de ratos Wistar obtidas em quatro intervalos de tempo após o insulto hipertérmico no décimo primeiro dia pós-natal (P11). Os intervalos temporais foram selecionados para avaliar as fases aguda (P12), latente (P30 e P60) e crônica (P120). A análise transcriptômica consistiu na construção de redes de co-expressão gênica, permitindo a identificação de módulos de genes e sua relação com os grupos experimentais e intervalos de tempo selecionados. Os genes também foram caracterizados hierarquicamente, identificando-se genes que conferem robustez às redes de co-expressão gênica (hubs). Além disso, foram avaliados o perfil de expressão diferencial de microRNAs e feita a análise integrada da expressão de microRNAs e expressão gênica dos hubs. Os resultados deste trabalho mostraram que: i) o insulto hipertérmico leva a alterações importantes no desenvolvimento e funcionamento cerebral ii) essas alterações estão associadas a uma assinatura temporal, presumivelmente da epileptogênese à readaptação do cérebro frente ao insulto precipitante inicial; iii) isso envolve um mecanismo de regulação das redes de co-expressão gênica por microRNAs. Esses resultados sugerem que as alterações transcricionais desencadeadas pelo insulto febril podem levar à reprogramação neuronal e ao remodelamento da cromatina, tornando o cérebro susceptível ao processo epiléptico crônico. Como nas epilepsias humanas por insulto febril, o modelo em rato reflete um processo que vai da epileptogênese à cronificação na fase adulta. Como muitos dos casos de epilepsia por insulto febril são refratários a drogas anticonvulsivantes, o entendimento temporal dos mecanismos moleculares envolvidos nesse tipo de epilepsia é relevante para se identificar alvos terapêuticos e desenvolver drogas anti-epileptogênicas / Complex febrile seizures during childhood represent a relevant risk factor for the development of epilepsy. Despite this fact, the molecular alterations induced by febrile seizures that make the brain susceptible to the process of epileptogenesis are still poorly understood. In this context, the animal models of febrile seizures induced by hyperthermia (HS) allow the study of the molecular alterations from a temporal perspective. Thus, we investigated the temporal alterations in the profiles of gene expression and microRNAs in explants of the hippocampal CA3 region of Wistar rats, here obtained at four-time intervals after the hyperthermal insult on the eleventh postnatal day (P11). Time intervals were selected to evaluate the acute (P12), latent (P30 and P60) and chronic (P120) phases. Transcriptomic analysis consisted of constructing gene co-expression networks, allowing the identification of gene modules related to selected time intervals. Genes were also characterized hierarchically identifying those that control the robustness of gene co-expression networks (hubs). In addition, the differential expression profile of microRNA and the integrated analysis of microRNA expression and hub\'s gene expression were evaluated. The results of this work showed that: i) hyperthermic insults lead to important changes in cerebral development and functioning related to febrile seizures; ii) each time interval shows a transcriptomic signature, probably reflecting the process from epileptogenesis to brain readaptation after the initial precipitating insult; iii) this process involves a mechanism of regulation of gene co-expression networks by microRNAs. These results suggest that transcriptional changes triggered by febrile insults may lead to neuronal reprogramming and chromatin remodeling, making the brain susceptible to the chronic epileptic process. Human epilepsy triggered by febrile insults in childhood is related to resistance to antiepileptic drugs and no anti-epileptogenic drug was developed so far. Therefore, a better understanding of the temporal mechanisms involved in the development of chronic epilepsy is mandatory in order to discover new therapeutic targets and, eventually, anti-epileptogenic drugs

As convulsões febris complexas durante a infância representam um fator de risco relevante para o desenvolvimento da epilepsia. Apesar desse fato, as alterações moleculares induzidas por essas crises febris, que tornam o cérebro susceptível ao processo de epileptogênese, ainda são pouco conhecidas. Nesse contexto, a utilização de modelos animais de crises febris induzidas por hipertermia (HS) permite o estudo das alterações moleculares a partir de uma análise temporal desse processo. Assim, neste trabalho foram investigadas as alterações temporais nos perfis de microRNAs e de expressão gênica em explantes da região CA3 hipocampal de ratos Wistar obtidas em quatro intervalos de tempo após o insulto hipertérmico no décimo primeiro dia pós-natal (P11). Os intervalos temporais foram selecionados para avaliar as fases aguda (P12), latente (P30 e P60) e crônica (P120). A análise transcriptômica consistiu na construção de redes de co-expressão gênica, permitindo a identificação de módulos de genes e sua relação com os grupos experimentais e intervalos de tempo selecionados. Os genes também foram caracterizados hierarquicamente, identificando-se genes que conferem robustez às redes de co-expressão gênica (hubs). Além disso, foram avaliados o perfil de expressão diferencial de microRNAs e feita a análise integrada da expressão de microRNAs e expressão gênica dos hubs. Os resultados deste trabalho mostraram que: i) o insulto hipertérmico leva a alterações importantes no desenvolvimento e funcionamento cerebral ii) essas alterações estão associadas a uma assinatura temporal, presumivelmente da epileptogênese à readaptação do cérebro frente ao insulto precipitante inicial; iii) isso envolve um mecanismo de regulação das redes de co-expressão gênica por microRNAs. Esses resultados sugerem que as alterações transcricionais desencadeadas pelo insulto febril podem levar à reprogramação neuronal e ao remodelamento da cromatina, tornando o cérebro susceptível ao processo epiléptico crônico. Como nas epilepsias humanas por insulto febril, o modelo em rato reflete um processo que vai da epileptogênese à cronificação na fase adulta. Como muitos dos casos de epilepsia por insulto febril são refratários a drogas anticonvulsivantes, o entendimento temporal dos mecanismos moleculares envolvidos nesse tipo de epilepsia é relevante para se identificar alvos terapêuticos e desenvolver drogas anti-epileptogênicas / Complex febrile seizures during childhood represent a relevant risk factor for the development of epilepsy. Despite this fact, the molecular alterations induced by febrile seizures that make the brain susceptible to the process of epileptogenesis are still poorly understood. In this context, the animal models of febrile seizures induced by hyperthermia (HS) allow the study of the molecular alterations from a temporal perspective. Thus, we investigated the temporal alterations in the profiles of gene expression and microRNAs in explants of the hippocampal CA3 region of Wistar rats, here obtained at four-time intervals after the hyperthermal insult on the eleventh postnatal day (P11). Time intervals were selected to evaluate the acute (P12), latent (P30 and P60) and chronic (P120) phases. Transcriptomic analysis consisted of constructing gene co-expression networks, allowing the identification of gene modules related to selected time intervals. Genes were also characterized hierarchically identifying those that control the robustness of gene co-expression networks (hubs). In addition, the differential expression profile of microRNA and the integrated analysis of microRNA expression and hub\'s gene expression were evaluated. The results of this work showed that: i) hyperthermic insults lead to important changes in cerebral development and functioning related to febrile seizures; ii) each time interval shows a transcriptomic signature, probably reflecting the process from epileptogenesis to brain readaptation after the initial precipitating insult; iii) this process involves a mechanism of regulation of gene co-expression networks by microRNAs. These results suggest that transcriptional changes triggered by febrile insults may lead to neuronal reprogramming and chromatin remodeling, making the brain susceptible to the chronic epileptic process. Human epilepsy triggered by febrile insults in childhood is related to resistance to antiepileptic drugs and no anti-epileptogenic drug was developed so far. Therefore, a better understanding of the temporal mechanisms involved in the development of chronic epilepsy is mandatory in order to discover new therapeutic targets and, eventually, anti-epileptogenic drugs