Brazilian experts' consensus on the treatment of infantile epileptic spasm syndrome in infants.

BACKGROUND: Infantile epileptic spasms syndrome (IESS) is a rare but severe condition affecting children early and is usually secondary to an identifiable brain disorder. It is related to psychomotor deterioration in childhood and epilepsy in adult life. Treatment is challenging as infantile spasms may not respond to most antiseizure medication, and relapse is frequent. OBJECTIVE: To evaluate the literature regarding treatment of IESS and provide a practical guidance to a healthcare system with limited resources. METHODS: An expert committee from the Brazilian Society of Child Neurology reviewed and discussed relevant scientific evidence in the treatment of IESS regarding the drugs available in Brazil. RESULTS: Oral prednisolone and vigabatrin are the most common drugs used as first-line therapy; they are efficient and affordable therapy as both are available in the Brazilian unified health system (SUS, in the Portuguese acronym). Intramuscular adrenocorticotropic hormone (ACTH) presents similar efficacy as oral prednisolone but has a higher cost and is not available in Brazil. Other antiseizure medications such as topiramate, levetiracetam, or benzodiazepines have limited response and are prescribed as adjuvant therapy. If the health service has nutritionists, a ketogenic diet should be implemented for those not responding to hormonal and vigabatrin treatment. Epilepsy surgery is mainly indicated for patients with focal lesions that do not respond to pharmacological therapy. CONCLUSION: Early treatment of IESS with efficient drugs is feasible in our country. Using standard protocols increases the odds of achieving complete cessation in a shorter time and decreases relapse.

ANTECEDENTES: A síndrome do espasmo epiléptico infantil (IESS) é uma condição rara, mas grave, que afeta crianças precocemente e geralmente é secundária a um distúrbio cerebral identificável, estando relacionada a deterioração psicomotora na infância e a epilepsia na vida adulta. O tratamento é desafiador, pois os espasmos infantis podem não responder à maioria dos medicamentos anticrises e as recidivas são frequentes. OBJETIVO: Avaliar a literatura sobre o tratamento de IESS e fornecer uma orientação prática para um sistema de saúde com recursos limitados. MéTODOS: Um comitê de especialistas da Sociedade Brasileira de Neurologia Infantil revisou e discutiu evidências científicas relevantes no tratamento da IESS em relação aos medicamentos disponíveis no Brasil. RESULTADOS: Prednisolona oral e vigabatrina são os fármacos mais comumente usados como terapia de primeira linha; são eficientes e acessíveis, já que ambos estão disponíveis no sistema único de saúde brasileiro (SUS). O ACTH intramuscular apresenta eficácia semelhante à prednisolona oral, mas tem custo mais elevado e não está disponível no Brasil. Outros medicamentos anticonvulsivos, como topiramato, levetiracetam ou benzodiazepínicos, têm resposta limitada e são prescritos como terapia adjuvante. Se o serviço de saúde tiver nutricionista, deve-se implementar dieta cetogênica para aqueles que não respondem ao tratamento hormonal e vigabatrina. A cirurgia de epilepsia é indicada principalmente para pacientes com lesões focais que não respondem à terapia farmacológica. CONCLUSãO: O tratamento precoce da IESS com fármacos eficazes é factível em nosso meio. O uso de protocolos padronizados aumenta as chances de alcançar a cessação completa em um tempo menor e diminui a recaída.

Brazilian experts' consensus on the treatment of infantile epileptic spasm syndrome in infants / Consenso de especialistas brasileiros sobre o tratamento da síndrome dos espasmos infantis em lactentes

Abstract Background Infantile epileptic spasms syndrome (IESS) is a rare but severe condition affecting children early and is usually secondary to an identifiable brain disorder. It is related to psychomotor deterioration in childhood and epilepsy in adult life. Treatment is challenging as infantile spasms may not respond to most antiseizure medication, and relapse is frequent. Objective To evaluate the literature regarding treatment of IESS and provide a practical guidance to a healthcare system with limited resources. Methods An expert committee from the Brazilian Society of Child Neurology reviewed and discussed relevant scientific evidence in the treatment of IESS regarding the drugs available in Brazil. Results Oral prednisolone and vigabatrin are the most common drugs used as first-line therapy; they are efficient and affordable therapy as both are available in the Brazilian unified health system (SUS, in the Portuguese acronym). Intramuscular adrenocorticotropic hormone (ACTH) presents similar efficacy as oral prednisolone but has a higher cost and is not available in Brazil. Other antiseizure medications such as topiramate, levetiracetam, or benzodiazepines have limited response and are prescribed as adjuvant therapy. If the health service has nutritionists, a ketogenic diet should be implemented for those not responding to hormonal and vigabatrin treatment. Epilepsy surgery is mainly indicated for patients with focal lesions that do not respond to pharmacological therapy. Conclusion Early treatment of IESS with efficient drugs is feasible in our country. Using standard protocols increases the odds of achieving complete cessation in a shorter time and decreases relapse.

Resumo Antecedentes A síndrome do espasmo epiléptico infantil (IESS) é uma condição rara, mas grave, que afeta crianças precocemente e geralmente é secundária a um distúrbio cerebral identificável, estando relacionada a deterioração psicomotora na infância e a epilepsia na vida adulta. O tratamento é desafiador, pois os espasmos infantis podem não responder à maioria dos medicamentos anticrises e as recidivas são frequentes. Objetivo Avaliar a literatura sobre o tratamento de IESS e fornecer uma orientação prática para um sistema de saúde com recursos limitados. Métodos Um comitê de especialistas da Sociedade Brasileira de Neurologia Infantil revisou e discutiu evidências científicas relevantes no tratamento da IESS em relação aos medicamentos disponíveis no Brasil. Resultados Prednisolona oral e vigabatrina são os fármacos mais comumente usados como terapia de primeira linha; são eficientes e acessíveis, já que ambos estão disponíveis no sistema único de saúde brasileiro (SUS). O ACTH intramuscular apresenta eficácia semelhante à prednisolona oral, mas tem custo mais elevado e não está disponível no Brasil. Outros medicamentos anticonvulsivos, como topiramato, levetiracetam ou benzodiazepínicos, têm resposta limitada e são prescritos como terapia adjuvante. Se o serviço de saúde tiver nutricionista, deve-se implementar dieta cetogênica para aqueles que não respondem ao tratamento hormonal e vigabatrina. A cirurgia de epilepsia é indicada principalmente para pacientes com lesões focais que não respondem à terapia farmacológica. Conclusão O tratamento precoce da IESS com fármacos eficazes é factível em nosso meio. O uso de protocolos padronizados aumenta as chances de alcançar a cessação completa em um tempo menor e diminui a recaída.

Clinical management and diagnosis of CLN2 disease: consensus of the Brazilian experts group.

Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rare neurodegenerative genetic disease that affects children in early life. Its classic form is rapidly progressive, leading to death within the first 10 years. The urge for earlier diagnosis increases with the availability of enzyme replacement therapy. A panel of nine Brazilian child neurologists combined their expertise in CLN2 with evidence from the medical literature to establish a consensus to manage this disease in Brazil. They voted 92 questions including diagnosis, clinical manifestations, and treatment of the disease, considering the access to healthcare in this country. Clinicians should suspect CLN2 disease in any child, from 2 to 4 years old, with language delay and epilepsy. Even though the classic form is the most prevalent, atypical cases with different phenotypes can be found. Electroencephalogram, magnetic resonance imaging, molecular and biochemical testing are the main tools to investigate and confirm the diagnosis. However, we have limited access to molecular testing in Brazil, and rely on the support from the pharmaceutical industry. The management of CLN2 should involve a multidisciplinary team and focus on the quality of life of patients and on family support. Enzyme replacement therapy with Cerliponase α is an innovative treatment approved in Brazil since 2018; it delays functional decline and provides quality of life. Given the difficulties for the diagnosis and treatment of rare diseases in our public health system, the early diagnosis of CLN2 needs improvement as enzyme replacement therapy is available and modifies the prognosis of patients.

Lipofuscinose ceróide neuronal (CLN2) é uma doença genética neurodegenerativa rara que afeta crianças nos primeiros anos de vida. A sua forma clássica é rapidamente progressiva, levando à morte nos primeiros 10 anos. A necessidade de um diagnóstico precoce aumenta com a disponibilidade do tratamento de terapia enzimática. Um painel de nove neurologistas infantis brasileiros combinou sua experiência em CLN2 com evidências da literatura médica para estabelecer um consenso no manejo desta doença no Brasil. Eles votaram 92 questões abordando diagnóstico, manifestações clínicas e tratamento, considerando o acesso à saúde no Brasil. Deve-se suspeitar de CLN2 em qualquer criança de 2 a 4 anos de idade que apresente atraso de linguagem e epilepsia. Apesar da forma clássica ser a mais prevalente, podem ser encontrados casos atípicos com diferentes fenótipos. Eletroencefalograma, ressonância magnética, testes moleculares e bioquímicos são as principais ferramentas para investigar e confirmar o diagnóstico. No entanto, o acesso aos testes moleculares é limitado no Brasil, necessitando contar com o apoio da indústria farmacêutica. O manejo da CLN2 deve envolver uma equipe multidisciplinar e focar na qualidade de vida dos pacientes e no apoio familiar. A terapia de reposição enzimática com Cerliponase alfa é um tratamento inovador aprovado no Brasil desde 2018; ele retarda o declínio funcional e proporciona qualidade de vida. Diante das dificuldades para o diagnóstico e tratamento de doenças raras em nosso sistema público de saúde, o diagnóstico precoce de CLN2 precisa de melhorias pois a terapia de reposição enzimática está disponível e modifica o prognóstico dos pacientes.

Clinical management and diagnosis of CLN2 disease: consensus of the Brazilian experts group / Manejo clínico e diagnóstico da doença CLN2: consenso do grupo de especialistas brasileiros

Abstract Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rare neurodegenerative genetic disease that affects children in early life. Its classic form is rapidly progressive, leading to death within the first 10 years. The urge for earlier diagnosis increases with the availability of enzyme replacement therapy. A panel of nine Brazilian child neurologists combined their expertise in CLN2 with evidence from the medical literature to establish a consensus to manage this disease in Brazil. They voted 92 questions including diagnosis, clinical manifestations, and treatment of the disease, considering the access to healthcare in this country. Clinicians should suspect CLN2 disease in any child, from 2 to 4 years old, with language delay and epilepsy. Even though the classic form is the most prevalent, atypical cases with different phenotypes can be found. Electroencephalogram, magnetic resonance imaging, molecular and biochemical testing are the main tools to investigateand confirm the diagnosis. However, we have limited access to molecular testing in Brazil, and rely on the support from the pharmaceutical industry. The management of CLN2 should involve a multidisciplinary team and focus on the quality of life of patients and on family support. Enzyme replacement therapy with Cerliponase α is an innovative treatment approved in Brazil since 2018; it delays functional decline and provides quality of life. Given the difficulties for the diagnosis and treatment of rare diseases in our public health system, the early diagnosis of CLN2 needs improvement as enzyme replacement therapy is available and modifies the prognosis of patients.

Resumo Lipofuscinose ceróide neuronal (CLN2) é uma doença genética neurodegenerativa rara que afeta crianças nos primeiros anos de vida. A sua forma clássica é rapidamente progressiva, levando à morte nos primeiros 10 anos. A necessidade de um diagnóstico precoce aumenta com a disponibilidade do tratamento de terapia enzimática. Um painel de nove neurologistas infantis brasileiros combinou sua experiência em CLN2 com evidências da literatura médica para estabelecer um consenso no manejo desta doença no Brasil. Eles votaram 92 questões abordando diagnóstico, manifestações clínicas e tratamento, considerando o acesso à saúde no Brasil. Deve-se suspeitar de CLN2 em qualquer criança de 2 a 4 anos de idade que apresente atraso de linguagem e epilepsia. Apesar da forma clássica ser a mais prevalente, podem ser encontrados casos atípicos com diferentes fenótipos. Eletroencefalograma, ressonância magnética, testes moleculares e bioquímicos são as principais ferramentas para investigar e confirmar o diagnóstico. No entanto, o acesso aos testes moleculares é limitado no Brasil, necessitando contar com o apoio da indústria farmacêutica. O manejo da CLN2 deve envolver uma equipe multidisciplinar e focar na qualidade de vida dos pacientes e no apoio familiar. A terapia de reposição enzimática com Cerliponase alfa é um tratamento inovador aprovado no Brasil desde 2018; ele retarda o declínio funcional e proporciona qualidade de vida. Diante das dificuldades para o diagnóstico e tratamento de doenças raras em nosso sistema público de saúde, o diagnóstico precoce de CLN2 precisa de melhorias pois a terapia de reposição enzimática está disponível e modifica o prognóstico dos pacientes.

Clinical profile of tuberous sclerosis complex patients with and without epilepsy: a need for awareness for early diagnosis.

BACKGROUND: Tuberous sclerosis complex (TSC) is a multisystemic disorder. Its clinical features manifest differently in several organs, prompting the need for better knowledge. OBJECTIVE: The goal of the present study is to evaluate the neurological findings of TSC, such as cerebral lesions and epilepsy, and to raise awareness of non-neurological findings that could contribute to an earlier diagnosis and treatment. METHODS: This was a natural history study of patients with a definitive diagnosis of TSC who were referred to a specialized outpatient clinic and followed-up for 2 years with clinical and radiological exams. RESULTS: A total of 130 TSC patients (59 males [45.4%], mean age 20.4 years old [1 to 56 years old]); 107 patients (82.3%) were diagnosed with epilepsy. Seizures predominantly began at < 1 year old (72.8%); focal seizures predominated (86.9%); epileptic spasms occurred in 34.5% of patients, and refractory epilepsy was present in 55.1%. Neuropsychiatric disorders, cortical tubers and cerebellar tubers were significantly more frequent in the epilepsy group. Moreover, rhabdomyomas were significantly more frequent in the epilepsy group (p = 0.044), while lymphangioleiomyomatosis was significantly less frequent in the epilepsy group (p = 0.009). Other non-neurological findings did not differ significantly between the groups with and without epilepsy. CONCLUSIONS: The present study of TSC patients demonstrated the predominantly neurological involvement and significantly higher proportion of TSC-associated neuropsychiatric disorders in the epilepsy group. Higher proportions of cortical and cerebellar tubers may be a risk factor for epilepsy and neurodevelopmental disorders.

ANTECEDENTES: O Complexo da esclerose tuberosa (CET) é uma doença multissistêmica. As apresentações clínicas em diferentes órgãos são diversas, necessitando um maior conhecimento da doença. OBJETIVO: O objetivo do presente estudo foi avaliar na CET o envolvimento neurológico, como lesões cerebrais e epilepsia, e chamar a atenção para achados não neurológicos que contribuiriam para o diagnóstico e tratamento precoces. MéTODOS: Estudo de história natural do CET em pacientes com critérios diagnósticos definidos encaminhados aleatoriamente para serviço especializado e que foram acompanhados, durante 2 anos, com exames clínicos e radiológicos. RESULTADOS: O total de 130 pacientes (59 do sexo masculino [45.4%]), idade média de 20,4 anos [1 a 56 anos]) foram avaliados; 107 pacientes (82.3%) foram diagnosticados com epilepsia. As crises epilépticas se iniciaram especialmente em pacientes < 1 ano de idade (72,8%); predomínio de crise focal (86,9%); ocorrência de espasmos infantis em 34,5% deles e de epilepsia refratária em 55,1%. A frequência de distúrbios neuropsiquiátricos, túberes corticais e túberes cerebelares foi significativamente mais frequente no grupo com epilepsia. Além disso, rabdomioma foi significativamente mais frequente no grupo com epilepsia (p = 0,044), enquanto a linfoangioleiomiomatose foi significativamente menos frequente (p = 0,009). Outros comprometimentos não neurológicos, como os oftalmológicos e os nefrológicos, não diferiram significativamente nos grupos com e sem epilepsia. CONCLUSõES: O presente estudo com pacientes com CET com e sem epilepsia pode demonstrar uma maior proporção significativa de transtornos neuropsiquiátricos associados ao CET no grupo com epilepsia. A maior proporção de túberes corticais e cerebelares parecem ser um fator de risco para epilepsia e para o comprometimento do neurodesenvolvimento.

Clinical profile of tuberous sclerosis complex patients with and without epilepsy: a need for awareness for early diagnosis / Perfil clínico de pacientes com complexo de esclerose tuberosa com e sem epilepsia: uma necessidade de conscientização para o diagnóstico precoce

Abstract Background Tuberous sclerosis complex (TSC) is a multisystemic disorder. Its clinical features manifest differently in several organs, prompting the need for better knowledge. Objective The goal of the present study is to evaluate the neurological findings of TSC, such as cerebral lesions and epilepsy, and to raise awareness of non-neurological findings that could contribute to an earlier diagnosis and treatment. Methods This was a natural history study of patients with a definitive diagnosis of TSC who were referred to a specialized outpatient clinic and followed-up for 2 years with clinical and radiological exams. Results A total of 130 TSC patients (59 males [45.4%], mean age 20.4 years old [1 to 56 years old]); 107 patients (82.3%) were diagnosed with epilepsy. Seizures predominantly began at < 1 year old (72.8%); focal seizures predominated (86.9%); epileptic spasms occurred in 34.5% of patients, and refractory epilepsy was present in 55.1%. Neuropsychiatric disorders, cortical tubers and cerebellar tubers were significantly more frequent in the epilepsy group. Moreover, rhabdomyomas were significantly more frequent in the epilepsy group (p = 0.044), while lymphangioleiomyomatosis was significantly less frequent in the epilepsy group (p = 0.009). Other non-neurological findings did not differ significantly between the groups with and without epilepsy. Conclusions The present study of TSC patients demonstrated the predominantly neurological involvement and significantly higher proportion of TSC-associated neuropsychiatric disorders in the epilepsy group. Higher proportions of cortical and cerebellar tubers may be a risk factor for epilepsy and neurodevelopmental disorders.

Resumo Antecedentes O Complexo da esclerose tuberosa (CET) é uma doença multissistêmica. As apresentações clínicas em diferentes órgãos são diversas, necessitando um maior conhecimento da doença. Objetivo O objetivo do presente estudo foi avaliar na CET o envolvimento neurológico, como lesões cerebrais e epilepsia, e chamar a atenção para achados não neurológicos que contribuiriam para o diagnóstico e tratamento precoces. Métodos Estudo de história natural do CET em pacientes com critérios diagnósticos definidos encaminhados aleatoriamente para serviço especializado e que foram acompanhados, durante 2 anos, com exames clínicos e radiológicos. Resultados O total de 130 pacientes (59 do sexo masculino [45.4%]), idade média de 20,4 anos [1 a 56 anos]) foram avaliados; 107 pacientes (82.3%) foram diagnosticados com epilepsia. As crises epilépticas se iniciaram especialmente em pacientes < 1 ano de idade (72,8%); predomínio de crise focal (86,9%); ocorrência de espasmos infantis em 34,5% deles e de epilepsia refratária em 55,1%. A frequência de distúrbios neuropsiquiátricos, túberes corticais e túberes cerebelares foi significativamente mais frequente no grupo com epilepsia. Além disso, rabdomioma foi significativamente mais frequente no grupo com epilepsia (p = 0,044), enquanto a linfoangioleiomiomatose foi significativamente menos frequente (p = 0,009). Outros comprometimentos não neurológicos, como os oftalmológicos e os nefrológicos, não diferiram significativamente nos grupos com e sem epilepsia. Conclusões O presente estudo com pacientes com CET com e sem epilepsia pode demonstrar uma maior proporção significativa de transtornos neuropsiquiátricos associados ao CET no grupo com epilepsia. A maior proporção de túberes corticais e cerebelares parecem ser um fator de risco para epilepsia e para o comprometimento do neurodesenvolvimento.

Oral dyspraxia in self-limited epilepsy with centrotemporal spikes: a comparative study with a control group / Dispraxia oral em epilepsia autolimitada com espículas centrotemporais: um estudo comparativo com grupo controle

ABSTRACT Background: self-limited epilepsy with centrotemporal spikes, previously considered benign focal childhood epilepsy with centrotemporal spikes show clinical signs of involvement of Rolandic areas, mainly lower area, which may affect the planning and execution of motor sequences. Objective: This study aimed to evaluated oral praxis in children with self-limited epilepsy with centrotemporal spikes and compare to the age-matched control group. Methods: This was a descriptive study with 74 children with self-limited epilepsy with centrotemporal spikes, with the classical forms according to International League Against Epilepsy, and between 4 and 15 years of age, selected from the child neurology outpatient clinic of the Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil, and 239 age-matched and educational level-matched (convenience sampling) control children. All children were submitted to the battery of oral volitional movements, which consisted of 44 tests for oral movement (tongue, lip, cheek, jaw, and palate) and 34 phonemes and consonant cluster tasks, with simple and sequenced oral movements. Results: The mean age and standard deviation (SD) of children with epilepsy was 9.08 years (SD 2.55) and of controls 9.61 years (SD 3.12). The results showed significant differences between the groups with a poorer performance of children with epilepsy compared to children without epilepsy in simple and particularly in sequenced movements. Conclusion: These findings can be attributed to the genetically determined immaturity of cortical structures related to motor planning in children with self-limited epilepsy with centrotemporal spikes.

RESUMO Antecedentes: Epilepsia autolimitada com descarga centrotemporal, previamente designada por epilepsia benigna focal infantil com espículas centrotemporais, mostra sinais clínicos de envolvimento de áreas rolândicas, principalmente área inferior, que podem afetar o planejamento e a execução de sequências motoras. Objetivo: Este estudo visou avaliar a práxis oral em crianças com epilepsia autolimitada com espículas centrotemporais e comparar com o grupo de controle de mesma idade e grau de escolaridade. Métodos: Tratou-se de um estudo descritivo, com 74 crianças com epilepsia autolimitada com espículas centrotemporais selecionadas no ambulatório de neurologia infantil do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brasil, e 239 crianças do grupo controle da mesma faixa etária e grau de escolaridade. Todas as crianças foram submetidas à bateria de tarefas de movimento oral volitivo, que inclui movimentos orais simples e sequenciados. Resultados: A idade média das crianças com epilepsia era de 9,08 anos (desvio padrão - DP 2,55) e dos controles 9,61 anos (DP 3,12). Os resultados mostraram diferenças significativas entre os grupos, com desempenho mais fraco das crianças com epilepsia em comparação ao das crianças saudáveis, em movimentos simples e particularmente em movimentos sequenciados. Conclusão: Esses resultados podem ser atribuídos à imaturidade geneticamente determinada das estruturas corticais relacionadas com o planejamento motor em crianças com epilepsia autolimitada com espículas centrotemporais.

Oral dyspraxia in self-limited epilepsy with centrotemporal spikes: a comparative study with a control group.

BACKGROUND: self-limited epilepsy with centrotemporal spikes, previously considered benign focal childhood epilepsy with centrotemporal spikes show clinical signs of involvement of Rolandic areas, mainly lower area, which may affect the planning and execution of motor sequences. OBJECTIVE: This study aimed to evaluated oral praxis in children with self-limited epilepsy with centrotemporal spikes and compare to the age-matched control group. METHODS: This was a descriptive study with 74 children with self-limited epilepsy with centrotemporal spikes, with the classical forms according to International League Against Epilepsy, and between 4 and 15 years of age, selected from the child neurology outpatient clinic of the Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil, and 239 age-matched and educational level-matched (convenience sampling) control children. All children were submitted to the battery of oral volitional movements, which consisted of 44 tests for oral movement (tongue, lip, cheek, jaw, and palate) and 34 phonemes and consonant cluster tasks, with simple and sequenced oral movements. RESULTS: The mean age and standard deviation (SD) of children with epilepsy was 9.08 years (SD 2.55) and of controls 9.61 years (SD 3.12). The results showed significant differences between the groups with a poorer performance of children with epilepsy compared to children without epilepsy in simple and particularly in sequenced movements. CONCLUSION: These findings can be attributed to the genetically determined immaturity of cortical structures related to motor planning in children with self-limited epilepsy with centrotemporal spikes.

Efficacy and safety of levetiracetam as adjunctive therapy for refractory focal epilepsy.

BACKGROUND: Epilepsy affects about 50 million people worldwide and around 30% of these patients have refractory epilepsy, with potential consequences regarding quality of life, morbidity and premature mortality. OBJECTIVE: The aim of treatment with antiseizure medications (ASMs) is to allow patients to remain without seizures, with good tolerability. Levetiracetam is a broad-spectrum ASM with a unique mechanism of action that differs it from other ASMs. It has been shown to be effective and safe for treating adults and children with epilepsy. METHODS: This was a phase III, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of levetiracetam in children and adults (4-65 years) as an adjuvant treatment for focal-onset seizures. It was conducted among 114 patients undergoing treatment with up to three ASMs. The primary efficacy analysis was based on the proportion of patients who achieved a reduction of ≥ 50% in the mean number of focal seizures per week, over a 16-week treatment period. The patients were randomized to receive placebo or levetiracetam, titrated every two weeks from 20 mg/kg/day or 1,000 mg/day up to 60 mg/kg/day or 3,000 mg/day. RESULTS: Levetiracetam was significantly superior to placebo (p = 0.0031); 38.7% of the participants in the levetiracetam group and 14.3% in the control group shows reductions in focal seizures. Levetiracetam was seen to have a favorable safety profile and an adverse event rate similar to that of placebo. CONCLUSION: Corroborating the results in the literature, levetiracetam was shown to be effective and safe for children and adults with refractory focal-onset epilepsy.

Efficacy and safety of levetiracetam as adjunctive therapy for refractory focal epilepsy / Eficácia e segurança do levetiracetam como terapia adjunta na epilepsia focal refratária

ABSTRACT Background: Epilepsy affects about 50 million people worldwide and around 30% of these patients have refractory epilepsy, with potential consequences regarding quality of life, morbidity and premature mortality. Objective: The aim of treatment with antiseizure medications (ASMs) is to allow patients to remain without seizures, with good tolerability. Levetiracetam is a broad-spectrum ASM with a unique mechanism of action that differs it from other ASMs. It has been shown to be effective and safe for treating adults and children with epilepsy. Methods: This was a phase III, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of levetiracetam in children and adults (4-65 years) as an adjuvant treatment for focal-onset seizures. It was conducted among 114 patients undergoing treatment with up to three ASMs. The primary efficacy analysis was based on the proportion of patients who achieved a reduction of ≥ 50% in the mean number of focal seizures per week, over a 16-week treatment period. The patients were randomized to receive placebo or levetiracetam, titrated every two weeks from 20 mg/kg/day or 1,000 mg/day up to 60 mg/kg/day or 3,000 mg/day. Results: Levetiracetam was significantly superior to placebo (p = 0.0031); 38.7% of the participants in the levetiracetam group and 14.3% in the control group shows reductions in focal seizures. Levetiracetam was seen to have a favorable safety profile and an adverse event rate similar to that of placebo. Conclusion: Corroborating the results in the literature, levetiracetam was shown to be effective and safe for children and adults with refractory focal-onset epilepsy.

RESUMO Introdução: A epilepsia afeta cerca de 50 milhões de pessoas em todo o mundo e aproximadamente 30% desses pacientes apresentam epilepsia refratária, com possíveis consequências na qualidade de vida, morbidade e mortalidade prematura. Objetivo: O objetivo do tratamento com fármacos antiepilépticos (FAEs) é permitir que os pacientes permaneçam sem crises epilépticas com boa tolerabilidade. O levetiracetam (LEV) é um FAE de amplo espectro, com mecanismo de ação único, diferente dos demais e que demonstra ser eficaz e seguro no tratamento de adultos e crianças. Métodos: Estudo de fase III, multicêntrico, randomizado, duplo-cego e controlado por placebo avalia a eficácia e a segurança do LEV em crianças e adultos (4-65 anos) como tratamento adjuvante para crises de início focal em 114 pacientes já tratados com até três FAEs. A análise de eficácia primária foi baseada na proporção de pacientes que apresentaram redução ≥50% no número médio de crises epilépticas focais semanais, durante 16 semanas. Os pacientes foram randomizados para receber placebo ou LEV, titulado a cada duas semanas de 20 mg/kg/dia ou 1.000 mg/dia até 60 mg/kg/dia ou 3.000 mg/dia. Resultados: LEV foi significativamente superior ao placebo (p=0,0031), com 38,7% dos participantes no grupo LEV e 14,3% no grupo controle que apresentaram redução das crises focais. LEV apresenta bom perfil de segurança com eventos adversos semelhantes ao placebo. Conclusão: Corroborando com os resultados da literatura, o levetiracetam mostra-se eficaz e seguro para crianças e adultos com epilepsia focal refratária.

Cognitive impact in children with "benign" childhood focal epilepsy with centrotemporal spikes

Abstract Background Cognitive alterations are associated with benign childhood focal epilepsy with centrotemporal spikes (BCECTS) including aspects of executive functions. Objectives This study presents the performance profile on attention and executive function tests of fifty-eight children (BCECTS, n = 30 and controls, n = 28) aged 8-13 years. Methods The following tools were employed: Vocabulary and Block Design subtests from the Wechsler Intelligence Scale for Children III, Stroop Test, Modified Card Sorting Test, Controlled Oral Word Association - FAS and Tower of London. Results Children with BCECTS presented average IQ measure, although their performance was statistically worse when compared to the control group. Children with BCECTS showed significantly lower performance compared to the control group in the following variables: total number of recollected words on the oral fluency test, total number of categories, categorization effect and total number of errors in MCST; and execution time for the Stroop Test Card 1. After controlling for the IQ effect, the total number of errors in the MCST did not show any significant difference between the groups. Discussion Children with BCECTS showed lower performance in attention and executive functions when compared to healthy children. The results suggest that the concept of "benign" BCECTS should be reconsidered.

The use of a formula-based ketogenic diet in children with refractory epilepsy.

The ketogenic diet (KD) is a nonpharmacologic treatment that has been used for refractory epilepsy since 1921. The KD is a high-fat, low-carbohydrate, and restricted protein diet, which is calculated and weighed for each individual patient. Introducing and maintaining the diet for a long time remains a challenge. In this study, we evaluated the acceptability, tolerance, and efficacy of a formula-based KD in 10 children with refractory epilepsy. The ketogenic formula tested herein caused only mild KD-related adverse events and adequate adherence. Moreover, 60% of patients had more than 50% seizure frequency reduction and 10% were seizure-free.

The use of a formula-based ketogenic diet in children with refractory epilepsy / O uso da dieta cetogênica a base de fórmula em crianças com epilepsia refratária

ABSTRACT The ketogenic diet (KD) is a nonpharmacologic treatment that has been used for refractory epilepsy since 1921. The KD is a high-fat, low-carbohydrate, and restricted protein diet, which is calculated and weighed for each individual patient. Introducing and maintaining the diet for a long time remains a challenge. In this study, we evaluated the acceptability, tolerance, and efficacy of a formula-based KD in 10 children with refractory epilepsy. The ketogenic formula tested herein caused only mild KD-related adverse events and adequate adherence. Moreover, 60% of patients had more than 50% seizure frequency reduction and 10% were seizure-free.

RESUMO A dieta cetogênica (DC) é um tratamento não farmacológico utilizado para epilepsia refratária desde 1921. A DC possui um alto teor de gordura, sendo restrita em carboidratos e adequada em proteínas, calculada e pesada para cada paciente. A introdução e manutenção da DC por um tempo prolongado permanece um desafio. Neste estudo foi avaliada a aceitação, tolerância e eficácia da DC baseada em fórmula em 10 crianças com epilepsia refratária. A DC apresentou adequada aderência e efeitos adversos leves. Além disso, 60% dos pacientes apresentaram mais de 50 % de redução frequência das crises e 10% ficaram livres de crises.

Sequential motor task (Luria's Fist-Edge-Palm Test) in children with benign focal epilepsy of childhood with centrotemporal spikes.

This study evaluated the sequential motor manual actions in children with benign focal epilepsy of childhood with centrotemporal spikes (BECTS) and compares the results with matched control group, through the application of Luria's fist-edge-palm test. The children with BECTS underwent interictal single photon emission computed tomography (SPECT) and School Performance Test (SPT). Significant difference occurred between the study and control groups for manual motor action through three equal and three different movements. Children with lower school performance had higher error rate in the imitation of hand gestures. Another factor significantly associated with the failure was the abnormality in SPECT. Children with BECTS showed abnormalities in the test that evaluated manual motor programming/planning. This study may suggest that the functional changes related to epileptiform activity in rolandic region interfere with the executive function in children with BECTS.

Sequential motor task (Luria's Fist-Edge-Palm Test) in children with benign focal epilepsy of childhood with centrotemporal spikes / Tarefa motora sequencial (Teste de Lúria punho-lado-palma) em crianças com epilepsia focal benigna da infância com descarga centrotemporal

This study evaluated the sequential motor manual actions in children with benign focal epilepsy of childhood with centrotemporal spikes (BECTS) and compares the results with matched control group, through the application of Luria's fist-edge-palm test. The children with BECTS underwent interictal single photon emission computed tomography (SPECT) and School Performance Test (SPT). Significant difference occurred between the study and control groups for manual motor action through three equal and three different movements. Children with lower school performance had higher error rate in the imitation of hand gestures. Another factor significantly associated with the failure was the abnormality in SPECT. Children with BECTS showed abnormalities in the test that evaluated manual motor programming/planning. This study may suggest that the functional changes related to epileptiform activity in rolandic region interfere with the executive function in children with BECTS.

Esse estudo avaliou ações motoras manuais sequenciais em crianças com epilepsia focal benigna da infância com descarga centrotemporal (EBICT) e comparou os resultados com o grupo controle pareado, através do teste de Lúria (punho-lado-palma). As crianças com EBICT realizaram single photon emission computed tomography (SPECT) interictal e Teste de Desempenho Escolar (TDE). Foram encontradas diferenças significativas entre os dois grupos nas atividades motoras de três movimentos iguais e três movimentos diferentes. As crianças com piores resultados no TDE e com SPECT alterado apresentaram mais erros no teste de imitação manual. Crianças com epilepsia fracassaram nos testes de avaliação motora que envolvem programação/planejamento. Esse estudo sugere que mudanças funcionais relacionadas à atividade epileptiforme na região rolândica interfere com as funções executivas de crianças com EBICT.

Electrophysiological and auditory behavioral evaluation of individuals with left temporal lobe epilepsy.

The purpose of this study was to determine the repercussions of left temporal lobe epilepsy (TLE) for subjects with left mesial temporal sclerosis (LMTS) in relation to the behavioral test-Dichotic Digits Test (DDT), event-related potential (P300), and to compare the two temporal lobes in terms of P300 latency and amplitude. We studied 12 subjects with LMTS and 12 control subjects without LMTS. Relationships between P300 latency and P300 amplitude at sites C3A1,C3A2,C4A1, and C4A2, together with DDT results, were studied in inter-and intra-group analyses. On the DDT, subjects with LMTS performed poorly in comparison to controls. This difference was statistically significant for both ears. The P300 was absent in 6 individuals with LMTS. Regarding P300 latency and amplitude, as a group, LMTS subjects presented trend toward greater P300 latency and lower P300 amplitude at all positions in relation to controls, difference being statistically significant for C3A1 and C4A2. However, it was not possible to determine laterality effect of P300 between affected and unaffected hemispheres.

Electrophysiological and auditory behavioral evaluation of individuals with left temporal lobe epilepsy / Avaliação eletrofisiológica e comportamental da audição em individuos com epilepsia em lobo temporal esquerdo

The purpose of this study was to determine the repercussions of left temporal lobe epilepsy (TLE) for subjects with left mesial temporal sclerosis (LMTS) in relation to the behavioral test-Dichotic Digits Test (DDT), event-related potential (P300), and to compare the two temporal lobes in terms of P300 latency and amplitude. We studied 12 subjects with LMTS and 12 control subjects without LMTS. Relationships between P300 latency and P300 amplitude at sites C3A1,C3A2,C4A1, and C4A2, together with DDT results, were studied in inter-and intra-group analyses. On the DDT, subjects with LMTS performed poorly in comparison to controls. This difference was statistically significant for both ears. The P300 was absent in 6 individuals with LMTS. Regarding P300 latency and amplitude, as a group, LMTS subjects presented trend toward greater P300 latency and lower P300 amplitude at all positions in relation to controls, difference being statistically significant for C3A1 and C4A2. However, it was not possible to determine laterality effect of P300 between affected and unaffected hemispheres.

O objetivo deste estudo foi determinar a repercussão da epilepsia de lobo temporal esquerdo (LTE) em indivíduos com esclerose mesial temporal esquerda (EMTE) em relação à avaliação auditiva comportamental-Teste Dicótico de Dígitos (TDD), ao Potencial Evocado Auditivo de Longa Latência (P300) e comparar o P300 do lobo temporal esquerdo e direito. Estudamos 12 indivíduos com EMTE (grupo estudo) e 12 indivíduos controle com desenvolvimento típico. Analisamos as relações entre a latência e amplitude do P300, obtidos nas posições C3A1,C3A2,C4A1 e C4A2 e os resultados obtidos no TDD. No TDD, o grupo estudo apresentou pior desempenho em relação ao grupo controle, sendo esta diferença estatisticamente significante em ambas as orelhas. Para o P300, observamos que em seis indivíduos com EMTE o potencial foi ausente. Para a latência e amplitude, verificamos que estes indivíduos apresentaram uma tendência ao aumento da latência e redução da amplitude para todas as posições em relação ao grupo controle, sendo estatisticamente significante em C3A1 e C4A2. Contudo, não foi possível determinar efeito de lateralidade do P300 entre o hemisfério afetado e não-afetado.

Mesial temporal sclerosis in children.

UNLABELLED: Mesial temporal sclerosis is the most frequent cause of drug-resistant temporal lobe epilepsy but has a satisfactory response to surgery, and is considered infrequent in children. OBJECTIVE: To evaluate the clinical, electrographic and radiological spectrum of the disease in children. METHOD: Retrospective study by review of charts of 44 children with a diagnosis of mesial temporal sclerosis on magnetic resonance imaging, attended at the "Hospital das Clínicas" of the University of São Paulo Faculty of Medicine. RESULTS: Febrile seizure was identified in the history of 54% of the patients. Injuries at the left side predominated in patients with schooling difficulties (p=0.049), in those with first seizures between six months and five years (p=0.021) and in those with complex febrile seizure (p=0.032). Thirteen patients were submitted to surgery and of these, eight remained without seizures. CONCLUSION: Febrile seizure may be related in a more direct way to the presence of left-side mesial temporal sclerosis.

Mesial temporal sclerosis in children

Mesial temporal sclerosis is the most frequent cause of drug-resistant temporal lobe epilepsy but has a satisfactory response to surgery, and is considered infrequent in children. OBJECTIVE: To evaluate the clinical, electrographic and radiological spectrum of the disease in children. METHOD: Retrospective study by review of charts of 44 children with a diagnosis of mesial temporal sclerosis on magnetic resonance imaging, attended at the "Hospital das Clínicas" of the University of São Paulo Faculty of Medicine. RESULTS: Febrile seizure was identified in the history of 54 percent of the patients. Injuries at the left side predominated in patients with schooling difficulties (p=0.049), in those with the first seizures between six months and five years (p=0.021) and in those with complex febrile seizure (p=0.032). Thirteen patients were submitted to surgery and of these, eight remained without seizures. CONCLUSION: Febrile seizure may be related in a more direct way to the presence of left-side mesial temporal sclerosis.

Em adultos, esclerose mesial temporal é a causa mais freqüente de epilepsia do lobo temporal intratável por medicamentos e que responde satisfatoriamente a cirurgia, sendo considerada pouco freqüente em criança. OBJETIVO: Avaliar o espectro clínico, eletrográfico e radiológico desta patologia em crianças. MÉTODO: Estudo retrospectivo, por revisão de prontuário de 44 crianças com diagnóstico de esclerose mesial temporal na ressonância magnética, atendidos no Hospital das Clínicas da Faculdade de Medicina de São Paulo. RESULTADO: Foi identificado que 54 por cento dos pacientes apresentaram antecedente de crise febril. Lesão no lado esquerdo predominou nos pacientes com dificuldade escolar (p=0.049), naqueles com primeiras crises entre seis meses e cinco anos (p=0,021) e naqueles com crise febril complicada (p=0,032). Treze pacientes foram operados, dos quais oito ficaram livres de crises. CONCLUSÃO: Crise febril pode estar relacionada de uma forma mais direta à presença de esclerose mesial temporal no lado esquerdo.

Clinic feature of the mesial temporal sclerosis in children: [review]

INTRODUCTION: Mesial temporal sclerosis is not a frequent cause of refractory epilepsy in children, and the its start age is uncertain. OBJECTIVE: To understand the clinic feature of children with mesial temporal sclerosis diagnosis. MATERIAL AND METHODS: It was done a literature review about this pathology in children, and it has been found a group of 4 articles that allow a general view about mesial temporal sclerosis in children and other group of 7 articles (case reports or small series) in which mesial temporal sclerosis was diagnosed until five years old. RESULTS: It was evaluated in the first group, febrile seizure that was the most frequent antecedent followed by a status epilepticus and the semiology of the seizures was characterized by oroalimentary automatism, gestural automatism, stunted movement and motor phenomenon.The group of children with mesial temporal sclerosis until five years old stood out due to the high incidence of status epilepticus (84,6 percent), by the number of children with altered neuropsycomotor development (46 percent), and by lesion in most of bilateral cases (53,8 percent) , suggesting that the bilateral form of the mesial temporal sclerosis might be a distinct pathology, and not necessarily the progression of a unilateral beginning picture. Another important thing to stand out in this group is the documentation by MR in edema in hippocampus after a status epilepticus and posterior atrophy of this structure. CONCLUSION: mesial temporal sclerosis can to appear still in early life and in any cases can to present an evolutional character and dependent from a previous aggression to the hippocampus.

INTRODUÇÃO: Esclerose mesial temporal não é uma causa freqüente de epilepsia de difícil controle em crianças, e a idade de seu aparecimento é incerta. OBJETIVO: Conhecer as características clínicas de crianças com diagnóstico de esclerose mesial temporal. MATERIAL E MÉTODO: Foi realizada uma revisão de literatura sobre esta patologia em crianças, sendo encontrado um grupo de quatro artigos que permitem uma visão geral sobre esclerose mesial temporal em crianças e outro grupo de sete artigos (relatos de caso ou series pequenas) onde esclerose mesial temporal foi diagnosticada até os cinco anos de idade. RESULTADOS: No primeiro grupo avaliado, crise febril foi o antecedente mais freqüente, seguido por estado de mal epiléptico, e a semiologia das crises foi caracterizada por automatismo oroalimentar, automatismo gestual, parada da movimentação e fenômeno motor. O grupo de crianças com esclerose mesial temporal diagnosticada até os cinco anos se destacou pela alta incidência de estado de mal epiléptico (84,6 por cento), pelo número de crianças com desenvolvimento neuropsicomotor alterado (46 por cento), e por lesão na maioria dos casos bilateral (53,8 por cento), sugerindo que a forma bilateral da esclerose mesial temporal possa ser uma patologia distinta, e não necessariamente a progressão de um quadro inicialmente unilateral. Outro ponto de destaque neste grupo é a documentação por ressonância magnética de edema em hipocampo após estado de mal epiléptico e posterior atrofia desta estrutura. CONCLUSÃO: Esclerose mesial temporal pode aparecer ainda na primeira infância e em alguns casos pode apresentar um caráter evolutivo e dependente de uma agressão prévia ao hipocampo.