Brazilian consensus recommendations on the diagnosis and treatment of autoimmune encephalitis in the adult and pediatric populations.

BACKGROUND: Autoimmune encephalitis (AIE) is a group of inflammatory diseases characterized by the presence of antibodies against neuronal and glial antigens, leading to subacute psychiatric symptoms, memory complaints, and movement disorders. The patients are predominantly young, and delays in treatment are associated with worse prognosis. OBJECTIVE: With the support of the Brazilian Academy of Neurology (Academia Brasileira de Neurologia, ABN) and the Brazilian Society of Child Neurology (Sociedade Brasileira de Neurologia Infantil, SBNI), a consensus on the diagnosis and treatment of AIE in Brazil was developed using the Delphi method. METHODS: A total of 25 panelists, including adult and child neurologists, participated in the study. RESULTS: The panelists agreed that patients fulfilling criteria for possible AIE should be screened for antineuronal antibodies in the serum and cerebrospinal fluid (CSF) using the tissue-based assay (TBA) and cell-based assay (CBA) techniques. Children should also be screened for anti-myelin oligodendrocyte glucoprotein antibodies (anti-MOG). Treatment should be started within the first 4 weeks of symptoms. The first-line option is methylprednisolone plus intravenous immunoglobulin (IVIG) or plasmapheresis, the second-line includes rituximab and/or cyclophosphamide, while third-line treatment options are bortezomib and tocilizumab. Most seizures in AIE are symptomatic, and antiseizure medications may be weaned after the acute stage. In anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, the panelists have agreed that oral immunosuppressant agents should not be used. Patients should be evaluated at the acute and postacute stages using functional and cognitive scales, such as the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Modified Rankin Scale (mRS), and the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). CONCLUSION: The present study provides tangible evidence for the effective management of AIE patients within the Brazilian healthcare system.

ANTECEDENTES: Encefalites autoimunes (EAIs) são um grupo de doenças inflamatórias caracterizadas pela presença de anticorpos contra antígenos neuronais e gliais, que ocasionam sintomas psiquiátricos subagudos, queixas de memória e distúrbios anormais do movimento. A maioria dos pacientes é jovem, e o atraso no tratamento está associado a pior prognóstico. OBJETIVO: Com o apoio da Academia Brasileira de Neurologia (ABN) e da Sociedade Brasileira de Neurologia Infantil (SBNI), desenvolvemos um consenso sobre o diagnóstico e o tratamento da EAIs no Brasil utilizando a metodologia Delphi. MéTODOS: Um total de 25 especialistas, incluindo neurologistas e neurologistas infantis, foram convidados a participar. RESULTADOS: Os especialistas concordaram que os pacientes com critérios de possíveis EAIs devem ser submetidos ao rastreio de anticorpos antineuronais no soro e no líquido cefalorraquidiano (LCR) por meio das técnicas de ensaio baseado em tecidos (tissue-based assay, TBA, em inglês) e ensaio baseado em células (cell-based assay, CBA, em inglês). As crianças também devem ser submetidas ao rastreio de de anticorpo contra a glicoproteína da mielina de oligodendrócitos (anti-myelin oligodendrocyte glycoprotein, anti-MOG, em inglês). O tratamento deve ser iniciado dentro das primeiras 4 semanas dos sintomas, sendo as opções de primeira linha metilprednisolona combinada com imunoglobulina intravenosa (IGIV) ou plasmaférese. O tratamento de segunda linha inclui rituximabe e ciclofosfamida. Bortezomib e tocilizumab são opções de tratamento de terceira linha. A maioria das crises epilépticas nas EAIs são sintomáticas, e os fármacos anticrise podem ser desmamadas após a fase aguda. Em relação à encefalite antirreceptor de N-metil-D-aspartato (anti-N-methyl-D-aspartate receptor, anti-NMDAR, em inglês), os especialistas concordaram que agentes imunossupressores orais não devem ser usados. Os pacientes devem ser avaliados na fase aguda e pós-aguda mediante escalas funcionais e cognitivas, como Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Modified Rankin Scale (mRS), e Clinical Assessment Scale in Autoimmune Encephalitis (CASE). CONCLUSãO: Esta pesquisa oferece evidências tangíveis do manejo efetivo de pacientes com EAIs no sistema de saúde Brasileiro.

Factor Analysis of the Brazilian Questionnaire on Adherence to Ketogenic Dietary Therapy: Keto-Check.

BACKGROUND: several strategies are used to assess adherence to ketogenic dietary therapies (KDTs), the most commonly used being ketonemia or ketonuria, despite their limitations. The purpose of this article is to carry out an exploratory and confirmatory factor analysis on the proposed Keto-check (adherence's KDT Brazilian questionnaire). METHODS: there was a methodological study of a quantitative nature, complementary to the analysis realized previously, with a complimentary sample. The factorial analysis was performed with Factor software for parallel exploratory analysis, replicability, and confirmatory factor analysis. Graphical representation was created according to the number of factors resulting from the analysis. RESULTS: 116 questionnaires were reached by complementary data collection (n = 69 actual data, complementing n = 47 previous data) through online forms. A polychoric correlation matrix suitability analysis resulted in a significant Bartlett statistic (p = 0.0001) and a Kaiser-Meyer-Olkin (KMO) test of 0.56. The parallel factorial analysis resulted in two factors, graphically represented as "efficacy" and "adherence". A confirmatory factor analysis, considered fair, indicated an RMSEA of 0.063, NNFI resulted in 0.872, CFI in 0.926, and GFI in 0.897. CONCLUSION: this study confirms the validity of Keto-check through a more detailed analysis. Adherence is the key to improving the effectiveness of KDTs; therefore, improving knowledge about it can lead to a better healthcare approach.

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.

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.

Validation of ketogenic diet adherence questionnaire: Keto-check.

BACKGROUND: The ketogenic diet is a therapeutic option to control drug-resistant epileptic seizures and has difficult compliance standards due to adverse effects, psychosocial factors, or dietary restriction. OBJECTIVE: To create and validate a ketogenic diet compliance questionnaire. METHODS: Methodological study, convergent care. The instrument was analyzed (construct validation) by five judges during two cycles of the Delphi technique. The judges assessed the relevance and clarity by using the Likert scale with three levels and made suggestions. The validation of the instrument was calculated using the agreement rate and content validity index (CVI). The application by two nutritionists made it possible to test reproducibility using the Kappa coefficient. When comparing the classification with a template developed by the health professionals who cared for the patients in question, the Pearson correlation and Fisher exact tests were used. For the reliability test, self-applied data were collected and evaluated using Cronbach Alpha coefficient. RESULTS: The questionnaire initially created with 11 multiple choice questions on a Likert scale was reduced to 10 questions with an agreement rate and the CVI classified as excellent after two rounds with judges. In the application of the tool, a kappa of 0.6087 was obtained, a Pearson that showed no significant difference between evaluators and a Cronbach α of 0.6483, with substantial consistency. CONCLUSIONS: This work resulted in the creation of an unprecedented and reliable questionnaire on adherence to the national ketogenic diet. Further studies should be performed to extrapolate the use of this questionnaire in different populations.

ANTECEDENTES: A dieta cetogênica é um tratamento para epilepsia refratária e tem difícil adesão devido aos efeitos adversos, fatores psicossociais ou à própria restrição alimentar. OBJETIVO: Criar e validar um questionário de adesão à dieta cetogênica. MéTODOS: Estudo metodológico, convergente assistencial. O instrumento foi analisado (validação de constructo) por cinco juízes durante dois ciclos da técnica Delphi. Os juízes avaliaram a pertinência e a clareza com respostas na escala Likert com três níveis, além de sugestões. A validação do instrumento foi calculada pela taxa de concordância e índice de validade de conteúdo (IVC). Posteriormente, houve aplicação por duas nutricionistas (reprodutibilidade), sendo analisada a concordância pelo coeficiente de Kappa. Ao comparar a classificação com um gabarito, elaborado pelos profissionais da saúde responsáveis pelos pacientes em questão, foram utilizados os coeficientes de correlação de Pearson e teste exato de Fisher. Para teste de fidedignidade, a coleta de dados auto-aplicados foi avaliada pelo coeficiente de Alpha de Cronbach. RESULTADOS: O questionário inicialmente criado com 11 questões de múltipla escolha em escala Likert foi reduzido para 10 questões com taxa de concordância e IVC excelentes após 2 rodadas com juízes. Na aplicação da ferramenta obteve-se coeficiente de Kappa de 0,6087, o coeficiente de Pearson não demostrou diferença significativa entre avaliadores, e o coeficiente α de Cronbach de 0,6483, com consistência substancial. CONCLUSõES: Este trabalho resultou na criação do inédito questionário nacional de adesão à dieta cetogênica, válido e fidedigno. Outros estudos devem ser realizados para extrapolar a utilização deste questionário em diferentes populações.

Micronutrient supplementation needs more attention in patients with refractory epilepsy under ketogenic diet treatment.

OBJECTIVES: This study evaluated the adequacy of micronutrient intake from the ketogenic diet (KD) with and without micronutrient supplementation according to age in Brazilian children and adolescents with refractory epilepsy undergoing KD treatment. METHODS: This study enrolled children and adolescents with refractory epilepsy who were up to 19 y of age. Nutrient intakes were monitored using 3 d food records before introducing micronutrient supplementation and 3 mo after starting KD treatment. The prevalence of micronutrient inadequacy was estimated by sex and age according to the estimated average requirement cutoff values. RESULTS: This study included 39 children and adolescents. The KD did not provide enough content of folate, calcium, and magnesium in all patients according to the dietary reference intake. Even after starting supplementation, calcium, phosphorus, and magnesium intake remained inadequate in the majority of patients. The supplementation effectively met the vitamin B12 recommendation in all age groups. CONCLUSIONS: KD treatment did not provide adequate levels of the monitored micronutrients. The supplementation improved but did not prevent the inadequacy of micronutrients such as calcium, magnesium, and phosphorus. The results highlight the importance of individual supplementation protocols and the need to monitor micronutrient intake according to age and sex.

Cannabinoids in Neurology - Position paper from Scientific Departments from Brazilian Academy of Neurology.

Cannabinoids comprehend endocannabinoids, phytocannabinoids, and synthetic cannabinoids, with actions both in the central and peripherical nervous systems. A considerable amount of publications have been made in recent years, although cannabis has been known for over a thousand years. Scientific Departments from the Brazilian Academy of Neurology described evidence for medical use in their areas. Literature is constantly changing, and possible new evidence can emerge in the next days or months. Prescription of these substances must be discussed with patients and their families, with knowledge about adverse events and their efficacy.

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.

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.

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.

Validation of ketogenic diet adherence questionnaire: Keto-check / Validação de questionário de adesão à dieta cetogênica: Keto-check

Abstract Background The ketogenic diet is a therapeutic option to control drug-resistant epileptic seizures and has difficult compliance standards due to adverse effects, psychosocial factors, or dietary restriction. Objective To create and validate a ketogenic diet compliance questionnaire. Methods Methodological study, convergent care. The instrument was analyzed (construct validation) by five judges during two cycles of the Delphi technique. The judges assessed the relevance and clarity by using the Likert scale with three levels and made suggestions. The validation of the instrument was calculated using the agreement rate and content validity index (CVI). The application by two nutritionists made it possible to test reproducibility using the Kappa coefficient. When comparing the classification with a template developed by the health professionals who cared for the patients in question, the Pearson correlation and Fisher exact tests were used. For the reliability test, self-applied data were collected and evaluated using Cronbach Alpha coefficient. Results The questionnaire initially created with 11 multiple choice questions on a Likert scale was reduced to 10 questions with an agreement rate and the CVI classified as excellent after two rounds with judges. In the application of the tool, a kappa of 0.6087 was obtained, a Pearson that showed no significant difference between evaluators and a Cronbach α of 0.6483, with substantial consistency. Conclusions This work resulted in the creation of an unprecedented and reliable questionnaire on adherence to the national ketogenic diet. Further studies should be performed to extrapolate the use of this questionnaire in different populations.

Resumo Antecedentes A dieta cetogênica é um tratamento para epilepsia refratária e tem difícil adesão devido aos efeitos adversos, fatores psicossociais ou à própria restrição alimentar. Objetivo Criar e validar um questionário de adesão à dieta cetogênica. Métodos Estudo metodológico, convergente assistencial. O instrumento foi analisado (validação de constructo) por cinco juízes durante dois ciclos da técnica Delphi. Os juízes avaliaram a pertinência e a clareza com respostas na escala Likert com três níveis, além de sugestões. A validação do instrumento foi calculada pela taxa de concordância e índice de validade de conteúdo (IVC). Posteriormente, houve aplicação por duas nutricionistas (reprodutibilidade), sendo analisada a concordância pelo coeficiente de Kappa. Ao comparar a classificação com um gabarito, elaborado pelos profissionais da saúde responsáveis pelos pacientes em questão, foram utilizados os coeficientes de correlação de Pearson e teste exato de Fisher. Para teste de fidedignidade, a coleta de dados auto-aplicados foi avaliada pelo coeficiente de Alpha de Cronbach. Resultados O questionário inicialmente criado com 11 questões de múltipla escolha em escala Likert foi reduzido para 10 questões com taxa de concordância e IVC excelentes após 2 rodadas com juízes. Na aplicação da ferramenta obteve-se coeficiente de Kappa de 0,6087, o coeficiente de Pearson não demostrou diferença significativa entre avaliadores, e o coeficiente α de Cronbach de 0,6483, com consistência substancial. Conclusões Este trabalho resultou na criação do inédito questionário nacional de adesão à dieta cetogênica, válido e fidedigno. Outros estudos devem ser realizados para extrapolar a utilização deste questionário em diferentes populações.

Ketogenic diet for epilepsy treatment.

The ketogenic diet (KD), a high-fat, low-carbohydrate, and adequate-protein diet is an established, effective nonpharmacologic treatment option for intractable childhood epilepsy. The KD was developed in 1921 and even though it has been increasingly used worldwide in the past decade, many neurologists are not familiar with this therapeutic approach. In the past few years, alternative and more flexible KD variants have been developed to make the treatment easier and more palatable while reducing side effects and making it available to larger group of refractory epilepsy patients. This review summarizes the history of the KD and the principles and efficacy of the classic ketogenic diet, medium-chain triglyceride(s) (MCT) ketogenic diet, modified Atkins diet, and low glycemic index treatment.

Projeto piloto de implantação de uma cozinha cetogênica para tratamento de epilepsia refratária / Pilot project of Implementation of a keto-kitchen for the treatment of refractory epilepsy / Proyecto piloto para implementar una cocina cetogénica para el tratamiento de la epilepsia refractaria

Objetivo: verificar alterações no consumo alimentar e hábitos de vida em pacientes com fibrose cística brasileiros durante o período de isolamento social devido a pandemia de COVID-19. Métodos: pesquisa transversal com levantamento de dados por meio de questionário elaborado pela equipe de nutricionistas especialistas no tratamento de pacientes com fibrose cística, com questões referentes às manifestações respiratórias recentes de pacientes ou familiares, alterações nos hábitos de aquisição e compras de alimentos e alterações quanto ao consumo de grupos alimentares e suplementos. Os dados foram tabulados e foi realizada uma análise descritiva. Resultados: 40,34% das famílias de pacientes com fibrose cística mudaram os hábitos de compras de alimentos, cerca de 40% dos pacientes diminuíram a prática de atividade física e aumentaram o tempo de uso de telas em mais de 50% durante o período da pandemia de COVID-19. Conclusões: Apesar de algumas dificuldades relacionadas à aquisição dos alimentos e alterações em hábitos de vida, houve manutenção do consumo alimentar da maioria dos grupos alimentares e suplementos pelos pacientes pediátricos com fibrose cística brasileiros durante o isolamento social devido a pandemia de COVID-19

Objective: This study describes the creation of the first ketogenic diet-teaching kitchen at a ketogenic reference center in Brazil aimed at developing ketogenic recipes and holding keto-culinary workshops with caregivers. Method: In this prospective study, 26 recipes were tested and assessed by sensory panel testing. Eighteen recipes were selected to be prepared in culinary workshops with parents or legal guardians of children with refractory epilepsy receiving the ketogenic diet as outpatients. All recipes were selected, calculated, and approved by registered dietitians. Results: Eight parents or legal guardians participated in four culinary workshops. The activities were extremely satisfactory: participants were able to clear out their doubts, learn, practice recipes, and develop new skills. In general, all participants enjoyed the prepared recipes and praised the culinary workshop. Conclusion: The ketogenic teaching kitchen enabled the development of ketogenic recipes adapted to Brazilian eating habits. Providing alternative meals to children is essential for enhancing compliance with the ketogenic diet because they contribute to expand the dietary repertoire of these patients. Future studies with high methodological quality should test the efficacy of the ketogenic kitchen in increasing compliance with the ketogenic diet in the long term.

Objetivo: Este estudio describe la creación de la primera cocina cetogénica para enseñar dieta cetogénica en un centro de referencia en Brasil, con el objetivo de desarrollar recetas cetogénicas y realizar talleres culinarios con los cuidadores. Método: En este estudio prospectivo, un panel sensorial probó y evaluó 26 recetas. Se seleccionaron dieciocho recetas para ser elaboradas en talleres de cocina con padres o tutores legales de niños con epilepsia refractaria que reciben una dieta cetogénica ambulatoria. Todas las recetas fueron seleccionadas, calculadas y aprobadas por nutricionistas. Resultados: Ocho padres o tutores participaron en cuatro talleres culinarios. Las actividades fueron sumamente satisfactorias: los participantes pudieron despejar sus dudas, aprender, practicar recetas y desarrollar nuevas habilidades. En general, a todos los participantes les gustaron las recetas elaboradas y elogiaron el taller de cocina. Conclusión: La cocina de enseñanza cetogénica permitió el desarrollo de recetas cetogénicas adaptadas a los hábitos alimentarios brasileños. Proporcionar comidas alternativas a los niños es fundamental para mejorar la adherencia a la dieta cetogénica, ya que contribuyen a ampliar el repertorio dietético de estos pacientes. Los estudios futuros con alta calidad metodológica deberían probar la efectividad de la cocina cetogénica para aumentar la adherencia a la dieta cetogénica a largo plazo.

Cannabinoids in Neurology - Position paper from Scientific Departments from Brazilian Academy of Neurology / Canabinoides em Neurologia - Artigo de posicionamento dos Departamentos Científicos da Academia Brasileira de Neurologia

ABSTRACT Cannabinoids comprehend endocannabinoids, phytocannabinoids, and synthetic cannabinoids, with actions both in the central and peripherical nervous systems. A considerable amount of publications have been made in recent years, although cannabis has been known for over a thousand years. Scientific Departments from the Brazilian Academy of Neurology described evidence for medical use in their areas. Literature is constantly changing, and possible new evidence can emerge in the next days or months. Prescription of these substances must be discussed with patients and their families, with knowledge about adverse events and their efficacy.

RESUMO Os canabinoides compreendem os endocanabinoides, fitocanabinoides e os canabinoides sintéticos e desempenham ações no sistema nervoso central e periférico. Uma quantidade enorme de publicações tem sido lançada nos últimos anos, embora a cannabis seja conhecida por milênios. Os Departamentos Científicos da Academia Brasileira de Neurologia descreveram as evidências do uso médico em suas áreas. A literatura está em constantes mudanças e possíveis novas evidências podem surgir nos próximos dias ou meses. A prescrição dessas substâncias deve ser discutida com os pacientes e suas famílias, com conhecimento sobre eventos adversos e sua eficácia.

Neurobiochemical mechanisms of a ketogenic diet in refractory epilepsy.

A ketogenic diet is an important therapy used in the control of drug-refractory seizures. Many studies have shown that children and adolescents following ketogenic diets exhibit an over 50% reduction in seizure frequency, which is considered to be clinically relevant. These benefits are based on a diet containing high fat (approximately 90% fat) for 24 months. This dietary model was proposed in the 1920s and has produced variable clinical responses. Previous studies have shown that the mechanisms underlying seizure control involve ketone bodies, which are produced by fatty acid oxidation. Although the pathways involved in the ketogenic diet are not entirely clear, the main effects of the production of ketone bodies appear to be neurotransmitter modulation and antioxidant effects on the brain. This review highlights the impacts of the ketogenic diet on the modulation of neurotransmitters, levels of biogenic monoamines and protective antioxidant mechanisms of neurons. In addition, future perspectives are proposed.

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.

Ketogenic diet for epilepsy treatment / Dieta cetogênica para o tratamento da epilepsia

ABSTRACT The ketogenic diet (KD), a high-fat, low-carbohydrate, and adequate-protein diet is an established, effective nonpharmacologic treatment option for intractable childhood epilepsy. The KD was developed in 1921 and even though it has been increasingly used worldwide in the past decade, many neurologists are not familiar with this therapeutic approach. In the past few years, alternative and more flexible KD variants have been developed to make the treatment easier and more palatable while reducing side effects and making it available to larger group of refractory epilepsy patients. This review summarizes the history of the KD and the principles and efficacy of the classic ketogenic diet, medium-chain triglyceride(s) (MCT) ketogenic diet, modified Atkins diet, and low glycemic index treatment.

RESUMO A dieta cetogênica, rica em gorduras, adequada em proteínas e pobre em carboidratos é uma opção de tratamento efetiva e bem estabelecida para epilepsia de difícil controle na infância. Foi desenvolvida em 1921 e nos últimos 20 anos tem sido utilizada em diferentes países e culturas, porém ainda é desconhecida entre muitos neurologistas e outras especialidades. Recentemente, no esforço de tornar a dieta mais palatável, de fácil administração e com menos efeitos adversos, dietas cetogênicas alternativas foram criadas, possibilitando a sua administração a um maior número de pacientes. Nesta revisão abordaremos a história, príncipios e eficácia da dieta cetogênica, da dieta com triglicérides de cadeia média, da dieta modificada de Atkins e da dieta com baixos índices glicêmicos.

Cefepime-induced encephalopathy in patient without renal failure.

This case report describes neurotoxicity in an older patient on cefepime 2 g twice a day. The 81-year-old male patient developed non-convulsive status epilepticus during cefepime treatment with 1 g twice a day. There was recovery 30 days after discontinuation of cefepime.

Neurobiochemical mechanisms of a ketogenic diet in refractory epilepsy

A ketogenic diet is an important therapy used in the control of drug-refractory seizures. Many studies have shown that children and adolescents following ketogenic diets exhibit an over 50% reduction in seizure frequency, which is considered to be clinically relevant. These benefits are based on a diet containing high fat (approximately 90% fat) for 24 months. This dietary model was proposed in the 1920s and has produced variable clinical responses. Previous studies have shown that the mechanisms underlying seizure control involve ketone bodies, which are produced by fatty acid oxidation. Although the pathways involved in the ketogenic diet are not entirely clear, the main effects of the production of ketone bodies appear to be neurotransmitter modulation and antioxidant effects on the brain. This review highlights the impacts of the ketogenic diet on the modulation of neurotransmitters, levels of biogenic monoamines and protective antioxidant mechanisms of neurons. In addition, future perspectives are proposed. .

Cefepime-induced encephalopathy in patient without renal failure / Encefalopatia induzida por cefepime em paciente sem insuficiência renal

This case report describes neurotoxicity in an older patient on cefepime 2 g twice a day. The 81-year-old male patient developed non-convulsive status epilepticus during cefepime treatment with 1 g twice a day. There was recovery 30 days after discontinuation of cefepime.

Este relato descreve neurotoxicidade em um paciente mais idoso em uso de cefepime na dose de 2 g duas vezes ao dia. O paciente de 81 anos desenvolveu estado epiléptico não-convulsivo durante o tratamento com 1 g de cefepime duas vezes ao dia. O paciente se recuperou depois de 30 dias, após a interrupção do cefepime.