Value of brain 18F-FDG PET/CT in the preoperative localization of epileptogenic foci in refractory epilepsy patients with negative MRI / 中华核医学与分子影像杂志

Objective:To evaluate the value of 18F-FDG PET/CT for preoperative localization of epileptogenic foci in refractory epilepsy patients with negative MRI. Methods:Clinical data (550 lobes) of 55 epilepsy patients (38 males, 17 females, age (20.0±8.1) years) with negative MRI who underwent preoperative 18F-FDG PET/CT-MRI between January 2014 and June 2020 at the First Affiliated Hospital of Jinan University were retrospectively analyzed. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of 18F-FDG PET/CT, video electroencephalogram (VEEG), PET/CT+ VEEG and PET/CT-VEEG for localizing epileptogenic foci were calculated using stereoelectroencephalography (SEEG) and the outcomes of at least 1 year of postoperative follow-up as reference standards. χ2 test was used to compare the efficiencies of different examination modalities for unilobar, multilobar and all patients. Results:The correct lateralization rate of epileptogenic foci was 92.6%(25/27) using PET/CT. The sensitivity, specificity, accuracy, PPV and NPV of PET/CT for localization of epileptogenic foci were 65.1%(54/83), 77.9%(364/467), 76.0%(418/550), 34.4%(54/157) and 92.6%(364/393), respectively. The sensitivities of PET/CT-VEEG for localization of epileptogenic foci in all patients and patients with multilobar epilepsy were higher than those of VEEG alone (75.9%(63/83) vs 45.8%(38/83), 68.6%(35/51) vs 31.4%(16/51); χ2 values: 15.80, 14.16, both P<0.001). The specificities of PET/CT+ VEEG for localization of epileptogenic foci in all patients and patients with unilobar epilepsy were higher than those of VEEG alone (97.6%(456/467) vs 94.6%(442/467), 97.9%(282/288) vs 94.1%(271/288); χ2 values: 5.66, 5.48; P values: 0.017, 0.019). The sensitivity of PET/CT-VEEG (PET/CT and VEEG concordance) for localization of epileptogenic foci was higher than that of PET/CT+ VEEG (PET/CT and VEEG discordance) (8/9 vs 28.4%(21/74); χ2=10.40, P=0.001), and its specificity and accuracy were higher than those of PET/CT-VEEG (PET/CT and VEEG discordance) (93.4%(57/61) vs 71.7%(291/406), 92.9%(65/70) vs 72.1%(346/480); χ2 values: 13.23, 13.96; both P<0.001). Conclusions:18F-FDG PET/CT can localize and lateralize epileptogenic foci in patients with negative MRI. The combination of 18F-FDG PET/CT and VEEG improves the sensitivity, specificity, and accuracy for epileptogenic foci detection. 18F-FDG PET/CT is more accurate in detecting epileptogenic foci when it is concordant with VEEG.

Clinical value of 18F-FDG PET/MR in localizing epileptogenic foci in refractory epilepsy / 中华核医学与分子影像杂志

Objective:To analyze the clinical value of 18F-FDG PET/MR for precise localization of epileptogenic foci in patients with refractory epilepsy. Methods:From February 2019 to December 2021, 81 patients (52 males, 29 females; age (30.0±10.9) years) with refractory epilepsy confirmed in Ruijin Hospital Shanghai Jiao Tong University School of Medicine were retrospectively enrolled. All patients underwent preoperative PET/MR exam, and the possible position of the epileptogenic foci were determined by PET/MR imaging and pre-surgical evaluation, then the stereoelectroencephalography (SEEG) electrodes were implanted. Surgery was performed, and outcome was assessed by using a modified Engel classification two years after surgery. χ2 test was used to compare the detection rates of MRI and PET/MR fusion imaging in localizing epileptogenic foci and the detection rates of epileptogenic foci in temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE) by PET/MR. Results:MRI correctly localized seizure foci in 38 patients, with the detection rate of 46.91%(38/81), while PET/MR detected seizure foci in 73 patients, with the detection rate of 90.12%(73/81; χ2=35.05, P<0.001). There were 63 TLE and 18 ETLE patients. The detection rate of PET/MR in localizing seizure foci in TLE patients was 95.24%(60/63), which was significantly higher than that in ETLE patients (13/18; χ2=5.94, P=0.015). After 2 years follow-up, the postoperative efficacy rate of TLE patients with Engel grades Ⅰ-Ⅱ was 76.19%(48/63), which was 13/18 of ETLE patients ( χ2=0.12, P=0.731). Conclusion:Hybrid PET/MR imaging can accurately locate epileptogenic foci, especially for MRI negative lesions, which provides precision imaging information for surgical planning and improves surgical success rate.

New onset refractory status epilepticus/febrile infection-related epilepsy syndrome: the new challenge in the diagnosis and treatment of status epilepticus / 中华神经科杂志

New onset refractory status epilepticus (NORSE) and its subcategory, febrile infection-related epilepsy syndrome (FIRES) are rare and devastating conditions, initial symptoms of which are often refractory status epilepticus. NORSE/FIRES is characterized by high mortality and disability, but unfortunately, due to the unclear pathogenesis, the diagnosis and treatment of NORSE/FIRES are very challenging. This editorial aims to summarize the key points and recent developments in the etiology, pathophysiology, diagnosis and management of these challenging conditions.

Drug-resistant epileptic rat models of cognitive impairment established by different ways: a comparative study / 中华神经医学杂志

Objective:To investigate the behavioral, electroencephalographic, and cognitive functional differences in drug-resistant epileptic rat models of cognitive impairment prepared by intraperitoneal injection of lithium chloride-pilocarpine followed by intracranial injection of pilocarpine or carbamylcholine.Methods:One hundred and sixty adult male SD rats were randomly divided into normal control group ( n=10), lithium chloride-pilocarpine group (establishing epileptic rat models by intraperitoneal injection of lithium chloride-pilocarpine, n=50), pilocarpine-pilocarpine group (intracranial injection of pilocarpine after intraperitoneal injection of lithium chloride-pilocarpine, n=50)and pilocarpine-carbamylcholine group (intracranial injection of carbamylcholine after intraperitoneal injection of lithium chloride-pilocarpine, n=50). Frequency and duration of spontaneously recurrent seizures (SRSs) were observed by video monitoring system, and 2 weeks after that, phenobarbital and phenytoin sodium were injected intraperitoneally to screen drug-resistant models. Frequency and amplitude of the epileptic waves in EEG were recorded by BL-420 Bio-signal Acquisition and Processing System. Novel object recognition experiment was used to detect the novel exploration, Y-maze free exploration experiment and new and different arm experiment were used to detect the spatial recognition and memory ability, and Morris water maze experiment was used to detect the spatial memory ability. Results:(1) Twenty-four rats (48.00%) survived in the lithium chloride-pilocarpine group, 25 (78.00%) in the pilocarpine-pilocarpine group, and 21 (65.62%) in the pilocarpine-carbamylcholine group; and ultimately 7, 9, and 8 drug-resistant epileptic rat models were identified, respectively; frequency and duration of SRSs in the pilocarpine-pilocarpine group and pilocarpine-carbamylcholine group were significantly higher/longer than those in the lithium chloride-pilocarpine group ( P<0.05). (2) The pilocarpine-pilocarpine group and pilocarpine-carbamylcholine group had significantly higher amplitude of the epileptic waves in EEG compared with the lithium chloride-pilocarpine group ( P<0.05); the frequency of the epileptic waves in EEG increased gradually in the lithium chloride-pilocarpine group, pilocarpine-pilocarpine group, and pilocarpine-carbamylcholine group ( P<0.05). (3) Discrimination index, accuracy, ratio of distance traveled in novel arm to total distance, and time of novel arm entries gradually decreased in the normal control group, lithium chloride-pilocarpine group, pilocarpine-pilocarpine group, and pilocarpine-carbamylcholine group, with significant differences ( P<0.05). (4) Compared with the normal control group, the pilocarpine-pilocarpine group and pilocarpine-carbamylcholine group had significantly decreased frequency in crossing the original platform ( P<0.05); compared with the normal control group, lithium-pilocarpine chloride group and pilocarpine-pilocarpine group, the pilocarpine-carbamylcholine group had statistically shorter distance of target quadrant activity ( P<0.05); number of entries in the target quadrant gradually decreased in the normal control group, lithium chloride-pilocarpine group, pilocarpine-pilocarpine group, and pilocarpine-carbamylcholine group, with significant differences ( P<0.05). Conclusion:Drug-resistant epileptic rat models established by intracranial injection of carbamylcholine after intraperitoneal injection of lithium chloride-pilocarpine have high survival rate, high SRSs rate, and severe cognitive impairment, which is suitable for studying drug-resistant epilepsy combined with cognitive impairment.

Ketogenic diet in pharmacoresistant epilepsies: a clinical nutritional assessment / Dieta cetogênica na epilepsia fármaco-resistente: avaliação clínica-nutricional

Abstract Background Epilepsies are among the most prevalent chronic neurological diseases, usually beginning in childhood. About 30% of children with epilepsies develop seizures that are difficult to control with medication. Recurrent epileptic seizures hinder diet intake, impairing the nutritional status. Although non-pharmacological interventions (e.g., ketogenic diet therapy) can improve epileptic seizure frequency, few studies analyzed their impact on the nutritional status of children and adolescents with epilepsies. Objective The aim was to evaluate the effects of a ketogenic diet on the nutritional status and clinical course of patients with pharmacoresistant epilepsies. Methods This cross-sectional study included patients under 18 years of age followed up at the Ketogenic Diet Ambulatory Clinic of the Instituto de Medicina Integral Prof. Fernando Figueira between December 2015 and December 2021. Socioeconomic, clinical, nutritional, and laboratory data were collected from medical records at different time points during the ketogenic diet. Results The sample comprised 49 patients aged between 5 months and 17 years (median = 4.4 years), mostly male (62.1%), and from Recife and the metropolitan region (51%). Underweight patients (BMI-for-age) improved their nutritional status in six months. However, patients who were normal weight and overweight maintained their nutritional status. Dyslipidemia was a common and short-term adverse effect. Moreover, the treatment decreased epileptic seizure frequency and antiseizure medication intake. Conclusion The ketogenic diet prevented malnutrition from worsening and reduced epileptic seizures and antiseizure medication intake.

Resumo Antecedentes A epilepsia, uma das doenças neurológicas crônicas mais prevalentes, tem geralmente início na infância. Cerca de 30% das crianças com epilepsia desenvolvem crises de difícil controle medicamentoso. As crises epilépticas recorrentes dificultam a ingestão alimentar, prejudicando o estado nutricional. Intervenções não farmacológicas, como a terapia com dieta cetogênica, podem melhorar a frequência das crises epilépticas, mas existem poucos estudos sobre a repercussão no estado nutricional da criança/adolescente. Objetivo Avaliar o efeito da terapia cetogênica sobre o estado nutricional e a evolução clínica da epilepsia fármaco-resistente. Métodos Estudo tipo corte transversal envolvendo menores de 18 anos acompanhados no Ambulatório de Dieta Cetogênica do Instituto de Medicina Integral Prof. Fernando Figueira entre dezembro de 2015 e dezembro de 2021. Dados socioeconômicos, clínicos, nutricionais e laboratoriais foram coletados nos prontuários dos pacientes em vários momentos da terapia cetogênica. Resultados A amostra foi composta por 49 pacientes com idades entre cinco meses e 17 anos (mediana = 4,4 anos), a maioria do sexo masculino (62,1%) e procedentes de Recife e região metropolitana (51%). Pacientes com baixo peso (de acordo com o IMC para idade) melhoraram seu estado nutricional em seis meses. No entanto, os pacientes com peso adequado e com sobrepeso mantiveram seu estado nutricional. A dislipidemia foi um efeito adverso frequente e de curta duração. Além disso, o tratamento reduziu a frequência de crises epilépticas e a dose de fármacos anticrises. Conclusão A dieta cetogênica preveniu o agravamento da desnutrição e reduziu as crises epilépticas e a dosagem de fármacos anticrises.

Ketogenic therapy in childhood and adolescence: recommendations of the Brazilian experts group / Terapia cetogênica na infância e adolescência: recomendações do grupo de especialistas brasileiros

Abstract Ketogenic dietary therapies (KDTs) are a safe and effective treatment for pharmacoresistant epilepsy in children. There are four principal types of KDTs: the classic KD, the modified Atkins diet (MAD), the medium-chain triglyceride (MCT) diet, and the low glycemic index diet (LGID). The International Ketogenic Diet Study Group recommends managing KDTs in children with epilepsy. However, there are no guidelines that address the specific needs of the Brazilian population. Thus, the Brazilian Child Neurology Association elaborated on these recommendations with the goal of stimulating and expanding the use of the KD in Brazil.

Resumo As terapias dietéticas cetogênicas (TDC) são um tratamento seguro e eficaz para epilepsia farmacorresistente em crianças. Existem quatro tipos principais de TDCs: a dieta cetogênica (DC) clássica, a dieta de Atkins modificada (DAM), a dieta de triglicerídeos de cadeia média (DTCM) e a dieta de baixo índice glicêmico (DBIG). O Grupo Internacional de Estudos de Dietas Cetogênicas (International Ketogenic Diet Study Group) propõe recomendações para o manejo da DC em crianças com epilepsia. No entanto, faltam diretrizes que contemplem as necessidades específicas da população brasileira. Assim, a Associação Brasileira de Neurologia Infantil elaborou essas recomendações com o objetivo de estimular e expandir o uso da DC no Brasil.

Dieta cetogénica y su influencia en el tratamiento de la epilepsia refractaria infantil / Ketogenic diet and its influence on the treatment of refractory epilepsy in children / Dieta cetogênica e sua influência no tratamento da epilepsia refratária em crianças

La dieta cetogénica durante muchos años utilizada como una alternativa en el tratamiento para la epilepsia refractaria infantil, que consiste en un alto consumo de grasas, reducidas cantidades de carbohidratos y las cantidades necesarias de proteína que permitan al paciente por medio de la producción de cetonas un correcto y adecuado aporte energético al cerebro y todo el SNC. Objetivo. Describir el uso de la dieta cetogénica en el tratamiento de la epilepsia refractaria infantil para determinar su efectividad en la reducción de convulsiones y mejora en la calidad de vida de los pacientes. Metodología. Se ha realizado una revisión sistemática de la literatura científica para examinar la relación entre la dieta cetogénica y su efecto en el tratamiento de la epilepsia refractaria infantil. Para identificar y seleccionar las fuentes de información, se aplicó la declaración PRISMA y se llevó a cabo una búsqueda bibliográfica exhaustiva en diversas bases de datos electrónicas, incluyendo PubMed, SCOPUS y SCIELO. Se utilizaron términos descriptores específicos como "dieta cetogénica", "influencia", "tratamiento", "epilepsia refractaria" y "niños", así como conectores como AND, OR o NOT para mejorar la precisión de la búsqueda. Conclusión. La dieta cetogénica ha demostrado ser efectiva en el tratamiento de la epilepsia refractaria al reducir en un 50% el número de crisis convulsivas y mejorar la cognición de los pacientes, lo que la convierte en una opción viable para el manejo de esta afección. Sin embargo, es importante tener en cuenta que la dieta cetogénica también puede tener efectos secundarios.

The ketogenic diet has been used for many years as an alternative in the treatment of refractory epilepsy in children, which consists of a high consumption of fats, reduced amounts of carbohydrates and the necessary amounts of protein to allow the patient, through the production of ketones, a correct and adequate energy supply to the brain and the entire CNS. Objective. To describe the use of the ketogenic diet in the treatment of refractory epilepsy in children to determine its effectiveness in reducing seizures and improving the quality of life of patients. Methodology. A systematic review of the scientific literature was conducted to examine the relationship between the ketogenic diet and its effect in the treatment of refractory epilepsy in children. To identify and select sources of information, the PRISMA statement was applied and a comprehensive literature search was conducted in various electronic databases, including PubMed, SCOPUS and SCIELO. Specific descriptor terms such as "ketogenic diet", "influence", "treatment", "refractory epilepsy" and "children" were used, as well as connectors such as AND, OR or NOT to improve search precision. Conclusion. The ketogenic diet has been shown to be effective in the treatment of refractory epilepsy by reducing the number of seizures by 50% and improving patients' cognition, making it a viable option for the management of this condition. However, it is important to keep in mind that the ketogenic diet can also have side effects.

A dieta cetogênica tem sido usada há muitos anos como um tratamento alternativo para epilepsia refratária em crianças, consistindo em um alto consumo de gorduras, quantidades reduzidas de carboidratos e as quantidades necessárias de proteínas para permitir ao paciente, por meio da produção de cetonas, um fornecimento correto e adequado de energia para o cérebro e todo o SNC. Objetivo. Descrever o uso da dieta cetogênica no tratamento da epilepsia refratária em crianças, a fim de determinar sua eficácia na redução das crises e na melhoria da qualidade de vida dos pacientes. Metodologia. Foi realizada uma revisão sistemática da literatura científica para examinar a relação entre a dieta cetogênica e seu efeito no tratamento da epilepsia refratária em crianças. Para identificar e selecionar as fontes de informação, foi aplicada a declaração PRISMA e realizada uma pesquisa abrangente da literatura em vários bancos de dados eletrônicos, incluindo PubMed, SCOPUS e SCIELO. Foram usados termos descritores específicos, como "dieta cetogênica", "influência", "tratamento", "epilepsia refratária" e "crianças", além de conectores como AND, OR ou NOT para melhorar a precisão da pesquisa. Conclusão. A dieta cetogênica demonstrou ser eficaz no tratamento da epilepsia refratária, reduzindo o número de convulsões em 50% e melhorando a cognição dos pacientes, o que a torna uma opção viável para o tratamento dessa condição. Entretanto, é importante observar que a dieta cetogênica também pode ter efeitos colaterais.

Estimulación de nervio vago en epilepsia refractaria y callosotomía previa sin mejoría. Reporte de caso / Vagus nerve stimulation in refractory epilepsy and previous callosotomy without vimprovement. Case report / Estimulação do nervo vago em epilepsia refratária e calosotomia prévia sem melhora. Relato de caso

La epilepsia refractaria tanto generalizada como focal, es una patología sumamente incapacitante, para el tratamiento de la misma se ha establecido a la callosotomía desde hace décadas como primera línea quirúrgica para su control, la cual puede presentar efectos secundarios importantes como síndrome de desconexión y pérdida de memoria, sin embargo, existen pacientes que no responden a la callosotomía y necesitan nuevas líneas de tratamiento, buscando en la estimulación de nervio vago una respuesta a su condición. Descripción del caso de estudio. Se presenta el caso de paciente masculino de 24 años de edad con antecedente patológico de convulsiones tipo tónico clónicas generalizadas confirmadas por video electroencefalograma de 24 horas, de predominio nocturno de 13 años de evolución, es sometido a 2 regímenes farmacológicos antiepilépticos diferentes en un período de 7 años de duración, posteriormente diagnosticado con epilepsia refractaria, por lo que se realiza callosotomía sin control de su cuadro clínico, el mismo año se realiza estimulación de nervio vago, presentando resultados favorables en su evolución. Conclusión. Luego de evidenciar el presente caso de estudio se concluye que el tratamiento de epilepsia refractaria con la colocación de un estimulador de nervio vago izquierdo asociado a un correcto régimen FAE es una alternativa muy eficaz para considerar en estos pacientes.

Refractory epilepsy, both generalized and focal, is an extremely disabling pathology. For its treatment, callosotomy has been established for decades as the first surgical line for its control, which can present important side effects such as disconnection and loss syndrome. by heart, however, there are patients who do not respond to callosotomy and need new lines of treatment, looking for an answer to their condition in vagus nerve stimulation. Description of the case study. We present the case of a 24-year-old male patient with a pathological history of generalized tonic-clonic seizures confirmed by a 24-hour video electroencephalogram, predominantly nocturnal for 13 years, undergoing 2 different antiepileptic pharmacological mechanisms over a period of 7 years in duration, later diagnosed with refractory epilepsy, for which callosotomy was performed without control of its clinical picture, the same year vagus nerve stimulation was performed, presenting favorable results in its evolution. Conclution. After evidencing the present case study, it is concluded that the treatment of refractory epilepsy with the placement of a left vagus nerve stimulator associated with a correct AED regimen is a very effective alternative to consider in these patients.

A epilepsia refratária, tanto generalizada quanto focal, é uma patologia extremamente incapacitante. Para seu tratamento, a calosotomia se estabeleceu há décadas como a primeira linha cirúrgica para seu controle, que pode apresentar importantes efeitos colaterais como desconexão e síndrome de perda., há pacientes que não respondem à calosotomia e precisam de novas linhas de tratamento, buscando resposta para sua condição na estimulação do nervo vago. Descrição do estudo de caso. Apresentamos o caso de um doente do sexo masculino, 24 anos, com antecedentes patológicos de crises tónico-clónicas generalizadas confirmadas por videoeletroencefalograma de 24 horas, predominantemente nocturnas há 13 anos, submetido a 2 mecanismos farmacológicos antiepilépticos diferentes ao longo de 7 anos de duração, posteriormente diagnosticada com epilepsia refratária, para a qual foi realizada calosotomia sem controle de seu quadro clínico, no mesmo ano foi realizada estimulação do nervo vago, apresentando resultados favoráveis em sua evolução. Conclusão. Depois de evidenciar o presente estudo de caso, conclui-se que o tratamento da epilepsia refratária com a colocação de um estimulador de nervo vago esquerdo associado a um esquema correto de DEA é uma alternativa muito eficaz a ser considerada nesses pacientes.

Research progress of drug-withdrawal in patients after epilepsy surgery / 中国神经精神疾病杂志

Epilepsy surgery is an effective treatment of drug-resistant epilepsy.Once patients became seizure free for certain period after epilepsy surgery,whether anti-seizure medications(ASMs)could be withdrawn is the primary concern of clinicians and patients.However,there is no consensus about management of anti-seizure medications in patients after epilepsy surgery.Patients after epilepsy surgery can withdraw ASMs when they become seizure free for 1 to 2 years.The dose reduction is usually done at every 2 to 3 months.For patients receiving multiple ASMs,each one should be individually tapered completely prior to the subsequent medication and the primary medication is always withdrawn in the end.Longer epilepsy duration prior to surgery,older age at surgery,patients with focal cortical dysplasia,incomplete resection of the epileptogenic zone and presence of interictal epileptiform discharges in postoperative EEG may predict the risk of seizure relapse in patients who underwent ASM withdrawal after epilepsy surgery.Patients with seizure relapse on ASM withdrawal generally have benign outcome after reinstitution of medical treatment.

Heterogeneidad clínica y molecular en los trastornos asociados con CDKL5 / Clinical and molecular heterogeneity in CDLK5 disorders

Resumen Introducción: El síndrome por deficiencia de CDKL5 es originado por variantes patogénicas en el gen CDKL5, con un espectro clínico variable que va desde pacientes con características del trastorno del espectro autista hasta epilepsia de inicio temprano y refractaria al tratamiento. Inicialmente fue considerado como una forma atípica de síndrome de Rett. Casos clínicos: Presentamos tres pacientes no relacionadas, evaluadas por retraso global del desarrollo y epilepsia refractaria. Los tres casos eran hemicigotos a una variante patógena de CDKL5. En una paciente se realizó panel de 306 genes asociados con epilepsia; en las otras dos se realizó microarreglo genómico comparativo. Las características clínicas y los hallazgos en el electroencefalograma y la resonancia magnética cerebral se han descrito clásicamente en el espectro de manifestaciones de este síndrome. Conclusiones: El síndrome por deficiencia de CDKL5 representa un reto para los médicos, ya que en muchos casos las manifestaciones clínicas y los estudios electroencefalográficos y de neuroimagen pueden ser inespecíficos. Debe sospecharse este síndrome ante la presencia de retraso global del desarrollo, fenotipo conductual autista y epilepsia, asociado o no con dismorfias. Dada la similitud entre diversas encefalopatías epilépticas, se deben solicitar paneles multigénicos que incluyan la secuenciación y el análisis de duplicación/deleción en los que se contemple este gen y sus posibles diagnósticos diferenciales, aunque sin olvidar la utilidad de las técnicas genómicas en casos poco claros.

Abstract Background: CDKL5 deficiency syndrome is caused by pathogenic variants in the CDKL5 gene, with a variable clinical spectrum ranging from patients with characteristics of autism spectrum disorder to early-onset epilepsy refractory to treatment. Initially, until the gene was discovered, it was considered an atypical form of Rett syndrome. This study aimed to describe the clinical and molecular heterogeneity in CDLK5 disorders among three female patients with CDKL5 pathogenic variants. Case reports: We reported three unrelated Mexican female patients evaluated for global developmental delay and epilepsy. All three cases were hemizygotes to a CDKL5 pathogenic variant. In one patient, we performed a 306 gene panel associated with epilepsy. In the other two cases, a human genomic microarray was performed. We describe their clinical features electroencephalogram and brain magnetic resonance evaluations. Conclusions: CDKL5 deficiency syndrome represents a challenge for clinicians since the clinical manifestations, electroencephalographic and neuroimaging studies can be non-specific. This syndrome should be suspected in the presence of global developmental delay, autistic behavioral phenotype and epilepsy, associated or not with dysmorphia. Given the similarity between various epileptic encephalopathies, multigene panels including sequencing and duplication/deletion analysis should be requested in which this gene and its possible differential diagnoses are considered, without forgetting the usefulness of genomic techniques in unclear cases.

Cannabidiol for the treatment of refractory epilepsy in children: a critical review of the literature / Canabidiol para o tratamento de epilepsia refratária em crianças: uma revisão crítica da literatura

Abstract Objective: The aim of this current report was to present a critical review of the use of cannabidiol (CBD) in the treatment of refractory epilepsies in the pediatric population. Data source: Literature review was carried out in the Medline (PubMed), Cochrane, and Scientific Electronic Library Online (SciELO) databases with the descriptors "Cannabidiol" and "Epilepsy." The search was not limited by the date of publication, language, or study design. A total of 69 articles were included in the review. Data synthesis: The efficacy of CBD in treating epileptic seizures has been confirmed by randomized controlled trials for Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex. The incidence of side effects reported in subjects of the studies is high. However, most studies indicate a good safety profile and tolerance to the drug, with most of the adverse effects being mild to moderate and transient. Conclusions: There is no consensus on the release of CBD as a therapeutic tool by the drug regulatory agencies worldwide. However, the use of CBD is promising since it has presented satisfactory results in crisis control in well-designed studies. In addition, this drug has a good safety and tolerance profile. However, further studies with a long follow-up period are needed to confirm its usefulness and the long-term safety in pediatric patients.

RESUMO Objetivo: Apresentar uma revisão crítica do uso de canabidiol no tratamento de epilepsias refratárias na população pediátrica. Fontes de dados: Revisão da literatura realizada nas bases de dados Medical Literature Analysis and Retrieval System Online (Medline/PubMed), Cochrane e Scientific Electronic Library Online (SciELO), com os descritores "cannabidiol" e "epilepsy". A busca não foi limitada por data de publicação, idioma ou desenho do estudo. Sessenta e nove artigos foram incluídos na revisão. Síntese dos dados: A eficácia do canabidiol no tratamento de crises epilépticas foi confirmada por ensaios clínicos randomizados para síndrome de Lennox-Gastaut, síndrome de Dravet e complexo de esclerose tuberosa. A incidência de efeitos colaterais relatados nos indivíduos dos estudos é alta. No entanto, a maioria dos estudos indica um bom perfil de segurança e tolerância ao medicamento, com efeitos adversos leves a moderados e transitórios. Conclusões: Não há consenso sobre a liberação do canabidiol como ferramenta terapêutica nas diversas agências reguladoras de medicamentos em todo o mundo. Entretanto, seu uso é promissor, uma vez que apresentou resultados satisfatórios no controle de crises em estudos bem delineados. Além disso, esse medicamento apresenta um bom perfil de segurança e tolerância. No entanto, mais estudos com longo período de acompanhamento são necessários para confirmar sua utilidade e sua segurança em longo prazo em pacientes pediátricos.

O uso do canabidiol em crianças com epilepsia resistente a medicamento e a diminuição na frequência das crises: revisão rápida / The use of cannabidiol in children with drug-resistant epilepsy and the decrease in the frequency of seizures: quick review

Uso de canabidiol (CDB) medicinal presente no óleo de canabis. Indicação: Tratamento de crianças portadoras de epilepsia refratária resistente a medicação e síndromes graves decorrentes. Pergunta: O uso do canabidiol em crianças com epilepsia resistente a medicamentos apresentaria diminuição na frequência de crises convulsivas? Objetivo: Investigar a eficácia e a segurança do canabidiol, em comparação a placebo, na manutenção da remissão em crianças com epilepsia refratária. Métodos: Revisão rápida de revisões sistemáticas, por meio de buscas bibliográficas realizadas nas bases PUBMED, SCOPUS, BVS, Cochrane Library. Foram utilizadas estratégias de buscas com vocabulário padronizado e avaliação da qualidade metodológica usando o checklist AMSTAR 2. Resultados: Foram selecionadas duas revisões sistemáticas que atendiam aos critérios de elegibilidade. O CDB quando comparado ao placebo reduziu 50% das convulsões para epilepsia refrataria (RR 1.69 [1.20 ­ 2.36]), para a síndrome de Lennox-Gastaut o RR foi 2.98 (IC 95%, 1.83 - 4.85) e para a síndrome de Dravet o RR foi 2.26 (IC 95% ,1.38 - 3.70). O CDB pode resultar em uma diminuição no apetite em dosagens maiores (RR = 2,10, IC 95% [0,96­4,62], embora não apresente diferença de efeito dos grupos comparadores. Conclusão: Duas revisões sistemáticas recentes o CDB quando comparado ao placebo reduziu 50% das convulsões para epilepsia refrataria e síndromes graves. Entretanto, existem poucos ensaios clínicos publicados na área

: Use of cannabidiol (CBD) present in cannabis oil. Indication: Treatment of children with drug-resistant refractory epilepsy and severe syndromes resulting. Question: Would the use of cannabidiol in children with drug-resistant epilepsy lead to a decrease in seizure frequency? Objective: to investigate the efficacy and safety of cannabidiol, compared to placebos, in maintaining remission in children with refractory epilepsy. Methods: Rapid review of systematic reviews, through a bibliographical search carried out in the PUBMED, SCOPUS, BVS, Cochrane Library databases. Predefined search strategies were followed, and the methodological quality of the included studies was evaluated using the AMSTAR 2 tool. Results: Two systematic reviews were selected, which met the eligibility criteria. CBD when compared to placebo reduce 50% of seizures for refractory epilepsy (RR 1.69, IC 95% [1.20 ­ 2.36]), for Lennox-Gastaut Syndrome the RR was foi 2.98 (IC 95%, 1.83 - 4.85) and for Dravet Syndrome o RR FOI 2.26 (IC 95% ,1.38 - 3.70). CBD may result in appetite decrease using high doses (RR = 2.10, 95% IC [0.96­ 4.62], with no statistical difference. Conclusion: Two recent systematics, CBD, when compared to placebo, presented 50% of seizures for refractory epilepsy and severe syndromes. However, there are few clinical trials published in the area

Retos en el diagnóstico y tratamiento de la Encefalitis de Rasmussen de inicio tardío: Reporte de tres casos / Challenges in diagnosis and treatment of late-onset Rasmussen encephalitis: Report of three cases

RESUMEN La encefalitis de Rasmussen es una entidad clínica poco frecuente caracterizada por epilepsia focal farmacorresistente, creciente déficit neurológico y hemiatrofia cerebral progresiva. Los abordajes diagnóstico y terapéutico son complejos, más aún en pacientes con inicio tardío de la enfermedad (adolescencia y adultez), en los cuales el cuadro clínico podría ser atípico cuando comparado con su presentación en niños. Se reporta una serie de tres casos clínicos de encefalitis de Rasmussen de inicio tardío, confirmados con evaluaciones histopatológicas e inmunohistoquímicas y en los cuales se obtuvo mejoría clínica tras ser intervenidos quirúrgicamente. Se efectúa también una revisión de la literatura sobre la evolución clínica y alternativas terapéuticas para el manejo de este tipo de presentación.

SUMMARY Rasmussen's encephalitis is an unusual clinical entity characterized by drug-resistant focal epilepsy, neurological deficit and progressive cerebral hemiatrophy. The diagnostic and therapeutic approach is complex, even more so in patients with Rasmussen's encephalitis of late onset (in adolescence and adulthood) whose clinical picture could be atypical when compared with its occurrence in children. We report a series of three clinical cases of late-onset Rasmussen's encephalitis confirmed by histopathology and immunohistochemistry evaluations and in which clinical improvement was achieved after surgical interventions. Literature reviews on the clinical evolution and therapeutic alternatives for this type of presentation are included.

EFFICACY OF CANNABIDIOL IN DRUG RESISTANT EPILEPSY IN A PRIVATE THIRD-LEVEL HOSPITAL

Introduction: In 2016, the ?rst results of phase III clinical trials showed bene?cial effects of CBD in treatment-resistant seizure disorders, To evaluate the ef?cacy of cannabidiol in patients with Objective: drug resistant epilepsy in a private third-level hospital. Descriptive, retrospective, observational and cross-sectional Methods: study. Inclusion criteria were patients under treatment with cannabidiol and drug resistant epilepsy from January 2017 to March 2022. Study variables were age, gender, evolution of epilepsy (years), epileptic syndromes, numbers of antiseizure drugs, reduction of seizures (more tan 50%), cannabidiol dose (mg/kg/day), treatment time (months) and adverse effects. Information was captured in Excel and analyzed in SPSS. 31 patients. The epileptic syndromes found were Lennox Gastaut 32%, Results: West 12.9%, Dravet 3.2%, Doose 3.2% and no syndromic 48.3%. Reduction of seizures more than 50% was shown in 25 patients (80.6%). Seizure free in 5 patients (16%). Cannabidiol dose was: <1 mg/kg/day (9.6%), 1-5 mg/kg/day (77.4%), >5 mg/kg/day (12.9%). Association was found between a decrease in the number of seizures and a higher dose of cannabidiol with statistical signi?cance (p<0.05). Our study suggests that cannabidiol reduces seizures with few adverse effects in drug Conclusion: resistant epilepsy

Use of lacosamide in children: experience of a tertiary medical care center in Brazil / Utilização da lacosamida em crianças: experiência de um centro terciário no Brasil

Abstract Background Lacosamide (LCM) is a third-generation anti-seizure drug approved in Europe and the United States, either as a monotherapy or adjunctive therapy, to treat partial-onset seizures in adults, adolescents, and children. In Brazil, LCM is licensed for treatment only in patients older than 16 years of age. Objective To evaluate a cohort of children presenting with refractory epilepsy who received LCM as an add-on therapy and observe the response and tolerability to the LCM treatment. Methods A retrospective cohort study conducted in a tertiary health care facility, which included 26 children, aged up to 16 years, who presented with refractory epilepsy and received LCM as an add-on treatment. The follow-up visits were scheduled every 3 months until 9 months of treatment with LCM. Results After 3 months of LCM administration, in 73.1% of the children, there was a reduction of > 50% in the frequency of seizures, and this clinical improvement was maintained in most patients (73.9%) for the following 9 months. Mild (such as, somnolence and behavioral changes) or severe (seizure worsening) adverse effects were observed in two and three children respectively. Among responders to LCM, there was a higher prevalence of males, fewer concomitant anti-seizure drugs, and lower percentage of patients using sodium channel blockers. Conclusions Lacosamide should be considered as an early treatment option in pediatric patients with refractory epilepsy, mainly focal seizures.

Resumo Antecedentes Lacosamida (LCM) é um fármaco anticrise de terceira geração aprovado na Europa e nos Estados Unidos, utilizado como monoterapia ou terapia adjuvante para tratar crises epilépticas focais em adultos, adolescentes e crianças. No Brasil, a LCM só é aprovada para tratamento em pacientes com mais de 16 anos de idade. Objetivo Avaliar uma coorte de crianças com epilepsia refratária que receberam LCM como terapia adjuvante e observar a resposta e tolerabilidade ao tratamento. Métodos Um estudo de coorte retrospectivo conduzido em uma unidade terciária de saúde, que incluiu 26 crianças de até 16 anos de idade que apresentavam epilepsia refratária e receberam um tratamento complementar com LCM. As visitas de acompanhamento foram agendadas a cada 3 meses, até 9 meses de tratamento com LCM. Resultados Após 3 meses de administração de LCM, em 73,1% das crianças, a frequência das crises teve uma redução maior do que 50%, e essa melhora clínica foi mantida na maioria dos pacientes (73,9%) pelos 9 meses seguintes. Efeitos adversos leves (como, sonolência e alterações comportamentais) ou graves (agravamento das crises) foram observados em duas e três crianças, respectivamente. Entre as crianças que responderam ao tratamento com LCM, houve uma maior prevalência do sexo masculino, o uso de um menor número de medicações anticrise associadas e o uso de bloqueadores dos canais de sódio. Conclusões A LCM deve ser considerada uma opção de tratamento precoce em pacientes pediátricos com epilepsia refratária, principalmente aqueles que apresentam crises focais.

Treatment approach to a patient with catamenial epilepsy. case report

ABSTRACT Introduction: Catamenial epilepsy refers to the worsening or exacerbation of seizures due to hormonal changes during the menstrual cycle. It is thought to be secondary to the neuroactive properties of endogenous steroid hormones and the natural cyclic variation in their serum levels throughout the menstrual cycle. Case presentation: A 31-year-old female patient from Bogotá (Colombia) was admitted to the emergency department due to an episode of tonic-clonic seizure associated with the menstrual period. Since the onset of the seizures was related to menstruation (every 28 days), it was established that the patient had structural focal epilepsy with catamenial features. Advantages of medical vs. surgical treatment were discussed during a multidisciplinary medical board and it was decided to start pharmacological treatment with progestogens, which resulted in complete remission of the seizures as established during a follow-up visit. Conclusions: Catamenial epilepsy should be considered as a cause of epilepsy refractory to antiepileptic medications. Furthermore, it should be approached from a multidisciplinary perspective and its management should be focused on improving the patients' quality of life.

RESUMEN Introducción. La epilepsia catamenial se define como un empeoramiento o la exacerbación de las crisis epilépticas en relación con el cambio hormonal durante el ciclo menstrual femenino. Se cree que esta se produce por las propiedades neuroactivas de las hormonas esteroides endógenas y la variación cíclica natural en sus niveles séricos a lo largo de dicho ciclo. Presentación del caso. Mujer de 31 años de Bogotá (Colombia), quien fue llevada al servicio de urgencias por un episodio de crisis epiléptica con convulsiones tonicoclónicas asociado al período menstrual. Debido a que la aparición de las crisis epilépticas se asociaba con la menstruación (cada 28 días), se estableció que la paciente presentaba epilepsia focal estructural de características catameniales. En junta médica multidisciplinar se discutieron las ventajas del manejo médico y el manejo quirúrgico, y se decidió instaurar tratamiento farmacológico con progestágenos, el cual, tras seguimiento, evidenció supresión total de las crisis. Conclusiones. La epilepsia catamenial debe considerarse como una causa de epilepsia refractaria al tratamiento antiepiléptico. Además, su abordaje debe ser multidisciplinario y su tratamiento debe ir enfocado a mejorar la calidad de vida de los pacientes.

Advance in application and efficacy of ketogenic diet therapy in drug-resistant epilepsy caused by gene mutation / 国际儿科学杂志

Genetic factors are important causes of drug-resistant epilepsy.In most cases, epilepsy caused by gene mutation cannot be controlled by existing antiepileptic drugs.Ketogenic diet controls seizures through multi-target mechanism, which is widely used in the treatment of drug-resistant epilepsy caused by gene mutation.In this paper, the advance in application and efficacy of ketogenic diet therapy in 23 kinds of gene mutation related drug-resistant epilepsy is reviewed, which involves energy metabolism, ion channel, mTOR signaling pathway and some other rare diseases.

Observation of clinical effects of Perampanel on the add-on therapy in 2-12 year-old children with drug-resistant epilepsy / 中华实用儿科临床杂志

Objective:To observe the clinical effect of Perampanel on the add-on therapy in children with drug-resistant epilepsy.Methods:Clinical data of children with drug-resistant epilepsy treated with add-on therapy of Perampanel in the Department of Pediatrics, Fujian Medical University Union Hospital from January to June 2020 were retrospectively analyzed, aiming to assess the therapeutic efficacy of Perampanel on the add-on therapy of drug-resistant epilepsy.The self-control effective rate of Perampanel before and after treatment were counted.Results:A total of 20 cases of 2-12 year-old children with drug-resistant epilepsy were collected, including 14 males and 6 females.Their mean age, age of onset and course of disease were (5.82±2.39) years, (3.41±1.96) years and (2.40±1.48) years, respectively.Among them, 1 case had simple partial seizures, 7 cases had complex partial seizures, 1 case had generalized seizures and 5 cases had epilepsy syndromes, there were 6 cases with undetermined seizure attack.After 3-month add-on therapy of Perampanel, 4 cases of children with drug-resistant epilepsy were seizure-free, 8 cases had the reduced frequency of seizure for 50% or more, 2 cases had the reduced duration of seizure, 1 case had the reduced severity of seizure, while 4 cases did not respond to perampanel and 1 case was aggravated.Based on the criteria of reduced frequency of seizure for more than 50%, the therapeutic efficacy of add-on therapy of Perampanel achieved 60% in children with drug-resistant epilepsy.Conclusions:The third generation of anti-seizure medication Perampanel can effectively reduce the frequency of seizure, especially in the elder children and those with certain epilepsy syndromes.

Differential expression of microRNAs profile in the peripheral blood of children with drug-resistant epilepsy / 中华实用儿科临床杂志

Objective:To study the profile of microRNAs (miRNAs) in the peripheral blood of children with drug-resistant epilepsy, and to find diagnostic biomarkers for early identification of drug-resistant epilepsy in children.Methods:Retrospective study.Five peripheral blood samples were collected from children in drug-resistant epilepsy group (group R), drug-responsive epilepsy group (group F) composed of the children with epilepsy in pediatric neurology clinic of the First Affiliated Hospital of Zhengzhou University from January 2018 to June 2019 and healthy control group (group J) composed of healthy children who underwent physical examination in the children′s health care clinic at the same time for analyzing miRNA profiles by high-throughput sequencing.In addition, peripheral blood samples were collected from children in R′ group (5 cases), F′ group (7 cases) and J′ group (6 cases) similarly for validating expression levels of 11 candidate miRNAs by quantificational real-time polymerase chain reaction (qPCR). Receiver operating characteristic curves (ROC) were plotted to analyze the diagnostic potential of 7 targeted miRNAs in distinguishing children with drug-resistant epilepsy from drug-responsive epilepsy.Target genes of the 7 validated miRNAs were predicted using online databases, which were then analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO). Kruskal-Wallis rank sum test was used for comparison among the three groups.Results:High-throughput sequencing found that compared with group F, there were 68 differentially expressed miRNAs in group R, involving 22 up-regulated and 46 down-regulated miRNAs.qPCR results showed that, expression trends of 7 miRNAs (let-7f, miR-99a-5p, miR-99b-5p, and miR-125a-5p, miR-125b-5p, miR-142-5p, miR-100) were consistent with high-throughput sequencing results among the 11 selected miRNAs.ROC analysis found that when the cut-off values of miR-99a-5p, miR-99b-5p, miR-125a-5p, miR-125b-5p, miR-142-5p and miR-100 were greater than 0.56, 1.00, 3.17, 2.24, 2.09 and 0.59, respectively, their area under curve (AUC) (≥0.871), sensitivity (≥80.0%) and specificity (≥85.7%) were relatively high, which were expected to be diagnostic marker for drug-resistant epilepsy in children.Among them, the diagnostic potential of miR-125b-5p was the best.Bioinformatics analysis found that miR-125b-5p was enriched in the regulation of hypoxia inducible factor-1 signaling pathway, insulin signaling pathway, pluripotent stem cell signaling pathway, mitogen-activated protein kinase signaling pathway, sphingomyelin signaling pathway, neurotrophic protein signaling pathway and mammalian target of rapamycin signaling pathway.Conclusions:The miRNA profile in the whole blood of children with drug-resistant epilepsy is significantly different from that in children with drug-responsive epilepsy.miR-125b-5p is expected to be a potential biomarker of drug-resistant epilepsy in children.

Effects of comprehensive rehabilitation nursing based on guided education and training on rehabilitation treatment in school-age children with drug-resistant epilepsy undergoing epileptogenic focus resection / 中国实用护理杂志

Objective:To evaluate the effects of comprehensive rehabilitation nursing based on guided education and training on rehabilitation treatment in school-age children with drug-resistant epilepsy undergoing epileptogenic focus resection.Methods:Fifty movement disorders school-age children with drug-resistant epilepsy undergoing epileptogenic focus resection in Institute of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University from January 2017 to December 2019 were enrolled in this study. The child patients were divided into the control group and the observation group according to the order of admission, with 25 cases in each group, and the control group was from January 2017 to June 2018 while the observation group was from July 2018 to December 2019. In the control group, routine nursing after epileptogenic focus resection and functional exercise were conducted. The observation group was treated with comprehensive rehabilitation nursing based on guided education and training. On the third day after operation, the day of discharge respectively, the motor function and activity of daily living of the two groups were evaluated. The satisfaction of children′s parents on nursing was compared between the two groups.Results:The scores of motor function on the third day after operation and the day of discharge were (57.0 ± 6.8), (73.0 ± 5.4) points respectively in the observation group, and those in the control group were (55.0 ± 5.6), (65.6 ± 5.9) points. There were significant differences intra group comparison ( t=-9.26, -6.48, both P<0.05). The activity of daily living scores on the third day after operation and the day of discharge were (45.2 ± 5.9), (74.2 ± 8.3) points respectively in the observation group, and those in the control group were (44.0 ± 5.8), (60.2 ± 7.6) points. There were significant differences intra group comparison ( t=-14.33, -8.51, both P<0.05). There were significant differences between the scores of motor function and the ability of daily living scores on the day of discharge in the observation group and the control group ( t values were -4.65, -6.25, both P<0.05). The satisfaction of children′s parents on nursing in the observation group and the control group were 96.0% (24/25), 72.0% (18/25) respectively. There was significant difference between the two groups ( χ 2=8.78, P<0.05). Conclusions:Rehabilitation nursing based on guided education and training can improve motor function and ability of daily living in movement disorders school-age children with drug-resistant epilepsy undergoing epileptogenic focus resection, promote the functional recovery of children after surgery and increase the satisfaction of children′s parents on nursing.