Ketogenic therapy in childhood and adolescence: recommendations of the Brazilian experts group.

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.

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.

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.

KPTN gene homozygous variant-related syndrome in the northeast of Brazil: A case report.

Alteration of the KPTN gene, responsible for the coding of kaptin (a protein involved in actin cytoskeletal dynamics), causes a syndrome characterized by macrocephaly, neurodevelopmental delay and epileptic seizures. We report the first Brazilian case of KPTN gene variation, previously described in nine subjects from four interlinked families from an Amish community in Ohio, two Estonian siblings and a 9-year-old boy from Kansas City. We report a case of KPTN-related syndrome in a 5-year-old child which presented macrocephaly, muscular hypotonia, and global development delay. The neurological examination revealed below-expected performance in coordination and balance tests, dyspraxia, and hand-mouth synkinesia. Expressive language was characterized by phono-articulatory imprecision, abundance of phonological processes and morphosyntactic immaturity. Neuropsychological assessment revealed intellectual disability with impairment of verbal and executive functions. Exome sequencing was performed. Analysis revealed a homozygous 2-nucleotide duplication c.597_598dup p.(Ser200Ilefs*55) in the KPTN gene, which is predicted to lead to a translational frameshift and formation of a premature stop codon. The phenotypic profile is similar to the cases described in the other families. Presence of macrocephaly and delayed development indicate the possibility of KPTN gene variation. Genetic testing should be carried out at an early stage in order to reach a timely diagnosis.

Novel ANKRD11 gene mutation in an individual with a mild phenotype of KBG syndrome associated to a GEFS+ phenotypic spectrum: a case report.

BACKGROUND: KBG syndrome is a very rare autosomal dominant disorder, characterized by macrodontia, distinctive craniofacial findings, skeletal findings, post-natal short stature, and developmental delays, sometimes associated with seizures and EEG abnormalities. So far, there have been over 100 cases of KBG syndrome reported. CASE PRESENTATION: Here, we describe two sisters of a non-consanguineous family, both presenting generalized epilepsy with febrile seizures (GEFS+), and one with a more complex phenotype associated with mild intellectual disability, skeletal and dental anomalies. Whole exome sequencing (WES) analysis in all the family members revealed a heterozygous SCN9A mutation, p.(Lys655Arg), shared among the father and the two probands, and a novel de novo loss of function mutation in the ANKRD11 gene, p.(Tyr1715*), in the proband with the more complex phenotype. The reassessment of the phenotypic features confirmed that the patient fulfilled the proposed diagnostic criteria for KBG syndrome, although complicated by early-onset isolated febrile seizures. EEG abnormalities with or without seizures have been reported previously in some KBG cases. The shared variant, occurring in SCN9A, has been previously found in several individuals with GEFS+ and Dravet syndrome. CONCLUSIONS: This report describe a novel de novo variant in ANKRD11 causing a mild phenotype of KGB syndrome and further supports the association of monogenic pattern of SCN9A mutations with GEFS+. Our data expand the allelic spectrum of ANKRD11 mutations, providing the first Brazilian case of KBG syndrome. Furthermore, this study offers an example of how WES has been instrumental allowing us to better dissect the clinical phenotype under study, which is a multilocus variation aggregating in one proband, rather than a phenotypic expansion associated with a single genomic locus, underscoring the role of multiple rare variants at different loci in the etiology of clinical phenotypes making problematic the diagnostic path. The successful identification of the causal variant in a gene may not be sufficient, making it necessary to identify other variants that fully explain the clinical picture. The prevalence of blended phenotypes from multiple monogenic disorders is currently unknown and will require a systematic re-analysis of large WES datasets for proper diagnosis in daily practice.

Transtorno obsessivo-compulsivo e tiques em pacientes com epilepsia / Obsesive-compulsive disorder and tic disorders in patients with epilepsy

Revisar as evidências da relação entre epilepsia, transtorno obsessivo-compulsivo (TOC) e transtornos de tiques. Revisão dos estudos mais relevantes investigando possíveis associações entre estes transtornos. Os transtornos psiquiátricos são frequentes em pacientes com epilepsia. Entretanto, a associação entre sintomas obsessivo-compulsivos, tiques e epilepsia ainda é pouco explorada na literatura. Os realtos de caso mais frequentes descrevem TOC e tiques em pacientes com epilepsia do lobo temporal e também após o tratamento cirúrgico da epilepsia. Considerando o quanto a presença desses transtornos pode afetar a qualidade de vida dos pacientes com epilepsia, é importante investigar a presença dos mesmos em pacientes com epilepsia e faz-se necessário que todo paciente candidato a cirurgia de epilepsia tenha uma avaliação psiquiátrica no pré-operatório e que seja acompanhado no pós-operatório

[Vectorial transmission of Chagas' disease in Mulungu do Morro, Northeastern of Brazil]. / Transmissão vetorial da doença de Chagas em Mulungu do Morro, Nordeste do Brasil.

A serological survey was carried out to determine the prevalence of Chagas' disease in municipality. The following variables were analyzed to identify the form of transmission of this disease: age, sex, clinical and transfusional history, degree of kinship and serology. Within the 863 municipalities we studied, we identified 265 individuals, with serology testing done on them and on their respective mothers. Of these, 232 tested negative serology for Chagas'disease and 33 (14.2%) positive. We found 9 (3.9%) patients, of 14.3 years. average age with vectorial transmission and 24 (10.3%), of 26.6 years. average age with probable, vertical and vectorial transmission. When we compare the two groups in regard to age averages and manner of transmission of Trypanosoma cruzi, we encounter a statistical significance. Our results suggest the existence of an active, vectorial transmission of Trypanosoma cruzi in Mulungu do Morro.

Transmissäo vetorial da doença de Chagas em Mulungu do Morro, Nordeste do Brasil / Vectorial transmission of Chagas' disease in Mulungu do Morro, Northeastern of Brazil

Após a realizaçäo de inquérito sorológico para determinar a prevalência de doença de Chagas no município, foram analisadas as variáveis: idade, sexo, história clínica e transfusional, grau de parentesco e sorologias, para a identificaçäo da forma de transmissäo da infecçäo. Foram analisados 863 munícipes. Identificamos 265 indivíduos cuja sorologia foi realizada também em suas respectivas mäes. Destes, 232 apresentavam sorologia negativa para doença de Chagas e 33 (14,2 por cento) foram positivos. Encontramos 9 (3,9 por cento) filhos com transmissäo vetorial (idade média de 14,3 anos) e 24 (10,3 por cento) filhos com mäes também positivas, com idade média de 26,6 anos. Quando comparamos os dois grupos em relaçäo às médias de idade e ao modo de transmissäo do Trypanosoma cruzi, encontramos diferença com significância estatística. Esta diferença poderia ser explicada pela instalaçäo das medidas de controle ou interrupçäo temporária da transmissäo. Os resultados sugerem que ainda existe transmissäo vetorial ativa do Trypanosoma cruzi em Mulungu do Morro

A expressão neurológica e o diagnóstico genético nas síndromes de Angelman, de Rett e do X-Frágil / Neurological manifestation and genetic diagnosis of Angelman, Rett and Fragile-X syndromes

Objetivo: discutir os aspectos clínicos, eletroencefalográficos e os mecanismos genéticos de três síndromes neurogenéticas, que se identificam como entidades nosológicas no grupo heterogêneo de patologias que cursam com retardo mental e autismo.Fontes dos dados: os autores realizaram revisão literária sobre cada síndrome do estudo, atualizando as informações,correlacio-nando e caracterizando as manifestações neurológicas, assim como a descrição dos mecanismos genéticos e a identificação dos marcadores biológicos.Síntese dos dados: houve a confirmação de que a síndrome de Rett é uma doença genética, conseqüente à mutação no gene MECP2, com variações clínicas que podem ser explicadas por diferentesmutações nesse gene. A síndrome de Angelman tem quatro mecanismos genéticos responsáveis pela variação fenotípica e pelos diferentes riscos de recorrência. Na síndrome do X-Frágil, o grau de comprometimento cognitivo está relacionado com o número de repetições dos trinucleotídeos. Conclusões: os diferentes mecanismos genéticos das três síndromes são responsáveis pela variabilidade clínica. Com a identificação de marcadores biológicos, o diagnóstico será mais precoce, ademais, poderão ser identificadas novas e mais sutis formas deexpressão

Prevalence of Chagas' disease in Mulungu do Morro northeastern Brazil.

OBJECTIVE: The aim of this paper is to describe the prevalence of T. Cruzi infection in patients of from Mulungu do Morro, a rural tropical region of Northeastern Brazil. METHODS: A cross-sectional study was performed. After randomly selecting samples of the population, and obtaining their consents, patients completed pretested epidemiological and clinical questionnaires. Serum samples from all patients were collected and screened for the presence of T. cruzi antibodies. RESULTS: Of 694 patients examined, 174 patients (25.1%) tested had a positive serology for Chagas' disease. Of the study population, 341 patients were male with 27% Chagas' disease prevalence, without a statistical difference. Illiteracy was the only variable related to T. cruzi infection in our population. CONCLUSION: In conclusion, our study points to the high prevalence of Chagas' disease among patients in Mulungu do Morro, suggesting that this region has a high frequency of infection and probably active vectorial transmission.

Taeniasis and cysticercosis prevalence in a small village from Northeastern Brazil.

UNLABELLED: Although not considered as an endemic region, the Northeast of Brazil has the necessary conditions for the development of taeniasis-cysticercosis complex. In a previous paper, we demonstrated that Mulungu do Morro municipality, in the State of Bahia, has a high seroprevalence to cysticercosis in epileptic patients. OBJECTIVE: to determine the prevalence of taeniasis and positive cysticercosis serology in the population of Mulungu do Morro. METHOD: blood and stool samples were collected from a random sampling of the population, by family. The identification of antibodies against T. solium cysticerci was made by EITB and T. solium antigens were identified using a polyclonal antibody-capture ELISA. RESULTS: the cysticercosis seroprevalence was 1.6% (C.I. = 0.8 to 2.8%) and the taeniasis prevalence 4.5% (C.I. = 3.0 to 6.5%). Seropositivity to cysticercosis was higher among those who lived in a house of a person testing positive for coproantigen, p=0.017. CONCLUSION: our results demonstrate that the taeniasis-cysticercosis complex is endemic in Mulungu do Morro. We believe that all areas in the world with the same socio-economic and sanitary characteristics are likely to have high prevalence of this parasite.

Taeniasis and cysticercosis prevalence in a small village from Northeastern Brazil

Although not considered as an endemic region, the Northeast of Brazil has the necessary conditions for the development of taeniasis-cysticercosis complex. In a previous paper, we demonstrated that Mulungu do Morro municipality, in the State of Bahia, has a high seroprevalence to cysticercosis in epileptic patients. OBJECTIVE: to determine the prevalence of taeniasis and positive cysticercosis serology in the population of Mulungu do Morro. METHOD: blood and stool samples were collected from a random sampling of the population, by family. The identification of antibodies against T. solium cysticerci was made by EITB and T. solium antigens were identified using a polyclonal antibody-capture ELISA. RESULTS: the cysticercosis seroprevalence was 1.6 percent (C.I. = 0.8 to 2.8 percent) and the taeniasis prevalence 4.5 percent (C.I. = 3.0 to 6.5 percent). Seropositivity to cysticercosis was higher among those who lived in a house of a person testing positive for coproantigen, p=0.017. CONCLUSION: our results demonstrate that the taeniasis-cysticercosis complex is endemic in Mulungu do Morro. We believe that all areas in the world with the same socio-economic and sanitary characteristics are likely to have high prevalence of this parasite

Prevalence of Chagas' disease in Mulungu do Morro Northeastern Brazil

OBJECTIVE - The aim of this paper is to describe the prevalence of T. Cruzi infection in patients of from Mulungu do Morro, a rural tropical region of Northeastern Brazil. METHODS - A cross-sectional study was performed. After randomly selecting samples of the population, and obtaining their consents , patients completed pretested epidemiological and clinical questionnaires. Serum samples from all patients were collected and screened for the presence of T. cruzi antibodies. RESULTS - Of 694 patients examined, 174 patients (25.1 percent) tested had a positive serology for Chagas' disease. Of the study population, 341 patients were male with 27 percent Chagas' disease prevalence, without a statistical difference. Illiteracy was the only variable related to T. cruzi infection in our population. CONCLUSION - In conclusion, our study points to the high prevalence of Chagas' disease among patients in Mulungu do Morro, suggesting that this region has a high frequency of infection and probably active vectorial transmission

[Neurological manifestation and genetic diagnosis of Angelman, Rett and Fragile-X syndromes] / A expressão neurológica e o diagnóstico genético nas síndromes de Angelman, de Rett e do X-Frágil.

OBJECTIVE: To discuss clinical and electroencephalographic aspects and the genetic mechanisms of three neurogenic syndromes that can be related to nosologic entities in the heterogenic pathological group presenting symptoms of mental retardation and autism. SOURCES: The authors carried out a bibliographic review on each syndrome involved, correlating and characterizing the neurological manifestations, as well as describing genetic mechanisms and identifying biological markers. SUMMARY OF THE FINDINGS: The authors were able to confirm that Rett Sydrome is a genetic disease resulting from the mutation of the MECP2 gene and clinical variations can be explained by different mutations in this gene. Angelman syndrome has four genetic mechanisms responsible for phenotypic variations and different risks of recurrence. In Fragile-X syndrome, the degree of cognitive impairment is related to the number of trinucleotide repeats. CONCLUSIONS: Different genetic mechanisms of the three syndromes are responsible for clinical variability. By identifying the biological markers, the diagnosis will be performed earlier and it will be possible to identify new subtle expressions of the disease.

Cysticercosis in epileptic patients of Mulungu do Morro Northeastern Brazil

With the aim to study the magnitude of infection by the metacestode of Taenia solium in a population of epileptic patients in the arid region of Bahia, Northeastern Brazil, we examined 200 consecutive cases who attended an ambulatory clinic in the disctrict of Mulungu do Morro. Sixty-six of the patients had a diagnosis of epilepsy. From them 10 (15.2 percent) presented antibodies against a specific fraction of antigens in Western blot, and 4 (6.0 percent) had circulating parasite products, as tested by capture ELISA. Only 1 case was positive for antibodies and antigens. We found that the frequency of seropositivity was related to the time without epileptic seizure. We conclude that cysticercosis is endemic in the region of Mulungu do Morro and that it is related to a benign form of epilepsy

Características clínicas e laboratoriais de meningites bacterianas em crianças / Clinical and laboratorial characteristics of bacterial meningitis in children

Foram analisados dados de prontuário de 528 crianças com faixa etária entre 1 mês e 15 anos e diagnóstico de meningite bacteriana aguda, admitidas no Hospital Couto Maia entre 1990 e 1992. Meningite bacteriana foi mais frequente em crianças com idade inferior a 1 ano (37,8 por cento). O agente etiológico mais comum foi H. influenzae (42,2 por cento). A letalidade global foi de 20,9 por cento e os fatores preditivos de pior prognóstico foram: ausência da "tríade classica" (febre, vômitos e rigidez de nuca), celularidade do líquido cefalorraquidiano inferior a 1000/mm3, idade inferior a 2 anos, presença de convulsoes, alteraçoes do nível de consciência e S. pneumoniae como agente causal.

Prognosis of bacterial meningitis in children

We studied the incidence and prognosis of acute neurologic complications in 281 children under 13 years of age with a diagnosis of acute bacterial meningitis. All the patients were examined daily by the same group of neurologists, using a standardized neurological examination. Patients with signs of encephalic lesions, unsatisfactory response to antibiotics or decreased level of consciousness were submitted to brain computer tomography. The overall lethality rate was 20.3 per cent and cases whose causative agent was identified presented a higher lethality rate (23.7 per cent) than those in which the agent was not found. The most important neurological abnormalities were meningeal signs (88.3 per cent) followed by decreased consciousness (47.7 per cent), irritability (35.2 per cent), seizures (22.4 per cent), fontanel bulging (20.6 per cent) and cranial nerve palsy (l4.2 per cent). Seizures, cranial nerve palsy and the absence of meningeal signs were related to higher rates of lethality. Diminished consciousness, seizures, subdural effusion, abscess and hydrocephalus were the most important complications, respectively. We can conclude that acute bacterial meningitis continues to be an important health problem in developing countries and that public health measures will be necessary to minimize the impact of sequelae and reduce the mortality rate in children with that pathology.