Use of lacosamide in children: experience of a tertiary medical care center in Brazil.

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.

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.

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.

Two-year follow-up of children with congenital Zika syndrome: the evolution of clinical patterns.

The aim of the study was to describe neurological manifestations in children with congenital Zika syndrome (CZS) in the first 2 years of age. In this prospective observational study, children with CZS treated at a university hospital received a neurological assessment and were evaluated using two neurodevelopmental scales (the Denver II test and the assessment of gross motor development of the World Health Organization) by a pediatric neurologist on admission to the study and at 4, 8, 12, 18, and 24 months of age. The data collected were stored in Microsoft Excel version 14.6.3. Thirty-eight children (27 males and 11 females; a median age of 4.3 months (interquartile range (IQR): 1.6-11.4)) with CZS were evaluated. Irritability was present in 50% and 27% of the children at 8 months and 24 months, respectively. Axial hypertonia was highly prevalent at 4 months (77%), with a decrease to 50% at 24 months. At all ages, spastic tetraparesis was the most common motor abnormality (> 80%). Twenty-seven (71%) participants were diagnosed with epilepsy, and the median age at seizure onset was 6 months (IQR: 3.5-8). The most frequent types of seizures were focal seizures and spasms, with spasms being the most frequent in the first year of life (52%) and focal crises being the most frequent in the second year of life (50%).Conclusion: This study allowed observation of neurological abnormalities over time, the evolution of epileptic manifestations, and recognition of new patterns of clinical neurological abnormalities, helping clinicians to recognize CZS earlier, minimizing the impact of new outbreaks. What is Known: • Clinical patterns of SZC patients at pre-established ages or date of data collection • More frequent studies with data collection of clinical-radiological features of patient's over his first year of life What is New: • Comprehensive clinical neurological progression data regarding CZS in the first 2 years of life, recognizing patterns • Hypothesis including a new CZS spectrum with milder clinical-radiological features.

Experience in diagnosing congenital Zika syndrome in Brazilian children born to asymptomatic mothers.

INTRODUCTION: Typical symptoms of primary Zika virus infection are not specific and share similarities with other arbovirus infections such as dengue fever and chikungunya. As acute infection can be asymptomatic in up to 73% of cases, infants with microcephaly represent a diagnostic challenge for pediatricians. We describe the frequency of congenital Zika syndrome (CZS) in Brazilian children born to asymptomatic pregnant mothers and its differential diagnosis. METHODS: This longitudinal, observational study was conducted on children with suspected CZS whose mothers did not report rash during pregnancy, referred to the reference hospital in a metropolitan area of ​ Rio de Janeiro, Brazil. The diagnosis of suspected CZS was based on Brazilian Ministry of Health protocol. RESULTS: Forty-three (17%) of 246 referred children were born to mothers without rash history during pregnancy. Thirteen (30%) of 43 children met the Brazilian Ministry of Health criteria for CZS, all with microcephaly (two post-natal). The other children included 11 cases with post-natal microcephaly due to hypoxic-ischemic encephalopathy (6), non-progressive encephalopathy of unknown etiology (2), microcephaly under investigation (2) and congenital toxoplasmosis (1); 17 children were misdiagnosed with microcephaly and progressed with normal head circumference during the follow-up period; one child was included because of epidemiological link and one was loss to follow-up. All children who underwent laboratory investigation for ZIKV infection during neonatal period had negative RT-qPCR tests. CONCLUSION: We emphasize the increasing importance of CZS in differential diagnosis of microcephaly at birth or post-natal period. Detailed clinical investigation assisted by neuroimaging tests may clarify the diagnosis of CZS when laboratory tests are not available during the acute phase of the disease.

Should arboviruses be the only diagnosis hypothesis in pregnant women in endemic areas presenting with a rash?

Listeria is an unusual pathogen that causes neonatal infection with high morbidity and mortality. We present the case of a premature newborn whose mother had a rash during pregnancy; the newborn had severe early sepsis because of Listeria monocytogenes and histopathologically suggestive findings of the placenta. Obstetricians and neonatologists should suspect listeriosis in cases with compatible epidemiological history, clinical features, and examination findings of the placenta.

Children Born to Mothers with Rash During Zika Virus Epidemic in Brazil: First 18 Months of Life.

OBJECTIVE: To better understand the clinical spectrum and course of congenital Zika syndrome (CZS) during the first 18 months of life of children whose mothers had rash during pregnancy. METHODS: This longitudinal observational study evaluated the clinical progress from birth until 18 months of life of children of mothers who developed rash during or up to 3 months before gestation. Maternal rash occurred from November 2015 to May 2017. The study subjects were divided into three groups: children whose mothers tested positive by RT-qPCR for Zika virus (ZIKV) (Group 1), children whose mothers tested negative by RT-qPCR for ZIKV (Group 2), and children whose mothers did not undergo any testing for ZIKV (Group 3) but tested negative for other congenital infections. RESULTS: Between April 2016 and July 2018, we studied 108 children: 43 in Group 1, 26 in Group 2 and 39 in Group 3. The majority of children were admitted into the study within 6 months of life. CZS was diagnosed in 26 children, equally distributed in Groups 1 and 3. Of 18 children with microcephaly, 6 were in Group 1 (1 postnatal) and 12 were in Group 3 (5 postnatal). Maternal rash frequency was 10 times higher during the first trimester than in the other trimesters (OR: 10.35; CI 95%: 3.52-30.41). CZS was diagnosed during the follow-up period in 14 (54%) cases. Developmental delays and motor abnormalities occurred in all children and persisted up to 18 months. Epilepsy occurred in 18 (69%) of the cases. CONCLUSIONS: Infants born of mothers exposed to ZIKV during pregnancy showed progression of developmental, motor and neurologic abnormalities even if they were born asymptomatic. Continued postnatal monitoring of such newborns is necessary to preclude disability-associated complications.

Should arboviruses be the only diagnosis hypothesis in pregnant women in endemic areas presenting with a rash?

Abstract Listeria is an unusual pathogen that causes neonatal infection with high morbidity and mortality. We present the case of a premature newborn whose mother had a rash during pregnancy; the newborn had severe early sepsis because of Listeria monocytogenes and histopathologically suggestive findings of the placenta. Obstetricians and neonatologists should suspect listeriosis in cases with compatible epidemiological history, clinical features, and examination findings of the placenta.

Sialorrhea in children with cerebral palsy / Sialorreia em crianças com paralisia cerebral

Abstract Objective: To review the literature on sialorrhea in children with cerebral palsy. Source of data: Non-systematic review using the keywords "sialorrhea" and "child" carried out in the PubMed®, LILACS®, and SciELO® databases during July 2015. A total of 458 articles were obtained, of which 158 were analyzed as they were associated with sialorrhea in children; 70 had content related to sialorrhea in cerebral palsy or the assessment and treatment of sialorrhea in other neurological disorders, which were also assessed. Data synthesis: The prevalence of sialorrhea is between 10% and 58% in cerebral palsy and has clinical and social consequences. It is caused by oral motor dysfunction, dysphagia, and intraoral sensitivity disorder. The severity and impact of sialorrhea are assessed through objective or subjective methods. Several types of therapeutic management are described: training of sensory awareness and oral motor skills, drug therapy, botulinum toxin injection, and surgical treatment. Conclusions: The most effective treatment that addresses the cause of sialorrhea in children with cerebral palsy is training of sensory awareness and oral motor skills, performed by a speech therapist. Botulinum toxin injection and the use of anticholinergics have a transient effect and are adjuvant to speech therapy; they should be considered in cases of moderate to severe sialorrhea or respiratory complications. Atropine sulfate is inexpensive and appears to have good clinical response combined with good safety profile. The use of trihexyphenidyl for the treatment of sialorrhea can be considered in dyskinetic forms of cerebral palsy or in selected cases.

Resumo Objetivo: Revisar a literatura referente à sialorreia em crianças com paralisia cerebral. Fonte de dados: Revisão não sistemática com as palavras-chave "sialorreia"; e "criança" feita nas bases de dados Pubmed®, Lilacs® e Scielo® em julho de 2015. Foram recuperados 458 artigos, 158 foram analisados por terem relação com sialorreia em crianças, foram aproveitados 70 com conteúdo relativo à sialorreia na paralisia cerebral ou à avaliação e ao tratamento da sialorreia em outros distúrbios neurológicos. Síntese dos dados: A sialorreia tem prevalência entre 10% e 58% na paralisia cerebral e implica consequências clínicas e sociais. É causada por disfunção motora oral, disfagia e distúrbio da sensibilidade intraoral. A gravidade e o impacto da sialorreia são avaliados por meio de métodos objetivos ou subjetivos. Estão descritas diversas formas de manejo terapêutico: treino para consciência sensorial e habilidades motoras orais, terapia farmacológica, injeção de toxina botulínica e tratamento cirúrgico. Conclusões: O tratamento mais eficaz e que aborda a causa da sialorreia nas crianças com paralisia cerebral é o treino para consciência sensorial e habilidades motoras orais, feito por um fonoaudiólogo. Injeção de toxina botulínica e o uso de anticolinérgicos têm efeito transitório e são auxiliares ao tratamento fonoaudiológico ou devem ser considerados nos casos de sialorreia moderada a grave ou com complicações respiratórias. O sulfato de atropina tem baixo custo e parece ter boa resposta clínica com bom perfil de segurança. O uso de triexifenidil para o tratamento da sialorreia pode ser considerado nas formas discinéticas de paralisia cerebral ou em casos selecionados.

Sialorrhea in children with cerebral palsy.

OBJECTIVE: To review the literature on sialorrhea in children with cerebral palsy. SOURCE OF DATA: Non-systematic review using the keywords "sialorrhea" and "child" carried out in the PubMed®, LILACS®, and SciELO® databases during July 2015. A total of 458 articles were obtained, of which 158 were analyzed as they were associated with sialorrhea in children; 70 had content related to sialorrhea in cerebral palsy or the assessment and treatment of sialorrhea in other neurological disorders, which were also assessed. DATA SYNTHESIS: The prevalence of sialorrhea is between 10% and 58% in cerebral palsy and has clinical and social consequences. It is caused by oral motor dysfunction, dysphagia, and intraoral sensitivity disorder. The severity and impact of sialorrhea are assessed through objective or subjective methods. Several types of therapeutic management are described: training of sensory awareness and oral motor skills, drug therapy, botulinum toxin injection, and surgical treatment. CONCLUSIONS: The most effective treatment that addresses the cause of sialorrhea in children with cerebral palsy is training of sensory awareness and oral motor skills, performed by a speech therapist. Botulinum toxin injection and the use of anticholinergics have a transient effect and are adjuvant to speech therapy; they should be considered in cases of moderate to severe sialorrhea or respiratory complications. Atropine sulfate is inexpensive and appears to have good clinical response combined with good safety profile. The use of trihexyphenidyl for the treatment of sialorrhea can be considered in dyskinetic forms of cerebral palsy or in selected cases.

Adverse events following yellow fever immunization: Report and analysis of 67 neurological cases in Brazil.

Neurological adverse events following administration of the 17DD substrain of yellow fever vaccine (YEL-AND) in the Brazilian population are described and analyzed. Based on information obtained from the National Immunization Program through passive surveillance or intensified passive surveillance, from 2007 to 2012, descriptive analysis, national and regional rates of YFV associated neurotropic, neurological autoimmune disease, and reporting rate ratios with their respective 95% confidence intervals were calculated for first time vaccinees stratified on age and year. Sixty-seven neurological cases were found, with the highest rate of neurological adverse events in the age group from 5 to 9 years (2.66 per 100,000 vaccine doses in Rio Grande do Sul state, and 0.83 per 100,000 doses in national analysis). Two cases had a combination of neurotropic and autoimmune features. This is the largest sample of YEL-AND already analyzed. Rates are similar to other recent studies, but on this study the age group from 5 to 9 years of age had the highest risk. As neurological adverse events have in general a good prognosis, they should not contraindicate the use of yellow fever vaccine in face of risk of infection by yellow fever virus.

Aspectos clínicos em 16 pacientes com diagnóstico tomográfico de esquizencefalia / Clinical findings in 16 patients with tomographic diagnosis of schizencephaly

OBJETIVO: Correlacionar o quadro clínico de um grupo de crianças com diagnóstico tomográfico de esquizencefalia com a extensão e localização das fendas. MATERIAIS E MÉTODOS: Estudo retrospectivo de prontuários do arquivo dos serviços de Neurologia e Genética Médica do Instituto Fernandes Figueira e Hospital Municipal Jesus, Rio de Janeiro, RJ, Brasil, no período de 2000 a 2003. Foram incluídos 16 pacientes, nove do sexo feminino e sete do sexo masculino, com diagnóstico tomográfico de esquizencefalia e analisados quanto a aspectos da tomografia computadorizada, desenvolvimento neuropsicomotor, déficit motor e cognitivo e epilepsia. RESULTADOS: Predominaram as fendas bilaterais em 10:16 pacientes, lábios abertos em 23:27 fendas e pequenas em 11:27 fendas. Das anomalias associadas à esquizencefalia, a ausência de septo pelúcido foi a mais freqüente (10:16 pacientes). Dos aspectos clínicos, 15 pacientes apresentaram atraso do desenvolvimento e déficit motor; seis apresentaram déficit cognitivo e dez apresentaram epilepsia. Em três pacientes observamos discordância entre o quadro clínico e o tamanho das fendas: embora as fendas fossem pequenas, o quadro clínico foi intenso, em virtude de presença de outras anomalias cerebrais. CONCLUSÃO: O quadro clínico guarda relação com o tamanho das fendas, independentemente da lateralidade, sendo mais intenso quando há associação com outras anomalias cerebrais.

OBJECTIVE: To establish a correlation between clinical features in a group of children with tomographic diagnosis of schizencephaly and clefts extent and localization. MATERIALS AND METHODS: Retrospective study of dossiers from the archives of Neurology and Medical Genetics Services at Instituto Fernandes Figueira/Fiocruz and Hospital Municipal Jesus, Rio de Janeiro, RJ, Brazil, in the period between 2000 and 2003. The study included 16 patients, nine female and seven male, with tomographic diagnosis of schizencephaly investigated for clinical findings, psychomotor development, motor/cognitive deficits and epilepsy. RESULTS: Predominance of bilateral clefts in 10:16 patients, open-lip schizencephaly type in 23:27 patients, and small lips in 11:27 patients. As regards anomalies associated with schizencephaly, pellucid septum absence was the most frequent one (10:16 patients). As regards clinical findings, 15 patients presented with developmental delay and motor deficit, six patients with cognitive deficit and ten with epilepsy. In three patients, we observed discordant clinical findings and cleft sizes, although the clefts were small, the clinical features severity was high because of other cerebral anomalies. CONCLUSION: The clinical features of schizencephaly are related to the size of the clefts, regardless laterality, presenting higher severity when associated with other cerebral anomalies.

A survey on inborn errors of metabolism in 323 neonates from the state of Rio de Janeiro, Brazil.

Inborn errors of metabolism (IEM) are a relevant cause of morbidity and death among children, and neonates in particular. However, little is known about the prevalence of these disorders in Brazilian newborns. Our laboratory of IEM (LABEIM) at the Department of Biochemistry, Institute of Chemistry, Federal University of Rio de Janeiro (UFRJ), has been working on the diagnosis of IEM since 1988. Out of 3,300 patients (90% children), screened and evaluated from 1989 to 2,000 because of a high clinical suspicion of having an IEM, 323 (9.8%) were neonates. Patients came from different regions of the state of Rio de Janeiro, in which lives approximately 8.5% of the total Brazilian population. Chemical tests, various chromatographic techniques and enzyme assays were performed in urine, plasma and in some cases, cerebrospinal fluid (CSF). This study describes our laboratory and the experience with the 323 investigated neonates, among which 28 cases (8.7%) of IEM were identified and 18 (5.6%), strongly suspected. All these cases were related mainly to the metabolism of amino acids, organic acids, lysosomal enzymes and carbohydrates. Furthermore, data on population, community and health services are presented.