Manejo del estado epiléptico en niños: encuesta en hospitales pediátricos de la Ciudad Autónoma de Buenos Aires / Management of status epilepticus in childhood: a survey conducted at pediatric hospitals in the City of Buenos Aires

Introducción. El estado epiléptico constituye la emergencia neurológica más frecuente. Si bien la mortalidad en niños es baja, su morbilidad puede superar el 20 %. Objetivo. Conocer las pautas de manejo del estado epiléptico referidas por médicos pediatras que atienden esta patología en forma habitual. Población y métodos. Estudio descriptivo, transversal, basado en una encuesta a médicos de tres hospitales pediátricos monovalentes de gestión pública de la Ciudad Autónoma de Buenos Aires. Resultados. Se administraron 292 encuestas (la tasa de respuesta completa alcanzó el 86 %); el 77 % se administró a pediatras y el 16 %, a especialistas en cuidados intensivos. Un 47 % de los participantes refiere indicar la primera benzodiacepina en el tiempo correcto; el 56 % utilizar diazepam intrarrectal en ausencia de un acceso intravenoso; el 95 % elige lorazepam como benzodiacepina inicial en caso de contar con acceso intravenoso; el 58 % refiere iniciar la etapa de fármacos de segunda línea en tiempo adecuado; el 84 % opta por fenitoína como fármaco inicial de segunda línea, un 33 % no cronometra el tiempo durante el tratamiento. La adherencia global a las recomendaciones internacionales fue del 17 %. Conclusiones. Nuestro estudio advierte una baja adherencia referida de los pediatras a las guías internacionales, en particular en las decisiones tiempo-dependientes. También se observó mayor heterogeneidad en las conductas terapéuticas a medida que se avanza en el algoritmo de tratamiento.

Introduction. Status epilepticus is the most common neurological emergency. Although mortality in children is low, morbidity may exceed 20%. Objective. To evaluate the management of status epilepticus by pediatricians who usually treat this condition. Population and methods. Descriptive, cross-sectional study based on a survey administered to physicians from 3 pediatric hospitals in the City of Buenos Aires. Results. A total of 292 surveys were administered (complete response rate as high as 86%); 77% were administered to pediatricians and 16% to intensive care specialists. Forty-seven percent of the participants reported that they administer the first dose of a benzodiazepine within the correct timeframe; 56% use intrarectal diazepam when intravenous access is not available; 95% choose lorazepam as the initial benzodiazepine if an intravenous access is available; 58% initiate the administration of a second-line drug within the correct timeframe; 84% administer phenytoin as the first-choice, second-line drug; and 33% do not measure treatment time. Overall adherence to international recommendations was 17%. Conclusions. Our study highlights poor adherence of pediatricians to international guidelines, particularly in time-dependent decisions. Greater heterogeneity was observed in treatment approaches as the treatment algorithm progressed.

Eficácia e segurança do Felbamato comparado a medicamentos disponíveis no SUS para o tratamento da epilepsia refratária em crianças e adultos: revisão rápida de evidências / Effectiveness and safety of Felbamate compared to drugs available in SUS for the treatment of refractory epilepsy in children and adults: rapid evidence review

Tecnologia: Felbamato. Indicação: Tratamento de epilepsia refratária. Pergunta: O Felbamato é mais eficaz e seguro comparado a anticonvulsivantes disponíveis no Sistema Único de Saúde (SUS) em pacientes com epilepsia refratária? Métodos: Revisão rápida de evidências (overview) de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Resultados: Foram selecionadas 2 revisões sistemáticas, que atendiam aos critérios de inclusão. Conclusão: O felbamato não demonstrou ser uma opção mais benéfica que os demais medicamentos disponíveis no SUS no tratamento de epilepsia refratária a medicamentos. Salienta-se que a maior parte das evidências eram de baixa certeza

Technology: Felbamate. Indication: Treatment of refractory epilepsy. Question: Is felbamate more effective and safer compared to anticonvulsants available in Brazilian Public Health System in patients with refractory epilepsy? Methods: A rapid review of evidence (overview) of systematic reviews, with bibliographic survey carried out in the PUBMED database, using a structured search strategy. The methodological quality of systematic reviews was assessed using AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Results: Two systematic reviews that met the inclusion criteria were selected. Conclusion: Felbamate did not prove to be a more beneficial option than the other drugs available in the Brazilian Public Health System in the treatment of drug-refractory epilepsy. It should be noted that most of the evidence was of low certainty

Uso del cannabis medicinal en niños con encefalopatías epilépticas farmacorresistentes. Experiencia en Hospital Garrahan / Use of medicinal cannabis in children with drug-resistant epileptic encephalopathies. Experience at Garrahan Hospital

Objetivo: Reportamos resultados sobre la efectividad, seguridad y tolerancia del cannabidiol como adyuvante terapéutico en pacientes pediátricos con encefalopatías epilépticas del desarrollo (EED) resistentes al tratamiento farmacológico y no farmacológico tras un seguimiento promedio de 20 meses. Métodos: Se realizó un estudio de cohorte prospectivo para evaluar la eficacia, la seguridad y la tolerancia del aceite de cannabis medicinal enriquecido con CBD añadido a los medicamentos anticonvulsivos estándar en niños con EED resistentes a los medicamentos atendidos en un único centro. Resultados: Entre octubre de 2018 y marzo de 2020, se incluyeron 59 pacientes. La edad media en el momento del inicio del protocolo fue de 10,5 años (rango, 2-17 años). La mediana de la duración del tratamiento fue de 20 meses (rango, 12-32). La mediana de edad en el momento de la primera convulsión fue de 8 meses (rango, 1 día - 10 años). Al final del seguimiento, el 78% de los niños tenía una disminución ≥ 50% en frecuencia de las crisis y el 47,5% tenía una disminución > 75%. Siete pacientes (11,9%) estaban libres de convulsiones. El número de crisis se redujo de una mediana de 305/mes a 90/mes, que supone una reducción media del 57% y una mediana del 71% (p < 0,0001). Los efectos adversos fueron en su mayoría leves o moderados. El CBD se interrumpió en 17 pacientes (28,8%) por falta de respuesta al tratamiento, aumento de la frecuencia de las convulsiones, intolerancia al fármaco o cumplimiento terapéutico insuficiente. Conclusión: En los niños con EED resistentes a los fármacos, el tratamiento a largo plazo del cannabis medicinal enriquecido con CBD como terapia adyuvante resultó ser seguro, bien tolerado y eficaz. Las reducciones sostenidas en la frecuencia de las convulsiones y la mejora de los aspectos de la vida diaria se observaron en comparación con nuestros preliminares (AU)

Objective: We report results on the effectiveness, safety, and tolerance of cannabidiol (CBD) as add-on therapy in children with developmental and epileptic encephalopathies (DEE) resistant to pharmacological and non-pharmacological treatment after a mean follow-up of 20 months. Methods: A prospective cohort study was conducted to evaluate the efficacy, safety, and tolerability of CBD-enriched medical cannabis oil added to standard antiseizure medications in children with drug-resistant DEEs seen at a single center. Results: Between October 2018 and March 2020, 59 patients were included. The median age at protocol initiation was 10.5 years (range, 2-17 years). Median treatment duration was 20 months (range, 12-32). The median age at the time of the first seizure was 8 months (range, 1 day - 10 years). At the end of follow-up, 78% of the children had a decrease ≥ 50% in seizure frequency and 47.5% had a decrease of > 75%. Seven patients (11.9%) were seizure free. The number of seizures was reduced from a median of 305/month to 90/month, accounting for a mean reduction of 57% and a median of 71% (p < 0.0001). Adverse effects were mostly mild or moderate. CBD was discontinued in 17 patients (28.8%) due to lack of response to treatment, increased seizure frequency, drug intolerance, or poor compliance. Conclusion: In children with drug-resistant DEE, long-term treatment with CBD-enriched medicinal cannabis as add-on therapy proved to be safe, well tolerated, and effective. Sustained reductions in seizure frequency and improvement in aspects of daily living were observed compared to our preliminary results (AU)

Vigabatrina comparado con hormona adrenocorticotrópica para el tratamiento de espasmos infantiles y Síndrome de West / Vigabatrin compared with adrenocorticotropic hormone for the treatment of infantile spasms and West Syndrome

OBJETIVO: Determinar los riesgos y beneficios del uso de vigabatrina comparada con hormona adrenocorticotrópica (ACTH) para el tratamiento de espasmos infantiles. MÉTODO: Se realizó una búsqueda en Epistemonikos. Se extrajeron datos desde las revisiones identificadas. Se realizó un metaanálisis a partir de estudios primarios y se utilizó el método GRADE para la presentación de resultados. RESULTADOS: Se identificaron nueve revisiones sistemáticas. Se observó que el uso de vigabatrina en comparación con ACTH disminuye la resolución de espasmos (RR 0,8, IC 95% 0,65 - 0,98) y podría disminuir la resolución de hipsarritmia (RR 0,71, IC 95% 0,48 - 1,05). No fue posible determinar si el uso de vigabatrina disminuye el riesgo de desarrollar efectos adversos (RR 0,75, IC 95% 0,23 - 2,45) por certeza de evidencia muy baja. CONCLUSIONES: La evidencia parece inclinarse a favor del uso de ACTH. Sin embargo debe considerarse la necesidad de nuevas investigaciones para esclarecer su seguridad.

OBJECTIVE: To determine the risks and benefits of the use of vigabatrin compared to ACTH for the treatment of infantile spasms. METHOD: A search in Epistemonikos was performed. Data were extracted from the identified reviews. A meta-analysis was performed from primary studies and the GRADE method was used to present the results. RESULTS: Nine systematic reviews were identified. Vigabatrin use compared to ACTH was found to decrease resolution of spasms (RR 0.8, 95% CI 0.65 - 0.98) and might decrease resolution of hypsarrhythmia (RR 0.71, 95% CI 0 .48 - 1.05). It was not possible to determine whether the use of vigabatrin reduces the risk of developing adverse effects (RR 0.75, 95% CI 0.23 - 2.45) due to very low certainty of evidence. CONCLUSIONS: The evidence seems to lean in favor of the use of ACTH. However, the need for new research should be considered to clarify its safety.

Tratamiento de la eclampsia y miastenia gravis: reporte de un caso y revisión de la literatura / Eclampsia treatment and myasthenia gravis: case report and review of literature

OBJETIVO: Reportar el caso de una gestante con miastenia grave (MG) más preeclampsia-eclampsia y crisis miasténica en el puerperio mediato, y realizar una revisión de la literatura sobre el manejo farmacológico. MÉTODO: Se presenta el caso de una mujer de 26 años con MG, primigesta de 36 semanas de gestación, quien cursó con eclampsia y recibió fenitoína por 24 horas. Tuvo parto espontáneo sin complicaciones y crisis miasténica al día 11 del puerperio asociada a infección de vías urinarias y sepsis. Se realiza revisión de la literatura en PubMed, Cochrane, Embase, LILACS y Scopus, empleando los términos "Hypertension, Pregnancy-Induced", "Preeclampsia" y "Eclampsia", combinados con "Myasthenia Gravis", durante el periodo de publicación de 1960 a junio 2020, en inglés y español. RESULTADOS: Se encontraron 12 reportes de caso, dos con eclampsia y MG; el caso aquí reportado es el número 13. Ocho pacientes no recibieron medicamentos profilácticos de eclampsia y tres de ellas convulsionaron. En las que se usó sulfato de magnesio, todas cursaron con crisis miasténica. CONCLUSIONES: La evidencia actual en cuanto a la profilaxis y el tratamiento de la eclampsia y la MG corresponde a reportes de casos. El uso de sulfato de magnesio está contraindicado en pacientes con MG, por lo que se han utilizado fenitoína y levetiracetam.

OBJECTIVE: To report a case of pregnant women with myasthenia gravis (MG), plus preeclampsia-eclampsia and myasthenic crisis in the mediate puerperium; to conduct a literature review regarding its pharmacological management. METHOD: 26-year-old primigravida with 36 weeks of gestation and previous history of MG, who developed eclampsia and was treated with phenytoin for 24 hours, with later spontaneous delivery without any complications nor new seizures; and myasthenic crisis on day 11 of the puerperium associated with urinary tract infection and sepsis. A literature review was conducted in PubMed, Cochrane, Embase, LILACS and Scopus, using the controlled vocabulary "Hypertension, Pregnancy-Induced", "Preeclampsia" and "Eclampsia", combined with "Myasthenia Gravis", between 1960 and June 2020, in English and Spanish. RESULTS: 12 case reports were found, two of these with eclampsia and MG, the case reported here was number 13. In eight cases patients did not receive any prophylactic drugs for eclampsia and three of them had convulsions. In the cases where magnesium sulfate was used, all developed myasthenic crisis. CONCLUSIONS: The current evidence regarding prophylactic management and treatment corresponds to case reports. The use of magnesium sulfate is contraindicated in patients with MG, therefore phenytoin and levetiracetam have been used.

Chemical composition of Zhumeria majdae essential oil and its effects on the expression of morphine withdrawal syndrome and tolerance to the anticonvulsant effect of morphine on pentylenetetrazole-induced seizures in mice / Composição química do óleo essencial de Zhumeria majdae e seus efeitos na expressão da síndrome de abstinência de morfina e tolerância ao efeito anticonvulsivante da morfina em crises induzidas por pentilenotetrazol em camundongos

Abstract Regarding the proven anticonvulsant effect of Zhumeria majdae essential oil (ZMEO) in previous studies we were prompted to investigate the ZMEO effects on the tolerance to the anticonvulsant effects of morphine and the morphine withdrawal syndrome. Tolerance to the morphine anticonvulsant effect was induced in mice by subcutaneous injection of 2.5 mg/kg of morphine for 4 days. Subsequent doses of ZMEO (20 mg/kg) were used to study the expression and development of morphine tolerance. Clonidine was used as the standard drug to inhibit the morphine withdrawal syndrome symptoms. To study the ZMEO effect on withdrawal syndrome, mice received appropriate morphine values for 4 days and on the fifth day, 60 min before administration of naloxone. The effective dose of ZMEO was determined and the number of jumps, stands and changes in the dry stool weight, as symptoms of withdrawal syndrome were evaluated. The dose of 20 mg/kg of ZMEO decreased the tolerance in development and expression groups significantly. Counting the number of jumping, standing and defecation were assessed 30 min after morphine and 1 h after the vehicle and clonidine. The dose of 40 mg/kg ZMEO decreased all the signs of withdrawal syndrome significantly. ZMEO was analyzed by GC/MS and linalool (53.1%) and camphor (23.8%) were characterized as the main components. The results suggest that ZMEO possesses constituent(s) that have activity against tolerance to the anticonvulsant effects of morphine and the morphine withdrawal symptoms.

Resumo Em relação ao efeito anticonvulsivante comprovado do óleo essencial de Zhumeria majdae (ZMEO) em estudos anteriores, fomos instigados a investigar os efeitos do ZMEO em relação à tolerância aos efeitos anticonvulsivantes da morfina e da síndrome de abstinência de morfina. A tolerância ao efeito anticonvulsivante da morfina foi induzida em camundongos por injeção subcutânea de 2,5 mg/kg de morfina por 4 dias. Doses subsequentes de ZMEO (20 mg/kg) foram utilizadas para estudar a expressão e o desenvolvimento da tolerância à morfina. A clonidina foi usada como droga padrão para inibir os sintomas da síndrome de abstinência da morfina. Para estudar o efeito do ZMEO na síndrome de abstinência, os camundongos receberam valores apropriados de morfina por 4 dias e, no 5º dia, 60 minutos antes da administração de naloxona. A dose efetiva de ZMEO foi determinada, e o número de saltos e de permanência e as alterações no peso das fezes secas, conforme os sintomas da síndrome de abstinência, foram avaliados. A dose de 20 mg/kg de ZMEO diminuiu significativamente a tolerância nos grupos de desenvolvimento e expressão. A contagem do número de saltos, permanência e defecação foi avaliada 30 minutos após a morfina e 60 minutos após o veículo e a clonidina. A dose de 40 mg/kg de ZMEO diminuiu significativamente todos os sinais da síndrome de abstinência. O ZMEO foi analisado por GC/MS, e linalol (53,1%) e cânfora (23,8%) foram caracterizados como os principais componentes. Os resultados sugerem que o ZMEO apresenta constituintes que possuem atividade contra a tolerância aos efeitos anticonvulsivantes da morfina e aos sintomas de abstinência da morfina.

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

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

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

Adherencia al tratamiento antiepiléptico en niños y a / Treatment compliance in children and adolescents with epilepsy

La adherencia de los pacientes a las indicaciones médicas es fundamental en la respuesta al tratamiento. En el caso de la epilepsia, una mala adherencia puede causar episodios de crisis epilépticas, hospitalizaciones y empeorar el pronóstico del paciente. En niños y adolescentes se ha descrito mala adherencia a los tratamientos antiepilépticos. Se han identificado factores que se relacionan a una mejor y peor adherencia, estar atentos a estos factores puede ayudar a mejorar la adherencia de los pacientes a tratamiento y prevenir complicaciones.

Patient's compliance to medical directions is essential in response to treatment. In the case of epilepsy, a low treatment compliance may result in seizures, hospitalizations and worsen the patients' long-term outcome. A low treatment adherence has been described in children and adolescents with epilepsy. There have been positive and negative factors identified for treatment adherence, physicians should be aware of them in order to improve the patients' compliance to treatment and help them have a better prognosis. Keywords: anticonvulsants, child, adolescent, treatment adherence and compliance.

Trends in prescribing patterns of antiepileptic drugs among older adult inpatients in a Brazilian tertiary center / Tendências no padrão de prescrição de drogas antiepilépticas em idosos internados em um centro terciário brasileiro

ABSTRACT Background: Data on prescribing patterns of antiepileptic drugs (AEDs) to older adult inpatients are limited. Objective: To assess changes in prescribing patterns of AEDs to older adult inpatients with late-onset epilepsy between 2009-2010 and 2015-2019, and to interpret any unexpected patterns over the 2015-2019 period. Methods: Patients aged ≥60 years with late-onset epilepsy from a tertiary center were selected. Demographic data, seizure characteristics and etiology, comorbidities, and comedications were analyzed, in addition to prescription regimens of inpatients taking AEDs to treat epilepsy. AED regimens were categorized into two groups: group 1 included appropriate AEDs (carbamazepine, oxcarbazepine, valproic acid, gabapentin, clobazam, lamotrigine, levetiracetam, topiramate, and lacosamide); and group 2 comprised suboptimal AEDs (phenytoin and phenobarbital). Multivariate logistic regression analysis was performed to identify risk factors for prescription of suboptimal AEDs. Results: 134 patients were included in the study (mean age: 77.2±9.6 years). A significant reduction in the prescription of suboptimal AEDs (from 73.3 to 51.5%; p<0.001) was found; however, phenytoin remained the most commonly prescribed AED to older adult inpatients. We also found an increase in the prescription of lamotrigine (from 5.5 to 33.6%) and levetiracetam (from 0 to 29.1%) over time. Convulsive status epilepticus (SE) and acute symptomatic seizures associated with remote and progressive etiologies were risk factors for the prescription of suboptimal AEDs. Conclusions: Phenytoin was the main suboptimal AED prescribed in our population, and convulsive SE and acute symptomatic seizures associated with some etiologies were independent risk factors for phenytoin prescription. These results suggest ongoing commitment to reducing the prescription of suboptimal AEDs, particularly phenytoin in Brazilian emergence rooms.

RESUMO Introdução: Os dados referentes à prescrição de drogas antiepilépticas (DAE) em pacientes idosos hospitalizados são limitados. Objetivo: Avaliar as mudanças no padrão de prescrição de DAE em idosos hospitalizados com epilepsia de início tardio, entre 2009-2010 e 2015-2019, e interpretar quaisquer padrões inesperados no período de 2015-2019. Métodos: Foram selecionados pacientes com ≥60 anos com epilepsia de início tardio admitidos em um centro terciário. Analisamos os dados demográficos, as características e etiologia das crises, as comorbidades e as comedicações. Foram avaliados os esquemas de prescrição das DAE no tratamento de epilepsia para pacientes internados. Os regimes de DAE foram categorizados em dois grupos: o grupo 1 incluiu as DAE apropriadas (carbamazepina, oxcarbazepina, ácido valproico, gabapentina, clobazam, lamotrigina, levetiracetam, topiramato e lacosamida); e o grupo 2 compreendeu as DAE subótimas (fenitoína e fenobarbital). A análise de regressão logística multivariada foi realizada para identificar fatores de risco para prescrição de DAE subótimas. Resultados: Foram incluídos 134 pacientes (idade média: 77,2±9,6 anos). Encontramos uma redução significativa do uso das DAE subótimas (73,3 para 51,5%; p<0.001); entretanto, a fenitoína permaneceu sendo a DAE mais prescrita para os idosos hospitalizados. Também encontramos um aumento na prescrição da lamotrigina (5,5 para 33,6%) e do levetiracetam (0 para 29,1%) no período. O estado de mal epiléptico (EME) convulsivo e as crises agudas sintomáticas que estiveram associadas a etiologias remotas e progressivas foram fatores de risco para prescrição de DAE subótimas. Conclusões: A fenitoína foi a principal DAE subótima prescrita em nossa população, e o EME convulsivo e as crises agudas sintomáticas associadas a algumas etiologias foram fatores independentes de risco para a prescrição da fenitoína. Esses resultados sugerem a necessidade de compromisso contínuo para reduzir a prescrição de DAE subótimas, particularmente a fenitoína nas salas de emergência brasileiras.

Anestesia para el paciente con traumatismo encéfalocraneano / Anesthesia for the Traumatic Brain Injury Patient

Traumatic brain injury (TBI) is the leading cause of death and disability for children and young adults. The Glasgow Coma Scale allows to classify TBI as mild, moderate and severe. Imaging studies show the heterogeneity of the diagnosis. Primary injury is caused by mechanical impact. Secondary injury contributes significantly to prognosis by exacerbating hypoperfusion and intracranial hypertension. Even in the absence of extracranial lesions, many patients with severe TBI present significant organ dysfunction, which transforms TBI into a multisystemic pathology. Most relevant systems compromised include cardiovascular, autonomic, respiratory and coagulation. The main aims of anesthetic management are: early decompression together with prevention, early detection, and management of determinants of secondary injury. To date, there are no techniques or drugs showing a significant impact on the outcome of TBI patients. On the other hand, maintaining good hemodynamic stability, adequate oxygenation and normocarbia all contribute to a better outcome.

El trauma encéfalocraneano (TEC) es la causa más importante de muerte y discapacidad de niños y adultos jóvenes. La escala de Glasgow permite clasificarlo en leve, moderado y severo. La imagenología da cuenta de la heterogeneidad del diagnóstico. La injuria primaria es la causada por el impacto mecánico. La injuria secundaria contribuye significativamente al pronóstico al exacerbar la hipoperfusión y la hipertensión endocraneana. Aun en ausencia de lesiones extracraneales, gran parte de los pacientes con TEC severo presenta disfunción orgánica significativa, lo que lo transforma en una patología multisistémica. Destacan el compromiso cardiovascular, autonómico, respiratorio y trastornos de la coagulación, entre otros. Los objetivos del manejo anestésico son: la descompresión precoz junto con la prevención, detección temprana y manejo de factores determinantes de injuria secundaria. No existe evidencia respecto de técnicas ni fármacos que hayan demostrado un impacto significativo en el manejo del TEC, más bien, impacta positivamente el mantener la estabilidad hemodinámica, una adecuada oxigenación y normocarbia.

Association of UGT1A6 gene polymorphism with clinical outcome in pediatric epileptic patients on sodium valproate monotherapy

Pediatric epilepsy comprises chronic neurological disorders characterized by recurrent seizures. Sodium valproate is one of the common antiseizure medications used for treatment. Glucuronide conjugation is the major metabolic pathway of sodium valproate, carried out by the enzyme uridine 5′-diphosphate (UDP) glucuronosyl transferase (UGT) whose gene polymorphisms may alter the clinical outcome. The objective of this study was to assess the association between UGT1A6 genetic polymorphism and clinical outcome in terms of efficacy and tolerability in pediatric epileptic patients on sodium valproate monotherapy. Pediatric epileptic patients (n=65) aged 2-18 years receiving sodium valproate monotherapy for the past one month were included. Genetic polymorphism patterns of UGT1A6 (T19G, A541G, A552C) were evaluated by PCR-RFLP. Clinical outcome was seizure control during the 6 months observation period. Tolerability was measured by estimating the hepatic, renal, and other lab parameters. Out of 65 patients, TT (40%), TG (57%), and GG (3%) patterns were observed in UGT1A6 (T19G) gene, AA (51%), AG (40%), and GG (9%) in (A541G) gene, and AA (43%), AC (43%), and CC (14%) in (A552C) gene. No statistical difference in clinical outcome was found for different UGT1A6 genetic polymorphism patterns. We concluded that different patterns of UGT1A6 genetic polymorphism were not associated with the clinical outcome of sodium valproate in terms of efficacy and tolerability. Sodium valproate was well-tolerated among pediatric patients with epilepsy and can be used as an effective antiseizure medication.

¿Encefalopatía o encefalitis por varicela-zóster? Una paciente con una punción lumbar engañosa / ENCEPHALOPATHY OR VARICELLA-ZOSTER ENCEPHALITIS? A PATIENT WITH A TRICKY LUMBAR PUNCTURE

La encefalopatía es un cuadro clínico característico de múltiples procesos neurológicos y sistémicos que no hay que confundir con la encefalitis, que es una inflamación cerebral, normalmente causadas por infecciones virales. Se presenta el caso de una mujer de 58 años con enfermedad renal crónica en diálisis peritoneal, que ingresa por sepsis de origen peritoneal con clínica de encefalopatía y crisis epilépticas parciales. La paciente presenta lesiones de herpes zóster en zona lumbar y se practica punción lumbar, con resultado del líquido cefalorraquídeo positivo para virus varicela-zóster, por lo que completa tratamiento con aciclovir. En la resonancia magnética no presenta ninguna alteración, y una segunda punción lumbar tras mejoría de las lesiones cutáneas es negativa. El curso de la paciente es fluctuante durante el ingreso, con mejoría significativa tras antibióticos, hemodiálisis y tratamiento antiepiléptico, y no respondiendo al aciclovir. La etiología sospechada es la debida al contexto infeccioso y metabólico de la paciente. Probablemente el resultado del líquido fue contaminado por la proximidad de las lesiones herpéticas, ya que además no es frecuente encontrar encefalitis infecciosas agudas sin alteraciones en las pruebas de imagen. La mejoría final fue debida tanto a la medicación antiepiléptica como al inicio de hemodiálisis

Encefalopathy is a clinical syndrome ocurring in multiple neurologic and systemic diseases which must not be mistaken with encephalitis, that is a cerebral inflammatory process, often caused by viral infections. We present the case of a 58-year-old woman with chronic renal failure receiving peritoneal dyalisis, who was admitted into hospital for sepsis secondary to infectious peritonitis, with encefalopathy and epileptic partial seizures. The patient presented lumbar herpetic cutaneous lesions and a lumbar punction is practiced, with a positive result in the cerebrospinal fluid for varicella-zoster virus. Treatment with aciclovir was completed. Her cerebral magnetic resonance was absolutely normal, and a second lumbar puncture when herpetic lesions got better was negative. The course is fluctuating during the stay, and a significant clinical improvement occurs after antibiotics, hemodyalisis and antiepileptic treatment. The patient did not respond to aciclovir. The suspected ethiology is the infectious and metabolic context. Positivity for the virus is thought to be a contamination from the nearby herpetic lesions. Also, it is rare for an infectious acute encephalitis to present with normal radiologic imaging. The final clinical improvement was probably due to hemodyalisis initiation and the antiepileptic treatment.

Anatomical, radiological and clinical features of mesial temporal lobe epilepsy: two illustrated cases reports / Aspectos anatômicos, radiológicos e clínicos da epilepsia do lobo temporal mesial: relato ilustrado de dois casos

Mesial temporal lobe epilepsy is the most commom form of focal epilepsy in adults. Its clinical features include focal seizure, dysmnestic symptoms ­ such as déjà vu or jamais vu ­ and autonomic or psychic aura. We reported two cases of mesial temporal lobe epilepsy with similar clinical features, but with entirely different etiologies. Mesial temporal sclerosis contributes up to 70% of all mesial temporal lobe epilepsy cases and MRI usually shows reduced hippocampal volume and increased signal intensity on T2-weighted imaging. Incomplete hippocampal inversion has uncertain relation with epilepsy and is characterized by an atypical verticalized and medially positioned anatomical pattern of the hippocampus and also a deep collateral sulcus.

A epilepsia do lobo temporal mesial é a forma mais comum de epilepsia focal em adultos. Suas características clínicas incluem crises focais, sintomas dismnésicos - como déjà vu ou jamais vu - e aura autonômica ou psíquica. Relatamos dois casos de pacientes com epilepsia do lobo temporal mesial com manifestações clínicas semelhantes, mas com etiologias completamente diferentes. A esclerose mesial temporal contribui com até 70% de todos os casos de epilepsia do lobo temporal mesial e, geralmente, na ressonância magnética, apresenta atrofia do hipocampo e hipersinal na imagem ponderada em T2. A rotação incompleta do hipocampo possui uma relação incerta com a epilepsia e é caracterizada por alteração da estrutura interna do hipocampo, com um sulco colateral verticalizado e profundo.

Discinesia paroxística primaria kinesiogénica y no kinesiogénica: Reporte de 3 casos y revisión de la literatura / Paroxysmal Kinesiogenic Dyskinesia and Paroxysmal Non-Kinesiogenic Dyskinesia: Three Case Reports and a Review

Las discinesias paroxísticas son un grupo de entidades consistentes en paroxismos de diversos movimientos anormales de corta duración asociados o no a factores precipitantes. Suele afectar a sujetos jóvenes y la prevalencia es desconocida. La fisiopatología es incierta; se han identificado ciertas mutaciones que expliquen su origen. Clínicamente se pueden manifestar como ataques paroxísticos de movimientos de tipo coreoatetósico, distónicos o balísticos de corta duración y con preservación de la conciencia. Los estudios electrofisiológicos y de imagen suelen ser normales. Este grupo de trastornos del movimiento hacen parte del diagnóstico diferencial de las crisis epilépticas. El pronóstico suele ser bueno y el tratamiento es sintomático con anticonvulsivantes. Se presentarán tres casos de dos tipos de trastornos paroxísticos del movimiento y revisión de la literatura.

Paroxysmal dyskinesias are a group of entities consisting of paroxysms of diverse abnormal movements of short duration, associated or not with precipitating factors. It usually affects young subjects and its prevalence is unknown. The pathophysiology is uncertain; some mutations have been identified that explain their origin. Clinically, they can manifest as paroxysmal attacks of choreoathetosis, dystonic or ballistic movements of short duration and with preservation of consciousness. Electrophysiological and imaging studies are usually normal. This group of movement disorders are part of the differential diagnosis of epileptic seizures. Prognosis is usually good and the treatment is symptomatic with anticonvulsants. Three cases of two types of paroxysmal movement disorders and a review of the current literature are presented.

Epilepsy and acute respiratory syndrome ­ related coronavirus 2 (SARS-CoV-2): are people with epilepsy at risk? / Epilepsia e síndrome respiratória aguda relacionada ao coronavírus 2 (SARS-CoV-2): as pessoas com epilepsia estão em risco?

In February 2020, the pandemic disease designated COVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has shown to be able to cause severe illness in some patients. Recent studies have hypothesized that the SARS-CoV-2 exploits the angiotensin-converting enzyme 2 (ACE2) receptor to gain entry inside the cells and so reach the central nervous system1. Amid this context, we have about 50 million people with epilepsy taking antiseizure drugs (ASDs) and or other medications (eg.: steroids, Cannabidiol, etc.) that are at risk to be infected by SARS-CoV-2 virus. So, we did an extensive review in the literature searching for recent studies that had explored the effects of the role of SARS-CoV-2 infection and epilepsy. We did not find evidence of poor outcomes between epilepsy and COVID-19. Regarding ASDs, we have found that enzyme inducers and inhibitors can have significant interactions with drugs that have been used to treat COVID-19 such as antiretrovirals, antibiotics, and antimalarial drugs. In contrast, others have fewer or no interactions with them as such as benzodiazepines, Lamotrigine, Levetiracetam, Topiramate, Perampanel, and so on. Besides that, the management of seizures in epileptic patients and status epilepticus should not be different from the usual protocol. However, the acknowledgment of these potential drug interactions could help in the right choice of ASDs, and also be aware of potential risk drug combinations and the importance in some cases of close monitoring of serum levels and adverse events.

Desde de Fevereiro de 2020, a doença pandêmica conhecida como COVID-19, causada pelo Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) tem se mostrado capaz de acometer gravemente alguns pacientes. Estudos recentes levantaram hipóteses de que o SARSCoV-2 explora o receptor da enzima conversora de angiotensina 2 (ACE2) para entrar no interior das células e atingir o sistema nervoso central1 . Nesse contexto, temos cerca de 50 milhões de pessoas com epilepsia em uso de medicações antiepilépticas (DAEs) e ou outras medicações (como corticoesteroides, Canabidiol, etc.). Por isso, fizemos uma extensa revisão na literatura, buscando estudos recentes que exploraram os efeitos do papel da infecção por SARS-CoV-2 e da epilepsia. Até o momento, não há evidências de que pessoas com epilepsia apresentam prognóstico ruim no que se refere ao COVID-19. No que se refere aos antiepilépticos, foi encontrado que indutores e inibidores enzimáticos são os que apresentam mais interação medicamentosa com drogas utilizadas no tratamento do COVID-19, tais como antirretrovirais, antibióticos, e drogas antimaláricas, enquanto outras apresentam pouca ou nenhuma interação com esses. Além disso, o manejo de crises epilépticas e estado de mal epiléptico não deve diferente do protocolo usual. No entanto, o reconhecimento das potenciais interações medicamentosas nesse contexto pode auxiliar na escolha correta do antiepiléptico, e alertar sobre os potenciais riscos de combinação entre drogas e a importância de em alguns casos monitorizar de perto os níveis séricos e eventos adversos.

Características clínicas del trastorno de déficit atencional e hiperactividad en epilepsia / Clinical features of the attentional deficit and hyperactivity disorder in epilepsy

La epilepsia y el trastorno por déficit de atención e hiperactividad (TDAH) son condiciones frecuentes en pediatría y suelen presentarse asociadas en muchos pacientes. Su relación es compleja y comparten comorbilidad psiquiátrica. Los pacientes con ambas condiciones conjuntas, epilepsia y TDAH, se presentan con igual frecuencia en ambos géneros, predominando la presentación inatenta. El déficit cognitivo incrementa el riesgo de asociar TDAH en pacientes con epilepsia. No hay evidencia suficiente para otros factores de riesgo, sin embargo, se puede anticipar su presencia en pacientes con algunos tipos de epilepsia y con modelos neuropsicológicos que evidencian la disfunción de redes subyacentes. Se revisa la relación con el control de crisis, las alteraciones electroencefalográficas y los fármacos antiepilépticos (FAEs). Se describen las recomendaciones para reducir efectos adversos de FAEs. El diagnóstico de TDAH en pacientes con epilepsia debe partir por la sospecha, a través de instrumentos clínicos y valoraciones de funcionamiento cognitivo. El tratamiento multimodal es recomendado para pacientes con TDAH con y sin epilepsia. Los psicoestimulantes se pueden usar con seguridad. La calidad de vida se afecta en pacientes y sus familias, por lo que la educación, pesquisa precoz y referencia para rehabilitación, están encaminadas a resolver las dificultades de estos pacientes. En caso contrario, se generan consecuencias negativas escolares, sociales y emocionales, que pueden ser relevantes y persistentes.

Epilepsy and attention deficit and hyperactivity disorder (ADHD) are frequent conditions in pediatrics. Their association is frequent and complex, often sharing psychiatric comorbidity. Patients who present epilepsy and ADHD, show equal frequency in both genders, with the inattentive type, as predominant presentation. Cognitive deficit increases the risk of associating ADHD in patients with epilepsy. There is not enough evidence for other risk factors, however there is enough information that allows to ant icipate its presence in some types of epilepsy, with neuropsychological models that evidence the underlying network dysfunction. The relationship with frequency and seizure control, electroencephalographic alterations and antiepileptic drugs (AEDs) is also reviewed. Recommendations to reduce adverse effects of AEDs are described. The diagnosis must therefore be based on suspicion, through clinical instruments and assessments of cognitive functioning. Multimodal treatment is also recommended in patients with ADHD with and without epilepsy. Psych stimulants can be used safely. The quality of life of the patients and their families is affected, so it is advisable for them to be supported by a specialized team that could provide education, early assessment and therapy. If they are omitted, the consequences can be negative at school, social environment and emotional development, which could be relevant and become persistent.

Diagnóstico de encefalite límbica não paraneoplásica de etiologia imunomediada: estudo de caso e revisão de literatura / Diagnosis of immune-mediated non-paraneoplastic limbic encephalitis: case report and literature review

A encefalite límbica vem sendo descrita como um distúrbio neurológico raro, que afeta seletivamente as estruturas do sistema límbico. Clinicamente, é caracterizada como uma desordem neurológica debilitante, que se desenvolve como encefalopatia rapidamente progressiva, causada por inflamação encefálica. Objetivamos aqui relatar um caso de encefalite do sistema límbico de provável etiologia autoimune para melhor conhecimento da comunidade médica, bem como averiguar métodos diagnósticos deste quadro. Paciente do sexo masculino, 59 anos, admitido em nosso serviço com queixa de confusão mental. O exame clínico evidenciou desorientação, disartria, paresia e parestesia no hemicorpo esquerdo, dificuldade de marcha, desvio de rima e histórico de epilepsia há 2 anos. No estudo por ressonância magnética do crânio, foram observadas extensas lesões que acometiam a região mesial do lobo temporal direito, todo o hipocampo e giro para-hipocampal direito, estendendo-se pelo fórnix até a porção posterior do hipocampo esquerdo, substância branca do lobo frontal bilateral. Mediante os resultados da investigação complementar, o paciente foi tratado com pulsoterapia de metilpredinisolona por 5 dias, resultando na regressão parcial dos sintomas. Atualmente, o paciente se encontra em seguimento ambulatorial para acompanhamento. A encefalite límbica é uma doença rara, porém muito importante de ser investigada e diagnosticada precocemente, uma vez que a progressão da doença pode causar incapacidade e sequelas irreversíveis.

Limbic encephalitis has been described as a rare neurological disorder affecting the limbic system structures selectively. Clinically, it is characterized as a debilitating neurological syndrome that develops as a quickly progressive encephalopathy caused by brain inflammation. This paper reports a case of limbic encephalitis, probably of autoimmune etiology, aiming to improve the knowledge of the medical community, and to promote a debate on diagnosis methods for this pathology. The patient is male, 59 years old, and was admitted at our service complaining of mental confusion. The clinical examination showed disorientation, dysarthria, left hemiparesis and paresthesia, gait difficulties, light asymmetrical smile, and history of epilepsy 2 years ago. The magnetic resonance imaging of skull showed extensive lesions affecting the mesial region of the right temporal lobe, the entire hippocampus, and right parahippocampal gyrus, extending through the fornix to the posterior portion of the left hippocampus, white matter of bilateral frontal lobe. Based on the complementary investigation results, the patient was treated with intravenous methylprednisolone for five days. Currently, he is being followed in the outpatient's department. Although being rare, limbic encephalitis shall be investigated and diagnosed early because its progression can lead to disability and irreversible sequelae

Estado epiléptico refractario en UCIP. Experiencia en un hospital de la Provincia de Buenos Aires / Refractory status epilepticus in the PICU. Experience at a hospital in the Province of Buenos Aires

Introducción: El estado epiléptico (EE) es la emergencia neurológica más frecuente en pediatría. Los pacientes que no responden al tratamiento estándar con dosis adecuadas de benzodiacepinas seguido de una droga antiepiléptica aceptable son definidos como Estado epiléptico Refractario (ER). Objetivo: caracterizar la población de niños con EE que ingresan a UCIP y determinar qué factores son predictores de refractariedad en esta población. Métodos: Estudio de casos y controles, retrospectivo. Población: niños con EE internados en UCIP desde Febrero 2015 a Febrero 2017. Casos: Estado epiléptico Refractario (ER). Controles: Estado epiléptico No Refractario (ENR). Se calculó el Odds Ratio (OR) individual para las distintas variables en Med Calc. Resultados: Se internaron 35 pacientes de los cuales 12 fueron casos y 23 controles. Hubo fiebre en 77% de los pacientes. En el total de niños estudiados hubo 11% con antecedente de convulsión febril, 11% con antecedente de epilepsia y 9% con antecedente de malformación del SNC. Los niños con antecedente de convulsión febril tuvieron 2,5 veces mayor riesgo de ER (OR: 2,58; IC 95%: 1,17-5,68). Los niños con EE que tenían antecedentes de enfermedad neurológica previa presentaron riesgo de ER 2,6 veces mayor que el grupo control (OR 2,60; IC 95%: 1,24-5,42). Discusión: Dado el aumento en la mortalidad de los pacientes con ER sería importante disponer de más herramientas para predecir este desenlace e iniciar tratamiento oportuno. Resultaría útil entrenar a los padres de niños con antecedente de convulsión febril en la aplicación de medicación antiepiléptica prehospitalaria, esto podría prevenir la farmacorresistencia, el daño neurológico y las complicaciones que acarrea el ingreso a UCIP. (AU)

Introduction: Status epilepticus (SE) is the most common neurologic emergency in children. Patients that do not respond to standard treatment with adequate doses of benzodiazepines followed by an acceptable antiepileptic drug are defined as having refractory status epilepticus (RSE). Objective: To characterize the population of children with SE admitted to the PICU and to determine predictive factors for refractoriness in this population. Methods: A retrospective case-control study was conducted. Population: Children with SE admitted to the PICU between February 2015 and February 2017. Cases: Refractory status pilepticus (RSE). Controls: Non-refractory status epilepticus (NRSE). Individual Odds Ratio (OR) was calculated for different variables using Med Calc. Results: 35 patients were admitted of whom 12 were cases and 23 controls. Overall, 77% of the patients had fever. Of all the children, 11% had a history of febrile seizures, 11% had history of epilepsy and 9% had a CNS malformation. Children with a history of febrile seizures had a 2.5-fold higher risk of developing RSE (OR: 2.58; 95% CI: 1.17-5.68). Children with SE that had a history of neurologic disease had a 2.6-fold higher risk of developing RSE than controls (OR 2.60; 95% CI: 1.24-5.42). Discussion: Given the increased mortality in children with RSE, availability of tools to predict this outcome in order to initiate early treatment is important. It would be useful to train the parents of children with a history of febrile seizures in the prehospital administration of antiepileptic drugs as this may prevent pharmaco-resistance, neurologic damage, and complication related to PICU admission (AU)