Fármacos antiepilépticos usados en el embarazo y sus consecuencias sobre los resultados fetales: una revisión de la literatura / Antiepileptic drugs used in pregnancy and their consequences on fetal outcomes: a review of the literature

Los riesgos teratogénicos ocasionados por la exposición intrauterina a fármacos antiepilépticos (FAE) son conocidos, por lo que su prescripción se mantiene bajo estricto control. Describir los efectos adversos fetales de la exposición a FAE durante la gestación, reportados en la literatura durante el período 2016-2022. Revisión sistematizada de estudios que reportaron los efectos adversos fetales inducidos por la exposición a FAE en mujeres embarazadas en tratamiento por diagnósticos neurológicos, principalmente de epilepsia. La búsqueda se realizó en PubMed, Cochrane, Web of Science, SCOPUS, Biblioteca Virtual en Salud, Lilacs y SciELO. Se identificaron 37 artículos distribuidos en 13 países de Asia, Europa, América del Norte y Oceanía. Se observaron resultados perinatales adversos, tanto físicos como cognitivos, en la mayoría de los estudios. Los fármacos identificados como los más utilizados en los últimos años fueron valproato, topiramato, carbamazepina, lamotrigina y levetiracetam. Los FAE tienen potencial teratogénico en distintos grados de riesgo, provocando anomalías congénitas o efectos adversos en múltiples sistemas del cuerpo humano, siendo los sistemas nervioso, circulatorio y osteomuscular los más afectados.

The teratogenic risks caused by intrauterine exposure to antiepileptic drugs (AED) are known, so their prescription is kept under strict control. To describe the fetal adverse effects AED exposure during gestation, reported in the literature during the period 2016-2022. Systematized review of studies that reported fetal adverse effects induced for the exposure to AED in pregnant women in treatment for neurological diagnoses, mainly epilepsy. The search was carried out in PubMed, Cochrane, Web of Science, SCOPUS, Virtual Health Library, Lilacs and SciELO. 37 articles distributed in thirteen countries in Asia, Europe, North America and Oceania were identified. Adverse perinatal outcomes, both physical and cognitive, were observed in most studies. The most common drugs identified were valproate, topiramate, carbamazepine, lamotrigine and levetiracetam. AED have teratogenic potential in different degrees of risk, causing congenital anomalies or adverse effects in multiple systems of the human body, being the nervous, circulatory and musculoskeletal systems the most affected.

Endogenous and exogenous serotonin, but not sumatriptan, ameliorate seizures and neuroinflammation in the pentylenetetrazole-induced seizure model in rats / A serotonina endógena e exógena, mas não o sumatriptano, melhora as convulsões e a neuroinflamação no modelo de convulsão induzida por pentilenotetrazol em ratos

ABSTRACT Background: Epilepsy has neuropsychiatric comorbidities such as depression, bipolar disorder, and anxiety. Drugs that target epilepsy may also be useful for its neuropsychiatric comorbidities. Objective: To investigate the effects of serotonergic modulation on pro-inflammatory cytokines and the seizures in pentylenetetrazole (PTZ)-induced seizure model in rats. Methods: Male Wistar rats were injected intraperitoneally with serotonin, selective serotonin reuptake inhibitor fluoxetine, 5-HT1B/D receptor agonist sumatriptan, or saline 30 min prior to PTZ treatment. Behavioral seizures were assessed by the Racine's scale. Concentrations of IL-1β, IL-6, and TNF-α in serum and brain tissue were determined by ELISA. Results: Serotonin and fluoxetine, but not sumatriptan, alleviated PTZ-induced seizures by prolonging onset times of myoclonic-jerk and generalized tonic-clonic seizures. The anti-seizure effect of fluoxetine was greater than that of serotonin. Likewise, serotonin and fluoxetine, but not sumatriptan, reduced PTZ-induced increases in the levels of IL-1β and IL-6 in both serum and brain tissue. None of the administered drugs including PTZ affected TNF-α concentrations. Conclusions: Our findings suggest that endogenous and exogenous serotonin exhibits anticonvulsant effects by suppressing the neuroinflammation. It seems that 5-HT1B/D receptors do not mediate anticonvulsant and anti-neuroinflammatory effects of serotonin.

RESUMO Antecedentes: A epilepsia apresenta comorbidades neuropsiquiátricas como depressão, transtorno bipolar e ansiedade. Os medicamentos que visam o tratamento da epilepsia podem ser úteis para a epilepsia e suas comorbidades neuropsiquiátricas. Objetivo: Investigar os efeitos da modulação serotonérgica em citocinas pró-inflamatórias e as convulsões no modelo de convulsão induzida por pentilenotetrazol (PTZ) em ratos. Métodos: Ratos Wistar machos foram injetados intraperitonealmente com serotonina, inibidor seletivo da recaptação da serotonina fluoxetina, sumatriptano agonista do receptor 5-HT1B / D ou solução salina 30 min antes do tratamento com PTZ. As crises comportamentais foram avaliadas pela escala de Racine. As concentrações de IL-1β, IL-6 e TNF-α no soro e tecido cerebral foram determinadas por ELISA. Resultados: A serotonina e a fluoxetina, mas não o sumatriptano, aliviaram as convulsões induzidas por PTZ ao prolongar os tempos de início das convulsões mioclônicas e tônico-clônicas generalizadas. O efeito anticonvulsivo da fluoxetina foi maior do que o da serotonina. Da mesma forma, a serotonina e a fluoxetina, mas não o sumatriptano, reduziram os aumentos induzidos por PTZ nos níveis de IL-1β e IL-6 no soro e no tecido cerebral. Nenhum dos medicamentos administrados, incluindo PTZ, alterou as concentrações de TNF-α. Conclusões: Nossos achados sugerem que a serotonina endógena e exógena exibe efeitos anticonvulsivantes por suprimir a neuroinflamação. Aparentemente, os receptores 5-HT1B / D não medeiam os efeitos anticonvulsivantes e anti-neuroinflamatórios da serotonina.

Eficácia do topiramato como terapia adicional em pacientes com estado epiléptico refratário: uma breve revisão sistemática / Efficacy of topiramate as an add-on therapy in patients with refractory status epilepticus: a short systematic review

RESUMO Objetivo: Identificar evidências atuais sobre topiramato para o estado de mal epiléptico refratário. Métodos: Foi revisada a literatura para investigar a eficácia do topiramato no tratamento de estado de mal epiléptico refratário. Os termos de busca utilizados foram: "status epilepticus", "refractory", "treatment" e "topiramate". Não se empregaram restrições. Resultados: A busca identificou 487 artigos que descreviam o uso de topiramato para tratamento de estado de mal epiléptico refratário e seus resultados. Relatos de caso, revisões e experimentos em animais foram excluídos. Após exclusão de duplicatas e aplicação dos critérios de inclusão e exclusão, restaram nove estudos. Realizaram-se análises descritivas e qualitativas, com os seguintes resultados: as taxas de resposta, definidas como término de crises até 72 horas após administração de topiramato, variaram entre 27% e 100%. A mortalidade variou de 5,9% a 68%. Desfechos funcionais positivos, definidos como alta hospitalar, volta à funcionalidade basal ou reabilitação, foram documentados por sete estudos, e as taxas variaram entre 4% e 55%. A maioria dos estudos reportou apenas efeitos colaterais leves ou ausentes. Conclusão: Topiramato foi efetivo em abortar estado de mal epiléptico refratário, apresentando baixa mortalidade e boa tolerabilidade. Portanto, topiramato poderia ser uma boa opção como terceira linha para estado de mal epiléptico refratário, porém mais estudos são necessários.

ABSTRACT Objective: To identify current evidence on the use of topiramate for refractory status epilepticus. Methods: We reviewed the literature to investigate the efficacy of topiramate in the treatment of refractory status epilepticus. The search terms used were "status epilepticus", "refractory", "treatment" and "topiramate". No restrictions were used. Results: The search yielded 487 articles that reported using topiramate as a treatment for refractory status epilepticus and its outcomes. Case reports, review articles, and animal experiments were excluded. After excluding duplicates and applying inclusion and exclusion criteria, nine studies were included for analyses. Descriptive and qualitative analyses were performed, and the results were as follows: response rates (defined as termination in-hospital until 72 hours after the administration of topiramate) varied from 27% to 100%. The mortality rate varied from 5.9% to 68%. Positive functional long-term outcomes, defined as discharge, back to baseline or rehabilitation, were documented by seven studies, and the rates ranged between 4% and 55%. Most studies reported no or mild adverse effects. Conclusion: Topiramate was effective in terminating refractory status epilepticus, presented relatively low mortality and was well tolerated. Therefore, topiramate could be a good option as a third-line therapy for refractory status epilepticus, but further studies are necessary.

Anticoncepción en mujeres epilépticas / Contraception in epileptic women

Resumen La elección de un método anticonceptivo considerado como altamente efectivo en mujeres epilépticas en edad fértil es importante, ya que requiere al momento de indicarlos tener en cuenta los criterios de elegibilidad y las posibles interacciones farmacológicas entre determinados tipos de fármacos anticonvulsivantes (principalmente las inductoras enzimáticas del sistema hepático P450 como: carbamacepina, fenitoína, fenobarbital, oxacarbamacepina, eslicarbazepina, rufinamida, lacosamida y topiramato en dosis altas) y ciertos métodos anticonceptivos (anticonceptivos orales combinados o solo con progesterona e implantes de progesterona subdérmicos) pudiendo acelerar el metabolismo de estas últimas con el consiguiente riesgo de fracaso o viceversa, reduciendo la concentración plasmática (como por ejemplo; lamotrigina) predisponiendo a crisis epilépticas, riesgo de embarazos no deseados, abortos, teratogenicidad por valproato, complicaciones materno fetal y dificultad en el manejo de la actividad epiléptica durante la gestación. En caso de asociarse ambas medicaciones, se debe considerar el uso combinado con un método de barrera u optar por la utilización de inyección de depósito de acetato de medroxiprogesterona o dispositivo intrauterino como anticoncepción. Está demostrado que el asesoramiento sobre planificación familiar en la primera consulta puede influenciar en la elección del método anticonceptivo y el inicio temprano de ácido fólico en caso de búsqueda de fertilidad. En conclusión, se debe analizar junto con las pacientes epilépticas las diferentes opciones terapéuticas con el fin de lograr y optimizar la mejor meta de cada uno.

Abstract The choice of a contraceptive method considered highly effective in epileptic women of childbearing age is important, since it requires taking into account the eligibility criteria and the possible pharmacological interactions between certain types of anti-seizure drugs (mainly enzyme inducers drugs of the hepatic system P450 such as: carbamazepine, phenytoin, phenobarbital, oxacarbamazepine, eslicarbazepine, rufinamide, lacosamide and topiramate in high doses) and certain contraceptive methods (oral contraceptives combined or only with progesterone and subdermal progesterone implants), which may accelerate the metabolism of the latter with the consequent risk of failure or vice versa, reduction of plasma concentration (such as lamotrigine) predisposing to seizures, risk of unwanted pregnancies, abortions, teratogenicity due to valproato, maternalfetal complications and difficulty in the management of epileptic activity during pregnancy. In case of prescribing both medications, the combined use with a barrier method should be considered or the use of a depot injection of medroxyprogesterone acetate or intrauterine device as contraception should be considered. Family planning counseling at the first visit has been shown to influence the choice of the contraceptive method and the early initiation of folic acid in the search for fertility. In conclusion, the different therapeutic options should be analyzed together with the epileptic patients in order to achieve and optimize the best goal for each one.

Anticonvulsivantes y su efecto en el metabolismo de la vitamina D: revisión del tema, a propósito de un caso / Anticonvulsants and their effect on the metabolism of vitamin D: literature review with case report

La epilepsia es una enfermedad neurológica frecuente que afecta a cerca de 50.000 millones de personas en el mundo. En Chile, la prevalencia estimada es de 10.8 a 17 por 1.000 habitantes. La primera opción para su tratamiento son los fármacos antiepilépticos (FAE) los cuales logran un aceptable control de enfermedad en la mayoría de los casos, sin embargo, tienen la potencialidad de desencadenar una serie de efectos adversos destacando entre ellos el desarrollo de hipocalcemia (HC) secundaria a hipovitaminosis D (HD), alteración que por lo general es leve y asintomática. Presentamos el caso de una mujer perimenopausica con antecedente de epilepsia en tratamiento con anticonvulsivante que desarrolla hipocalcemia severa. Además revisamos los mecanismos descritos a través de los cuales los FAE afectan el metabolismo de esta vitamina.

Epilepsy is a common neurological disease that affects about 50,000 million people in the world. The estimated prevalence is 10.8 to 17 per 1.000 inhabitants in Chile. The first option for its treatment are antiepileptic drugs (AEDs) which achieve an acceptable control of the disease in most cases, however, they have the potential to trigger a series of adverse effects (AE) highlighting among them the development of hypocalcemia (HC) secondary to hypovitaminosis D (HD), an alteration that is generally mild and asymptomatic. We present the case of a perimenopausal woman with a history of epilepsy under treatment with an anticonvulsant who develops severe hypocalcemia. We also review the mechanisms described through which AEDs affect the metabolism of this vitamin.

Hipovitaminosis D en niños y adultos en un prestador de salud del Uruguay y su relación con el uso de antiepilépticos / The effect of antiepileptic drugs in adult and child hypovitaminosis D in a Uruguayan health institution / Hipovitaminose D em crianças e adultos em um provedor de saúde uruguaio e sua relação com o uso de medicamentos antiepilépticos

Resumen: Introducción: la hipovitaminosis D se encuentra ampliamente extendida a nivel mundial, con consecuencias clínicas a nivel óseo y extraóseo. Entre los factores que la causan se encuentran los antiepilépticos (AE). En Uruguay no se conoce su prevalencia en niños ni en pacientes que reciben AE. Objetivos: conocer la prevalencia de hipovitaminosis D de niños y adultos en un prestador de salud y compararla con la prevalencia en pacientes bajo tratamiento con AE. Método: estudio descriptivo, transversal, realizado entre marzo y diciembre de 2017. Las variables analizadas fueron: niveles de vitamina D, calcio, fósforo, fosfatasa alcalina y parathormona intacta. Se consideró insuficiencia de vitamina D niveles menores de 30 ng/ml y déficit niveles menores de 20 ng/ml. Resultados: se incluyeron 113 pacientes, 60 niños y 53 adultos. La prevalencia global de insuficiencia de vitamina D fue de 89% y déficit de 60%. En niños expuestos a AE, la media de vitamina D fue 17,5 ng/ml, y en niños no expuestos 19,6 ng/ml. En adultos la media de vitamina D fue de 18,1 en expuestos a AE y 16,9 en no expuestos. La diferencia de medias no fue estadísticamente significativa en niños ni en adultos. Se observaron niveles de calcemia significativamente descendidos en niños y adultos con AE. Conclusiones: la insuficiencia de vitamina D fue cercana a 90% y el déficit superó el 50%. No se encontraron diferencias significativas entre grupos en hipovitaminosis D, pero se observaron niveles de calcemia reducidos en los expuestos a AE. Es necesario continuar analizando los factores que la causan y sus consecuencias clínicas.

Summary: Introduction: hypovitaminosis D is a highly spread condition worldwide, with clinical consequences that affect bone directly, among other manifestations. Antiepileptic drugs are among factors that cause this deficiency. In Uruguay, there is no information about hypovitaminosis D in children or patients who receive antiepileptic drugs. Objectives: to learn about the prevalence of hypovitaminosis D in children and adults in a health institution and to compare it with the prevalence in patients receiving antiepileptic drugs. Method: descriptive, transversal study conducted from March through December, 2017. The following variables were analysed: vitamin D, calcium, phosphorous, alkaline phosphatase and intact parathyroid hormone. Vitamin D insufficiency was defined as vitamin D levels of less than 30 ng per mL and deficiency as D levels of less than 20 ng per mL. Results: 113 patients were included in the study, 60 of which were children and 53 adults. Global prevalence of vitamin D insufficiency was 89% and deficiency was 60%. In children taking antiepileptic drugs, the average vitamin D value was 17.5 ng/ml and it was 19.6 ng/ml for those not exposed to those drugs. In adults, the average vitamin D value was 18.1 in the population taking antiepileptic drugs and 16.9 in patients not taking that medication. The difference between average values was not statistically significant in children or adults. Calcemia levels observed were significantly lower in both children and adults taking antiepileptic drugs. Conclusions: vitamin D insufficiency was close to 90% and deficiency was over 50%. No significant differences were found between hypovitaminosis D groups, although reduced calcemia was observed in patients exposed to antiepileptic drugs. Further studies are necessary to analyse factors that cause this condition and its clinical consequences.

Resumo: Introdução: a hipovitaminose D está amplamente difundida em todo o mundo, com consequências clínicas a nível ósseo e extraósseo. Entre os fatores que a causam estão os medicamentos antiepilépticos (AE). No Uruguai, sua prevalência em crianças ou em pacientes adultos recebendo AE não é conhecida. Objetivos: conhecer a prevalência de hipovitaminose D em crianças e adultos em um prestador de serviços de saúde e compará-la com a prevalência em pacientes em tratamento com AE. Método: estudo transversal descritivo realizado entre março e dezembro de 2017. As variáveis analisadas foram: níveis de vitamina D, cálcio, fósforo, fosfatase alcalina e paratormona intacta. Níveis menores que 30 ng / ml e níveis de déficit menores que 20 ng / ml foram considerados como insuficiência de vitamina D. Resultados: foram incluídos 113 pacientes, 60 crianças e 53 adultos. A prevalência global de insuficiência de vitamina D foi de 89% e déficit de 60%. Em crianças expostas à AE, a média de vitamina D foi de 17,5 ng / ml e em crianças não expostas de 19,6 ng / ml. Em adultos, a média de vitamina D foi de 18,1 nos expostos ao AE e de 16,9 nos não expostos. A diferença nas médias não foi estatisticamente significativa nas crianças nem nos adultos. Níveis de cálcio significativamente diminuídos foram observados em crianças e adultos com EA. Conclusões: a insuficiência de vitamina D foi próxima a 90% e o déficit ultrapassou 50%. Não foram encontradas diferenças significativas entre os grupos na hipovitaminose D, mas níveis reduzidos de cálcio foram observados naqueles expostos a EA. É necessário continuar analisando os fatores que o causam e suas consequências clínicas.

Efficacy and safety of levetiracetam versus phenytoin as second-line drugs for the treatment of children with convulsive status epilepticus: a Meta analysis / 中国当代儿科杂志

OBJECTIVE@#To systematically evaluate the efficacy and safety of levetiracetam (LEV) versus phenytoin (PHT) as second-line drugs for the treatment of convulsive status epilepticus (CSE) in children.@*METHODS@#English and Chinese electronic databases were searched for the randomized controlled trials comparing the efficacy and safety of LEV and PHT as second-line drugs for the treatment of childhood CSE. RevMan 5.3 software was used for data analysis.@*RESULTS@#Seven studies with 1 434 children were included. The Meta analysis showed that compared with the PHT group, the LEV group achieved a significantly higher control rate of CSE (@*CONCLUSIONS@#LEV has a better clinical effect than PHT in the treatment of children with CSE and does not increase the incidence rate of adverse events.

Vitamin D deficiency in pediatric patients using antiepileptic drugs: systematic review with meta-analysis / Deficiência de vitamina D em pacientes pediátricos que fazem uso de fármacos antiepilépticos - revisão sistemática com metanálise

Abstract Objectives: To measure the prevalence of vitamin D deficiency (through the 25-hydroxyvitamin D metabolite) in pediatric patients using antiepileptic drugs. Source of data: Meta-analysis of studies identified through search in the PubMed, Embase, LILACS, and Cochrane Library databases, on February 19, 2019. Summary of data: A total of 748 articles were identified, 29 of which were relevant to the objectives of this study. The prevalence of vitamin D deficiency found was 0.32 (95% CI = 0.25-0.41; I 2 = 92%, p < 0.01). In the subgroup analyses, the most significant results were observed in the group of patients using cytochrome P450-inducing antiepileptic drugs, with a prevalence of 0.33 (95% CI = 0.21-0.47; I 2 = 86%, p < 0.01) and, considering the study design, in the subgroup of cohort studies, with a prevalence of 0.52 (95% CI = 0.40-0.64; I 2 = 76%, p < 0.01). Conclusions: Taking into account the deleterious effects of vitamin D deficiency on the bone health of individuals using antiepileptic drugs, it is suggested to include in their care 25-hydroxyvitamin D monitoring, cholecalciferol supplementation, and treatment of the deficiency, when present.

Resumo Objetivos: Mensurar a prevalência de deficiência de vitamina D (através do metabólito 25-hidroxivitamina D) em pacientes pediátricos em uso de fármacos antiepilépticos. Fonte dos dados: Metanálise de estudos identificados por meio de pesquisa nas bases de dados Pubmed, Embase, LILACS e Cochrane em 19 de fevereiro de 2019. Síntese dos dados: Foram identificados 748 artigos, dos quais 29 mostraram-se relevantes aos objetivos deste estudo. A prevalência de deficiência de vitamina D encontrada foi de 0,32 (IC 95% = 0,25-0,41) (I2 = 92%, p < 0,01). Nas análises por subgrupos, os resultados mais expressivos foram observados no grupo de pacientes em uso de fármacos antiepilépticos indutores do citocromo P450, que apresentou prevalência de 0,33 (IC 95% = 0,21-0,47) (I2 = 86%, p < 0,01). Considerou-se o delineamento dos estudos, no subgrupo de estudos de coorte, com prevalência de 0,52 (IC 95% = 0,40-0,64) (I2 = 76%, p < 0,01). Conclusões: Levando-se em consideração os efeitos deletérios da deficiência de vitamina D na saúde óssea dos sujeitos em uso de fármacos antiepilépticos, sugere-se incluir em seu atendimento, o monitoramento de 25-hidroxivitamina D, suplementação com colecalciferol e tratamento de deficiência quando existente.

Causative drugs for drug-induced cutaneous reactions in central China: a 608-case analysis

Abstract Background: Reports regarding the causative drugs of drug-induced cutaneous adverse reactions in China are indistinct, such that different regions have reported the spectrum of drugs differs substantially in different clinical conditions. Objective: To explore the causative drugs that led to cutaneous reactions. Methods: Adverse drug reaction reports from central China were collected and divided into cutaneous adverse reactions and severe cutaneous adverse reactions groups. Cases were reviewed retrospectively for causative drugs. Results: The male:female ratio was equal in both cutaneous adverse reactions and severe cutaneous adverse reactions. In cutaneous adverse reactions (n = 482), the highest incidence happened between 51 and 60 years of age and the top three causative drugs were antibiotics (48%), Chinese medicine (16%), and allopurinol (9%). In severe cutaneous adverse reactions (n = 126), the highest incidence happened between 41 and 50 years of age and the top three causative drugs were sedative-hypnotics and antiepileptics (39%), antibiotics (22%), and allopurinol (15%). Carbamazepine was the most frequently used single-drug (16/18) in sedative-hypnotics and antiepileptics. β-lactams were the most frequently used antibiotics that induced both cutaneous adverse reactions and severe cutaneous adverse reactions. Study limitations: The small sample size, retrospective design, collection of cutaneous adverse reactions and severe cutaneous adverse reactions at different time frames and locations, and exclusion of patients taking more than five medications are limitations of the study. Conclusions: Gender does not affect cutaneous adverse reactions and severe cutaneous adverse reactions. The top three drugs to induce cutaneous adverse reactions are antibiotics, Chinese medicine, and allopurinol, while those that triggered severe cutaneous adverse reactions are sedative-hypnotics and antiepileptics, antibiotics, and allopurinol. Carbamazepine is the most frequent single drug that induces severe cutaneous adverse reactions. β-lactams are the most frequently used antibiotics that induce both cutaneous adverse reactions and severe cutaneous adverse reactions.

Vinpocetina de liberación prolongada: un posible tratamiento adyuvante en crisis epiléptica de inicio focal / Extended-release vinpocetine: a possible adjuvant treatment for focal onset epileptic seizures

Resumen Introducción: La vinpocetina de liberación prolongada ha demostrado ser efectiva en el control de crisis de inicio focal en pacientes epilépticos con una baja frecuencia de eventos adversos. Se realizó un estudio clínico para evaluar la eficacia y tolerabilidad de la vinpocetina como tratamiento adyuvante en pacientes con este padecimiento. Métodos: Se realizó un estudio clínico, doble ciego, de grupos paralelos. Se reclutaron 87 pacientes con diagnóstico de epilepsia focal tratados con uno a tres fármacos antiepilépticos. Los pacientes se aleatorizaron para ser tratados con vinpocetina (n = 41) o placebo (n = 46) de manera adyuvante a su tratamiento, e ingresaron a la fase basal (4 semanas), a la fase de titulación (4 semanas) y a la fase de evaluación (8 semanas) conservando estables las dosis de la vinpocetina y de los fármacos antiepilépticos. Resultados: La vinpocetina fue más efectiva que el placebo en la reducción de las crisis al finalizar la fase de evaluación (p < 0.0001). El 69% de los pacientes tratados con vinpocetina presentaron una reducción mayor al 50% en las crisis en comparación con el 13% de los pacientes tratados con placebo. No se presentaron diferencias significativas en cuanto a la presencia de efectos adversos en los pacientes tratados con vinpocetina comparados con los tratados con placebo. Los eventos adversos más frecuentes observados con vinpocetina fueron cefalea (7.9%) y diplopía (5.2%). Conclusiones: Como tratamiento adyuvante, la vinpocetina (2 mg/kg/día) redujo eficazmente la frecuencia de crisis epilépticas y demostró ser bien tolerada. Presenta un amplio perfil de seguridad y eventos adversos conocidos, que son transitorios y sin secuelas.

Abstract Background: Extended-release vinpocetine is effective to control focal onset epileptic seizures with a low rate of adverse events. A clinical study was performed to evaluate the efficacy and tolerability of vinpocetine as an adjuvant treatment in patients with this condition. Methods: A double-blind clinical study of parallel groups was conducted, in which 87 patients with a diagnosis of focal epilepsy treated with one to three antiepileptic drugs were recruited. Patients were randomized to receive vinpocetine (n = 41) or placebo (n = 46) adjuvant to their treatment. Patients entered the baseline phase (4 weeks), the titration phase (4 weeks) and the evaluation phase (8 weeks), maintaining stable doses of vinpocetine and their respective antiepileptic drug treatment. Results: Vinpocetine was more effective than placebo in reducing seizures at the end of the evaluation phase (p < 0.0001). Sixty-nine percent of the vinpocetine-treated patients had a 50% reduction in seizures compared to 13% of placebo-treated patients. No significant differences in the presence of adverse effects in patients treated with vinpocetine compared to those treated with placebo were observed. The most frequent adverse events observed with vinpocetine were headache (7.9%) and diplopia (5.2%). Conclusions: As an adjuvant treatment, vinpocetine (2 mg/kg/day) effectively reduced the frequency of epileptic seizures and proved to be well tolerated. Vinpocetine has a wide safety profile and well-known adverse events, which are transient and with no sequelae.

Perfil de pacientes em idade reprodutiva tratadas por epilepsia / Profile of patients in reproductive age treated by epilepsy

Objetivo: Descrever o perfil de pacientes em idade reprodutiva internadas por epilepsia nas regiões brasileiras em 5 anos, elucidando os riscos promovidos por ela durante a gravidez e abordando o gerenciamento do quadro. Métodos: Pesquisa e análise de dados disponibilizados pelo Departamento de Informática do Sistema Único de Saúde (DATASUS), acerca das internações em mulheres em idade reprodutiva (10 a 49 anos) por epilepsia, avaliando a ocorrência, de acordo com faixa etária, etnia e região do Brasil, no período de janeiro de 2012 a dezembro de 2016. Resultados: No total, foram notificadas 42.204 internações de mulheres em idade reprodutiva associadas à epilepsia, estando a maior parte delas (22,66%) na faixa de 20 a 29 anos e na de 40 a 49 anos (22,59%). O Sudeste correspondeu a 43,01% do total de casos (18.152), seguido pela Região Sul, com 9.456 registros (22,4%), e pelo Nordeste (8.245; 19,53%). A etnia mais atingida foi a de brancas (15.804; 37,44% dos atendimentos) e pardas (12.200; 28,9%). Conclusão: O planejamento da gravidez em mulheres epilépticas contribui para redução dos riscos tanto maternos quanto fetais, pois permite ao prescritor e à gestante pesar quais os benefícios e os malefícios de cada terapia anticonvulsivante disponível. Vale lembrar que uma abordagem individualizada da paciente epiléptica grávida por equipe multidisciplinar se faz necessária para melhorar os desfechos e prevenir internações por crises convulsivas. (AU)

Objective: To describe the profile of female patients in childbearing age hospitalized due to epilepsy in the Brazilian regions in 5 years, elucidating the risks it causes during pregnancy, and addressing the management of the condition. Methods: Research and analysis of data provided by the Informatics Department of the Unified Health System (DATASUS), concerning hospitalizations of women of childbearing age (10-49 years) due to epilepsy, evaluating the occurrence according to age, ethnicity and the region in Brazil, from January 2012 to December 2016. Results: A total of 42,204 admissions of women of childbearing age due to epilepsy were reported, with most of them in the age group from 20 to 29 years old (22,66%), and in the 40-49 age group (22.59%). The Southeast Region accounted for 43.01% of the total number of cases (18,152), followed by the South Region, with 9,456 records (22.4%), and the Northeast (8,245 - 19.53%). The most affected ethnic group was the white one (15,804; 37,44% of the admissions) and brown one (12,200; 28,9%). Conclusion: Pregnancy planning in epileptic women contributes to both maternal and fetal risk reduction, since it allows the prescriber and the pregnant woman to weigh the benefits and harms of each available anticonvulsant therapy. It is worth remembering that an individualized, multidisciplinary approach of the epileptic pregnant patient is necessary to improve the outcomes, and to prevent hospitalizations due to seizures. (AU)

Síndrome de sensibilidad a drogas con eosinofilia y síntomas sistémicos (DRESS) atípico por carbamazepina, a propósito de un caso pediátrico / Drug sensitivity syndrome with eosinophilia and atypical symptoms (DRESS) by carbamazepine: a case report

Introducción: El síndrome de sensibilidad a drogas con eosinofilia y síntomas sistémicos (DRESS) generalmente es acompañado por eosinofilia. Es una enfermedad que pone en peligro la vida del paciente. Se presenta como reacción adversa a infecciones y a medicamentos, usualmente asociada al uso de antiepilépticos. Caso clínico: Paciente de 6 años, masculino, con antecedente de Epilepsia de reciente diagnóstico, que consultó en Servicio de Urgencias dos semanas después de iniciar tratamiento con Carbamazepina, por cuadro caracterizado por eritema de predominio facial, exacerbado con la exposición al sol. Posteriormente presentó fiebre con episodios hasta 40 °C, que se asoció a convulsiones. Después de un exhaustivo estudio se concluyó DRESS atípico (sin eosinofilia), iniciando tratamiento corticoideo con favorable respuesta clínica. Discusión: El síndrome de DRESS, es una enfermedad de difícil diagnóstico por sus múltiples diagnósticos diferenciales y falta de criterios diagnósticos. Es esencial la suspensión inmediata del fármaco causante, para evitar progresión de la enfermedad e iniciar tratamiento precoz.

Background: The drug sensitivity syndrome with eosinophilia and systemic symptoms (DRESS) is usually accompanied by eosinophilia. It is a disease that endangers the life of the patient. It occurs as an adverse reaction to infections and medications, usually associated with the use of antiepileptics. Case report: A 6-year-old patient, male, with a recent diagnosis of epilepsy, who consulted the Emergency Department two weeks after initiating treatment with Carbamazepine because of a condition characterized by facial predominance erythema, exacerbated by sun exposition. Subsequently presented fever with episodes up to 40 ° C, which was associated with seizures. After an exhaustive study, atypical DRESS syndrome (without eosinophilia) was made, initiating corticoid treatment with favorable clinical response. Discussion: DRESS syndrome is a disease difficult to diagnose because of its multiple differential diagnoses and lack of diagnostic criteria. Immediate suspension of the causative drug is essential to prevent progression of the disease and initiate early treatment Keywords: Drug Hypersensitivity Syndrome, Carbamazepine, Corticoid.

Levetiracetam and lamotrigine effects as mono- and polytherapy on bone mineral density in epileptic patients / Efeitos do levetiracetam e lamotrigina, em mono e politerapia, na densidade mineral óssea de pacientes epilépticos

ABSTRACT The purpose of this study was to determine the effect of lamotrigine (LTG) and levetiracetam (LEV) as mono- and polytherapy on biochemical markers of bone turnover and bone mineral density in Egyptian adult patients with epilepsy. Methods Forty-eight patients were divided into four groups: two received monotherapy of either LTG or LEV, and the other two groups received polytherapy comprising (valproate [VPA] + LTG or VPA + LEV). Thirty matched healthy participants were included in the study. Participants completed a nutritional and physical activity questionnaire. Biochemical markers of bone and mineral metabolism and bone mineral density of the lumbar spine were measured at baseline and at six months. Results In the LEV monotherapy group, the bone formation markers showed a significant decrease in serum alkaline phosphatase and serum osteocalcin levels while the bone resorption marker showed a significant increase in urinary deoxypyridinoline levels. After six months of treatment, bone mineral density showed a significant decrease in all treated groups, while among monotherapy groups, this significant decrease was more prevalent in the LEV monotherapy group compared with the LTG monotherapy group. Furthermore, there was significant negative correlation between urinary deoxypyridinoline levels and bone mineral density in the LEV monotherapy group. Conclusion Using new generation antiepileptics, LEV monotherapies and polytherapy showed harmful effects on bone but LTG did not.

RESUMO O objetivo deste estudo foi determinar o efeito da lamotrigina (LTG) e levetiracetam (LEV) como mono e politerapia em marcadores bioquímicos de remodelação óssea e densidade mineral óssea em pacientes adultos egípcios com epilepsia. Métodos Quarenta e oito pacientes foram divididos em quatro grupos: dois grupos receberam monoterapia de LTG ou LEV e os outros dois grupos receberam politerapia (valproato [VPA] + LTG ou VPA + LEV). Trinta participantes saudáveis controle foram incluídos no estudo. Os participantes preencheram um questionário nutricional e de atividade física. Marcadores bioquímicos do metabolismo ósseo e mineral e densidade mineral óssea da coluna lombar foram medidos no início e aos seis meses. Resultados No grupo de monoterapia LEV, os marcadores de formação óssea mostraram uma diminuição significativa nos níveis séricos de fosfatase alcalina e osteocalcina sérica, enquanto o marcador de reabsorção óssea mostrou um aumento significativo nos níveis de desoxipiridinolina urinária. Após seis meses de tratamento, a densidade mineral óssea mostrou uma diminuição significativa em todos os grupos tratados, enquanto entre os grupos de monoterapia, esta diminuição significativa foi mais prevalente no grupo de monoterapia LEV em comparação com o grupo de monoterapia LTG. Além disso, houve correlação negativa significativa entre os níveis de desoxipiridinolina urinária e densidade mineral óssea no grupo de monoterapia LEV. Conclusão Utilizando antiepilépticos de nova geração, as monoterapias LEV e a politerapia mostraram efeitos prejudiciais no osso, mas a LTG não.

Síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos debido a la carbamazepina: Caso pediátrico / Drug reaction with eosinophilia and systemic symptoms due to carbamazepine: Pediatric case

Entre las reacciones medicamentosas graves en la piel, se encuentran el síndrome de Stevens-Johnson, la necrólisis epidérmica tóxica y el síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos (drug reaction with eosinophilia and systemic symptoms; DRESS, por sus siglas en inglés), que son poco comunes en la población pediátrica (incidencia: 1/1000-10 000 niños), sin embargo, tienen mal pronóstico. El síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos consiste en erupciones cutáneas, alteraciones hematológicas, linfadenopatía y afectación de órganos. Se presenta el caso de un paciente masculino de 12 años que desarrolló esta patología después de iniciar el tratamiento anticonvulsivo con carbamazepina. Se considera que es importante que el personal de la salud tenga conocimiento de esta enfermedad para que sea incluida entre los diagnósticos diferenciales de pacientes con afecciones similares, ya que este síndrome es potencialmente mortal.

Severe skin reactions include Stevens-Johnson Syndrome, toxic epidermal necrolysis and Drug reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, which are uncommon in the pediatric population (incidence 1/1000-10 000 children), but they have bad prognosis. Drug-sensitive Syndrome with eosinophilia and systemic symptoms consists in rash, hematological abnormalities, lymphadenopathy and organ involvement. We report the case of a 12-year-old male patient who developed this pathology after initiating anticonvulsant therapy with carbamazepine. We consider that it is important to be aware of this disease and to include it among the differential diagnoses in patients with similar conditions because this syndrome is life-threatening.

Síndrome por Infusión de propofol en un caso de estatus epiléptico refractario / Propofol infusion syndrome in a refractory epileptic status case

INTRODUCCIÓN: El síndrome por infusión de propofol (SIP) es una reacción adversa poco frecuente, pero potencialmente letal descrita por la utilización de dicho fármaco en infusión intravenosa (IV) continua. El diagnóstico se basa en la combinación de acidosis metabólica, rabdomiolisis, hiperkalemia, hepatomegalia, insuficiencia renal, hiperlipidemia, arritmias e insuficiencia cardiaca rápida mente progresiva. OBJETIVO: Presentación de un caso clínico de SIP y revisión de literatura. CASO CLÍNICO: Paciente femenino de 6 años de edad con antecedentes de epilepsia secundaria a extensa alteración del desarrollo cortical hemisférico derecho. Presentó estatus epiléptico refractario que requirió ingreso a Unidad de Cuidados Intensivos para soporte vital y tratamiento, el que incluyó como terapia de tercera línea infusión intravenosa continua de propofol en dosis progresivas hasta alcanzar una tasa 10 mg/kg/h. Cursó con compromiso hemodinámico y a las 24 h de iniciado el tratamiento se observó alza de la creatinifosfokinasa (CK), acidosis metabólica y lactacidemia elevada, y luego de descartar otras causas se planteó el diagnóstico de SIP por lo que se suspendió la droga, logrando estabilización hemodinámica a las 24 h. DISCUSIÓN: El diagnóstico de SIP es complejo, se debe considerar en pacientes que estén recibiendo el fármaco y presenten acidosis metabólica o insuficiencia cardiaca. Los factores que más influyen en la mortalidad son la dosis acumulativa de la droga, la presencia de fiebre y lesión encéfalo craneana. En el caso descrito la paciente recibió una dosis mayor a 4 mg/ kg/h que es la dosis máxima recomendada y respondió favorablemente luego de 12 h después de la suspensión del fármaco.

INTRODUCTION: Propofol Infusion Syndrome (PRIS) is a rare but potentially lethal adverse reaction secondary to the continuous intravenous infusion of this drug. The diagnosis is based on the com bination of metabolic acidosis, rhabdomyolysis, hyperkalemia, hepatomegaly, renal failure, hyperli pidemia, arrhythmias, and rapidly progressive heart failure. OBJECTIVE: To report a case of PRIS and literature review. CLINICAL CASE: A 6-year-old female patient with history of epilepsy secondary to large malformation of cortical development of the right hemisphere. The patient presented a refractory status epilepticus that required admission to the Intensive Care Unit for life support and treatment, which included continuous intravenous infusion of propofol at 10 mg/kg/h. She developed hemo dynamic instability, and after 24 h of treatment an increase of creatine phosphokinase (CPK) levels, metabolic acidosis and elevated lactacidemia were observed. After ruling out other causes, PRIS was diagnosed; therefore, the drug was suspended, achieving hemodynamic stabilization after 24 hours. DISCUSSION: The diagnosis of PRIS is complex and should be considered in patients who are receiving this drug and present metabolic acidosis or heart failure. The factors that most influence mortality are the cumulative dose of the drug, the presence of fever, and cranial brain injury. In the case described, the patient received a dose higher than 4 mg/kg/h, which is the maximum recommended dose, and responded favorably 12 hours after stopping the drug.

Epilepsia na gravidez / Epilepsy in pregnancy

As epilepsias constituem uma das mais frequentes condições neurológicas encontradas na gravidez, ocorrendo entre 0,5% e 1% das gestações. O risco de morte materna está aumentado em 10 vezes nas grávidas epilépticas. Na gestante, o diagnóstico adequado é fundamental, já que deve ser afastada a possibilidade de se tratar de crise de eclâmpsia, doença exclusiva do período gravídico-puerperal. A preocupação materna quanto aos efeitos adversos (malformações) das drogas antiepilépticas no bebê pode levar à descontinuação ou redução da dose do medicamento, aumentando o risco de convulsão ou de morte súbita e inesperada na epilepsia (SUDEP). Nesta revisão foi dada atenção única e exclusiva às recomendações do Royal College of Obstetricians and Gynaecologists.(AU)

Epilepsiy is one of the most frequent neurological conditions found in pregnancy, occurring in 0.5 to 1% of pregnancies. The maternal death risk is increased 10-fold in epileptic pregnancies. In pregnant women, its adequate diagnosis is essential, since eclampsia is a differential diagnosis, which is disease exclusive to the pregnancy-puerperal period. Maternal concerns about the adverse effects (malformations) of antiepileptic drugs in the infant may lead to the discontinuation or reduction of the drug dose, increasing the risk of seizure or sudden and unexpected death in epilepsy (SUDEP). In this review exclusive attention was given to the recommendations of the Royal College of Obstetricians and Gynecologists.(AU)

Uso de pregabalina en el tratamiento de la lumbociatalgia / Pregabalin for treatment of low back pain

La lumbociatalgia es un problema clínico común, que en la mayoría de los casos se autolimita y se puede tratar en forma conservadora, usando medidas no farmacológicas y analgésicos como paracetamol o los antiinflamatorios no esteroi-deos. Otro medicamento muy utilizado en nuestro medio es la pregabalina, a pesar de que no se encuentra aprobada para dicha indicación. En este trabajo, el autor se pregunta acerca de la utilidad clínica de la pregabalina y luego de hacer una búsqueda bibliográfica sobre la evidencia más actualizada y de mejor calidad acerca del tema, concluye que no es efectiva para lumbociatalgia y que se acompaña de efectos adversos significativos. Esto coincide con las recomenda-ciones de las guías internacionales, que en su mayoría desaconsejan el uso de anticonvulsivantes para la lumbalgia. (AU)

Sciatica is a common clinical situation, in most cases self-limited and which can be managed conservatively with nonpharmaco-logic treatment and analgesics, such as paracetamol or nonsteroidal anti-inflammatory drugs. Pregabalin is also commonly used, despite not being approved for this indication. In this article, the author queries about the clinical usefulness of pregabalin, and after carrying out a bibliographic search of the most recent and best-quality evidence, concludes that it is not effective in sciatica while it causes significant adverse effects. This is in line with the recommendations of most international guidelines,that do not recommend the use of anticonvulsivants drugs for the treatment of lumbalgia. (AU)