De trastorno neuropsiquiátrico a insulinoma, corrección diagnóstica y resolución mediante resección pancreática mayor / From a neuropsychiatric disorder to the correct diagnosis of insulinoma resolved by major pancreatic resection

RESUMEN El insulinoma es un tumor pancreático poco frecuente con una incidencia del 0,4%, generalmente benigno. Se presenta más frecuentemente en mujeres con una relación 2:1. Es el tumor neuroendocrino funcionante más común del páncreas1, responsable del 70 al 75% de hiperinsulinemía en la práctica clínica. El diagnóstico suele representar un desafío, y el retraso diagnóstico poner en riesgo la vida del paciente. El tratamiento quirúrgico es curativo en más del 90% de los casos; la táctica conservadora, siempre que sea posible, es la de elección. Informamos acerca de una duodenopancreatectomía cefálica (DPC) por insulinoma en un paciente de sexo masculino, con mala interpretación diagnóstica previa de enfermedad neuropsiquiátrica y tratado con anticonvulsivantes.

ABSTRACT Insulinomas are rare pancreatic tumors usually benign with an incidence of 0.4%. They are more common in women with a female-to-male ratio of 2:1. It is the most common functioning neuroendocrine tumor of the pancreas and is responsible for 70-75% of hyperinsulinemia in clinical practice1. The diagnosis is often a challenge, and a delay in diagnosis can have serious consequences for the patient. Surgical treatment is curative in more than 90% of cases, and the conservative approach is the treatment of choice whenever possible. We report the case of a cephalic pancreaticoduodenectomy (CPD) due to an insulinoma in a male patient with a previous misdiagnosis of a neuropsychiatric disorder treated with anticonvulsants.

Irrational Use of Medications among Adults with Insomnia: An Observational Study at a Sleep Clinic in Mexico.

BACKGROUND: To determine the patterns of irrational use of medications among a sample of adult patients with insomnia. METHODS: We included 89 adult patients diagnosed with chronic insomnia who had consumed medications for this disorder during the 12 months prior to admission to a specialized Sleep Disorders Clinic (SDC) in Mexico City. With a 13-item survey, information was gathered on patterns of medication use and irrational use, considering therapeutic indications, dose, route of administration, and duration of treatment. RESULTS: The participants had taken hypnotics (65%), antidepressants (21%), anticonvulsants (8%), and antipsychotics (6%), and 92% had irrational use of their medication. Irrational use was greatest with benzodiazepines and antipsychotics. There were two main types of irrational use: (1) 47% of participants had consumed a drug unsuitable for their condition, although it was almost always prescribed by a doctor, and (2) 43% had consumed a drug for longer than the maximum time recommended. CONCLUSION: It is worrisome to find that the irrational use of medications to treat insomnia, especially benzodiazepines and antipsychotics is widespread. Although most participants had acquired their medication by prescription, for many the drug was inappropriate to treat their condition. It should be mandatory that patients with insomnia receive specialized medical attention in primary clinical care.

Treatment of pilocarpine-induced epileptic seizures in adult male mice / Tratamento de crises epilépticas induzidas por pilocarpina em camundongos adultos machos

Epilepsy is one of the most common neurological disorders affecting most social, economic and biological aspects of human life. Most patients with epilepsy have uncontrolled seizures and drug side effects despite the medications. Patients with epilepsy often have problems with attention, memory, and information processing speed, which may be due to seizures, underlying causes, or anticonvulsants. Therefore, improving seizure control and reducing or changing the anti-epileptic drugs can solve these problems, but these problems will not be solved in most cases. In this work, we looked at the effects of pioglitazone, a Peroxisome Proliferator-Activated Receptor agonist used to treat type 2 diabetes, on pilocarpine-induced seizures in mice. The Racine scale was used to classify pilocarpine-induced convulsions. After that, all of the animals were beheaded, and the brain and hippocampus were dissected. Finally, biochemical techniques were used to determine the levels of Malondialdehyde and Catalase activity, as well as Superoxide Dismutase and Glutathione Reductase in the hippocampus. The results of this investigation suggest that pioglitazone's antioxidant action may play a key role in its neuroprotective properties against pilocarpine-induced seizure neuronal damage.

A epilepsia é um dos distúrbios neurológicos mais comuns que afetam a maioria dos aspectos sociais, econômicos e biológicos da vida humana. A maioria dos pacientes com epilepsia tem convulsões não controladas e apresenta efeitos colaterais de medicamentos. Pacientes com epilepsia, geralmente, têm problemas de atenção, memória e velocidade de processamento de informações, ocasionados por convulsões, causas subjacentes ou anticonvulsivantes. Portanto, melhorar o controle das crises e reduzir ou alterar as drogas antiepilépticas pode resolver esses problemas, mas, na maioria dos casos, eles não serão resolvidos. Neste trabalho, analisamos os efeitos da pioglitazona, um agonista do receptor ativado por proliferador de peroxissoma usado para tratar diabetes tipo 2, em convulsões induzidas por pilocarpina em camundongos. A escala de Racine foi usada para classificar as convulsões induzidas pela pilocarpina. Em seguida, todos os animais foram decapitados, e o cérebro e o hipocampo foram dissecados. Finalmente, técnicas bioquímicas foram utilizadas para determinar os níveis de atividade do malondialdeído e da catalase, bem como da superóxido dismutase e glutationa redutase no hipocampo. Os resultados desta investigação sugerem que a ação antioxidante da pioglitazona pode desempenhar um papel fundamental em suas propriedades neuroprotetoras contra o dano neuronal convulsivo induzido pela pilocarpina.

Practices in the prescription of antiseizure medications: is it time to change? / Práticas na prescrição de medicamentos anticrise: está na hora de mudar?

Abstract The treatment of epilepsy has advanced over the past 30 years through the development of new antiseizure medications (ASMs). Unfortunately, not all of them have been approved yet in Brazil, and many are still underused. When comparing new ASMs to older ones, they are generally not more effective in treating epilepsy. However, they offer better tolerability, with fewer interactions and long-term side effects, especially for patients with comorbidities or those requiring polytherapy. Enzyme induction caused by older ASMs is associated with increased cholesterol levels, drug interactions with decreased effects of statins and other cardiovascular medications, anticoagulants, chemotherapy, immunosuppressors, anti-infective agents (including HIV treatment), antidepressants, and contraceptives. Additionally, they can reduce levels of vitamin D and sex hormones, as well as decrease bone density. The increasing concern about these effects during life, especially after prolonged exposure, has led most developed countries to change prescription patterns in favor of new ASMs, particularly levetiracetam and lamotrigine. Both are also considered the safest options for women of childbearing age. Regrettably, the prescription trends in Brazil have remained largely unchanged over time. This can be partially attributed to the slower approval process of ASM and the reluctance of general physicians and neurologists to embrace these new concepts. In this concise review, we highlight the various advantages linked to the new ASM, aiming to promote a shift in the prescription pattern for ASM. The selection of ASM should be customized according to individual characteristics, and practical suggestions for choosing ASMs are provided in this paper.

Resumo O tratamento da epilepsia avançou nos últimos 30 anos com o desenvolvimento de novos medicamentos anticrise (MAC). Infelizmente, nem todos estão aprovados no Brasil e muitos ainda são subutilizados. Os novos MAC não são mais eficazes que os antigos, mas apresentam melhor tolerabilidade, menos interações e efeitos colaterais a longo prazo, especialmente para pacientes com comorbidades ou que necessitam de politerapia. A indução enzimática causada pelos MAC antigos está associada ao aumento dos níveis de colesterol, interações medicamentosas com redução do efeito das estatinas e outros medicamentos cardiovasculares, anticoagulantes, quimioterapia, imunossupressores, agentes anti-infecciosos (incluindo tratamento do HIV), antidepressivos e contraceptivos. Além disso, podem reduzir os níveis de vitamina D e hormônios sexuais, podendo afetar a massa óssea. A crescente preocupação sobre estes efeitos ao longo da vida, com a exposição prolongada, levou a maioria dos países desenvolvidos a modificar o padrão de prescrição com maior uso dos novos MAC, especialmente levetiracetam e lamotrigina. Ambos são considerados as opções mais seguras para mulheres em idade fértil. Infelizmente, as tendências de prescrição no Brasil permaneceram praticamente inalteradas ao longo do tempo. Isto pode ser parcialmente explicado pela lentidão no processo de aprovação dos MAC e à resistência dos médicos generalistas e neurologistas em adotar estes novos conceitos. Nesta revisão, destacamos as vantagens dos novos MAC e a necessidade da mudança no padrão de prescrição também no Brasil. A escolha do MAC deve ser feita de acordo com as características individuais dos pacientes e sugestões práticas são apresentadas.

Alterations in salivary biochemical composition and redox state disruption induced by the anticonvulsant valproic acid in male rat salivary glands.

OBJECTIVE: To investigate the effects of the anticonvulsant valproic acid (VPA) on salivary glands in male rat using biochemical, functional, histomorphometric, and redox state parameters. MATERIALS AND METHODS: Twenty-four male Wistar rats were randomly distributed into three groups (n = 8 per group): Control (0.9% saline solution), VPA100 (100 mg/kg), and VPA400 (400 mg/kg). After 21 consecutive days of treatment with by intragastric gavage. Pilocarpine-induced saliva was collected to determine salivary flow rate, pH, buffering capacity, and biochemical composition. Analyses of histomorphometric parameters and redox balance markers were performed on the parotid and submandibular glands. RESULTS: Salivary flow rate, pH, buffering capacity, total protein, potassium, sodium, and chloride were similar between groups. However, phosphate and calcium were reduced in VPA400, while amylase was increased in both VPA100 and VPA400. We did not detect significant differences in the areas of acini, ducts, and connective tissue in the salivary glands between the groups. There were no significant changes in the redox status of the submandibular glands. In turn, in the parotid glands we detected reduced total oxidizing capacity and lipid peroxidation, measured as thiobarbituric acid reactive substances (TBARs) and higher uric acid concentration in both the VPA100 and VPA400 groups, and increased superoxide dismutase (SOD) in the VPA400 group. CONCLUSION: Chronic treatment with VPA modified the salivary biochemical composition and caused disruption in the redox state of the parotid gland in rats.

Metabolic Adverse Effects of Psychotropic Drug Therapy: A Systematic Review.

This review aimed to investigate the metabolic alterations associated with psychopharmacological treatment of neuropsychiatric disorders, which can significantly impact patients' physical health and overall quality of life. The study utilized the PRISMA methodology and included cross-sectional, retrospective studies, and randomized clinical trials from reputable databases like SCOPUS, CLARIVATE, SCIENCE DIRECT, and PUBMED. Out of the 64 selected studies, various psychotropic drug classes were analyzed, including antidepressants, anticonvulsants, and antipsychotics. Among the antidepressants, such as amitriptyline, Imipramine, and clomipramine, weight gain, constipation, and cardiovascular effects were the most commonly reported metabolic adverse effects. SSRI antidepressants like Fluoxetine, Sertraline, Citalopram, Escitalopram, and Paroxetine exhibited a high prevalence of gastrointestinal and cardiac alterations. Regarding anticonvulsants, valproic acid and Fosphenytoin were associated with adverse reactions such as weight gain and disturbances in appetite and sleep patterns. As for antipsychotics, drugs like Clozapine, Olanzapine, and Risperidone were linked to weight gain, diabetes, and deterioration of the lipid profile. The findings of this review emphasize the importance of continuous monitoring for adverse effects, particularly considering that the metabolic changes caused by psychopharmacological medications may vary depending on the age of the patients. Future research should focus on conducting field studies to further expand knowledge on the metabolic effects of other commonly prescribed psychotropic drugs. Overall, the study highlights the significance of understanding and managing metabolic alterations induced by psychopharmacological treatment to enhance patient care and well-being.

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

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

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

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

Prophylactic antiseizure drugs for spontaneous intracerebral hemorrhage: An updated systematic review and meta-analysis.

BACKGROUND: There is concern that recommendations on prophylactic antiseizure drugs (PASDs) for patients with spontaneous intracerebral hemorrhage (sICH) are biased by studies using older drugs and no electrographic monitoring. AIMS: We performed a systematic review and meta-analysis to determine whether PASDs in patients with sICH reduced seizure occurrence and improved functional outcomes. We included analyses of newer trials, newer antiseizure drugs, and effectiveness in patients with consistent electrographic monitoring. METHODS: Medline, Embase, and Cochrane were searched from inception until 12 August 2022, to identify studies with patients with sICH treated with PASDs, regardless of study design. The studied outcomes were functional status and occurrence of seizures. RESULTS: Fourteen studies were included, including 6742 patients. Risk of bias was low overall. There was no effect of PASD on seizure occurrence overall (odds ratio (OR) 0.73, 95% confidence interval (CI) 0.47-1.15), but they were associated with reduced occurrence in studies with electrographic monitoring (OR 0.36, 95% CI 0.18-0.70). There was no effect of PASDs on functional outcomes (OR 1.15; 95% CI 0.91-1.47) or mortality (OR 0.85, 95% CI 0.65-1.11). CONCLUSION: Prophylactic antiseizure medications after sICH reduce seizures in studies with electroencephalogram monitoring in high-risk patients. However, this benefit did not reflect in the improvement of functional outcomes, even in studies with newer, less toxic, antiseizure drugs.

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

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.

Uso de antiepilépticos en niños hospitalizados en el Hospital Pediátrico, Centro Hospitalario Pereira Rossell / Use of antiepileptic drugs in children hospitalized at the Pereira Rossell Pediatric Hospital / Uso de drogas antiepilépticas em crianças internadas no Hospital Pediátrico Pereira Rossell

Introducción: indicaciones off label, estrecho margen terapéutico, variabilidad farmacocinética, interacciones farmacológicas constituyen algunos de los problemas a abordar en el uso crónico de antiepilépticos (AE). Caracterizar su perfil de uso es necesario para promover su prescripción racional. Objetivo: Describir el perfil de uso de AE en menores de 15 años hospitalizados en el Centro Hospitalario Pereira Rossell entre 1/07/2020 y 31/12/2020. Material y método: estudio descriptivo, de menores de 15 años hospitalizados en cuidados moderados en tratamiento con AE. Variables: tipo y número de AE, motivo de la indicación, vía de administración, dosis, uso asociado con psicofármacos, adherencia. Resultados: recibían AE 113 pacientes, mediana edad 7 años, 50,4% sexo femenino. Motivo de la indicación: epilepsia (grupo A) 50,4% y otras patologías (grupo B) 49,6%. Mediana de edad: 2,7 años grupo A vs. 11,5 años grupo B. El AE más indicado fue levetiracetam en el grupo A (35%) y ácido valproico en el grupo B (35,7%). La asociación con psicofármacos se registró en 8,7% grupo A vs. 44,6% en el grupo B. Conclusiones: predominó el uso de levetiracetam en pacientes epilépticos. La mitad de los pacientes recibieron AE para patologías diferentes a la epilepsia, mayoritariamente psiquiátricas. En este grupo predominó el uso de ácido valproico. El análisis de esta serie permite una aproximación al conocimiento del perfil de uso de AE en los niños asistidos en este centro, y por tanto de los principales problemas a abordar. Futuros estudios multicéntricos con población ambulatoria son necesarios para mejorar el conocimiento y contribuir al uso racional de los mismos.

Introduction: off-label prescription, narrow therapeutic margin, pharmacokinetic variability, drug interaction, are some of the problems to consider in the chronic use of antiepileptic drugs (AEDs). It is necessary to characterize their utilization profile in order to promote rational prescription. Objective: to describe the utilization profile of AEDs in children under 15 years of age hospitalized at the Pereira Rossell Pediatric Hospital from 7/01/2020 to 12/31/2020. Material and Methods: descriptive study of children under 15 years of age hospitalized in moderate care units receiving treatment with AEDs. Variables: type and number of AEDs, reason for the prescription, dose, associated use of psychotropic drugs, compliance. Results: 113 patients received AEDs, median age 7 years, 50.4% females. Reason for prescription; epi- lepsy (group A) 50.4%, other pathologies (group B) 49.6%. Median age in group A 2.7 years, versus 1.1.5 years in group B. Most frequently prescribed AEDs was levetiracetam in group A (35%) and valproic acid in group B (37,7%). Association with psychotropic drugs was present in 8.7% of group A versus 44.6% of group B. Conclusions: levetiracem use was predominant in epileptic patients. Half of the patients received AEDs for pathologies other than epilepsy, mostly psychiatric. In this group the use of valproic acid was predominant. Analysis of this series enables an approximation to the understanding of the profile of AEDs use in children assisted at this Hospital, and there- fore an approximation to the problems to be considered. Future multicenter studies with an outpatient population are necessary to expand our knowledge and to contribute to a rational use of these drugs.

Introdução: indicações off-label, margem terapêutica estreita, variabilidade farmacocinética, interações farmacológicas são alguns dos problemas a serem abordados no uso crônico de drogas antiepilépticas (EA). Caracterizar seu perfil de uso é necessário para promover sua prescrição racional. Objetivo: descrever o perfil de utilização da AE em crianças menores de 15 anos internadas no Centro Hospitalar Pereira Rossell entre 01/07/2020 e 31/12/2020. Material e Métodos: estudo descritivo de crianças menores de 15 anos internadas em cuidados moderados em tratamento de EA. Variáveis: tipo e número de EAs, motivo da indicação, via de administração, dose, uso associado a psicotrópicos, adesão. Resultados: 113 pacientes receberam EA, com meia idade de 7 anos, 50,4% do sexo feminino. Motivo da indicação: epilepsia (grupo A) 50,4% e outras patologias (grupo B) 49,6%. Mediana de idade: 2,7 anos grupo A vs. 11,5 anos grupo B. O EA mais indicado foi Levetiracetam no grupo A (35%) e ácido valpróico no grupo B (35,7%). A associação com psicotrópicos foi registrada em 8,7% do grupo A vs. 44,6% no grupo B. Conclusões: o uso de Levetiracetam em pacientes epilépticos predominou. A metade dos pacientes recebeu AE por outras patologias que não foram a epilepsia, principalmente psiquiátricas. Nesse grupo, predominou o uso do ácido valpróico. A análise desta série permite aproximar o conhecimento do perfil de uso da AE nas crianças atendidas nesse centro e, portanto, a aproximação aos principais problemas a serem abordados. Futuros estudos multicêntricos com população ambulatorial são necessários para aprimorar o conhecimento e contribuir para sua utilização racional.

Polycystic ovary syndrome and the new antiepileptic drugs: A systematic review.

OBJECTIVE: To evaluate the presence of polycystic ovary syndrome (PCOS) in women of reproductive age with the use of antiepileptic drugs. METHODS: A systematic literature review of observational analytical studies (cohort, cross-sectional and case-control), from January 1966 to January 2021 on PCOS in women of reproductive age with the use of the antiepileptics. The search covered the Cochrane, MEDLINE, Embase and LILACS databases. INCLUSION CRITERIA: Studies reporting the frequency of PCOS with the antiepileptic drugs in women of reproductive age. EXCLUSION CRITERIA: studies that did not have categorically relevant measurements, those published as abstracts only, and studies of investigational treatment. Data extraction was performed based on the PECOT strategy, considering the method of intervention, methodological quality, and presence of PCOS with the antiepileptic drugs. RESULTS: A total of 2043 references were obtained from which 22 articles were selected by title and abstract. Four articles met the inclusion criteria. No articles were found describing the risk of PCOS upon exposure to levetiracetam, felbamate, gabapentin, lacosamide, pregabalin, rufinamide, tiagabine, topiramate, vigabatrin, or zonisamide. Only articles related to oxcarbazepine and lamotrigine were found, in which the frequency of PCOS was like that found in women without epilepsy. CONCLUSIONS: The anticonvulsants are probably safer, but the risk of developing PCOS associated with the antiepileptics cannot be established, since there are insufficient studies.

Déficit de vitamina D en niños y adolescentes que reciben tratamiento antiepiléptico. Estudio descriptivo / Vitamin D deficiency in children and adolescents receiving antiepileptic treatment. Descriptive study

Resumen Introducción: la hipovitaminosis D es un problema prevalente en la población general y muy frecuente en niños; relacionado a diferentes patologías o factores como el uso de medicamento antiepilépticos (MAEs), principalmente aquellos inductores enzimáticos del citocromo P450, ampliamente relacionados con la salud ósea. Razón por la que este estudio busca determinar la distribución de insuficiencia de Vitamina D en niños tratados farmacológicamente para la epilepsia, así como establecer factores asociados basándose en características sociodemográficas, clínicas y terapéuticas. Metodología: estudio descriptivo, transversal, retrospectivo con 103 pacientes con epilepsia en manejo con MAEs, asistentes a la consulta de neuropediatría en un hospital de tercer nivel, se tomó información de las historias clínicas de niños entre 0 y 18 años durante enero del 2016 y junio del 2019. Se construyó un modelo multivariado en relación a la presencia de insuficiencia de vitamina D y valores normales de esta. Resultados: el 44,7% presentaron insuficiencia de vitamina D, mientras 6,8% de pacientes presentó deficiencia, de los cuales 4 tenían historia de fracturas. Se encontró asociación estadísticamente significativa con la insuficiencia en pacientes que residen en área rural (ORa=4,2 (IC95=1,3-13,4) p=0,013), pertenecen a nivel socio económico bajo (Ora=2,9 (IC95%=1,1-77) p=0,030) y padecen epilepsia refractaria (Ora=3,1 (IC95%=1-8,7) p=0,033). Conclusiones: la hipovitaminosis D es frecuente en paciente con epilepsia en manejo farmacológico con MAE. La insuficiencia se asoció con epilepsia refractaria, nivel socioeconómico bajo y provenir de área rural, por lo que se recomienda vigilancia rutinaria de los niveles de vitamina D y suplementación en aquellos pacientes con déficit. MÉD.UIS.2022;35(1): 71-9

Abstract Hypovitaminosis D is a prevalent problem in the general population and very common in children; related to different pathologies or factors such as the use of antiepileptic drugs (MAEs), mainly those enzymatic inducers of cytochrome P450, broadly related with bone health. Reason why this study seeks to determine the distribution of vitamin D insufficiency in children with epilepsy in pharmacological treatment and to establish associated factors based on sociodemographic, clinical, and therapeutic characteristics. Methodology: descriptive, cross- sectional, retrospective study with 103 patients with epilepsy in management with MAEs, attending the neuropaediatric consultation in a third-level hospital, information was taken from the medical records of children between 0 and 18 years of age during January 2016 and June 2019. A multivariate model was built in relation to the presence of vitamin D insufficiency and its normal values. Results: 44.7% of patients had vitamin D insufficiency, while 6.8% had deficiency, of which 4 had a history of fractures. A statistically significant association with insufficiency was found in patients residing in rural areas (ORa=4.2 (IC95=1.3-13.4) p=0.013), they belong to a low socio-economic level (Ora=2.9 (95% CI=1.1-77) p=0.030) and suffering from refractory epilepsy (Ora=3.1 (95% CI=1-8.7) p=0.033). Conclusions: hypovitaminosis D is frequent in a patient with epilepsy under pharmacological management with MAE. Insufficiency was associated with refractory epilepsy, low socioeconomic status and coming from rural areas, so routine monitoring of vitamin D levels is recommended in those patients with deficits. MÉD.UIS.2022;35(1): 71-9

Encefalopatia hiperamonêmica associada ao valproato na hemorragia subaracnóidea: um diagnóstico a considerar / Valproate-associated hyperammonemic encephalopathy in subarachnoid hemorrhage: a diagnosis to consider

RESUMO Objetivo: A hemorragia subaracnóidea é uma doença prevalente com alta morbidade e mortalidade. Inúmeras complicações contribuem para a lesão cerebral e desafiam o médico no diagnóstico e tratamento. A encefalopatia hiperamonêmica associada ao valproato é uma entidade rara, subdiagnosticada, grave e importante a ser considerada. Apresentamos o caso de um paciente com hemorragia subaracnóidea que recebeu profilaxia anticonvulsivante com valproato e evoluiu com piora neurológica associada a níveis plasmáticos elevados de amônia e descargas periódicas no eletroencefalograma, sem outras causas identificáveis. A interrupção do tratamento com ácido valproico e a normalização dos níveis plasmáticos de amônia resultaram em melhora do quadro neurológico e eletroencefalográfico.

ABSTRACT Objective: Subarachnoid hemorrhage is a prevalent disease with high morbidity and mortality. Numerous complications contribute to brain injury and defy the clinical practitioner on diagnosis and management. Valproate-associated hyperammonemic encephalopathy is a rare, underdiagnosed, serious and important entity to consider. We present a case of a patient with subarachnoid hemorrhage who received anticonvulsant prophylaxis with valproate and developed neuroworsening associated with high levels of ammoniemia and periodic discharge electroencephalographic patterns without other identifiable causes. Discontinuing valproic acid treatment and normalization of ammoniemia resulted in improvement in clinical and electroencephalographic neurological status.

Analysis of Gabapentin's Efficacy in Tinnitus Treatment: A Systematic Review.

OBJECTIVES: Tinnitus can be a chronic symptom that brings disability and distress. Some studies suggested that gabapentin might be effective on tinnitus relief. The objective of the study is to perform a systematic review in order to evaluate the efficacy of oral gabapentin in patients with tinnitus. METHODS: A literature search was conducted in English and following the recommendations from PRISMA. The terms used were: ("tinnitus" OR "subjective tinnitus") AND ("gabapentin"). The study selection was performed following the eligibility criteria in accordance to the PICOS (population, intervention, comparison, outcome, study design) strategy-patients with tinnitus; oral gabapentin; placebo; reduction of tinnitus severity questionnaires scores; prospective, double-blind, randomized controlled trial, respectively. The selected studies were included in qualitative synthesis. The studies were analyzed according to Joanna Briggs Institute's critical appraisal checklist for randomized controlled trials. RESULTS: One hundred twenty-one studies were found in 9 databases and 8 studies were found in gray literature. After study selection, 6 articles were read in full. Then, 2 studies were excluded and 4 were included in qualitative synthesis. All 4 articles were analyzed according to critical evaluation checklist. CONCLUSIONS: There is insufficient evidence to recommend the use of gabapentin for patients with tinnitus.

Estado epiléptico refractario de inicio reciente (NORSE): caso clínico / New-onset refractory status epilepticus (NORSE): case report

El estado epiléptico refractario de inicio reciente (NORSE) es una emergencia neurológica que conlleva una elevada morbimortalidad, y como tal, genera altos costos debido a su complejo plan terapéutico y al requerimiento de una evaluación rápida y secuencial. Es una entidad clínica de mal pronóstico y su principal etiología es la encefalitis autoinmune, sin embargo, es de difícil diagnóstico y en ocasiones no se logra establecer una causa clara. Se describe el caso de una paciente joven sin antecedentes clínicos de importancia, quien presentó múltiples episodios convulsivos refractarios a anticonvulsivantes y sedación profunda, sin tolerar retiro de la sedoanalgesia por reaparición de crisis en el electroencefalograma. Presentó estudios de líquido cefalorraquídeo, infecciosos, neuroimágenes y de autoinmunidad sin alteraciones. Cursó con neumonía asociada al cuidado de la salud, que evolucionó a disfunción orgánica múltiple y fallecimiento. No se encontraron alteraciones anatomopatológicas post mortem que explicaran la causa del estado epiléptico. El estado epiléptico refractario de inicio reciente es una condición que representa un reto tanto diagnóstico como terapéutico. Se describe su abordaje diagnóstico y las opciones de tratamiento, además, se realiza una revisión corta de la literatura disponible hasta el momento

New-onset refractory status epilepticus (NORSE) is a neurological emergency with high morbidity and mortality, that results in elevated costs due to its complex therapeutic management and the requirement for a rapid and sequential evaluation. It is a condition with a poor prognosis and its main etiology is autoimmune encephalitis. However, it is difficult to diagnose and sometimes a clear cause cannot be established. The case of a young female with no relevant medical history is described. She presented multiple seizure episodes refractory to anticonvulsants and deep sedation, without tolerating withdrawal of sedoanalgesia due to reappearance of seizures in the electroencephalogram. She presented studies of cerebrospinal fluid, infections, neuroimaging and autoimmunity without alterations. She had healthcare-associated pneumonia, which progressed to multiple organ dysfunction and death. No post-mortem anatomopathological alterations were found to explain the cause of the status epilepticus. New-onset refractory status epilepticus is a condition that represents both a diagnostic and therapeutic challenge. Its diagnostic approach and treatment options are described, as well as a brief review of the available literature

Toxic epidermal necrolysis associated with anticonvulsants / Necrólisis epidérmica tóxica asociada a anticonvulsivantes

ABSTRACT Background and Objectives: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are considered as a continuum of the same process. TEN or Lyell Syndrome is the most severe form. Both entities involve an acute mucocutaneous blistering reaction associated with systemic inflammation. Materials and Methods: We present a case of a young woman who developed TEN following concomitant treatment with valproate, lamotrigine, and phenobarbital. Despite the extensive mucocutaneous detachment (over 90%), prognostic evaluation was favorable (SCORTEN score 2; probability of survival 88%), and this patient evolved satisfactorily. Five days after admission, valproate was reinitiated without any subsequent adverse reaction. Results: Causality evaluation identified both lamotrigine and phenobarbital as "very probable" (ALDEN score = 6) causes and valproate as "very unlikely" (ALDEN score = 0) cause of TEN. Conclusions: SJS and TEN are true life-threatening medical emergencies. This case emphasizes the importance of early diagnosis and treatment, including the discontinuation of the causative agent, which can be lifesaving.

RESUMEN Antecedentes y objetivos: El síndrome de Stevens-Johnson (SSJ) y la necrólisis epidérmica tóxica (NET) se consideran un continuum del mismo proceso. La NET o síndrome de Lyell es la forma más grave. Ambas entidades implican una reacción ampollosa mucocutánea aguda asociada con inflamación sistémica. Materiales y métodos: Presentamos el caso de una mujer joven que desarrolló NET posterior al tratamiento concomitante con valproato, lamotrigina y fenobarbital. A pesar del extenso desprendimiento mucocutáneo (más del 90%), la evaluación pronóstica fue favorable (puntuación SCORTEN 2; probabilidad de supervivencia 88%), y esta paciente evolucionó satisfactoriamente. Cinco días después de su ingreso, se reinició el valproato sin ninguna reacción adversa posterior. Resultados: La evaluación de causalidad identificó tanto la lamotrigina como el fenobarbital como causas "muy probables" (puntuación ALDEN = 6) y el valproato como causas "muy improbables" (puntuación ALDEN = 0) de NET. Conclusiones: El SJS y la NET son verdaderas emergencias médicas potencialmente letales. Este caso enfatiza la importancia del diagnóstico y tratamiento tempranos, incluida la interrupción del agente causal, lo cual puede salvar la vida del paciente.

Drug Reaction with eosinophilia and systemic symptoms with alopecia universalis and vitiligo / Reação a drogas com eosinofilia e sintomas sistêmicos associada a alopecia universal e vitiligo

ABSTRACT: Drug reactions with eosinophilia and systemic symptoms (DRESS) are rare and potentially fatal adverse hypersen-sitivity reaction to some drugs, especially anticonvulsants.The syndrome affects not only the skin but also other organs, especially the liver. The incidence can vary from 1 to 5 cases per 10.000 patients exposed to anticonvul-sants. The recognition of the syndrome is of fundamental importance since the mortality rate is between 10 and 40%. Once the diagnosis is established, the triggering drug must be identified and discontinued. Corticosteroids are usually associated with therapy. Autoimmune sequelae have been reported, including vitiligo and rarely alopecia. Alopecia universalis is a variant of alopecia areata, characterized by hair loss throughout the body. We report a case of DRESS, associated with two autoimmune dermatological diseases: alopecia universalis and vitiligo. (AU)

RESUMO: A reação a drogas com eosinofilia e sintomas sistêmicos (DRESS) é uma rara e potencialmente fatal reação adversa de hipersensibilidade, decorrente de alguns medicamentos, principalmente os anticonvulsivantes. A síndrome não afeta apenas a pele, mas também outros órgãos, principalmente o fígado. A incidência pode variar de 1 a 5 casos por 10.000 pacientes expostos aos anticonvulsivantes. O reconhecimento da síndrome é de fundamental importân-cia devido a taxa de mortalidade entre 10-40%. Uma vez estabelecido o diagnóstico, deve-se identificar o medica-mento desencadeante e suspendê-lo. O corticosteróide geralmente é associado na terapia. Sequelas autoimunes foram relatadas, incluindo vitiligo e raramente alopecia. A alopecia universal é uma variante da alopecia areata, caracterizada pela perda de pelos em todo o corpo. Relatamos um caso de DRESS, associado a duas doenças au-toimunes dermatológicas: alopecia universal e vitiligo. (AU)

Genetic Susceptibility to Drug Teratogenicity: A Systematic Literature Review.

Since the 1960s, drugs have been known to cause teratogenic effects in humans. Such teratogenicity has been postulated to be influenced by genetics. The aim of this review was to provide an overview of the current knowledge on genetic susceptibility to drug teratogenicity in humans and reflect on future directions within the field of genetic teratology. We focused on 12 drugs and drug classes with evidence of teratogenic action, as well as 29 drugs and drug classes with conflicting evidence of fetal safety in humans. An extensive literature search was performed in the PubMed and EMBASE databases using terms related to the drugs of interest, congenital anomalies and fetal development abnormalities, and genetic variation and susceptibility. A total of 29 studies were included in the final data extraction. The eligible studies were published between 1999 and 2020 in 10 different countries, and comprised 28 candidate gene and 1 whole-exome sequencing studies. The sample sizes ranged from 20 to 9,774 individuals. Several drugs were investigated, including antidepressants (nine studies), thalidomide (seven studies), antiepileptic drugs (five studies), glucocorticoids (four studies), acetaminophen (two studies), and sex hormones (estrogens, one study; 17-alpha hydroxyprogesterone caproate, one study). The main neonatal phenotypic outcomes included perinatal complications, cardiovascular congenital anomalies, and neurodevelopmental outcomes. The review demonstrated that studies on genetic teratology are generally small, heterogeneous, and exhibit inconsistent results. The most convincing findings were genetic variants in SLC6A4, MTHFR, and NR3C1, which were associated with drug teratogenicity by antidepressants, antiepileptics, and glucocorticoids, respectively. Notably, this review demonstrated the large knowledge gap regarding genetic susceptibility to drug teratogenicity, emphasizing the need for further efforts in the field. Future studies may be improved by increasing the sample size and applying genome-wide approaches to promote the interpretation of results. Such studies could support the clinical implementation of genetic screening to provide safer drug use in pregnant women in need of drugs.

Análise do nível de conhecimento das manifestações orais causadas pelo uso de anticonvulsivantes / Analysis of knowledge level of oral manifestations caused by the use of anticonvulsants

Analisar o nível de conhecimento dos usuários de anticonvulsivantes e dos cirurgiões-dentistas a res peito das manifestações orais ocasionadas pela medicação. Trata-se de um estudo transversal realizado no munícipio de Vitória de Santo Antão, em Pernambuco, no qual participaram 30 Odontólogos e 16 usuários de anticonvulsivantes das unidades de saúde da família do município. Foram aplicados questionários sobre o conhecimento dos profissionais e percepção dos usuários sobre as manifestações orais ocasionadas pela medicação. Para avaliar associação entre duas variáveis categóricas foi utilizado teste Exato de Fisher, quando a condição para utilização do teste Qui-quadrado não foi verificada. A análise dos dados demonstrou que 86,7% dos cirurgiões-dentistas conhecem os anticonvulsivantes e 50,0% dos usuários não receberam orientação do dentista sobre a medicação e os seus efeitos adversos. Há escassez de conhecimentos específicos sobre os efeitos adversos do uso de anticonvulsivantes na cavidade bucal por parte dos usuários e cirurgiões-dentistas... (AU)

To analyze the knowledge level of anticonvulsants users and the dental surgeons concerning the oral manifestations caused by the medication. A cross-sectional study conducted in Vitória de Santo Antão, Pernambuco, Brazil, with participation of 30 dentists and 16 anticonvulsants users from the city's family health units. Questionnaires about the knowledge of professionals and users' perception of manifestations in the oral cavity caused by the medication. Fisher's Exact test was used to assess the association between two categorical variables when the condition for using the chi-square test was not verified. The data analysis showed that 86,7% of dental surgeons know the anticonvulsants and 50,0% of users do not receive orientation from the dentist about the medication and its adverse effects. There is a shortage of specific knowledge about the adverse effects of the use of anticonvulsants in the oral cavity, by users and dental surgeons... (AU)