Postoperative Seizure Prophylaxis in Meningioma Resection: A Systematic Review and Meta-Analysis.

BACKGROUND: Seizures in the early postoperative period may impair patient recovery and increase the risk of complications. The aim of this study is to determine whether there is any advantage in postoperative seizure prophylaxis following meningioma resection. METHODS: This systematic review was conducted in accordance with PRISMA guidelines. PUBMED, Web of Science, Embase, Science Direct, and Cochrane were searched for papers until April 2023. RESULTS: Among nine studies, a total of 3249 patients were evaluated, of which 984 patients received antiepileptic drugs (AEDs). No significant difference was observed in the frequency of seizure events between patients who were treated with antiepileptic drugs (AEDs) and those who were not. (RR 1.22, 95% CI 0.66 to 2.40; I2 = 57%). Postoperative seizures occurred in 5% (95% CI: 1% to 9%) within the early time period (<7 days), and 9% (95% CI: 1% to 17%) in the late time period (>7 days), with significant heterogeneity between the studies (I2 = 91% and 97%, respectively). In seizure-naive patients, the rate of postoperative seizures was 2% (95% CI: 0% to 6%) in the early period and increased to 6% (95% CI: 0% to 15%) in the late period. High heterogeneity led to the use of random-effects models in all analyses. CONCLUSIONS: The current evidence does not provide sufficient support for the effectiveness of prophylactic AED medications in preventing postoperative seizures in patients undergoing meningioma resection. This underscores the importance of considering diagnostic criteria and conducting individual patient analysis to guide clinical decision-making in this context.

Development of Antiepileptic Drugs throughout History: From Serendipity to Artificial Intelligence.

This article provides a comprehensive narrative review of the history of antiepileptic drugs (AEDs) and their development over time. Firstly, it explores the significant role of serendipity in the discovery of essential AEDs that continue to be used today, such as phenobarbital and valproic acid. Subsequently, it delves into the historical progression of crucial preclinical models employed in the development of novel AEDs, including the maximal electroshock stimulation test, pentylenetetrazol-induced test, kindling models, and other animal models. Moving forward, a concise overview of the clinical advancement of major AEDs is provided, highlighting the initial milestones and the subsequent refinement of this process in recent decades, in line with the emergence of evidence-based medicine and the implementation of increasingly rigorous controlled clinical trials. Lastly, the article explores the contributions of artificial intelligence, while also offering recommendations and discussing future perspectives for the development of new AEDs.

Antiepileptic and anesthetic drugs in the intensive care unit. Their impact on non-convulsive status epilepticus mortality.

BACKGROUND: Status epilepticus (SE) is a neurological emergency. Non-convulsive status epilepticus (NCSE) can only be diagnosed by electroencephalogram (EEG) because the motor clinical symptoms are usually subtle or absent, with high mortality. The best treatment is still unknown. OBJECTIVES: Our aim was to assess anticonvulsive and anesthetic drugs in NCSE and their correlation with Epidemiology-based Mortality Score in Status Epilepticus (EMSE), Status Epilepticus Severity Score (STESS) and mortality. METHODS: Retrospective, observational, descriptive, cross-sectional study. Ninety patients in intensive care unit over 18 years-old (57 females [63.3%] and 33 males [36.6%], mean age 63.5 years [SD ± 19]) with NCSE, at the Buenos Aires British Hospital. Data was collected between January 2018 and June 2021. An adjusted multivariate statistical analysis was performed. Ninety-five (95%) CI, p < 0.05 as statistically significant. EMSE and STESS were used in this study. RESULTS: Total mortality rate was 37.8% (34/90), and in patients = 65 years-old (54/90) it was 40.7% (22/54). Patients with 0-2 STESS (11/90) were discharged, while those with STESS = 3 (79/90) had a 43% death rate (34/79). Patients with EMSE < 34 (27/90) had 7.4% (2/27) death rate, while those with EMSE = 34 (63/90) had 50.8% (32/63). No significant differences were found in survival with regard to the number of antiepileptic drugs administered. Patients treated with anesthetics presented a 2.6-fold death risk increase (95% CI 1.001-6.83). DISCUSSION: It could be assumed that mortality rate increases 2.6-fold when patients are treated with anesthetic drugs, regardless of the number of antiepileptic drugs previously administered.

Introducción: El estado de mal epiléptico (SE) es una emergencia neurológica. El SE no convulsivo (SENC) se diagnostica únicamente por electroencefalograma debido a la ausencia o sutileza de sintomatología clínica motora, con una mortalidad elevada. No se conoce aún el mejor tratamiento. Objetivos: Evaluar drogas anticonvulsivas y anestésicas en el SENC y su correlación con Epidemiology-based Mortality Score in Status Epilepticus (EMSE), Status Epilepticus Severity Score (STESS) y el índice de mortalidad. Métodos: Estudio retrospectivo, observacional, descriptivo, de corte transversal. Noventa pacientes = 18 años (57 mujeres [63.3%] y 33 hombres [36.6%], media de edad 63.5 años [DS ± 19]) con diagnóstico de SENC, en el Hospital Británico. Estudio realizado entre enero 2018 y junio 2021. Análisis estadístico multivariado ajustado. IC 95% p < 0.05 como estadísticamente significativo. Se utilizaron escalas de EMSE y STESS. Resultados: La mortalidad total fue de 37.8% (34/90). Los pacientes = 65 años (54/90) presentaron una mayor tasa de muerte 40.7% (22/54), todos aquellos con STESS de 0-2 (11/90) egresaron, mientras que entre los que presentaron = 3 (79/90) el 43% (34/79) falleció. De los pacientes con EMSE < 34 (27/90) dos fallecieron (7.4%) y de aquellos con EMSE = 34 (63/90) falleció el 50.8% (32/63). No hallamos diferencias significativas entre cantidad de drogas antiepilépticas utilizadas y supervivencia. Pacientes con anestésicos tuvieron un aumento del riesgo de muerte 2.6 veces (IC 95% 1.001-6.83). Discusión: De acuerdo a esto la mortalidad con drogas anestésicas aumenta, independientemente de la cantidad de drogas anticonvulsivas utilizadas previamente.

[Depression in patients with epilepsy: experience in a private hospital in Argentina]. / Depresión en pacientes con epilepsia. Experiencia en un hospital privado de Argentina.

INTRODUCTION: Depression is the most frequent psychiatric disorder in patients with epilepsy, with an estimated prevalence between 35% and 60%, associated with poorer control of epileptic seizures. Despite the high prevalence of depression, many patients are not diagnosed, presenting a worse clinical course and quality of life. There are no prevalence studies in our population. The main objective was to determinate the prevalence of depression in epilepsy and its relationship with seizure control. MATERIALS AND METHODS: It is a prospective, descriptive and cross-sectional study of a cohort of patients who underwent the Depression Inventory in Patients with Neurological Disorders for Epilepsy (NDDI-E) and the data from the medical records were analyzed. RESULTS: A total of 121 patients were inluded, and the prevalence of depression was 43% (n:52), of whom 77% were women (p = 0.01). A 63% of patients with depression was diagnosed in this study. Most of them with good seizure control (70%) did not present depression, while the majority of those with poor (57%) and regular (63%) seizure control presented depression (p < 0.001). DISCUSSION: Comorbidity between depression and epilepsy is highly prevalent, negatively influencing the control of epileptic seizures. Most patients are underdiagnosed. Screening for major depression in patients with epilepsy is necessary, contributing to the clinical improvement.

Introducción: La depresión es el trastorno psiquiátrico más frecuente en pacientes con epilepsia, con una prevalencia estimada entre 35% y 60%, asociándose a un peor control de crisis epilépticas. A pesar de la gran prevalencia de depresión, muchos pacientes no son diagnosticados, presentando una peor evolución clínica y calidad de vida. No existen estudios de prevalencia en nuestro medio. El objetivo fue determinar la prevalencia de depresión en epilepsia y su relación con el control de crisis. Materiales y métodos: Es un estudio prospectivo, descriptivo y transversal de una cohorte de pacientes a los cuales se les realizó el Inventario de Depresión en Pacientes con Trastornos Neurológicos para Epilepsia (NDDIE) y se analizaron datos de las historias clínicas. Resultados: Se incluyeron 121 pacientes, la prevalencia de depresión fue 43% (n:52), el 77% eran mujeres (p = 0.01). Del total de pacientes con depresión, el 63% fue diagnosticado en este estudio. La mayoría tuvo buen control de la crisis (70%) y no presentó depresión, mientras que la mayoría con mal (57%) y regular (63%) control de la crisis presentó depresión (p < 0.001). Discusión: La comorbilidad entre depresión y epilepsia es altamente prevalente, influyendo negativamente en el control de las crisis epilépticas. La mayoría de los pacientes se encuentran subdiagnosticados. El tamizaje de la depresión mayor en aquellos con epilepsia es necesario, contribuyendo a la mejoría clínica.

Depresión en pacientes con epilepsia. Experiencia en un hospital privado de Argentina / Depression in patients with epilepsy: experience in a private hospital in Argentina

Resumen Introducción: La depresión es el trastorno psiquiátrico más frecuente en pacientes con epilepsia, con una prevalencia estimada entre 35% y 60%, asociándose a un peor control de crisis epilép ticas. A pesar de la gran prevalencia de depresión, muchos pacientes no son diagnosticados, presentando una peor evolución clínica y calidad de vida. No existen estudios de prevalencia en nuestro medio. El objeti vo fue determinar la prevalencia de depresión en epilepsia y su relación con el control de crisis. Materiales y métodos: Es un estudio prospectivo, descriptivo y transversal de una cohorte de pacientes a los cuales se les realizó el Inventario de Depresión en Pacientes con Trastornos Neurológicos para Epilepsia (NDDI-E) y se analizaron datos de las historias clínicas. Resultados: Se incluyeron 121 pacientes, la prevalencia de depresión fue 43% (n:52), el 77% eran mujeres (p = 0.01). Del total de pacientes con depresión, el 63% fue diagnosticado en este estudio. La mayoría tuvo buen control de la crisis (70%) y no presentó depresión, mientras que la mayoría con mal (57%) y regular (63%) control de la crisis presentó depresión (p < 0.001). Discusión: La comorbilidad entre depresión y epilepsia es altamente prevalente, influyendo negativamen te en el control de las crisis epilépticas. La mayoría de los pacientes se encuentran subdiagnosticados. El tamizaje de la depresión mayor en aquellos con epilepsia es necesario, contribuyendo a la mejoría clínica.

Abstract Introduction: Depression is the most frequent psychiatric disorder in patients with epilepsy, with an estimated prevalence between 35% and 60%, associated with poorer control of epileptic seizures. Despite the high prevalence of depression, many patients are not diagnosed, presenting a worse clinical course and quality of life. There are no prevalence studies in our population. The main objective was to determinate the prevalence of depression in epilepsy and its relationship with seizure control. Materials and methods: It is a prospective, descriptive and cross-sectional study of a cohort of patients who underwent the Depression Inventory in Pa tients with Neurological Disorders for Epilepsy (NDDI-E) and the data from the medical records were analyzed. Results: A total of 121 patients were inluded, and the prevalence of depression was 43% (n:52), of whom 77% were women (p = 0.01). A 63% of patients with depression was diagnosed in this study. Most of them with good seizure control (70%) did not present depression, while the majority of those with poor (57%) and regular (63%) seizure control presented depression (p < 0.001). Discussion: Comorbidity between depression and epilepsy is highly prevalent, negatively influencing the control of epileptic seizures. Most patients are underdiagnosed. Screening for major depression in patients with epilepsy is necessary, contributing to the clinical improvement.

Levetiracetam Mechanisms of Action: From Molecules to Systems.

Epilepsy is a chronic disease that affects millions of people worldwide. Antiepileptic drugs (AEDs) are used to control seizures. Even though parts of their mechanisms of action are known, there are still components that need to be studied. Therefore, the search for novel drugs, new molecular targets, and a better understanding of the mechanisms of action of existing drugs is still crucial. Levetiracetam (LEV) is an AED that has been shown to be effective in seizure control and is well-tolerable, with a novel mechanism of action through an interaction with the synaptic vesicle protein 2A (SV2A). Moreover, LEV has other molecular targets that involve calcium homeostasis, the GABAergic system, and AMPA receptors among others, that might be integrated into a single mechanism of action that could explain the antiepileptogenic, anti-inflammatory, neuroprotective, and antioxidant properties of LEV. This puts it as a possible multitarget drug with clinical applications other than for epilepsy. According to the above, the objective of this work was to carry out a comprehensive and integrative review of LEV in relation to its clinical uses, structural properties, therapeutical targets, and different molecular, genetic, and systemic action mechanisms in order to consider LEV as a candidate for drug repurposing.

Acute exposure to environmentally relevant concentrations of phenytoin damages early development and induces oxidative stress in zebrafish embryos.

Phenytoin (PHE) is an antiepileptic drug that has been widely used in clinical practice for about 80 years. It is mainly used in the treatment of tonic-clonic and partial seizures. The widespread consumption of this drug around the world has led to PHE being introduced into water bodies through municipal, hospital, and industrial effluent discharges. Since the toxic effects of this drug on aquatic species has been scarcely explored, the aim of this work was to investigate the influence of low (25-400 ngL-1) and high (500-1500 ngL-1) environmentally relevant concentrations of PHE on the development and oxidative status of zebrafish (Danio rerio) embryos. The toxicity of PHE was evaluated from 12 to 96 h after fertilization in D. rerio at concentrations between 25 and 1500 ngL-1. In both the control group and the 0.05% DMSO system, no malformations were observed, all embryos developed normally after 96 h. The severity and frequency of malformations increased with increasing PHE concentration compared to embryos in the control group. Malformations observed included developmental delay, hypopigmentation, miscellaneous (more than one malformation in the same embryo), modified chorda structure, tail malformation, and yolk deformation. Concerning the biomarkers of oxidative stress, an increase in the degree of lipid peroxidation, protein carbonylation, and hydroperoxide content was observed (p < 0.05) concerning the control. In addition, a significant increase (p < 0.05) in antioxidant enzymes (SOD, CAT, and GPx) was observed at low exposure concentrations (25-400 ngL-1), with a decrease in enzyme activity at high concentrations (500-1500 ngL-1). Our IBR analysis demonstrated that oxidative damage biomarkers got more influence at 500ngL-1 of PHE. The results demonstrated that PHE may affect the embryonic development of zebrafish and that oxidative stress may be involved in the generation of this embryotoxic process.

Factors involved in time reduction between seizure relapses in patients with epilepsy attending emergency rooms in Medellín, Colombia.

BACKGROUND: Seizure relapses are the leading cause of admission to emergency rooms (ER) in people with epilepsy. OBJECTIVE: To analyze administrative and clinical factors associated with the duration between seizure relapses in people with epilepsy admitted to the Neurological Institute of Colombia (Medellin) between July 2018 and July 2019. MATERIALS AND METHODS: A retrospective follow-up study of 156 patients over 18 years old, diagnosed with epilepsy, and treated for over a year. The outcome variable was the time between seizure relapses, identified through the record of ER attendances. In addition, difficulties in the prescription filling process (delay, omission, or brand change) and clinical characteristics were analyzed as potential associated influence factors. The statistical analysis was performed using the Prentice, Williams & Peterson-Gap Time survival model for recurrent events. Finally, Adjusted Hazard Ratios (aHR) with 95% confidence intervals (95%CI) are also presented. RESULTS: One hundred fifty-six patients were analyzed. Their average age of diagnosis was 15.5 years (SD = 22.5), the median number of monthly seizures was 3 (SD = 9.3), and 50.6% were women. Moreover, difficulties in the prescription filling process were associated with a time reduction between seizure relapses (aHR = 2.61; 95%CI 1.49-4.57), showing a similar impact as having a history of three or four types of events (aHR = 2.96; 95%CI 1.23-7.12) and neuropsychiatric comorbidity (aHR = 1.89; 95%CI 1.04-3.54). CONCLUSION: Neuropsychiatric comorbidity, history of several types of events, and experiencing difficulties with prescription filling are associated with lower benefit from treatment to control seizure relapses.

Stability Indicating Methods for Determination of Third Generation Antiepileptic Drugs and Their Related Substances.

The third generation of antiepileptic drugs that have been approved by international regulatory agencies between 2007 and 2018 include rufinamide, stiripentol, eslicarbazepine acetate, lacosamide, perampanel, brivaracetam and everolimus. As part of demonstrating their safety profile, stability indicating methods are developed to monitor these drugs and their impurities. In this context, this review describe some characteristics, impurities and the stability indicating methods used for the determination of these drugs and the presence of their related substances. Through a search in official compendia and scientific articles, fifty-six analytical methodologies were identified up to October 2020. The methodologies were developed using techniques of HPLC, UPLC, HPTLC, GC and UV/Vis spectrophotometry. A majority of the methods (∼70%) employed HPLC-UV. A number of these antiepileptic drugs were found to have had a small number of studies related to their stability and for the detection of impurities. The presentation of the current level of research on third generation antiepileptic drugs highlights the need for new stability and safety studies that are necessary to develop new pharmaceutical products containing these drugs.

Mandible bone density in adolescents with cerebral palsy using antiepileptic drugs / Densidade óssea da mandíbula em adolescentes com paralisia cerebral em uso de drogas antiepilépticas

Objective: The aim of this study was to assess the bone density of the mandible in adolescents with cerebral palsy (CP) treated with antiepileptic drugs using one beam computed tomography (CBCT). Methods: The study was carried out with 18 adolescents aged 12­18 years, undergoing routine dental treatment at the dental clinic of APCD-São Caetano do Sul. CBCT scans were of divided into two groups: G1 adolescents with CP using antiepileptic drugs and G2 normoactive adolescents. A single dentomaxillofacial radiologist assessed and evaluated the images using Dental Slice software and Image J. Fisher's exact tests as well as paired and unpaired Student's t-tests were performed. Results: Groups differed significantly with regard in the values of density (p < 0.001), with G1 presenting lower values compare to G2. G1 showed significantly lower density means on the right side, left side, and right/left sides of the mandible edge than G2 (p < 0.001). Conclusion: CP patients using antiepileptic drugs show evidence of bone mineral density loss of the mandible.(AU)

Objetivo: O objetivo deste estudo foi avaliar a densidade ótica óssea da mandíbula em adolescentes com paralisia cerebral (PC) tratados com drogas antiepilépticas por meio de tomográfica computadorizada de feixe cônico (TCFC). Métodos: O estudo foi realizado com 18 adolescentes de 12 a 18 anos, em tratamento odontológico de rotina na clínica odontológica da APCD-São Caetano do Sul. As TCFC foram divididas em dois grupos: G1 adolescentes com PC em uso de antiepilépticos e G2 adolescentes normoativos. Um único radiologista dentomaxilofacial assessou e avaliou as imagens usando usando os softwares Dental Slice e Image J. Os testes exatos de Fisher, bem como os testes t de Student pareados e não pareados foram realizados. Resultados: Os grupos diferiram significativamente quanto aos valores de densidade óptica (p <0,001), com o grupo G1 apresentando valores menores em relação ao G2. O grupo G1 apresentou médias de densidade óptica significativamente menores nos lados direito, esquerdo e direito / esquerdo da borda da mandíbula do que o G2 (p <0,001). Conclusão: Pacientes com PC em uso de drogas antiepilépticas apresentam evidências de perda de densidade óssea da mandíbula (AU)

Benzodiazepine partially reverses tonic-clonic seizures induced by thiocolchicoside

Seizures are a disorder caused by structural brain lesions, life-threatening metabolic derangements, or drug toxicity. The present study describes the behavior related to proconvulsant activity induced by thiocolchicoside (TCC) in rats and investigates the electrocorticographic patterns of this behavior and the effectiveness of classic antiepileptic drugs used to control these seizures. Forty-nine adult male Wistar rats were used and divided into two phases of our experimental design: 1) evaluation of seizure-related behavior and electrocorticographic patterns induced by TCC and 2) evaluation of the efficacy of classical antiepileptic drugs to control the proconvulsive activity caused by TCC. Our results showed that TCC induced tonic-clonic seizures that caused changes in electrocorticographic readings, characteristic of convulsive activity, with average amplitude greater than that induced by pentylenetetrazole. Treatment with anticonvulsants, especially diazepam, reduced the electrocorticographic outbreaks induced by TCC. The results suggested that TCC caused seizures with increased power in brain oscillations up to 40 Hz and that diazepam may partially reverse the effects.

A review of antiepileptic drugs: Part 1 occurrence, fate in aquatic environments and removal during different treatment technologies.

Antiepileptic drugs (AEDs) are the main treatment for people with epilepsy. However, in recent years, more and more people are using them for other indications such as: migraine, chronic neuropathic pain, and mood disorders. Consequently, the prescriptions and consumption of these drugs are increasing worldwide. In WWTPs, AEDs can resist degradation processes, such as photodegradation, chemical degradation and/or biodegradation. Until now, only constructed wetlands and photocatalysis have shown good removal rates of AEDs from wastewater. However, their effectiveness depends on the specific conditions used during the treatment. Since the consumption of AEDs has increased in the last decade and their degradation in WWTPs is poor, these drugs have been largely introduced into the environment through the discharge of municipal and/or hospital effluents. Once in the environment, AEDs are distributed in the water phase, as suspended particles or in the sediments, suggesting that these drugs have a high potential for groundwater contamination. In this first part of the AEDs review is designed to fill out the current knowledge gap about the occurrence, fate and removal of these drugs in the aquatic environment. This is a review that emphasizes the characteristics of AEDs as emerging contaminants.

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

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

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

Personalized Medicine Using Cutting Edge Technologies for Genetic Epilepsies.

Epilepsy is the most common chronic neurologic disorder in the world, affecting 1-2% of the population. Besides, 30% of epilepsy patients are drug-resistant. Genomic mutations seem to play a key role in its etiology and knowledge of strong effect mutations in protein structures might improve prediction and the development of efficacious drugs to treat epilepsy. Several genetic association studies have been undertaken to examine the effect of a range of candidate genes for resistance. Although, few studies have explored the effect of the mutations into protein structure and biophysics in the epilepsy field. Much work remains to be done, but the plans made for exciting developments will hold therapeutic potential for patients with drug-resistance. In summary, we provide a critical review of the perspectives for the development of individualized medicine for epilepsy based on genetic polymorphisms/mutations in light of core elements such as transcriptomics, structural biology, disease model, pharmacogenomics and pharmacokinetics in a manner to improve the success of trial designs of antiepileptic drugs.

Neuropolybin: A new antiseizure peptide obtained from wasp venom.

Epilepsy accounts for one of the most serious neurological disorders, and its treatment remains a challenge, due to high cost and harmful side effects. Bioactive molecules extracted from arthropod venoms are considered a promising therapy since these compounds are known for their highly selective and potent profiles. The purpose of this study was to identify and characterize the potential antiseizure effect of the peptide Ppnp7, extracted from the venom of the social wasp Polybia paulista, and also the effect of the bioinspired peptide, named Neuropolybin, in the same parameters. Additionally, we also evaluated the electroencephalographic (EEG) profile in the PTZ-induced acute seizures in animals treated with Neuropolybin, and potential adverse effects of both peptides in general spontaneous activity (Open Field analysis). Interestingly, Ppnp7 and Neuropolybin showed a noteworthy antiseizure effect in rats and mice, respectively. Curves of protection against the maximum seizure were obtained for both peptides, and EEG records demonstrated that Neuropolybin protected 80% of animals from tonic-clonic seizures when applied with a dose of 3 nmol (an approximate Ppnp7 ED50 found in rats). Neuropolybin and Ppnp7 did not cause changes in the general spontaneous activity of the animals in any of the doses evaluated. Therefore, this study demonstrated how compounds isolated from wasps' venom may be essential resources in the search for new drugs, and can also be considered valuable therapeutic and biotechnological tools for the study and future treatment of epileptic disorders.

Characterization and Outcomes of Epileptic Seizures in Mexican Pediatric Patients With Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

Introduction Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most common autoimmune encephalitides. The frequency of anti-NMDAR encephalitis is known to exceed the frequency of any individual viral encephalitis in young subjects. Epileptic seizures are a cardinal symptom in anti-NMDAR encephalitis; a significant amount of pediatric patients exhibit seizures as the first symptom of the disease, and most of them will develop them during the acute phase. The use of antiepileptic drugs (AEDs) is a cornerstone of the treatment of these patients, but the choice of agent and duration of treatment is currently unknown. Materials and methods This was a single-center retrospective review case series of all pediatric patients with a confirmed diagnosis of anti-NMDAR encephalitis and epileptic seizures admitted to the National Institute of Pediatrics in Mexico City from January 2012 to July 2019. Results We included a total of 31 patients (males 64.5%, median age: 10 years). No patient showed evidence of teratoma; only 38% of cases had a viral prodrome. Most patients initially exhibited psychiatric symptoms (51%), but the leading cause in soliciting medical assistance was the presence of epileptic seizures (71%). About 85% of patients presented epileptic seizures during the course of the illness, predominantly focal onset seizures (42% focal to bilateral tonic-clonic seizures, 32% focal seizures with impaired awareness). Electroencephalogram (EEG) was abnormal in 97% of patients; the characteristic extreme delta brush pattern was found in 9% of patients. Two AEDs on average were required to control seizures during the acute stage. In six (19%) patients, human herpesvirus (HHV) was detected in cerebrospinal fluid (CSF); all of them had epileptic seizures, which were more resistant to pharmacological treatment during the acute phase, requiring a higher number of AED (median 2.5 vs. 2). The development of epilepsy after acute encephalitis was uncommon; at 24 months, only one patient continued to have epileptic seizures. One of the factors most closely related to the persistence of epileptic seizures was the inadequate response to immunotherapy after four weeks. The functional prognosis was generally good; at a two-year follow-up, only two (10%) patients had a significant disability [modified Rankin Scale (mRS) score: 3-5]; both patients had seizures at a one-year follow-up. Conclusions Sustained use of AEDs after the acute phase of anti-NMDAR encephalitis is controversial. We found that the continuation of AEDs after the acute phase could be considered in the following scenarios: status epilepticus (SE), inadequate response to immunotherapy at four weeks, and a high mRS score at discharge and during follow-up. In other cases, discontinuation of AED may be warranted. More studies are needed in our country to replicate these results.

Niveles de vitamina D en pacientes con tratamiento anticonvulsivante para epilepsia que asistieron a la consulta externa de un hospital de tercer nivel de Colombia / Vitamin D levels in patients receiving anticonvulsant treatment for epilepsy in an outpatient clinic in Colombia

RESUMEN INTRODUCCIÓN: La vitamina D actúa en múltiples tejidos y procesos fisiológicos. El objetivo del estudio fue determinar los niveles de vitamina D en pacientes con epilepsia tratados con anticonvulsivantes. MATERIAL Y MÉTODOS: Estudio observacional, descriptivo, de corte transversal en pacientes con diagnóstico de epilepsia que asistieron al servicio de consulta externa de un hospital de tercer nivel de atención de Neiva, Colombia, entre marzo y octubre de 2018. Se midieron los niveles séricos de vitamina D, paratohormona, albúmina y calcio. RESULTADOS: Una muestra de 90 pacientes. La mediana de edad fue de 36,5 (rango 18-81 años), 46 (51,1%) presentaron niveles bajos de vitamina D (38,8% en rango de insuficiencia y 12,2% rango de deficiencia). Se documentó asociación entre el sexo femenino y niveles insuficientes y deficientes de vitamina D, el no realizar ejercicio con niveles insuficientes de vitamina D, la exposición diaria al sol menor de 15 minutos y el no realizar caminata con niveles deficientes de vitamina D. El déficit de vitamina D se asoció con incremento de los niveles de paratohormona, mediana 103,9 pg/ml (rango 30,7-182,9 pg/ml, P <0,01). No se encontraron diferencias entre los niveles de vitamina D y el uso de monoterapia, politerapia, ni con la utilización fármacos inductores enzimáticos. CONCLUSIONES: En pacientes con terapia anticonvulsivante es frecuente encontrar niveles insuficientes/ deficientes de vitamina D aunque no se encontró asociación con el uso de monoterapia, politerapia o inductores enzimáticos hepáticos.

SUMMARY INTRODUCTION: Vitamin D acts in many tissues and different physiological processes. The objective was to determine vitamin D levels in patients with epilepsy treated with anticonvulsants. MATERIALS AND METHOD: Observational, descriptive, cross-section study in consecutive patients with epilepsy who attended the Neurology outpatient service of a university hospital in Neiva, Colombia, between March and October 31, 2018. We obtained serum levels of vitamin D, parathormone, albumin and calcium. RESULTS: There were 90 patients with a median age of 36.5 (range 18-81 years), 46 (51.1%) had low levels of vitamin D (38.8% in the range of insufficiency and 12.2% with deficiency). Females had more insufficient and deficient levels of vitamin D; not exercising was associated with insufficient levels of vitamin D, daily exposure to the sun under 15 minutes and not walking, with deficient levels of vitamin D. Vitamin D deficiency was associated with an increase in parathyroid hormone levels, median 103.9 pg / ml (range 30.7 - 182.9 pg / ml, P <0.01). No difference was found between vitamin D levels and the use of monotherapy, polytherapy, or the use of enzyme-inducing drugs. CONCLUSIONS: In epileptic patients with anticonvulsants it is common to find insufficient / deficient levels of vitamin D although we found no association with the use of monotherapy, polytherapy or hepatic enzyme inducers.

Interactions between in vivo neuronal-glial markers, side of hippocampal sclerosis, and pharmacoresponse in temporal lobe epilepsy.

OBJECTIVE: To evaluate the interactions of metabolic neuronal-glial changes with the presence and hemispheric-side of hippocampal sclerosis (HS) and its potential role in predicting pharmacoresistance in temporal lobe epilepsy (TLE). METHODS: We included structural magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1 H-MRS) metabolic data for 91 patients with unilateral TLE and 50 healthy controls. We measured the values of total N-acetyl aspartate/total creatine (tNAA/tCr), glutamate/tCr (Glu/tCr), and myo-inositol/tCr (mIns/tCr). To assess the influence of the pharmacoresponse and hemispheric-side of HS on metabolic data, the relationship between clinical and MRI data, and the predictive value of NAA/Cr, we used analysis of variance/covariance and built a logistic regression model. We used bootstrap simulations to evaluate reproducibility. RESULTS: Bilateral tNAA/tCr reduction was associated with pharmacoresistance and with left HS, a decrease of Glu/tCr ipsilateral to the seizure focus was associated with pharmacoresistance, and ipsilateral mIns/tCr increase was related to pharmacoresistance and the presence of left HS. The logistic regression model containing clinical and 1 H-MRS data discriminated pharmacoresistance (area under the curve [AUC] = 0.78). However, the reduction of tNAA/tCr was the main predictor, with the odds 2.48 greater for pharmacoresistance. SIGNIFICANCE: Our study revealed a spectrum of neuronal-glial changes in TLE, which was associated with pharmacoresistance, being more severe in left-sided HS and less severe in MRI-negative TLE. These noninvasive, in vivo biomarkers provide valuable additional information about the interhemispheric differences in metabolic dysfunction, seizure burden, and HS, and may help to predict pharmacoresistance.

Epilepsia y Variables. Departamento de Neurología, Hospital de Clínicas del año 2016 al 2018 / Epilepsy and Variables. Department of Neurology, Hospital de Clínicas from 2016 to 2018

En el mundo hay unos 50 millones de personas con epilepsia. En países de ingresos bajos y medianos sugieren una proporción mucho mayor, entre 7 y 14 por 1000 personas. Las poblaciones pobres y las que viven en situaciones de vulnerabilidad, en particular en los países de ingresos bajos y medianos, soportan una carga desproporcionadamente alta; lo que supone una amenaza para la salud pública y el desarrollo económico y social. 1 Por el que el propósito de estudio fue conocer la característica epidemiológica de esta población. Se analizaron 281 fichas de pacientes con epilepsia, en un periodo de dos años, comprendidos entre 16 y 91 años. Resultados: 51.9% corresponde al sexo masculino y el 48.1% al femenino. El 63,34% presentó crisis focal. El 59,2 de los casos de epilepsia, se acompañan de trastornos psiquiátricos. Solo el 5% ha afirmado haber padecido algún efecto adverso a la medicación. Se desconoce la causa de epilepsia en un 58,58%. Dentro las causas de epilepsia secundaria; el Accidente Cerebro Vascular (ACV) se encuentra en un 22.4%. Llamativamente el 30.2% de los pacientes no cuenta con estudio de imagen de encéfalo. El 41.93% presentó crisis con el tratamiento, pero el 50% de los pacientes realiza tratamiento de forma irregular. El 53,73% presentaba tratamiento con un único fármaco anticonvulsivante, siendo la Carbamacepina la más utilizada. Conclusión: La Epilepsia tiene una alta prevalencia dentro de los desórdenes neurológicos. Afecta al sexo masculino de forma más importante, siendo la crisis focal la más frecuente. La baja asociación con trastornos psiquiátricos encontrados; nos obliga a hacer hincapié a ser más exhaustivos en la búsqueda de estos. En un alto porcentaje se desconoce la causa. Las causas más frecuentes de epilepsia secundaria fueron ACV y Traumatismo de Cráneo. Un porcentaje considerable continúan con crisis por incumpliendo del tratamiento. La Carbamacepina, el Ácido Valproico y la Fenitoína son los más utilizados, debidos a los costos y accesibilidad de los mismos, se deben establecer esfuerzos para proponer estrategias de intervención, para facilitar el seguimiento de los pacientes y que estos se puedan también beneficiar de nuevos fármacos anticonvulsivantes.

In the world there are about 50 million people with epilepsy. In low and middle income countries they suggest a much higher proportion, between 7 and 14 per 1000 people. Poor populations and those living in vulnerable situations, particularly in low and middle income countries, carry a disproportionately high burden; which poses a threat to public health and economic and social development. 1 Whereby the purpose of the study was to know the epidemiological characteristic of this population. Were analyzed 281 records of patients with epilepsy, over a period of two years, between 16 and 91 years. Results: 51.9% correspond to the male sex and 48.1% to the female. 63.34% presented focal crisis. 59.2 of epilepsy cases are accompanied by psychiatric disorders. Only 5% have claimed to have suffered any adverse effect to the medication. The cause of epilepsy in 58.58% is unknown. Within the causes of secondary epilepsy; Stroke is 22.4%. Notably, the 30.2% of patients do not have a brain imaging study; 41.93% presented a crisis with treatment, but 50% of patients performed irregular treatment. 53.73% had treatment with a single anticonvulsant drug, with Carbamazepine being the most used. Conclusion: Epilepsy has a high prevalence within neurological disorders. It affects the male sex more importantly, with the focal crisis being the most frequent. The low association with psychiatric disorders found; it forces us to emphasize being more exhaustive in the search for these. The cause is unknown in a high percentage. The most frequent causes of secondary epilepsy were CVA and Skull Trauma. A considerable percentage continue with crisis due to non-compliance with treatment. Carbamazepine, Valproic Acid and Phenytoin are the most used, due to their costs and accessibility, efforts should be established to propose intervention strategies, to facilitate the monitoring of patients and so that they can also benefit from new anticonvulsant drugs.