Evaluating a Venom-Bioinspired Peptide, NOR-1202, as an Antiepileptic Treatment in Male Mice Models.

Epilepsy, a neurological disorder characterized by excessive neuronal activity and synchronized electrical discharges, ranks among the most prevalent global neurological conditions. Despite common use, antiepileptic drugs often result in adverse effects and lack effectiveness in controlling seizures in temporal lobe epilepsy (TLE) patients. Recent research explored the potential of occidentalin-1202, a peptide inspired by Polybia occidentalis venom, in safeguarding Wistar rats from chemically induced seizures. The present study evaluated the new analog from occidentalin-1202 named NOR-1202 using acute and chronic pilocarpine-induced models and an acute kainic acid (KA) male mice model. NOR-1202 was administered through the intracerebroventricular (i.c.v.), subcutaneous, or intraperitoneal routes, with stereotaxic procedures for the i.c.v. injection. In the acute pilocarpine-induced model, NOR-1202 (i.c.v.) protected against generalized seizures and mortality but lacked systemic antiepileptic activity. In the KA model, it did not prevent generalized seizures but improved survival. In the chronic TLE model, NOR-1202's ED50 did not differ significantly from the epileptic or healthy groups regarding time spent in spontaneous recurrent seizures during the five-day treatment. However, the NOR-1202 group exhibited more seizures than the healthy group on the second day of treatment. In summary, NOR-1202 exhibits antiepileptic effects against chemoconvulsant-induced seizures, but no effect was observed when administered systemically.

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.

Brain Neuroplasticity after Treatment with Antiseizure: A Review.

Epilepsy is a disease characterized by the periodic occurrence of seizures. Seizures can be controlled by antiseizure medications, which can improve the lives of individuals with epilepsy when given proper treatment. Therefore, this study aimed to review the scientific literature on brain neuroplasticity after treatment with antiseizure drugs in different regions of the brain. According to the findings, that several antiseizure, such as lamotrigine, diazepam, levetiracetam, and valproic acid, in addition to controlling seizures, can also act on neuroplasticity in different brain regions. The study of this topic becomes important, as it will help to understand the neuroplastic mechanisms of these drugs, in addition to helping to improve the effectiveness of these drugs in controlling the disease.

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.

A new class of peptides from wasp venom: a pathway to antiepileptic/neuroprotective drugs.

The ability of venom-derived peptides to disrupt physiological processes in mammals provides an exciting source for pharmacological development. Our research group has identified a new class of neuroactive peptides from the venom of a Brazilian social wasp, Polybia occidentalis, with the potential pharmacological profile to treat epilepsies. The study was divided into five phases: Phase 1 concerned the extraction, isolation and purification of Occidentalin-1202(n) from the crude venom, followed by the synthesis of an identical analogue peptide, named Occidentalin-1202(s). In Phase 2, we described the effects of both peptides in two acute models of epilepsy-kainic acid and pentylenetetrazole-induced model of seizures-and measured estimated ED50 and therapeutic index values, electroencephalographic studies and C-fos evaluation. Phase 3 was a compilation of advanced tests performed with Occidentalin-1202(s) only, reporting histopathological features and its performance in the pilocarpine-induced status epilepticus. After the determination of the antiepileptic activity of Occidentalin-1202(s), Phase 4 consisted of evaluating its potential adverse effects, after chronic administration, on motor coordination (Rotarod) and cognitive impairment (Morris water maze) tests. Finally, in Phase 5, we proposed a mechanism of action using computational models with kainate receptors. The new peptide was able to cross the blood-brain barrier and showed potent antiseizure effects in acute (kainic acid and pentylenetetrazole) and chronic (temporal lobe epilepsy model induced by pilocarpine) models. Motor and cognitive behaviour were not adversely affected, and a potential neuroprotective effect was observed. Occidentalin-1202 can be a potent blocker of the kainate receptor, as assessed by computational analysis, preventing glutamate and kainic acid from binding to the receptor's active site. Occidentalin-1202 is a peptide with promising applicability to treat epilepsy and can be considered an interesting drug model for the development of new medicines.

Simultaneous Estimation and Validation of Four Antiepileptic Drugs from Bulk and Formulations Using Reverse Phase HPLC

Abstract Epilepsy is a disorder of the central nervous system, in which the nerve cell activity in the brain is disturbed causing seizures. The objective was to develop an RP-HPLC method for consistent simultaneous quantitation of four antiepileptic drugs Levetiracetam (LVT), Lamotrigine (LTG), Phenobarbital (PBT) and Phenytoin (PTY). An isocratic method was developed on C18 column in JASCO HPLC using 5 mM potassium phosphate buffer (pH 6) and acetonitrile as the mobile phase at a flow rate of 1ml/min and detected at 230 nm using UV detector. The mean retention time for LVT, LTG, PBT and PTY were found as 2.55, 3.55, 4.65 and 5.99 minutes respectively. The method was validated as per ICH guidelines and was found to be acceptable. The %RSD value was <2.0 % thus stating the developed method was precise for the drugs in the given range. The accuracy values were within 85-115% of the recovery range. The specificity of the method was evaluated by an assay of marketed formulation, and it showed a percent content between 90-110% w/w for all the four drugs. The proposed analytical method was simple, accurate and robust and was precisely able to resolve the four major antiepileptic drugs. Hence, the current method can be applied successfully for routine examination of these drugs

Silencing of the GluN1-NMDA Glutamate Receptor Subunit by Intranasal siRNA Increases the Latency Time for Seizures in the Pilocarpine Rodent Model of Epilepsy.

Temporal lobe epilepsy (TLE) is the most prevalent and treatment-refractory type of epilepsy. Among the different mechanisms associated with epileptogenesis, overstimulation of glutamatergic neurotransmission has been associated with the onset and progression of seizures in TLE. Experimental evidence indicates that blocking the N-methyl-D-aspartate (NMDA) receptor or suppressing the expression of its subunit, mainly GluN1, may be effective in preventing epileptic seizures. Small interfering RNA (siRNA) has received attention as a potential therapeutic tool due to the inhibition of gene expression in some diseases. The present work evaluated the potential silencing effect of intranasal administration of an siRNA conjugate against the GluN1 subunit in animals submitted to the pilocarpine model of epilepsy. The results showed that the siRNA conjugate transfection system silences the GluN1 subunit in the hippocampus of rats when administered intranasally. As demonstrated by the RT-qPCR and Western blotting approaches, the silencing of GluN1 was specific for this subunit without affecting the amount of mRNA for other subunits. Silencing increased the latency time for the first tonic-clonic seizure when compared to controls. The overlapping of findings and the validation of the intranasal route as a pharmacological route of siRNA targeting the GluN1 subunit give the work a significant biotechnological interest.

[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.

Deep Brain Stimulation for Refractory Temporal Lobe Epilepsy. Current Status and Future Trends.

A comparative analysis of the targets for deep brain stimulation (DBS) to treat refractory temporal lobe epilepsy and the rationale for its use is presented, with an emphasis on the latency to obtain the significant antiepileptic effect and the long-term seizure control. The analysis includes consideration of surgical techniques currently used to optimize antiseizure effects and decrease surgical risks. Seizure control is similar for programed DBS and DBS responsive to abnormal cortical or subcortical electroencephalogram (EEG) activity. There is no difference in the long-term seizure control between programmed and responsive and intermittent or continuous DBS. However, intermittent programed DBS may have a significant antiseizure effect starting in the first month when applied to a non-sclerotic tissue such as the parahippocampal cortex. DBS induces no neuropsychological deterioration.

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.

Topiramate treatment in Wistar rats during childhood induces sex-specific vascular dysfunction in adulthood.

The present study determined whether treatment during childhood with topiramate (TPM), a new generation antiepileptic drug, results in altered aortic reactivity in adult male and female rats. We also sought to understand the role of endothelium-derived contractile factors in TPM-induced vascular dysfunction. Male and female Wistar rats were treated with TPM (41 mg/kg/day) or water (TPM vehicle) by gavage during childhood (postnatal day, 16-28). In adulthood, thoracic aorta reactivity to phenylephrine (phenyl), as well as aortic thickness and expression of cyclooxygenases (COX-1 and COX-2), NOX2, and p47phox were evaluated. The aortic response to phenyl was increased in male and female rats from the TPM group when compared with the control group. In TPM male rats, the hyperreactivity to phenyl was abrogated by the inhibition of NADPH oxidase and COX-2, while in female rats, responses were restored only by inhibition of COX-2. In addition, TPM male rats presented aortic hypertrophy and increased expression of NOX-2 and p47phox, while TPM female rats showed increased COX-2 aortic expression. Taken together, for the first-time, the present study provides evidence that treatment with TPM during childhood causes vascular dysfunction in adulthood, and that the mechanism underlying the vascular effects of TPM is sex-specific.

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.

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.

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)

Cutaneous adverse reactions associated with antiseizure medication: clinical characteristics and implications in epilepsy treatment.

OBJECTIVE: To describe the clinical characteristics of cutaneous adverse reactions and cross-sensitivity induced by antiseizure medications and compare the pattern of use of antiseizure medications in patients with epilepsy according to skin rash history. METHODS: We analysed patients with a history of skin rash presenting for up to 12 weeks after initiating antiseizure medication. The history of skin rash was verified by medical charts, interviews, and identification of skin lesions by patients based on illustrative images. The minimum follow-up period was eight months. The control group comprised epilepsy patients with regular antiseizure medication use for at least 12 weeks without skin rash. We included 109 cases and 99 controls. RESULTS: The median (interquartile range) period from the index rash was six years (2-11). Carbamazepine was the trigger medication in 48% of cases and induced skin rashes in all patients with cross-sensitivity and carbamazepine exposure. Stevens-Johnson syndrome, toxic epidermal necrolysis, or drug reactions with eosinophilia and systemic symptoms affected 36% of cases. Carbamazepine- or oxcarbazepine-induced maculopapular exanthema occurred earlier (median: one week) than that induced by other antiseizure medications (median: three weeks) (p=0.006). Cross-sensitivity was more common in patients with at least one episode of Stevens-Johnson syndrome (29%) and Stevens-Johnson/toxic epidermal necrolysis overlap (50%) than in patients with maculopapular exanthema (8%) (p=0.01). Although most cases were mild, the pattern of antiseizure medication use differed from that of controls, with a lower proportion of antiseizure medication typically associated with severe cutaneous adverse reactions (carbamazepine, phenytoin, phenobarbital, primidone, oxcarbazepine, and lamotrigine) (p<0.001). Most cases exposed to high-risk medication, however, did not develop cross-sensitivity. SIGNIFICANCE: Cutaneous adverse reaction history may influence antiseizure medication use. Cross-sensitivity is more common in severe cases and most patients are affected by mild, self-limited skin rashes. Further research should consider the relevance of mild skin rashes in lifelong epilepsy treatment.