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The article delves into the significance of recognizing variations among direct-acting oral anticoagulants (DOACs) when treating patients with epilepsy, particularly in relation to concomitant antiseizure medications (ASMs). It suggests that edoxaban may be the preferred DOAC for patients with epilepsy, especially when paired with mild to moderate CYP3A-inducing ASMs. The study also cautions about potential interactions with CYP3A4/P-gp inhibiting ASMs, advising careful monitoring, especially with cannabidiol. Additionally, the article explores the association between non-vitamin K oral anticoagulants and the risk of major bleeding in patients with nonvalvular atrial fibrillation, emphasizing the importance of assessing drug interactions for effective and safe treatment. [Extracted from the article]

This document explores the relationship between antiepileptic drugs (AEDs), folate, one-carbon metabolism, genetics, and epigenetics. It highlights the potential complications that can arise from AEDs interfering with folate metabolism, such as cognitive, mood, and psychiatric issues. The document also discusses the risks associated with the use of valproate, a commonly used AED, and emphasizes the importance of folic acid supplementation during pregnancy, especially for women taking AEDs. Further research is needed to fully understand the mechanisms involved and develop preventive measures. The document does not provide any specific recommendations or conclusions. [Extracted from the article]

Introduction: Epilepsy is a disorder characterised by two or more recurrent seizures that are unprovoked by any immediately identifiable cause. Additionally, it can lead to psychological issues, including anxiety and depression, as well as societal problems such as increased social stigma and withdrawal. Physical exercise regimens incorporated into the treatment plan can benefit epilepsy patients; however, these are often not included by medical experts or epilepsy patients themselves due to the stigma associated with the condition, apprehension that exercise might trigger seizures, or a lack of knowledge about the benefits of physical activity. Aim: To evaluate the effect of physical exercise on cardiovascular endurance and fitness levels in adults with and without epilepsy. Materials and Methods: A quasi-experimental study consisting of a pre-and post-design with a control group was conducted over a duration of six months. For both groups, participants were given exercise interventions three times a week for six months (from March 2022 to August 2022), with each session lasting 60 minutes. The outcome measures evaluated included the Shuttle Walk Test (SWT) and maximal oxygen consumption (VO2 max). For normally distributed data, an unpaired t-test was used to compare data between groups, while repeated measures Analysis of Variance (ANOVA) was used to compare data within the same group. A significance level of p-value =0.05 was considered. Results: The mean SWT scores in the control group at baseline, at the end of the 1st month, the 3rd month, and the 6th month were 6.62±1.32 m, 6.94±3.62 m, 7.46±2.69 m, and 8.36±3.16 m, respectively. In the experimental group, the mean SWT scores were 5.96±0.02 m, 6.68±2.24 m, 7.02±1.41 m, and 7.90±2.08 m, respectively. The mean VO2 max values in the experimental group at baseline, at the end of the 1st month, the 3rd month, and the 6th month were 29.76±4.29 m, 30.24±4.01 m, 33.40±2.17 m, and 35.45±3.68 m, respectively. In the control group, the mean VO2 max values were 29.59±5.68 m, 30.09±5.60 m, 31.22±3.48 m, and 33.88±4.26 m, respectively. Conclusion: The study concluded that the physical exercise intervention conducted for adults with and without epilepsy improved cardiovascular fitness and aerobic endurance. Therefore, patients with epilepsy should be encouraged to participate in some form of physical activity. [ABSTRACT FROM AUTHOR]

Epilepsy remains a disease that affects many people around the world. With the development of new drugs to treat this condition, the importance of therapeutic drug monitoring continues to rise and remains a challenge for the medical community. This review article explores recent advances in the detection of antiepileptic drugs across various sample types commonly used for drug monitoring, with a focus on their applications and impact. Some of these new methods have proven to be simpler, greener, and faster, making them easier to apply in the context of therapeutic drug monitoring. Additionally, besides the classic use of blood and its derivatives, there has been significant research into the application of alternative matrices due to their ease of sample collection and capacity to reflect drug behavior in blood. These advances have contributed to increasing the efficacy of therapeutic drug monitoring while enhancing its accessibility to the population. [ABSTRACT FROM AUTHOR]

Background and Objectives: The objective of this paper is to determine the rate and predictors of non-adherence to antiseizure medications in Saudi Arabia. Materials and Methods: A cross-sectional study which involved questionnaires and data collection from patients' medical records was conducted at neurology clinics. The rate of non-adherence to antiseizure medications was measured using "the Medication Adherence Rating Scale" (MARS). Predictors of non-adherence to antiseizure medications were evaluated using a multidimensional questionnaire specific to epilepsy. Results: One hundred and sixty-two patients participated in the study. The mean (SD) age was 34.1 (10.4) years, and 56% were male. Epilepsy was controlled (i.e., seizure-free ≥ 1 year) in 42% of patients. The mean ± SD (range) MARS scores were 7.80 ± 1.59 (2–10). Out of 162 patients, 58 (36%) patients had MARS scores ≤ 7 out of 10. The most frequently rated predictor for non-adherence was poor seizure control, which was reported by around 36% of patients. Forgetfulness, dosing frequency, and social stigma were also among the commonest predictors of non-adherence to antiseizure medications that were rated by approximately 27%, 24%, and 22% of the patients, respectively. The impacts of several socio-demographic and clinical factors on adherence were assessed. In the regression analysis, the odds of non-adherence in a patient who experienced adverse effects were twice that of a patient who did not have adverse effects (p = 0.113). Furthermore, females, employers, and patients who had comorbidity, those with focal epilepsy, those on polytherapy of antiseizure medication, and those receiving multiple doses per day, were all more likely (but not significantly, p > 0.05) to be non-adherent compared to their counterparts. Conclusions: The significance of this study is that it reveals that adherence to antiseizure medications is suboptimal in Saudi Arabia. Poor seizure control, forgetfulness, dosing frequency, and social stigma were the primary patient-reported predictors of non-adherence in epilepsy. This emphasizes the importance of routine evaluation of adherence in practice to identify and address what individual patients perceive as a barrier to adherence with antiseizure medications. [ABSTRACT FROM AUTHOR]

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening skin lesion triggered by hypersensitive drug reaction. They are characterized by extensive epidermal necrosis and skin exfoliation. Fulminant type 1 diabetes mellitus (FT1DM) is featured by a rapid-onset of hyperglycemia with ketoacidosis due to severely destroyed β-cell function. Fulminant type 1 diabetes mellitus as a sequela of SJS/TEN has rarely been reported. Case presentation: We present a 73-year-old female patient who developed SJS/TEN skin allergic reaction after taking carbamazepine and phenytoin for 35 days. Then, hyperglycemia and diabetic ketoacidosis occurred 20 days after discontinuation of antiepileptic drugs. A very low serum C-peptide level (8.79 pmol/l) and a near-normal glycosylated hemoglobin level met the diagnostic criteria for fulminant T1DM. Intravenous immunoglobulin (IVIG) and insulin were promptly administered, and the patient recovered finally. Conclusions: This rare case indicates that monitoring blood glucose is necessary in SJS/TEN drug reaction, and comprehensive therapy with rehydration, insulin, antibiotics, and IVIG may improve the prognosis. [ABSTRACT FROM AUTHOR]

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Introduction: Epilepsy is a disorder characterised by two or more recurrent seizures that are unprovoked by any immediately identifiable cause. Additionally, it can lead to psychological issues, including anxiety and depression, as well as societal problems such as increased social stigma and withdrawal. Physical exercise regimens incorporated into the treatment plan can benefit epilepsy patients; however, these are often not included by medical experts or epilepsy patients themselves due to the stigma associated with the condition, apprehension that exercise might trigger seizures, or a lack of knowledge about the benefits of physical activity. Aim: To evaluate the effect of physical exercise on cardiovascular endurance and fitness levels in adults with and without epilepsy. Materials and Methods: A quasi-experimental study consisting of a pre-and post-design with a control group was conducted over a duration of six months. For both groups, participants were given exercise interventions three times a week for six months (from March 2022 to August 2022), with each session lasting 60 minutes. The outcome measures evaluated included the Shuttle Walk Test (SWT) and maximal oxygen consumption (VO2 max). For normally distributed data, an unpaired t-test was used to compare data between groups, while repeated measures Analysis of Variance (ANOVA) was used to compare data within the same group. A significance level of p-value ≤0.05 was considered. Results: The mean SWT scores in the control group at baseline, at the end of the 1st month, the 3rd month, and the 6th month were 6.62±1.32 m, 6.94±3.62 m, 7.46±2.69 m, and 8.36±3.16 m, respectively. In the experimental group, the mean SWT scores were 5.96±0.02 m, 6.68±2.24 m, 7.02±1.41 m, and 7.90±2.08 m, respectively. The mean VO2 max values in the experimental group at baseline, at the end of the 1st month, the 3rd month, and the 6th month were 29.76±4.29 m, 30.24±4.01 m, 33.40±2.17 m, and 35.45±3.68 m, respectively. In the control group, the mean VO2 max values were 29.59±5.68 m, 30.09±5.60 m, 31.22±3.48 m, and 33.88±4.26 m, respectively. Conclusion: The study concluded that the physical exercise intervention conducted for adults with and without epilepsy improved cardiovascular fitness and aerobic endurance. Therefore, patients with epilepsy should be encouraged to participate in some form of physical activity.

Abstract Background Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening skin lesion triggered by hypersensitive drug reaction. They are characterized by extensive epidermal necrosis and skin exfoliation. Fulminant type 1 diabetes mellitus (FT1DM) is featured by a rapid-onset of hyperglycemia with ketoacidosis due to severely destroyed β-cell function. Fulminant type 1 diabetes mellitus as a sequela of SJS/TEN has rarely been reported. Case presentation We present a 73-year-old female patient who developed SJS/TEN skin allergic reaction after taking carbamazepine and phenytoin for 35 days. Then, hyperglycemia and diabetic ketoacidosis occurred 20 days after discontinuation of antiepileptic drugs. A very low serum C-peptide level (8.79 pmol/l) and a near-normal glycosylated hemoglobin level met the diagnostic criteria for fulminant T1DM. Intravenous immunoglobulin (IVIG) and insulin were promptly administered, and the patient recovered finally. Conclusions This rare case indicates that monitoring blood glucose is necessary in SJS/TEN drug reaction, and comprehensive therapy with rehydration, insulin, antibiotics, and IVIG may improve the prognosis.

OBJECTIVE: This study was undertaken to evaluate how the challenges in the recruitment and retention of participants in clinical trials for focal onset epilepsy have changed over time. METHODS: In this systematic analysis of randomized clinical trials of adjunct antiseizure medications for medication-resistant focal onset epilepsy, we evaluated how the numbers of participants, sites, and countries have changed since the first such trial in 1990. We also evaluated the proportion of participants who completed each trial phase and their reasons for early trial exit. We analyzed these trends using mixed effects generalized linear models accounting for the influence of the number of trial sites and trial-specific variability. RESULTS: The number of participants per site has steadily decreased over decades, with recent trials recruiting fewer than five participants per site (reduction by .16 participants/site/year, p  .20). SIGNIFICANCE: This historical analysis highlights the increasing challenges with participant recruitment and retention, as well as increasing placebo response. It serves as a call to action to change clinical trial design to address these challenges.

Abstract Background/aim The most commonly prescribed anti-seizures medications (ASMs) for the treatment of epilepsy are currently topiramate, zonisamide, lacosamide, carbamazepine and levetiracetam. The objective of this study was to examine the correlation between preoperative, intraoperative, and postoperative metabolic acidosis and the use of ASMs prior to craniotomy operations. Materials and methods This retrospective cross-sectional study evaluated patients who underwent intracranial surgery with craniotomy under general anaesthesia between May 2020 and April 2023 and used ASMs. The patients were classified into four groups based on the pharmacological mechanisms of action of the ASMs administered before intracranial surgery (Group-I, zonisamide or topiramate; Group-II, lacosamide; Group-III, carbamazepine; Group-IV, levetiracetam). Metabolic acidosis severity was defined based on base excess (BE) levels: mild (-3 to -5), moderate (-5 to -10), and severe (below − 10). The study investigated the correlation between ASMs and the severity of metabolic acidosis in preoperative, intraoperative, and postoperative blood gas measurements. Results Out of 35 patients, 24 patients underwent intracranial surgery and 11 patients underwent epilepsy surgery. There were statistically significant differences in the severity of metabolic acidosis between preoperative (p

Sleep disorders occur twice as often in epilepsy patients compared to healthy people and have a negative impact on seizure control and general quality of life. International and Russian publications on the effect of perampanel (PER) on sleep emphasise the positive effect of the drug on sleep quality, daytime sleepiness and sleep architecture.Objective: to evaluate the effect of PER (Fycompa®) on sleep quality and daytime sleepiness when used as an adjunct antiepileptic drug (AED) in the treatment of epilepsy in adults.Material and methods. The study included 106 patients aged 18 to 73 years with absolute predominance of focal epilepsy (n=96) who were prescribed PER as an adjunctive AED when previous therapy was insufficient, regardless of whether or not complaints of insomnia were present. The study was conducted from April 2022 to June 2023. The maximum observation period was 12 months. The study was multicenter (10 Russian clinical centres) and designed as an observational study, with patients being monitored prospectively, but some of the indicators were collected retrospectively, taking into account the conditions of real-life clinical practice. We assessed: sleep quality using the Pittsburgh Insomnia Scale (Ya.I. Levin modification), daytime sleepiness according to the Epworth scale, anxiety/depression level (Hospital Anxiety and Depression Scale, HADS), adverse events (AEs), efficacy/tolerability of combination therapy with PER for epilepsy at baseline, and after 1, 3, 6 and 12 months of therapy based on the number of completed questionnaires at each visit in the real-life clinical practice.Results. After a follow-up period of 12 months, the retention rate for complex therapy with PER was 84.9%. PER was discontinued in 15.1% of patients and in only 5.7% due to AEs. The most common AE was dizziness, which was observed with a frequency of over 10% (n=21), followed by irritability (n=9) and drowsiness (n=9) with the same frequency. No new, previously undescribed AEs were observed in this study. The use of PER as an additional AED led to a significant reduction in daytime sleepiness and an improvement in sleep quality after the first month of use; by the 12-month follow-up period, the daytime sleepiness index gradually decreased and reached normal levels, and sleep quality improved. The use of PER as part of a complex therapy led to a significant reduction in the initially elevated anxiety level.Conclusion. The use of PER as an additional AED in adults in dynamics significantly improves sleep quality and reduces daytime sleepiness after the first month of use, regardless of the duration of the disease and the order of PER administration. The use of PER as part of a complex therapy led to a decrease in the initially elevated anxiety level from subclinical to normal.

Background: The spectrum of cutaneous drug reactions encompasses a broad range from benign rashes to potentially life-threatening conditions. The present study aims to comprehensively investigate the frequency, type, causality, preventability, and severity of adverse drug reactions (CADRs) occurring during hospitalization. Methods: Conducted at SKIMS Medical College Hospital over a comprehensive six-month duration, this study systematically monitored the occurrence of cutaneous drug reactions. These reactions' causality, severity, and preventability assessments were meticulously conducted using established classifications such as the Wills and Brown classification, WHO criteria, Hartwig scale, and modified Schumock and Thornton scales. Result and discussion: Involving a cohort of 300 admissions, the study identified an incidence of adverse drug reactions (CADRs) at 8%. Detailed analysis revealed no significant associations between CADRs and gender, drug allergy history, or the number of drugs administered. Notably, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), particularly Dapsone, emerged as the most common drug class associated with cutaneous adverse drug reactions (CADRs), accounting for 41.67% of cases. Antibiotics, including linezolid (12.5%) and amikacin (12.5%), followed closely. Itching (37.5%), followed by red raised lesions (33.33%), emerged as the predominant reported reactions, showcasing associations with various drugs. Notably, a significant proportion of CADRs were categorized as mild (50%), with 95.83% deemed not preventable. Conclusion: The prevalence of mild reactions, particularly linked to NSAIDs and antibiotics, underscores the nuanced complexities in drug responses. The research enriches the broader comprehension of adverse drug reactions, underscoring the imperative for meticulous surveillance and scholarly inquiry to elevate patient safety.

Background/aim: The most commonly prescribed anti-seizures medications (ASMs) for the treatment of epilepsy are currently topiramate, zonisamide, lacosamide, carbamazepine and levetiracetam. The objective of this study was to examine the correlation between preoperative, intraoperative, and postoperative metabolic acidosis and the use of ASMs prior to craniotomy operations. Materials and methods: This retrospective cross-sectional study evaluated patients who underwent intracranial surgery with craniotomy under general anaesthesia between May 2020 and April 2023 and used ASMs. The patients were classified into four groups based on the pharmacological mechanisms of action of the ASMs administered before intracranial surgery (Group-I, zonisamide or topiramate; Group-II, lacosamide; Group-III, carbamazepine; Group-IV, levetiracetam). Metabolic acidosis severity was defined based on base excess (BE) levels: mild (-3 to -5), moderate (-5 to -10), and severe (below − 10). The study investigated the correlation between ASMs and the severity of metabolic acidosis in preoperative, intraoperative, and postoperative blood gas measurements. Results: Out of 35 patients, 24 patients underwent intracranial surgery and 11 patients underwent epilepsy surgery. There were statistically significant differences in the severity of metabolic acidosis between preoperative (p < 0.001), intraoperative (p < 0.001) and postoperative (p = 0.01) groups. The preoperative mean BE of group-I was − 4.7, which was statistically lower than that of group-III (p = 0.01) and group-IV (p < 0.001). Intraoperatively and postoperatively, group-I had a mean BE of -7.5 and − 3.2, respectively, which was statistically lower than that of groups II (p = 0.007; p = 0.04), III (p = 0.002; p = 0.03), and IV (p < 0.001; p = 0.009). There was no statistically significant difference in BE between groups II, III and IV at all three time points. Group I had the lowest BE at all three time points. Intraoperative bicarbonate was administered to all patients in group I, whereas no intraoperative bicarbonate was required in the other groups. In group I, 50% of patients required postoperative intensive care. Conclusion: The use of ASMs in patients undergoing surgery is important in terms of mortality and morbidity. Topirimat and zonisamide are ASMs that can cause preoperative, intraoperative and postoperative metabolic acidosis. Patients receiving topirimat or zonisamide are particularly susceptible to metabolic acidosis. Special care should be taken in the management of anaesthesia in patients receiving these drugs, and monitoring of the perioperative metabolic status is essential. [ABSTRACT FROM AUTHOR]

Cenobamate (CNB) is one of the newer antiseizure medications for the treatment of focal-onset seizures. The cognitive profile of CNB is not yet known in detail. Here we present the case of an 18-year-old male high school student with epilepsy who received adjunctive CNB. Under 400 mg/d of CNB in combination with lamotrigine, a neuropsychological reassessment revealed a severe deterioration of the formerly normal episodic memory functions, while executive functions remained unaffected. The de novo memory deficit had already led to a collapse in school performance and he unexpectedly failed to obtain the general qualification for university entrance. Given the beneficial effect of CNB on seizure control, a dose reduction of CNB to 200 mg/d and introduction of valproic acid was performed. This led to a full recovery of objective memory performance. To our knowledge this is the very first report of a dose-dependent, selective and severe decline in episodic memory performance under CNB, potentially impeding academic achievement. The findings call for a cognitive monitoring of CNB which also addresses episodic memory in addition to executive functions. Systematic studies on episodic memory upon CNB treatment would help to appreciate the scope of this apparently reversible adverse effect. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Research points to disparities in disease burden and access to medical care in epilepsy. We studied the association between socioeconomic status (SES) and antiseizure medication (ASM) use in pregnancies with maternal epilepsy. Methods: We conducted a cross‐sectional study consisting of 21 130 pregnancies with maternal epilepsy identified from Nordic registers during 2006–2017. SES indicators included cohabitation status, migrant background, educational attainment, and household income. Main outcomes were the proportion and patterns of ASM use from 90 days before pregnancy to birth. We applied multiple imputation to handle SES variables with 2%–4% missingness. We estimated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) using modified Poisson regression with the highest SES category as reference. Results: Mothers with the highest education and the highest income quintile used ASMs least frequently (56% and 53%, respectively). We observed increased risks of ASM discontinuation prior to or during the first trimester for low SES. The risk estimates varied depending on the SES indicator from aRR = 1.27 for low income (95% CI: 1.03–1.57) to aRR = 1.66 for low education (95% CI: 1.30–2.13). Migrant background was associated with ASM initiation after the first trimester (aRR 2.17; 95% CI 1.88–2.52). Low education was associated with the use of valproate during pregnancy in monotherapy (aRR 1.70; 95% CI 1.29–2.24) and in polytherapy (aRR 2.65; 95% CI 1.66–4.21). Low education was also associated with a 37% to 39% increased risk of switching from one ASM to another depending on the ASM used. For the other SES indicators, aRRs of switching varied from 1.16 (foreign origin; 95% CI 1.08–1.26) to 1.26 (not married or cohabiting; 95% CI 1.17–1.36). Significance: Low SES was associated with riskier patterns of ASM use: discontinuation, late initiation, and switching during pregnancy. These findings may reflect unplanned pregnancies, disparities in access to preconception counseling, and suboptimal care. [ABSTRACT FROM AUTHOR]

Valproate is the most effective medication for generalised epilepsies, and several specific epilepsy syndromes. For some people, it will be the only medication to establish seizure remission, and withdrawing it carries risks of seizure recurrence and Sudden Unexpected Death in Epilepsy (SUDEP). It is also of proven efficacy for bipolar disorder and migraine prevention. Guidelines based on observational and epidemiological studies stress that maternal valproate related teratogenicity and neurodevelopmental effects are significantly higher than for other antiseizure medications (ASMs). It should, therefore, only be used if other medications are ineffective and after balancing the teratogenicity risk. Regulatory restrictions have changed prescribing practices and reduced valproate use. The number of other medications that must be trialled in the different conditions for which valproate has effectiveness and the consequences of the lack of efficacy of those drugs leading to significant harm including death remains unexplored. Risk minimisation measures (RMMs) for valproate, chiefly Pregnancy Prevention practices (PPP), consider foetal risk and not risk to people living with epilepsy. In the United Kingdom (UK), limitations relating to valproate use in all people < 55 years commenced in January 2024. While the evidence in child-bearing women is not disputed, the data in males are based on animal models, case reports, and one commissioned, unpublished, non-peer reviewed report unavailable to the UK public, stakeholder charities or professionals. Evidence suggests that 30–40% of people switching from valproate have breakthrough seizures. Thus, an estimated 21,000–28000 people in the UK will imminently be exposed to the potential hazards of breakthrough seizures, including death. There is little government investment in monitoring the effects of these changes to valproate prescribing on patient health and quality of life. This review summarises the history of valproate regulation, evidence underpinning it and argues how the latest regulations in the UK do not align with the country's medical regulatory bodies ethical principles nor with the Montgomery principles of informed patient choice and autonomy. It dissects how such regulations infringe Common Law principles, nor give due regard for patient outcomes beyond reproduction. The paper looks to provide recommendations to redress these concerns while appreciating the core need for such governance to emerge in the first place. [ABSTRACT FROM AUTHOR]

Objective: Epilepsy is one of the most common neurological diseases on a global scale and the second most common neurological disease during pregnancy. The aim of our study is to evaluate the pregnancy outcomes and complications of pregnant women diagnosed with epilepsy followed in our clinic. Material and Methods: Between March 2018–2022, 147 pregnant women who were followed up in our hospital and diagnosed with epilepsy were examined. Demographic and clinical findings of all patients were compared retrospectively according to drug use history and seizure frequency during pregnancy. Results: There was no significant difference in mean birth weight and mean week of birth according to drug use groups (p=0.385, p=0.115, respectively). There was no significant difference between the drug use groups in terms of the presence of spontaneous abortion and history of preterm birth (p=0.360, p=0.210, respectively). No significant relationship was found between seizure frequency and seizure type (p=0.245). No significant relationship was found between seizure frequency and antiepileptic drug use (p=0.640). The average age of pregnant women with a history of polytherapy was 32.6±8.4 and was found to be significantly higher than the other groups (p=0.042). When the groups were evaluated according to drug use history, it was seen that the duration of epilepsy was significantly longer in the polytherapy group (p=0.044). When the groups were evaluated according to drug use history, it was seen that the cesarean section rate was significantly higher in the polytherapy group (p=0.038). Conclusion: Today, we think that pregnant women diagnosed with epilepsy have a high probability of giving birth to a healthy baby, spontaneous miscarriages are not more common than expected, and there is no significant difference between birth weight or week of birth and the treatment applied during pregnancy. The study also shows that with an appropriate approach and follow-up, it is possible to achieve positive results similar to those in the general population. [ABSTRACT FROM AUTHOR]

The objective of this study was to assess the impact of acute and chronic treatment with oxcarbazepine on its anticonvulsant activity, neurological adverse effects, and protective index in mice. Oxcarbazepine was administered in four protocols: once or twice daily for one week (7 × 1 or 7 × 2) and once or twice daily for two weeks (14 × 1 or 14 × 2). A single dose of the drug was employed as a control. The anticonvulsant effect was evaluated in the maximal electroshock test in mice. Motor and long-term memory impairment were assessed using the chimney test and the passive avoidance task, respectively. The concentrations of oxcarbazepine in the brain and plasma were determined via high-performance liquid chromatography. Two weeks of oxcarbazepine treatment resulted in a significant reduction in the anticonvulsant (in the 14 × 1; 14 × 2 protocols) and neurotoxic (in the 14 × 2 schedule) effects of this drug. In contrast, the protective index for oxcarbazepine in the 14 × 2 protocol was found to be lower than that calculated for the control. No significant deficits in memory or motor coordination were observed following repeated administration of oxcarbazepine. The plasma and brain concentrations of this anticonvulsant were found to be significantly higher in the one-week protocols. Chronic treatment with oxcarbazepine may result in the development of tolerance to its anticonvulsant and neurotoxic effects, which appears to be dependent on pharmacodynamic mechanisms. [ABSTRACT FROM AUTHOR]

Background: Hyperekplexia is a rare neurogenetic disorder that is classically characterized by an exaggerated startle response to sudden unexpected stimuli. This study aimed to determine clinical and genetic characteristics of our patients with hyperekplexia. Methods: The age of onset and diagnosis, familial and perinatal history, clinical course, complications, metabolic screening tests, magnetic resonance imaging (MRI), medications, neuropsychometric evaluations, and gene mutations of patients diagnosed with hyperekplexia were reviewed retrospectively. Results: All hyperekplexia patients had displayed neonatal excessive startle response and muscle stiffness, which we accepted as the major form of the disorder. Sixteen patients had mutations in genes associated with hyperekplexia. The ages at clinical diagnosis and genetic confirmation ranged from newborn to 16 years old and from 2.5 to 19 years, respectively. Nine patients (56.25%) were initially misdiagnosed with epilepsy. Seven patients (43.75%) carried a diagnosis of intellectual disability, defined here as a total IQ <80. Delayed gross motor development was detected in 4 patients (25%), and speech delay was reported in 3 (18.75%). Mutations in GLRA1 (NM_000171.4) and SLC6A5 (NM_004211.5) were identified in 13 (81.25%) and 3 patients (18.75%), respectively. Fifteen of the 16 patients (93.75%) showed autosomal recessive inheritance. Only 1 patient (6.25%) showed autosomal dominant inheritance. Conclusion: Although hyperekplexia is a potentially treatable disease, it can be complicated by delayed speech and/or motor acquisition and also by intellectual disability. This study shows that hyperekplexia is not always a benign condition and that all patients diagnosed with hyperekplexia should be evaluated for neuropsychiatric status and provided with genetic testing. [ABSTRACT FROM AUTHOR]

Objective: Levetiracetam is widely used in the emergency setting. Safety and tolerability of undiluted levetiracetam is prevalent in adults but is limited in pediatrics. The purpose is to determine the safety and tolerability of rapid administration of undiluted levetiracetam in pediatric patients. Methods: A retrospective, single-center, observational study was conducted in pediatric patients who received undiluted levetiracetam intravenous push. The primary outcome was adverse reactions, extravasation, need for intravenous line replacement, and discontinuation due to adverse reactions. The secondary outcome was turnaround time between ordering and administering first doses. Results: One hundred fourteen patients were included. Injection site reactions occurred in 7 patients. Extravasation occurred in 4 patients. Two patients required intravenous line replacement. There were no adverse events leading to discontinuation of levetiracetam. No difference was seen in the time from order to administration. Conclusion: Rapid administration of undiluted levetiracetam in pediatric patients was safe and well tolerated. [ABSTRACT FROM AUTHOR]

Purpose: The purpose was to examine the correlation of antiseizure medication drug dose estimated from prescription fill records from prescription registers with blood levels during pregnancy. Methods: We conducted a Nation‐wide study of mothers who gave birth in Denmark between 1 January 2014 and 31 December 2018 using data from Danish Prescription and Laboratory Registers. We identified mothers with blood level measurements of antiseizure medication. The main exposure was estimated antiseizure medication dosage estimated from pregnancy‐filled prescriptions in the Danish Prescription Register. The main outcome was the correlation of estimated dose with mean blood level of antiseizure medication in pregnancy. For privacy reasons, the number of blood level measurement and prescription fills were rounded to nearest 10, but proportions reported as exact values. Results: Among 298 560 pregnancies, we identified pregnancies with recorded prescription fill from the prescription register for valproate (N = 90), lamotrigine (N = 1360), levetiracetam (N = 340), topiramate (N = 100), and carbamazepine (N = 60). In these pregnancies, blood level measurements were available in 50 (53%) pregnancies for valproate, 850 (62%) pregnancies for lamotrigine, 320 (93%) pregnancies for levetiracetam, 50 (68%) pregnancies for carbamazepine, and 40 (35%) pregnancies for topiramate. Pearsons's correlation coefficients for the correlation of estimated antiseizure medication dose with mean blood levels were 0.67 (p < 0.0001) for valproate, 0.63 (p < 0.0001) for lamotrigine, 0.63 (p < 0.0001) for levetiracetam, 0.76 (<0.0001) for carbamazepine and 0.89 (<0.0001) for topiramate. Conclusions: Dose of antiseizure medication estimated from prescription fills was a good proxy for blood levels and thus for biological exposure in pregnancy, suggesting that administrative prescription fill records may be a valuable resource for estimating exposure to antiseizure medication in pregnancy. [ABSTRACT FROM AUTHOR]

Epilepsy, a complex neurological disorder, is influenced by intricate interactions within cortical, hippocampal, or thalamocortical neuronal networks, presenting a genetically complex condition with non-Mendelian inheritance patterns. This complexity is underscored by the involvement of numerous “susceptibilities” or “modifier” genes, complicating the assessment of risk and therapy outcomes. A critical inquiry in epilepsy treatment involves understanding how genetic diversity impacts treatment strategies and efficacy. Pharmacogenomic advancements have elaborated the connection between genetic variants and antiseizure medication (ASM) safety and response, marking a shift towards precision medicine in epilepsy care. Notably, genetic screening for variants such as HLA-B*1502 and HLA-A*3101 has demonstrated significant efficacy in preventing severe hypersensitivity reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), particularly among specific ethnic populations. However, putting pharmacogenomic discoveries into clinical practice faces numerous challenges, including educational, legal, and economic barriers, emphasizing the need for broader acceptance and integration of pharmacogenomic data. This review synthesizes recent studies on pharmacogenomics in epilepsy, highlighting the current advances and prospects for personalizing epilepsy treatment through genetic insights, aiming to enhance ASM safety, reduce adverse effects, and improve treatment outcomes. Through a comprehensive examination of the genetic basis of epilepsy and its influence on pharmacotherapy, this review endeavors to contribute to the evolving landscape of precision medicine in epilepsy care, advocating for a more individualized and effective treatment approach.

Background. Сognitive impairment is one of the major epilepsy-related comorbidities. Upon long-term disease course, a decline in cognitive functions occurs in about 70–80% of cases. Juvenile myoclonic epilepsy (JME) is one of the most common forms of epilepsy (about 9.3%). Compared with other forms of idiopathic generalized epilepsy, JME is featured with high risk of seizures along with lowered patient compliance to treatment as well as a danger of developing drug resistance that may be a cause of cognitive disorder.Objective: to review research publications on cognitive impairment in JME, discuss its putative causes, describe neuropsychological profile for JME patients.Material and methods. The search was carried out in eLibrary, PubMed/MEDLINE, and Google Scholar databases using keywords and their combinations: “cognitive impairment”, “cognitive disorder”, “cognitive functions”, “neuropsychology”, “epilepsy”, “juvenile myoclonic epilepsy”, “JME”, “idiopathic generalized epilepsy”, “antiepileptic drugs”. We analyzed the articles published over the past 5 years and some earlier works of significant scientific interest. All articles were published in English or Russian languages.Results. A total of 895 articles were found in databases. Comprehensive screening, evaluation of full-text articles eligibility in accordance with the criteria for selecting and deleting duplicates allowed to include 3 scientific publications in Russian and 67 scientific publications in English in the literature review. The main causes of cognitive impairment in JME patients were analyzed followed by describing relevant neuropsychological profile. Diagnostic tools and current opportunities for correction of cognitive disfunctions were considered as well.Conclusion. The underlying causes of cognitive impairment in JME patients are multifactorial in nature and require further research. However, in this patient cohort prominent obstacles remain in identifying and timely correcting such disorders. Approving uniform diagnostic and therapeutic standards, developing rehabilitation methods for cognitive impairment in epilepsy will help improve the quality of life in JME patients.

Abstract Background Dravet Syndrome (DS) is a rare and severe form of childhood epilepsy that is often refractory to conventional antiepileptic drugs. Emerging evidence suggests that Cannabidiol (CBD) offer therapeutic benefits for DS. This review aims to evaluate the efficacy and safety of CBD in pediatric patients with DS based on data from ten clinical trials. Methods A review was conducted to identify clinical trials assessing the efficacy and safety of CBD in pediatric patients diagnosed with DS. PubMed, MEDLINE, Scopus, Web of Science, and relevant grey literature were systematically searched for relevant articles up to October 2023, and clinical trials within the last 10 years were included. The search strategy incorporated controlled vocabulary terms and keywords related to "Cannabidiol," "Dravet Syndrome," and "pediatric patients." Results The analysis revealed promising efficacy outcomes. Notably, CBD demonstrated substantial reductions in seizure frequency, with some patients achieving seizure freedom. The findings emphasised the consistency of CBD's efficacy across different patient subgroups. The safety profile of CBD was generally acceptable, with adverse events often being manageable. Conclusion This review consolidates evidence from multiple clinical trials, affirming the potential of CBD as a promising treatment option for pediatric patients with DS. While further research is needed to address existing knowledge gaps, CBD's efficacy and acceptable safety profile make it a valuable addition to the therapeutic tools for DS.

Abstract Background Evidence‐based recommendations for antiepileptic drug selection in cats beyond phenobarbital are limited, and additional studies are needed for cats where seizures remain inadequately controlled by administration of phenobarbital alone or for cats that cannot safely receive phenobarbital. Objective To compare seizure frequency in cats before and after oral administration of zonisamide and describe adverse clinical or clinicopathologic effects in this cohort. Animals Fifty‐seven cats with a history of seizures. Methods Multicenter, retrospective study. Median number of seizures per month and number of seizure days per month were compared before and after administration of zonisamide in all cats, a subgroup of cats with idiopathic epilepsy (IE), and a subgroup of cats receiving zonisamide as sole therapy. Clinical and clinicopathologic adverse effect data were also reported. Results A median decrease of 1 (P = .001, 95% confidence interval (CI) [−1.0, −0.5]) seizure per month, and 1 (P = .003, 95% CI [−1.5, −0.2]) seizure days per month was found across all cats after oral administration of zonisamide. The subgroup with IE showed median decreases of 1 (P = .03, 95% CI [−2.0, −0.5]) and 2 (P = .01, 95% CI [−2.5, −1.0]), respectively. The most common clinical adverse effects were sedation (17%), ataxia (11%), hyporexia (17%), and emesis (5%). One cat developed mild nonregenerative anemia, 2 cats developed mild metabolic acidosis, and 6 cats showed mild increases in ALT and ALP. Conclusion Zonisamide was well tolerated and efficacious in controlling seizure activity in most cats.

Epileptogenic seizures, or status epilepticus (SE), leads to excitotoxic injury in hippocampal and limbic neurons in the kainic acid (KA) animal model of temporal lobe epilepsy (TLE). Here, we have further characterized neural activity regulated methylaminoisobutryic acid (MeAIB)/glutamine transport activity in mature rat hippocampal neurons in vitro that is inhibited by riluzole (IC50 = 1 μM), an anti-convulsant benzothiazole agent. We screened a library of riluzole derivatives and identified SKA-41 followed by a second screen and synthesized several novel chlorinated aminothiazoles (SKA-377, SKA-378, SKA-379) that are also potent MeAIB transport inhibitors in vitro, and brain penetrant following systemic administration. When administered before KA, SKA-378 did not prevent seizures but still protected the hippocampus and several other limbic areas against SE-induced neurodegeneration at 3d. When SKA-377 - 379, (30 mg/kg) were administered after KA-induced SE, acute neural injury in the CA3, CA1 and CA4/hilus was also largely attenuated. Riluzole (10 mg/kg) blocks acute neural injury. Kinetic analysis of SKA-378 and riluzoles' blockade of Ca2+-regulated MeAIB transport in neurons in vitro indicates that inhibition occurs via a non-competitive, indirect mechanism. Sodium channel NaV1.6 antagonism blocks neural activity regulated MeAIB/Gln transport in vitro (IC50 = 60 nM) and SKA-378 is the most potent inhibitor of NaV1.6 (IC50 = 28 μM) compared to NaV1.2 (IC50 = 118 μM) in heterologous cells. However, pharmacokinetic analysis suggests that sodium channel blockade may not be the predominant mechanism of neuroprotection here. Riluzole and our novel aminothiazoles are agents that attenuate acute neural hippocampal injury following KA-induced SE and may help to understand mechanisms involved in the progression of epileptic disease.

• The NLRP3 inflammasome is a biomarker of temporal lobe epilepsy. • NLRP3 inflammasome creates a pro-inflammatory and pro-convulsive environment. • Intervention of NLRP3 inflammasome shows antiepileptic and neuroprotective effects. • Regulating NLRP3 inflammasome is a novel strategy for antiepileptic drug discovery. Epilepsy is one of the most widespread and complex diseases in the central nervous system (CNS), affecting approximately 65 million people globally, an important factor resulting in neurological disability-adjusted life year (DALY) and progressive cognitive dysfunction. Medication is the most essential treatment. The currently used drugs have shown drug resistance in some patients and only control symptoms; the development of novel and more efficacious pharmacotherapy is imminent. Increasing evidence suggests neuroinflammation is involved in the occurrence and development of epilepsy, and high expression of NLRP3 inflammasome has been observed in the temporal lobe epilepsy (TLE) brain tissue of patients and animal models. The inflammasome is a crucial cause of neuroinflammation by activating IL-1β and IL-18. Many preclinical studies have confirmed that regulating NLRP3 inflammasome pathway can prevent the development of epilepsy, reduce the severity of epilepsy, and play a neuroprotective role. Therefore, regulating NLRP3 inflammasome could be a potential target for epilepsy treatment. In summary, this review describes the priming and activation of inflammasome and its biological function in the progression of epilepsy. In addition, we reviewes the current pharmacological researches for epilepsy based on the regulation of NLRP3 inflammasome, aiming to provide a basis and reference for developing novel antiepileptic drugs. [ABSTRACT FROM AUTHOR]

This article discusses the relationship between aggressive behavior and Dravet syndrome, a rare form of early-onset genetic epileptic syndrome. It highlights the challenges in defining and measuring aggression and emphasizes the need for specific tools to assess aggressive behavior in individuals with Dravet syndrome. The article also explores the potential role of antiepileptic drugs in exacerbating behavioral problems, including aggression. It concludes by emphasizing the importance of improving the identification and treatment of behavioral and psychiatric comorbidities in individuals with Dravet syndrome. The article highlights the need for comprehensive behavioral assessment tools for individuals with Dravet syndrome and the lack of attention to adverse effects on behavior caused by antiepileptic drugs. It also emphasizes the importance of developing specific assessment tools for Dravet syndrome and other developmental and epileptic encephalopathies to improve care for individuals with these conditions. The document provides a list of references for various research articles related to epilepsy and its impact on individuals and their caregivers. These articles cover topics such as behavioral and emotional problems in children with epilepsy, the impact of developmental and epileptic encephalopathies on caregivers, comorbidities associated with Dravet syndrome and Lennox-Gastaut syndrome, and the psychosocial impact of caring for children with Dravet syndrome. They provide valuable insights into the challenges faced by individuals with epilepsy and their families, as well as potential treatment options and strategies for improving quality of life. Another article titled "Pediatrics 136, [Extracted from the article]

Background: Patients with supratentorial cavernous malformations (SCMs) commonly present with seizures. First-line treatments for cavernoma-related epilepsy (CRE) include conservative management (antiepileptic drugs (AEDs)) and surgery. We compared seizure outcomes of CRE patients after early (≤6 months) vs. delayed (>6 months) surgery. Methods: We compared outcomes of CRE patients with SCMs surgically treated at our large-volume cerebrovascular center (1 January 2010–31 July 2020). Patients with 1 sporadic SCM and ≥1-year follow-up were included. Primary outcomes were International League Against Epilepsy (ILAE) class 1 seizure freedom and AED independence. Results: Of 63 CRE patients (26 women, 37 men; mean ± SD age, 36.1 ± 14.6 years), 48 (76%) vs. 15 (24%) underwent early (mean ± SD, 2.1 ± 1.7 months) vs. delayed (mean ± SD, 6.2 ± 7.1 years) surgery. Most (32 (67%)) with early surgery presented after 1 seizure; all with delayed surgery had ≥2 seizures. Seven (47%) with delayed surgery had drug-resistant epilepsy. At follow-up (mean ± SD, 5.4 ± 3.3 years), CRE patients with early surgery were more likely to have ILAE class 1 seizure freedom and AED independence than those with delayed surgery (92% (44/48) vs. 53% (8/15), p = 0.002; and 65% (31/48) vs. 33% (5/15), p = 0.03, respectively). Conclusions: Early CRE surgery demonstrated better seizure outcomes than delayed surgery. Multicenter prospective studies are needed to validate these findings. [ABSTRACT FROM AUTHOR]

Epilepsy is a chronic clinical disorder and does not have a rational treatment, which basically aims to prevent seizure activity. Therefore, developing new treatment strategies that can intervene in epileptogenesis will make important contribution to epilepsy treatment. In order to find new compounds and develop new treatment strategies, here, we explored the potential antiepileptic effects of Allium schoenoprasum L. commonly known as chives. Two different epilepsy models were used to study the potential antiepileptic effects of A. schoenoprasum L. The first epilepsy model was induced by intracortical injection of 500 IU penicillin. The second epilepsy model was induced by injecting pentylenetetrazol (PTZ) at the dose of 60 mg intraperitoneally (i.p.). In the penicillin model, the animals were given A. schoenoprasum L. extract (200 or 400 mg/kg i.p.) after penicillin was applied and electrocortical activity was recorded for 120 min. In the PTZ model, the animals were given A. schoenoprasum L. extract at doses of 200 or 400 mg/kg orally for 7 days, after which the PTZ was applied, and tonic-clonic seizures were video recorded. A. schoenoprasum L. did not significantly change either the spike frequency or amplitude in the penicillin epilepsy model. Although it did not change the seizure score in the PTZ epilepsy model it reduced the death rate and significantly decreased the tonic-clonic seizure duration. The result suggests that A. schoenoprasum L. may have antiepileptic effects when applied chronically. [ABSTRACT FROM AUTHOR]

Epilepsy, a chronic neurological disorder necessitating prolonged antiepileptic medication, has been associated with deficiencies in vitamin D and related bone disorders in children. This study aims to investigate the prevalence of vitamin D deficiency, calcium deficiency, and bone diseases in children undergoing antiepileptic drug (AED) therapy. A retrospective study was conducted on 60 children (0-16 years old) with epilepsy at King Fahad Specialist Hospital-Dammam from 2016 to 2018. Participants were administered 800 IU/day of vitamin D for 6 months. Comprehensive assessments, including tests for calcium, phosphorus, 25-hydroxyvitamin D (25-OHD), 1,25-hydroxyvitamin D (1,25 OHD), parathyroid hormone (PTH), thyroid function [thyroid-stimulating hormone (TSH)], alkaline phosphatase (ALP), and bone density, were performed after 6 months of oral vitamin D supplementation. No significant associations were observed between age, sex, age of onset, duration of epilepsy, symptoms of vitamin D deficiency, dietary factors, and the levels of calcium, phosphorus, 25-OHD, 1,25-OHD, PTH, TSH, ALP, and bone scan. Carbamazepine (CBZ) was the only AED that affected bone metabolism in general (P = 0.024). Calcium was mostly found to be abnormal after using AED with vitamin D (800 IU/day) for 6 months (P = 0.05). 25-OHD deficiency was associated with use of CBZ in pediatric epilepsy. Considering its potential impact on bone metabolism, higher vitamin D doses may be advisable for children on long-term AED therapy to mitigate these abnormalities. [ABSTRACT FROM AUTHOR]

Aims: The objective of this meta‐analysis was to determine whether maternal exposure to folate antagonists is associated with increased rates of congenital heart disease in offspring. Methods: A comprehensive search for articles in the MEDLINE (PubMed) and EMBASE databases published up to 21 August 2023 was performed. The search strategy was not limited by study design but only for articles in the English language. Results: Analysis of 6 cohort studies and 5 cross‐sectional studies, published between 1976 and 2020, showed significant increase in rate of congenital heart disease (odds ratio 1.55, 95% confidence interval, 1.28–1.87) when exposed to folate antagonists compared with the control. Further subgroup analysis showed the increased rate for exposure to both dihydrofolate reductase inhibitors and antiepileptic drugs separately. No differences were observed when analyses were stratified by timing of study. Conclusion: Administration of folate antagonists within the 12‐week period preceding conception and throughout the second and third months of gestation exhibited a statistically significant elevation in the susceptibility to congenital heart diseases. Notably, the protective effect of folic acid supplementation was reported in cases of congenital heart disease linked to dihydrofolate reductase inhibitors but not that associated with antiepileptic drugs. [ABSTRACT FROM AUTHOR]

To investigate the association between the presence and severity of seizures in asphyxiated newborns and their neurodevelopmental outcome at ages two and five years. Retrospective data analysis from a prospectively collected multicenter cohort of 186 term-born asphyxiated newborns undergoing therapeutic hypothermia (TH) in 11 centers in the Netherlands and Belgium. Seizures were diagnosed by amplitude-integrated electroencephalography (EEG) and raw EEG signal reading up to 48 hours after rewarming. Neurodevelopmental outcome was assessed by standardized testing at age two and five years. Primary outcome was death or long-term neurodevelopmental impairment (NDI) including cerebral palsy. Associations were calculated using univariate and multivariate logistic regression analyses adjusting for Thompson score and a validated brain magnetic resonance imaging (MRI) score. Seventy infants (38%) had seizures during TH or rewarming, and 44 (63%) of these needed two or more antiseizure medications (ASMs). Overall mortality was 21%. Follow-up data from 147 survivors were available for 137 infants (93%) at two and for 94 of 116 infants (81%) at five years. NDI was present in 26% at two and five years. Univariate analyses showed a significant association between seizures and death or NDI, but this was no longer significant after adjusting for Thompson and MRI score in the multivariate analysis; this was also true for severe seizures (need for two or more ASMs) or seizures starting during rewarming. The presence or severity of seizures in newborns undergoing TH for hypoxic-ischemic encephalopathy was not independently associated with death or NDI up to age five years after adjusting for several confounders. [ABSTRACT FROM AUTHOR]

Objective: To investigate the serum biomarkers in patients with drug-resistant epilepsy (DRE). Methods: A total of 9 DRE patients and 9 controls were enrolled. Serum from DRE patients was prospectively collected and analyzed for potential serum biomarkers using TMT18-labeled proteomics. After fine quality control, bioinformatics analysis was conducted to find differentially expressed proteins. Pathway enrichment analysis identified some biological features shared by differential proteins. Protein-protein interaction (PPI) network analysis was further performed to discover the core proteins. Results: A total of 117 serum differential proteins were found in our study, of which 44 were revised upwards and 73 downwards. The up-regulated proteins mainly include UGGT2, PDIA4, SEMG1, KIAA1191, CCT7 etc. and the downregulated proteins mainly include ROR1, NIF3L1, ITIH4, CFP, COL11A2 etc. Pathway enrichment analysis identified that the upregulated proteins were mainly enriched in processes such as immune response, extracellular exosome, serine-type endopeptidase activity and complement and coagulation cascades, and the down-regulated proteins were enriched in signal transduction, extracellular exosome, zinc/calcium ion binding and metabolic pathways. PPI network analysis revealed that the core proteins nodes include PRDX6, CAT, PRDX2, SOD1, PARK7, GSR, TXN, ANXA1, HINT1, and S100A8 etc. Conclusion: The discovery of these differential proteins enriched our understanding of serum biomarkers in patients with DRE and potentially provides guidance for future targeted therapy. [ABSTRACT FROM AUTHOR]

Objective: This meta-analysis aimed to assess the effectiveness and safety of novel antiepileptic drugs (AEDs) in treating epilepsy in patients with brain tumors (BTRE). Methods: A search was conducted on PubMed, EMBASE, Web of Science, and the Cochrane Library from inception to February 2023, with English language restriction. Results: In this meta-analysis, 18 clinical trials involving 755 BTRE patients were included to assess the efficacy and safety of novel AEDs in BTRE treatment. At the last follow-up, a =50% reduction in seizure frequency was experienced by 72% of patients (random-effects model, 95% CI = 0.64-0.78) using novel AEDs. At the last follow-up, seizure freedom was experienced by 34% of patients (random-effects model, 95% CI = 0.28-0.41) using novel AEDs. The pooled incidence of AEs was found to be 19% (95% CI: 13%-26%), with a withdrawal rate due to adverse effects of only 3%. Comparable efficacy and incidence of adverse effects were observed between lacosamide and perampanel. Conclusion: This meta-analysis suggests that novel antiepileptic drugs are deemed effective for seizure control in brain tumor patients, particularly when used as adjunctive therapy. Although lacosamide and perampanel received more focus in studies, no significant difference was observed in the efficacy and adverse reactions of these two drugs in seizure control. Further randomized controlled trials are deemed necessary to validate our findings. [ABSTRACT FROM AUTHOR]

Background: Dravet Syndrome (DS) is a rare and severe form of childhood epilepsy that is often refractory to conventional antiepileptic drugs. Emerging evidence suggests that Cannabidiol (CBD) offer therapeutic benefits for DS. This review aims to evaluate the efficacy and safety of CBD in pediatric patients with DS based on data from ten clinical trials. Methods: A review was conducted to identify clinical trials assessing the efficacy and safety of CBD in pediatric patients diagnosed with DS. PubMed, MEDLINE, Scopus, Web of Science, and relevant grey literature were systematically searched for relevant articles up to October 2023, and clinical trials within the last 10 years were included. The search strategy incorporated controlled vocabulary terms and keywords related to "Cannabidiol," "Dravet Syndrome," and "pediatric patients." Results: The analysis revealed promising efficacy outcomes. Notably, CBD demonstrated substantial reductions in seizure frequency, with some patients achieving seizure freedom. The findings emphasised the consistency of CBD's efficacy across different patient subgroups. The safety profile of CBD was generally acceptable, with adverse events often being manageable. Conclusion: This review consolidates evidence from multiple clinical trials, affirming the potential of CBD as a promising treatment option for pediatric patients with DS. While further research is needed to address existing knowledge gaps, CBD's efficacy and acceptable safety profile make it a valuable addition to the therapeutic tools for DS. [ABSTRACT FROM AUTHOR]

Cerebral cavernous malformation is an angiographically occult, well-circumscribed, benign hamartoma consisting of thin-walled sinusoidal vascular channels. Intracranial mucormycosis represents one of the most severe manifestations of mucor infection. We, hereby, report a case of cavernous malformation made rarer with concomitant mucormycosis. A 22-year-old female presented with left-sided facial seizures since age of 7 years and headache for the past 3 years. Magnetic resonance imaging brain revealed a right posterior frontal lobe cavernous malformation. Right frontal craniotomy with excision of cavernoma was done. Gross examination showed a solid cystic mass with multiple mulberry protrusions. Histopathological examination revealed features of cavernous malformation with evidence of mucormycosis. A final diagnosis of cavernous malformation with mucormycosis was rendered and microbiological studies were advised. To the best of our knowledge, this is the first case report of a cerebral cavernous malformation with mucormycosis in an immunocompetent patient without any risk factor. [ABSTRACT FROM AUTHOR]

Background: Evidence‐based recommendations for antiepileptic drug selection in cats beyond phenobarbital are limited, and additional studies are needed for cats where seizures remain inadequately controlled by administration of phenobarbital alone or for cats that cannot safely receive phenobarbital. Objective: To compare seizure frequency in cats before and after oral administration of zonisamide and describe adverse clinical or clinicopathologic effects in this cohort. Animals: Fifty‐seven cats with a history of seizures. Methods: Multicenter, retrospective study. Median number of seizures per month and number of seizure days per month were compared before and after administration of zonisamide in all cats, a subgroup of cats with idiopathic epilepsy (IE), and a subgroup of cats receiving zonisamide as sole therapy. Clinical and clinicopathologic adverse effect data were also reported. Results: A median decrease of 1 (P =.001, 95% confidence interval (CI) [−1.0, −0.5]) seizure per month, and 1 (P =.003, 95% CI [−1.5, −0.2]) seizure days per month was found across all cats after oral administration of zonisamide. The subgroup with IE showed median decreases of 1 (P =.03, 95% CI [−2.0, −0.5]) and 2 (P =.01, 95% CI [−2.5, −1.0]), respectively. The most common clinical adverse effects were sedation (17%), ataxia (11%), hyporexia (17%), and emesis (5%). One cat developed mild nonregenerative anemia, 2 cats developed mild metabolic acidosis, and 6 cats showed mild increases in ALT and ALP. Conclusion: Zonisamide was well tolerated and efficacious in controlling seizure activity in most cats. [ABSTRACT FROM AUTHOR]

A variety of terms, such as "antiepileptic," "anticonvulsant," and "antiseizure" have been historically applied to medications for the treatment of seizure disorders. Terminology is important because using terms that do not accurately reflect the action of specific treatments may result in a misunderstanding of their effects and inappropriate use. The present International League Against Epilepsy (ILAE) position paper used a Delphi approach to develop recommendations on English‐language terminology applicable to pharmacological agents currently approved for treating seizure disorders. There was consensus that these medications should be collectively named "antiseizure medications". This term accurately reflects their primarily symptomatic effect against seizures and reduces the possibility of health care practitioners, patients, or caregivers having undue expectations or an incorrect understanding of the real action of these medications. The term "antiseizure" to describe these agents does not exclude the possibility of beneficial effects on the course of the disease and comorbidities that result from the downstream effects of seizures, whenever these beneficial effects can be explained solely by the suppression of seizure activity. It is acknowledged that other treatments, mostly under development, can exert direct favorable actions on the underlying disease or its progression, by having "antiepileptogenic" or "disease‐modifying" effects. A more‐refined terminology to describe precisely these actions needs to be developed. [ABSTRACT FROM AUTHOR]

Objective: Rapid administration of antiseizure medications is a critical concept in the treatment of status epilepticus. Although undiluted levetiracetam (LEV) doses of up to 2500 mg have been evaluated, minimal data exist to support the safety of loading doses up to 4500 mg. This study will evaluate intravenous (IV) push administration of undiluted LEV from 2500 to 4500 mg for safety outcomes as well as tolerability. Methods: This is a retrospective, observational, cohort analysis of adult patients who received at least one loading dose of undiluted IV push LEV from October 15, 2019, to April 30, 2022, at a large academic medical center in Phoenix, Arizona. Relevant outcomes include the safety and tolerability of rapid administration of undiluted LEV at higher loading doses. Results: We evaluated 518 loading doses in 518 unique patients included during the study period. LEV was a new medication for witnessed or suspected seizures in 80.3% of patients, with 31.2% having a documented history of epilepsy or seizure disorder. At the time of LEV administration, 52.9% of patients were on a general medicine floor, 34.3% were in the intensive care unit, and 12.7% were in the emergency department. The median loading dose of LEV was 3600 mg (3000–4000 mg), with 4000 mg being the most common loading dose given. Peripheral IV lines were documented as the only available line in 78.6% of patients for loading dose administration. No adverse events associated with LEV administration were documented. Significance: Rapid IV administration of undiluted doses of LEV is both safe and tolerable in loading doses of 2500–4500 mg, allowing for rapid drug administration in the setting of status epilepticus. [ABSTRACT FROM AUTHOR]

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Epilepsy is a neurological disorder characterized by high morbidity, high recurrence, and drug resistance. Enhanced signaling through the excitatory neurotransmitter glutamate is intricately associated with epilepsy. Metabotropic glutamate receptors (mGluRs) are G protein-coupled receptors activated by glutamate and are key regulators of neuronal and synaptic plasticity. Dysregulated mGluR signaling has been associated with various neurological disorders, and numerous studies have shown a close relationship between mGluRs expression/activity and the development of epilepsy. In this review, we first introduce the three groups of mGluRs and their associated signaling pathways. Then, we detail how these receptors influence epilepsy by describing the signaling cascades triggered by their activation and their neuroprotective or detrimental roles in epileptogenesis. In addition, strategies for pharmacological manipulation of these receptors during the treatment of epilepsy in experimental studies is also summarized. We hope that this review will provide a foundation for future studies on the development of mGluR-targeted antiepileptic drugs.

BACKGROUND: Seizure outcomes after lesionectomy have been proven to be equivalent to excision, which ablates the epileptogenic cortex with the lesion. Different forms of resection surgery, as well as temporal lobectomy, are being investigated as therapeutic options for people with focal epilepsy who have not responded to medication. Although seizure control is the primary goal of epilepsy surgery, lowering or quitting antiepileptic drugs (AEDs) following epilepsy surgery is also an essential goal for patients and epileptologists. CASE PRESENTATION: We described a thirteen-year-old female who had suffered from headaches and multiple bouts of complex partial seizures for three years before undergoing surgery for a well-circumscribed lesion occupying the medial portion of the left temporal lobe next to the pole, with modest compression of the ipsilateral crus of the midbrain. Following surgery, the patient was kept on levetiracetam and phenytoin, which was later converted to a single antiepileptic drug with complete seizure control. CONCLUSION: Patients on multiple antiepileptic drugs for control of temporal lobe lesional seizures can be kept on a single antiepileptic drug after resection of the lesion and slowly the dose can be reduced. [ABSTRACT FROM AUTHOR]

Background. In the phenotype of cerebral palsy, motor and mental disorders are often accompanied by epilepsy. Congenital epilepsy has been intensively researched in recent years. Special attention is drawn to epilepsy caused by congenital disturbance of the excitability of the neuronal membrane due to canalopathies.Aim. To analyze a large number of genes associated with the development of the cerebral palsy phenotype and distribute them according to determinable traits.Materials and methods. The results of clinical and genetic analysis of 136 cases of cerebral palsy with epilepsy are presented. The patients were divided into groups according to the syndromes according to the classification of cerebral palsy. Epileptic syndromes were divided into three groups: focal childhood epilepsy with structural brain changes and benign epileptiform discharges in electroencephalogram – 41 (30.1 %) cases, structural focal epilepsy – 37 (27.2 %) cases, epileptic encephalopathies – 58 (42.7 %) cases. Pathogenic variants in genes were confirmed by next generation sequencing Sanger methods of venous blood.Results. The performed risk analysis showed that in the presence of disorders in genes attributed to the group of regulation of the formation and functioning of the cytoskeleton, the risk of lack of remission is significantly lower than in other dominants, while abnormalities in genes attributed to the group of regulation of the function of the mitochondrial apparatus significantly increase the risks of failure to achieve remission and need in polytherapy.Conclusion. Probably, the violation of energy metabolism in the cell neutralizes the stabilization of the neuronal membrane under the action of anticonvulsants. The determinant of the formation and functioning of the cytoskeleton, according to our preliminary data, is largely associated with the formation of malformations of the brain. In this case, the refractoriness of epilepsy may be secondary and determined by the severity of structural changes in the brain

Background: As initial monotherapy, individuals with epilepsy are treated with both conventional and newer antiepileptic drugs (AEDs). The differences in their relative effectiveness and safety as a group, however, have not been thoroughly studied. Objective: To evaluate and compare the effectiveness and safety of conventional and newer anti-epileptic drugs in epileptic patients. Material and methods: A prospective comparative study was done in 126 epileptic patients. Patients divided into two groups Group A and B of 63 each received conventional and newer antiepileptic drugs respectively. Patients were allocated the AED based on type of epilepsy, patient characteristics and drug characteristics by the treating physician. Patients maintained a seizure diary which they filled weekly and this seizure diary was evaluated at 6 weeks and 12 weeks of follow up. Patients were assessed for adverse drug reactions (ADRs) at 0, 6 and 12 weeks of follow up and also for spontaneous reported ADRs at any time during the study. Results: In both group A and group B, our study demonstrated that seizure freedom, seizure severity, and time before first seizure did not differ significantly (p>0.5). Except for cognitive dysfunction, impaired memory, and swollen gums, which were more frequent in the conventional anti-epileptics group, the ADR profiles of both group of medications were similar. Phenytoin was found to cause gum swelling and cognitive impairment. No subject experienced a serious adverse event. Conclusion: Newer Antiepileptics as monotherapy are equally efficacious as conventional antiepileptics but may offer a better safety profile to epileptic patients.

Background and Objectives: The objective of this paper is to determine the rate and predictors of non-adherence to antiseizure medications in Saudi Arabia. Materials and Methods: A cross-sectional study which involved questionnaires and data collection from patients’ medical records was conducted at neurology clinics. The rate of non-adherence to antiseizure medications was measured using “the Medication Adherence Rating Scale” (MARS). Predictors of non-adherence to antiseizure medications were evaluated using a multidimensional questionnaire specific to epilepsy. Results: One hundred and sixty-two patients participated in the study. The mean (SD) age was 34.1 (10.4) years, and 56% were male. Epilepsy was controlled (i.e., seizure-free ≥ 1 year) in 42% of patients. The mean ± SD (range) MARS scores were 7.80 ± 1.59 (2–10). Out of 162 patients, 58 (36%) patients had MARS scores ≤ 7 out of 10. The most frequently rated predictor for non-adherence was poor seizure control, which was reported by around 36% of patients. Forgetfulness, dosing frequency, and social stigma were also among the commonest predictors of non-adherence to antiseizure medications that were rated by approximately 27%, 24%, and 22% of the patients, respectively. The impacts of several socio-demographic and clinical factors on adherence were assessed. In the regression analysis, the odds of non-adherence in a patient who experienced adverse effects were twice that of a patient who did not have adverse effects (p = 0.113). Furthermore, females, employers, and patients who had comorbidity, those with focal epilepsy, those on polytherapy of antiseizure medication, and those receiving multiple doses per day, were all more likely (but not significantly, p > 0.05) to be non-adherent compared to their counterparts. Conclusions: The significance of this study is that it reveals that adherence to antiseizure medications is suboptimal in Saudi Arabia. Poor seizure control, forgetfulness, dosing frequency, and social stigma were the primary patient-reported predictors of non-adherence in epilepsy. This emphasizes the importance of routine evaluation of adherence in practice to identify and address what individual patients perceive as a barrier to adherence with antiseizure medications.

Epilepsy remains a disease that affects many people around the world. With the development of new drugs to treat this condition, the importance of therapeutic drug monitoring continues to rise and remains a challenge for the medical community. This review article explores recent advances in the detection of antiepileptic drugs across various sample types commonly used for drug monitoring, with a focus on their applications and impact. Some of these new methods have proven to be simpler, greener, and faster, making them easier to apply in the context of therapeutic drug monitoring. Additionally, besides the classic use of blood and its derivatives, there has been significant research into the application of alternative matrices due to their ease of sample collection and capacity to reflect drug behavior in blood. These advances have contributed to increasing the efficacy of therapeutic drug monitoring while enhancing its accessibility to the population.